U.S. patent application number 16/570129 was filed with the patent office on 2020-03-05 for antibody constructs for cdh19 and cd3.
The applicant listed for this patent is AMGEN INC., AMGEN RESEARCH (MUNICH) GMBH. Invention is credited to Brian Mingtung Chan, Patrick Hoffmann, M. Shawn Jeffries, Chadwick Terence King, Roman Kischel, Peter Kufer, Bryan Lemon, Ralf Lutterbuse, Zheng Pan, Doris Rau, Tobias Raum, Holger Wesche, Dineli Wickramasinghe, Shouhua Xiao.
Application Number | 20200071405 16/570129 |
Document ID | / |
Family ID | 50137614 |
Filed Date | 2020-03-05 |
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United States Patent
Application |
20200071405 |
Kind Code |
A1 |
Xiao; Shouhua ; et
al. |
March 5, 2020 |
ANTIBODY CONSTRUCTS FOR CDH19 AND CD3
Abstract
The present invention provides to a antibody construct
comprising a first human binding domain capable of binding to human
CDH19 on the surface of a target cell and a second domain capable
of binding to human CD3 on the surface of a T cell. Moreover, the
invention relates to a nucleic acid sequence encoding the antibody
construct, a vector comprising said nucleic acid sequence and a
host cell transformed or transfected with said vector. Furthermore,
the invention relates a process for the production of the antibody
construct of the invention, a medical use of said antibody
construct and a kit comprising said antibody construct.
Inventors: |
Xiao; Shouhua; (Foster City,
CA) ; Pan; Zheng; (Fremont, CA) ;
Wickramasinghe; Dineli; (San Francisco, CA) ;
Jeffries; M. Shawn; (Indianapolis, IN) ; King;
Chadwick Terence; (North Vancouver, CA) ; Chan; Brian
Mingtung; (Port Coquitlam, CA) ; Kufer; Peter;
(Munich, DE) ; Lutterbuse; Ralf; (Munich, DE)
; Raum; Tobias; (Munich, DE) ; Hoffmann;
Patrick; (Munich, DE) ; Rau; Doris; (Munich,
DE) ; Kischel; Roman; (Munich, DE) ; Lemon;
Bryan; (Mountain View, CA) ; Wesche; Holger;
(San Francisco, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
AMGEN RESEARCH (MUNICH) GMBH
AMGEN INC. |
Munich
Thousand Oaks |
CA |
DE
US |
|
|
Family ID: |
50137614 |
Appl. No.: |
16/570129 |
Filed: |
September 13, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
14165330 |
Jan 27, 2014 |
|
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16570129 |
|
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61785147 |
Mar 14, 2013 |
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61756991 |
Jan 25, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07K 2317/626 20130101;
C07K 16/2896 20130101; A61K 47/60 20170801; C07K 2317/569 20130101;
C07K 2317/21 20130101; C07K 16/3053 20130101; C07K 2317/73
20130101; C07K 2317/77 20130101; C07K 2317/622 20130101; A61P 35/04
20180101; C07K 16/468 20130101; C07K 2319/00 20130101; C07K 2317/31
20130101; C07K 2317/565 20130101; C07K 2317/33 20130101; A61P 35/00
20180101; A61K 2039/505 20130101; C07K 16/28 20130101; C07K 16/2809
20130101; C07K 2317/92 20130101 |
International
Class: |
C07K 16/28 20060101
C07K016/28; C07K 16/30 20060101 C07K016/30; A61K 47/60 20060101
A61K047/60; C07K 16/46 20060101 C07K016/46 |
Claims
1. An isolated multispecific antibody construct comprising a first
human binding domain capable of binding to human CDH19 on the
surface of a target cell and a second domain capable of binding to
human CD3 on the surface of a T cell.
2. The antibody construct according to claim 1, wherein the first
binding domain comprises a VH region comprising CDR-H1, CDR-H2 and
CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3
selected from the group consisting of: (a) CDR-H1 as depicted in
SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as
depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID NO: 220,
CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as depicted in SEQ
ID NO: 222, CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted
in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as
depicted in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251
and CDR-L3 as depicted in SEQ ID NO: 252, CDR-H1 as depicted in SEQ
ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted
in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as
depicted in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO:
927, CDR-H1 as depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ
ID NO: 83, CDR-H3 as depicted in SEQ ID NO: 909, CDR-L1 as depicted
in SEQ ID NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3
as depicted in SEQ ID NO: 927, CDR-H1 as depicted in SEQ ID NO: 52,
CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID
NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in
SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 926, CDR-H1 as
depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53,
CDR-H3 as depicted in SEQ ID NO: 904, CDR-L1 as depicted in SEQ ID
NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as
depicted in SEQ ID NO: 926, CDR-H1 as depicted in SEQ ID NO: 1126,
CDR-H2 as depicted in SEQ ID NO: 1127, CDR-H3 as depicted in SEQ ID
NO: 1128, CDR-L1 as depicted in SEQ ID NO: 1129, CDR-L2 as depicted
in SEQ ID NO: 1130 and CDR-L3 as depicted in SEQ ID NO: 1131,
CDR-H1 as depicted in SEQ ID NO: 1165, CDR-H2 as depicted in SEQ ID
NO: 1166, CDR-H3 as depicted in SEQ ID NO: 1167, CDR-L1 as depicted
in SEQ ID NO: 1168, CDR-L2 as depicted in SEQ ID NO: 1169 and
CDR-L3 as depicted in SEQ ID NO: 1170, CDR-H1 as depicted in SEQ ID
NO: 1334, CDR-H2 as depicted in SEQ ID NO: 1335, CDR-H3 as depicted
in SEQ ID NO: 1336, CDR-L1 as depicted in SEQ ID NO: 1337, CDR-L2
as depicted in SEQ ID NO: 1338 and CDR-L3 as depicted in SEQ ID NO:
1339, CDR-H1 as depicted in SEQ ID NO: 1347, CDR-H2 as depicted in
SEQ ID NO: 1348, CDR-H3 as depicted in SEQ ID NO: 1349, CDR-L1 as
depicted in SEQ ID NO: 1350, CDR-L2 as depicted in SEQ ID NO: 1351
and CDR-L3 as depicted in SEQ ID NO: 1352, and CDR-H1 as depicted
in SEQ ID NO: 1360 CDR-H2 as depicted in SEQ ID NO: 1361, CDR-H3 as
depicted in SEQ ID NO: 1362, CDR-L1 as depicted in SEQ ID NO: 1363,
CDR-L2 as depicted in SEQ ID NO: 1364 and CDR-L3 as depicted in SEQ
ID NO: 1365, CDR-H1 as depicted in SEQ ID NO: 1425 CDR-H2 as
depicted in SEQ ID NO: 1426, CDR-H3 as depicted in SEQ ID NO: 1427,
CDR-L1 as depicted in SEQ ID NO: 1428, CDR-L2 as depicted in SEQ ID
NO: 1429 and CDR-L3 as depicted in SEQ ID NO: 1430, CDR-H1 as
depicted in SEQ ID NO: 1438 CDR-H2 as depicted in SEQ ID NO: 1439,
CDR-H3 as depicted in SEQ ID NO: 1440, CDR-L1 as depicted in SEQ ID
NO: 1441, CDR-L2 as depicted in SEQ ID NO: 1442 and CDR-L3 as
depicted in SEQ ID NO: 1443; (b) CDR-H1 as depicted in SEQ ID NO:
124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in
SEQ ID NO: 126, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as
depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO:
294, CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in
SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 132, CDR-L1 as
depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299
and CDR-L3 as depicted in SEQ ID NO: 300, CDR-H1 as depicted in SEQ
ID NO: 136, CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as
depicted in SEQ ID NO: 138, CDR-L1 as depicted in SEQ ID NO: 304,
CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ
ID NO: 306, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as
depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 144,
CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID
NO: 311 and CDR-L3 as depicted in SEQ ID NO: 312, CDR-H1 as
depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149,
CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID
NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as
depicted in SEQ ID NO: 318, CDR-H1 as depicted in SEQ ID NO: 166,
CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID
NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted
in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 336, CDR-H1
as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO:
125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in
SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as
depicted in SEQ ID NO: 294, CDR-H1 as depicted in SEQ ID NO: 124,
CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID
NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted
in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 928, CDR-H1
as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO:
125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in
SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as
depicted in SEQ ID NO: 929, CDR-H1 as depicted in SEQ ID NO: 166,
CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID
NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted
in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 336, CDR-H1
as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO:
167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in
SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as
depicted in SEQ ID NO: 942, CDR-H1 as depicted in SEQ ID NO: 166,
CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID
NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted
in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 943, CDR-H1
as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO:
149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in
SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as
depicted in SEQ ID NO: 318, CDR-H1 as depicted in SEQ ID NO: 148,
CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID
NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted
in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 937, CDR-H1
as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO:
149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in
SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as
depicted in SEQ ID NO: 938, CDR-H1 as depicted in SEQ ID NO: 148,
CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID
NO: 919, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted
in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 938, CDR-H1
as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO:
143, CDR-H3 as depicted in SEQ ID NO: 144, CDR-L1 as depicted in
SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as
depicted in SEQ ID NO: 935, CDR-H1 as depicted in SEQ ID NO: 142,
CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID
NO: 918, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted
in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 935, CDR-H1
as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO:
143, CDR-H3 as depicted in SEQ ID NO: 918, CDR-L1 as depicted in
SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as
depicted in SEQ ID NO: 936, CDR-H1 as depicted in SEQ ID NO: 136,
CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID
NO: 138, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted
in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 933, CDR-H1
as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO:
137, CDR-H3 as depicted in SEQ ID NO: 917, CDR-L1 as depicted in
SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as
depicted in SEQ ID NO: 934, CDR-H1 as depicted in SEQ ID NO: 130,
CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID
NO: 132, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted
in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 930, CDR-H1
as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO:
131, CDR-H3 as depicted in SEQ ID NO: 916, CDR-L1 as depicted in
SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as
depicted in SEQ ID NO: 931, CDR-H1 as depicted in SEQ ID NO: 130,
CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID
NO: 916, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted
in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 932, CDR-H1
as depicted in SEQ ID NO: 1009, CDR-H2 as depicted in SEQ ID NO:
1010, CDR-H3 as depicted in SEQ ID NO: 1011, CDR-L1 as depicted in
SEQ ID NO: 1012, CDR-L2 as depicted in SEQ ID NO: 1013 and CDR-L3
as depicted in SEQ ID NO: 1014, CDR-H1 as depicted in SEQ ID NO:
1022, CDR-H2 as depicted in SEQ ID NO: 1023, CDR-H3 as depicted in
SEQ ID NO: 1024, CDR-L1 as depicted in SEQ ID NO: 1025, CDR-L2 as
depicted in SEQ ID NO: 1026 and CDR-L3 as depicted in SEQ ID NO:
1027, CDR-H1 as depicted in SEQ ID NO: 1035, CDR-H2 as depicted in
SEQ ID NO: 1036, CDR-H3 as depicted in SEQ ID NO: 1037, CDR-L1 as
depicted in SEQ ID NO: 1038, CDR-L2 as depicted in SEQ ID NO: 1039
and CDR-L3 as depicted in SEQ ID NO: 1040, CDR-H1 as depicted in
SEQ ID NO: 1074, CDR-H2 as depicted in SEQ ID NO: 1075, CDR-H3 as
depicted in SEQ ID NO: 1076, CDR-L1 as depicted in SEQ ID NO: 1077,
CDR-L2 as depicted in SEQ ID NO: 1078 and CDR-L3 as depicted in SEQ
ID NO: 1079, CDR-H1 as depicted in SEQ ID NO: 1100, CDR-H2 as
depicted in SEQ ID NO: 1101, CDR-H3 as depicted in SEQ ID NO: 1102,
CDR-L1 as depicted in SEQ ID NO: 1103, CDR-L2 as depicted in SEQ ID
NO: 1104 and CDR-L3 as depicted in SEQ ID NO: 1105, CDR-H1 as
depicted in SEQ ID NO: 1113, CDR-H2 as depicted in SEQ ID NO: 1114,
CDR-H3 as depicted in SEQ ID NO: 1115, CDR-L1 as depicted in SEQ ID
NO: 1116, CDR-L2 as depicted in SEQ ID NO: 1117 and CDR-L3 as
depicted in SEQ ID NO: 1118, CDR-H1 as depicted in SEQ ID NO: 1243,
CDR-H2 as depicted in SEQ ID NO: 1244, CDR-H3 as depicted in SEQ ID
NO: 1245, CDR-L1 as depicted in SEQ ID NO: 1246, CDR-L2 as depicted
in SEQ ID NO: 1247 and CDR-L3 as depicted in SEQ ID NO: 1248,
CDR-H1 as depicted in SEQ ID NO: 1256, CDR-H2 as depicted in SEQ ID
NO: 1257, CDR-H3 as depicted in SEQ ID NO: 1258, CDR-L1 as depicted
in SEQ ID NO: 1259, CDR-L2 as depicted in SEQ ID NO: 1260 and
CDR-L3 as depicted in SEQ ID NO: 1261, CDR-H1 as depicted in SEQ ID
NO: 1269, CDR-H2 as depicted in SEQ ID NO: 1270, CDR-H3 as depicted
in SEQ ID NO: 1271, CDR-L1 as depicted in SEQ ID NO: 1272, CDR-L2
as depicted in SEQ ID NO: 1273 and CDR-L3 as depicted in SEQ ID NO:
1274, CDR-H1 as depicted in SEQ ID NO: 1282, CDR-H2 as depicted in
SEQ ID NO: 1283, CDR-H3 as depicted in SEQ ID NO: 1284, CDR-L1 as
depicted in SEQ ID NO: 1285, CDR-L2 as depicted in SEQ ID NO: 1286
and CDR-L3 as depicted in SEQ ID NO: 1287, and CDR-H1 as depicted
in SEQ ID NO: 1295, CDR-H2 as depicted in SEQ ID NO: 1296, CDR-H3
as depicted in SEQ ID NO: 1297, CDR-L1 as depicted in SEQ ID NO:
1298, CDR-L2 as depicted in SEQ ID NO: 1299 and CDR-L3 as depicted
in SEQ ID NO: 1300; (c) CDR-H1 as depicted in SEQ ID NO: 94, CDR-H2
as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID NO: 96,
CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted in SEQ ID
NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1 as
depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO: 101,
CDR-H3 as depicted in SEQ ID NO: 102, CDR-L1 as depicted in SEQ ID
NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as
depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 118,
CDR-H2 as depicted in SEQ ID NO: 119, CDR-H3 as depicted in SEQ ID
NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted
in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, CDR-H1
as depicted in SEQ ID NO: 154, CDR-H2 as depicted in SEQ ID NO:
155, CDR-H3 as depicted in SEQ ID NO: 156, CDR-L1 as depicted in
SEQ ID NO: 322, CDR-L2 as depicted in SEQ ID NO: 323 and CDR-L3 as
depicted in SEQ ID NO: 324, CDR-H1 as depicted in SEQ ID NO: 100,
CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID
NO: 912, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted
in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1
as depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO:
101, CDR-H3 as depicted in SEQ ID NO: 913, CDR-L1 as depicted in
SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as
depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 94,
CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID
NO: 910, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted
in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1
as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95,
CDR-H3 as depicted in SEQ ID NO: 911, CDR-L1 as depicted in SEQ ID
NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as
depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 118,
CDR-H2 as depicted in SEQ ID NO: 119, CDR-H3 as depicted in SEQ ID
NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted
in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, CDR-H1
as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO:
914, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in
SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as
depicted in SEQ ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 154,
CDR-H2 as depicted in SEQ ID NO: 155, CDR-H3 as depicted in SEQ ID
NO: 920, CDR-L1 as depicted in SEQ ID NO: 322, CDR-L2 as depicted
in SEQ ID NO: 323 and CDR-L3 as depicted in SEQ ID NO: 324, CDR-H1
as depicted in SEQ ID NO: 996, CDR-H2 as depicted in SEQ ID NO:
997, CDR-H3 as depicted in SEQ ID NO: 998, CDR-L1 as depicted in
SEQ ID NO: 999, CDR-L2 as depicted in SEQ ID NO: 1000 and CDR-L3 as
depicted in SEQ ID NO: 1001, CDR-H1 as depicted in SEQ ID NO: 1048,
CDR-H2 as depicted in SEQ ID NO: 1049, CDR-H3 as depicted in SEQ ID
NO: 1050, CDR-L1 as depicted in SEQ ID NO: 1051, CDR-L2 as depicted
in SEQ ID NO: 1052 and CDR-L3 as depicted in SEQ ID NO: 1053, and
CDR-H1 as depicted in SEQ ID NO: 1087, CDR-H2 as depicted in SEQ ID
NO: 1088, CDR-H3 as depicted in SEQ ID NO: 1089, CDR-L1 as depicted
in SEQ ID NO: 1090, CDR-L2 as depicted in SEQ ID NO: 1091 and
CDR-L3 as depicted in SEQ ID NO: 1092; (d) CDR-H1 as depicted in
SEQ ID NO: 4, CDR-H2 as depicted in SEQ ID NO: 5, CDR-H3 as
depicted in SEQ ID NO: 6, CDR-L1 as depicted in SEQ ID NO: 172,
CDR-L2 as depicted in SEQ ID NO: 173 and CDR-L3 as depicted in SEQ
ID NO: 174, CDR-H1 as depicted in SEQ ID NO: 10, CDR-H2 as depicted
in SEQ ID NO: 11, CDR-H3 as depicted in SEQ ID NO: 12, CDR-L1 as
depicted in SEQ ID NO: 178, CDR-L2 as depicted in SEQ ID NO: 179
and CDR-L3 as depicted in SEQ ID NO: 180, CDR-H1 as depicted in SEQ
ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted
in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as
depicted in SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO:
198, CDR-H1 as depicted in SEQ ID NO: 34, CDR-H2 as depicted in SEQ
ID NO: 35, CDR-H3 as depicted in SEQ ID NO: 36, CDR-L1 as depicted
in SEQ ID NO: 202, CDR-L2 as depicted in SEQ ID NO: 203 and CDR-L3
as depicted in SEQ ID NO: 204, CDR-H1 as depicted in SEQ ID NO: 46,
CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID
NO: 48, CDR-L1 as depicted in SEQ ID NO: 214, CDR-L2 as depicted in
SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as
depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 59,
CDR-H3 as depicted in SEQ ID NO: 60, CDR-L1 as depicted in SEQ ID
NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as
depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 64,
CDR-H2 as depicted in SEQ ID NO: 65, CDR-H3 as depicted in SEQ ID
NO: 66, CDR-L1 as depicted in SEQ ID NO: 232, CDR-L2 as depicted in
SEQ ID NO: 233 and CDR-L3 as depicted in SEQ ID NO: 234, CDR-H1 as
depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 71,
CDR-H3 as depicted in SEQ ID NO: 72, CDR-L1 as depicted in SEQ ID
NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as
depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 160,
CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID
NO: 162, CDR-L1 as depicted in SEQ ID NO: 328, CDR-L2 as depicted
in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1
as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47,
CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID
NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as
depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46,
CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID
NO: 902, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted
in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1
as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47,
CDR-H3 as depicted in SEQ ID NO: 903, CDR-L1 as depicted in SEQ ID
NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as
depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46,
CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID
NO: 48, CDR-L1 as depicted in SEQ ID NO: 925, CDR-L2 as depicted in
SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as
depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907,
CDR-H3 as depicted in SEQ ID NO: 72, CDR-L1 as depicted in SEQ ID
NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as
depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 70,
CDR-H2 as depicted in SEQ ID
NO: 907, CDR-H3 as depicted in SEQ ID NO: 908, CDR-L1 as depicted
in SEQ ID NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3
as depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 28,
CDR-H2 as depicted in SEQ ID NO: 901, CDR-H3 as depicted in SEQ ID
NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in
SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as
depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905,
CDR-H3 as depicted in SEQ ID NO: 906, CDR-L1 as depicted in SEQ ID
NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as
depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 58,
CDR-H2 as depicted in SEQ ID NO: 905, CDR-H3 as depicted in SEQ ID
NO: 60, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in
SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as
depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161,
CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID
NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 160,
CDR-H2 as depicted in SEQ ID NO: 921, CDR-H3 as depicted in SEQ ID
NO: 162, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted
in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 940, CDR-H1
as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO:
161, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in
SEQ ID NO: 941, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 28,
CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID
NO: 30, CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as depicted in
SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as
depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as
depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 28,
CDR-H2 as depicted in SEQ ID NO: 901, CDR-H3 as depicted in SEQ ID
NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in
SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as
depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 970,
CDR-H2 as depicted in SEQ ID NO: 971, CDR-H3 as depicted in SEQ ID
NO: 972, CDR-L1 as depicted in SEQ ID NO: 973, CDR-L2 as depicted
in SEQ ID NO: 974 and CDR-L3 as depicted in SEQ ID NO: 975, CDR-H1
as depicted in SEQ ID NO: 1061, CDR-H2 as depicted in SEQ ID NO:
1062, CDR-H3 as depicted in SEQ ID NO: 1063, CDR-L1 as depicted in
SEQ ID NO: 1064, CDR-L2 as depicted in SEQ ID NO: 1065 and CDR-L3
as depicted in SEQ ID NO: 1066, CDR-H1 as depicted in SEQ ID NO:
1139, CDR-H2 as depicted in SEQ ID NO: 1140, CDR-H3 as depicted in
SEQ ID NO: 1141, CDR-L1 as depicted in SEQ ID NO: 1142, CDR-L2 as
depicted in SEQ ID NO: 1143 and CDR-L3 as depicted in SEQ ID NO:
1144, CDR-H1 as depicted in SEQ ID NO: 1152, CDR-H2 as depicted in
SEQ ID NO: 1153, CDR-H3 as depicted in SEQ ID NO: 1154, CDR-L1 as
depicted in SEQ ID NO: 1155, CDR-L2 as depicted in SEQ ID NO: 1156
and CDR-L3 as depicted in SEQ ID NO: 1157, CDR-H1 as depicted in
SEQ ID NO: 1178, CDR-H2 as depicted in SEQ ID NO: 1179, CDR-H3 as
depicted in SEQ ID NO: 1180, CDR-L1 as depicted in SEQ ID NO: 1181,
CDR-L2 as depicted in SEQ ID NO: 1182 and CDR-L3 as depicted in SEQ
ID NO: 1183, CDR-H1 as depicted in SEQ ID NO: 1191, CDR-H2 as
depicted in SEQ ID NO: 1192, CDR-H3 as depicted in SEQ ID NO: 1193,
CDR-L1 as depicted in SEQ ID NO: 1194, CDR-L2 as depicted in SEQ ID
NO: 1195 and CDR-L3 as depicted in SEQ ID NO: 1196, CDR-H1 as
depicted in SEQ ID NO: 1204, CDR-H2 as depicted in SEQ ID NO: 1205,
CDR-H3 as depicted in SEQ ID NO: 1206, CDR-L1 as depicted in SEQ ID
NO: 1207, CDR-L2 as depicted in SEQ ID NO: 1208 and CDR-L3 as
depicted in SEQ ID NO: 1209, CDR-H1 as depicted in SEQ ID NO: 1217,
CDR-H2 as depicted in SEQ ID NO: 1218, CDR-H3 as depicted in SEQ ID
NO: 1219, CDR-L1 as depicted in SEQ ID NO: 1220, CDR-L2 as depicted
in SEQ ID NO: 1221 and CDR-L3 as depicted in SEQ ID NO: 1222,
CDR-H1 as depicted in SEQ ID NO: 1230, CDR-H2 as depicted in SEQ ID
NO: 1231, CDR-H3 as depicted in SEQ ID NO: 1232, CDR-L1 as depicted
in SEQ ID NO: 1233, CDR-L2 as depicted in SEQ ID NO: 1234 and
CDR-L3 as depicted in SEQ ID NO: 1235, CDR-H1 as depicted in SEQ ID
NO: 1308, CDR-H2 as depicted in SEQ ID NO: 1309, CDR-H3 as depicted
in SEQ ID NO: 1310, CDR-L1 as depicted in SEQ ID NO: 1311, CDR-L2
as depicted in SEQ ID NO: 1312 and CDR-L3 as depicted in SEQ ID NO:
1313, CDR-H1 as depicted in SEQ ID NO: 1321, CDR-H2 as depicted in
SEQ ID NO: 1322, CDR-H3 as depicted in SEQ ID NO: 1323, CDR-L1 as
depicted in SEQ ID NO: 1324, CDR-L2 as depicted in SEQ ID NO: 1325
and CDR-L3 as depicted in SEQ ID NO: 1326, CDR-H1 as depicted in
SEQ ID NO: 1373, CDR-H2 as depicted in SEQ ID NO: 1374, CDR-H3 as
depicted in SEQ ID NO: 1375, CDR-L1 as depicted in SEQ ID NO: 1376,
CDR-L2 as depicted in SEQ ID NO: 1377 and CDR-L3 as depicted in SEQ
ID NO: 1378, CDR-H1 as depicted in SEQ ID NO: 1386, CDR-H2 as
depicted in SEQ ID NO: 1387, CDR-H3 as depicted in SEQ ID NO: 1388,
CDR-L1 as depicted in SEQ ID NO: 1389, CDR-L2 as depicted in SEQ ID
NO: 1390 and CDR-L3 as depicted in SEQ ID NO: 1391, CDR-H1 as
depicted in SEQ ID NO: 1399, CDR-H2 as depicted in SEQ ID NO: 1400,
CDR-H3 as depicted in SEQ ID NO: 1401, CDR-L1 as depicted in SEQ ID
NO: 1402, CDR-L2 as depicted in SEQ ID NO: 1403 and CDR-L3 as
depicted in SEQ ID NO: 1404, CDR-H1 as depicted in SEQ ID NO: 1412,
CDR-H2 as depicted in SEQ ID NO: 1413, CDR-H3 as depicted in SEQ ID
NO: 1414, CDR-L1 as depicted in SEQ ID NO: 1415, CDR-L2 as depicted
in SEQ ID NO: 1416 and CDR-L3 as depicted in SEQ ID NO: 1417; and
(e) CDR-H1 as depicted in SEQ ID NO: 76, CDR-H2 as depicted in SEQ
ID NO: 77, CDR-H3 as depicted in SEQ ID NO: 78, CDR-L1 as depicted
in SEQ ID NO: 244, CDR-L2 as depicted in SEQ ID NO: 245 and CDR-L3
as depicted in SEQ ID NO: 246, CDR-H1 as depicted in SEQ ID NO: 88,
CDR-H2 as depicted in SEQ ID NO: 89, CDR-H3 as depicted in SEQ ID
NO: 90, CDR-L1 as depicted in SEQ ID NO: 256, CDR-L2 as depicted in
SEQ ID NO: 257 and CDR-L3 as depicted in SEQ ID NO: 258, CDR-H1 as
depicted in SEQ ID NO: 106, CDR-H2 as depicted in SEQ ID NO: 107,
CDR-H3 as depicted in SEQ ID NO: 108, CDR-L1 as depicted in SEQ ID
NO: 274, CDR-L2 as depicted in SEQ ID NO: 275 and CDR-L3 as
depicted in SEQ ID NO: 276, CDR-H1 as depicted in SEQ ID NO: 112,
CDR-H2 as depicted in SEQ ID NO: 113, CDR-H3 as depicted in SEQ ID
NO: 114, CDR-L1 as depicted in SEQ ID NO: 280, CDR-L2 as depicted
in SEQ ID NO: 281 and CDR-L3 as depicted in SEQ ID NO: 282, CDR-H1
as depicted in SEQ ID NO: 106, CDR-H2 as depicted in SEQ ID NO:
107, CDR-H3 as depicted in SEQ ID NO: 108, CDR-L1 as depicted in
SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID NO: 275 and CDR-L3 as
depicted in SEQ ID NO: 276, and CDR-H1 as depicted in SEQ ID NO:
983, CDR-H2 as depicted in SEQ ID NO: 984, CDR-H3 as depicted in
SEQ ID NO: 985, CDR-L1 as depicted in SEQ ID NO: 986, CDR-L2 as
depicted in SEQ ID NO: 987 and CDR-L3 as depicted in SEQ ID NO:
988.
3. The antibody construct according to claim 2, wherein the first
binding domain comprises a VH region selected from the group
consisting of VH regions (a) as depicted in SEQ ID NO: 362, SEQ ID
NO: 364, SEQ ID NO: 485, SEQ ID NO: 486, SEQ ID NO: 487, SEQ ID NO:
492, SEQ ID NO: 493, SEQ ID NO: 494, SEQ ID NO:495, SEQ ID NO:1133,
SEQ ID NO:1172, SEQ ID NO:1341, SEQ ID NO: 1354, SEQ ID NO: 1367,
SEQ ID NO: 1432, and SEQ ID NO: 1445; (b) as depicted in SEQ ID NO:
342, SEQ ID NO: 366, SEQ ID NO: 370, SEQ ID NO: 344, SEQ ID NO:
372, SEQ ID NO: 368, SEQ ID NO: 496, SEQ ID NO: 497, SEQ ID NO:
498, SEQ ID NO: 499, SEQ ID NO: 500, SEQ ID NO: 508, SEQ ID NO:
509, SEQ ID NO: 510, SEQ ID NO: 511, SEQ ID NO: 512, SEQ ID NO:
519, SEQ ID NO: 520, SEQ ID NO: 521, SEQ ID NO: 522, SEQ ID NO:
523, SEQ ID NO: 524, SEQ ID NO: 525, SEQ ID NO: 526, SEQ ID NO:
527, SEQ ID NO: 528, SEQ ID NO: 529, SEQ ID NO: 530, SEQ ID NO:
531, SEQ ID NO: 532, SEQ ID NO: 533, SEQ ID NO: 534, SEQ ID NO:
535, SEQ ID NO: 536, SEQ ID NO: 537, SEQ ID NO: 538, SEQ ID NO:
1016, SEQ ID NO: 1029, SEQ ID NO: 1042, SEQ ID NO: 1081, SEQ ID NO:
1107, SEQ ID NO: 1120, SEQ ID NO: 1250, SEQ ID NO: 1263, SEQ ID NO:
1276, SEQ ID NO: 1289, and SEQ ID NO: 1302; (c) as depicted in SEQ
ID NO: 338, SEQ ID NO: 354, SEQ ID NO: 378, SEQ ID NO: 356, SEQ ID
NO: 476, SEQ ID NO: 477, SEQ ID NO: 478, SEQ ID NO: 479, SEQ ID NO:
480, SEQ ID NO: 481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO:
484, SEQ ID NO: 501, SEQ ID NO: 502, SEQ ID NO: 503, SEQ ID NO:
504, SEQ ID NO: 505, SEQ ID NO: 506, SEQ ID NO: 517, SEQ ID NO:
518, SEQ ID NO: 1003, SEQ ID NO: 1055, and SEQ ID NO: 1094; (d) as
depicted in SEQ ID NO: 352, SEQ ID NO: 360, SEQ ID NO: 388, SEQ ID
NO: 386, SEQ ID NO: 340, SEQ ID NO: 346, SEQ ID NO: 374, SEQ ID NO:
348, SEQ ID NO: 390, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO:
465, SEQ ID NO: 466, SEQ ID NO: 467, SEQ ID NO: 468, SEQ ID NO:
469, SEQ ID NO: 470, SEQ ID NO: 471, SEQ ID NO: 472, SEQ ID NO:
473, SEQ ID NO: 474, SEQ ID NO: 475, SEQ ID NO: 488, SEQ ID NO:
489, SEQ ID NO: 490, SEQ ID NO: 491, SEQ ID NO: 513, SEQ ID NO:
514, SEQ ID NO: 515, SEQ ID NO: 516, SEQ ID NO: 540, SEQ ID NO:
541, SEQ ID NO: 542, SEQ ID NO: 543, SEQ ID NO: 977, SEQ ID NO:
1068, SEQ ID NO: 1146, SEQ ID NO: 1159, SEQ ID NO: 1185, SEQ ID NO:
1198, SEQ ID NO: 1211, SEQ ID NO: 1224, SEQ ID NO: 1237, SEQ ID NO:
1315, SEQ ID NO: 1328, SEQ ID NO: 1380, SEQ ID NO: 1393, SEQ ID NO:
1406, and SEQ ID NO: 1419; and (e) as depicted in SEQ ID NO: 376,
SEQ ID NO: 392, SEQ ID NO: 358, SEQ ID NO: 350, SEQ ID NO: 507, and
SEQ ID NO: 990.
4. The antibody construct according to claim 2, wherein the first
binding domain comprises a VL region selected from the group
consisting of VL regions (a) as depicted in SEQ ID NO: 418, SEQ ID
NO: 420, SEQ ID NO: 580, SEQ ID NO: 581, SEQ ID NO: 582, SEQ ID NO:
587, SEQ ID NO: 588, SEQ ID NO: 589, SEQ ID NO:590, SEQ ID NO:1135,
SEQ ID NO:1174, SEQ ID NO:1343, SEQ ID NO: 1356, SEQ ID NO: 1369,
SEQ ID NO: 1434, and SEQ ID NO: 1447; (b) as depicted in SEQ ID NO:
398, SEQ ID NO: 422, SEQ ID NO: 426, SEQ ID NO: 400, SEQ ID NO:
428, SEQ ID NO: 424, SEQ ID NO: 591, SEQ ID NO: 592, SEQ ID NO:
593, SEQ ID NO: 594, SEQ ID NO: 595, SEQ ID NO: 603, SEQ ID NO:
604, SEQ ID NO: 605, SEQ ID NO: 606, SEQ ID NO: 607, SEQ ID NO:
614, SEQ ID NO: 615, SEQ ID NO: 616, SEQ ID NO: 617, SEQ ID NO:
618, SEQ ID NO: 619, SEQ ID NO: 620, SEQ ID NO: 621, SEQ ID NO:
622, SEQ ID NO: 623, SEQ ID NO: 624, SEQ ID NO: 625, SEQ ID NO:
626, SEQ ID NO: 627, SEQ ID NO: 628, SEQ ID NO: 629, SEQ ID NO:
630, SEQ ID NO: 631, SEQ ID NO: 632, SEQ ID NO: 633, SEQ ID NO:
1018, SEQ ID NO: 1031, SEQ ID NO: 1044, SEQ ID NO: 1083, SEQ ID NO:
1109, SEQ ID NO: 1122, SEQ ID NO: 1252, SEQ ID NO: 1265, SEQ ID NO:
1278, SEQ ID NO: 1291, and SEQ ID NO: 1304; (c) as depicted in SEQ
ID NO: 394, SEQ ID NO: 410, SEQ ID NO: 434, SEQ ID NO: 412, SEQ ID
NO: 571, SEQ ID NO: 572, SEQ ID NO: 573, SEQ ID NO: 574, SEQ ID NO:
575, SEQ ID NO: 576, SEQ ID NO: 577, SEQ ID NO: 578, SEQ ID NO:
579, SEQ ID NO: 596, SEQ ID NO: 597, SEQ ID NO: 598, SEQ ID NO:
599, SEQ ID NO: 600, SEQ ID NO: 601, SEQ ID NO: 612, SEQ ID NO:
613, SEQ ID NO: 1005, SEQ ID NO: 1057, and SEQ ID NO: 1096; (d) as
depicted in SEQ ID NO: 408, SEQ ID NO: 416, SEQ ID NO: 444, SEQ ID
NO: 442, SEQ ID NO: 396, SEQ ID NO: 402, SEQ ID NO: 430, SEQ ID NO:
404, SEQ ID NO: 446, SEQ ID NO: 558, SEQ ID NO: 559, SEQ ID NO:
560, SEQ ID NO: 561, SEQ ID NO: 562, SEQ ID NO: 563, SEQ ID NO:
564, SEQ ID NO: 565, SEQ ID NO: 566, SEQ ID NO: 567, SEQ ID NO:
568, SEQ ID NO: 569, SEQ ID NO: 570, SEQ ID NO: 583, SEQ ID NO:
584, SEQ ID NO: 585, SEQ ID NO: 586, SEQ ID NO: 608, SEQ ID NO:
609, SEQ ID NO: 610, SEQ ID NO: 611, SEQ ID NO: 635, SEQ ID NO:
636, SEQ ID NO: 637, SEQ ID NO: 638, SEQ ID NO: 979, SEQ ID NO:
1070, SEQ ID NO: 1148, SEQ ID NO: 1161, SEQ ID NO: 1187, SEQ ID NO:
1200, SEQ ID NO: 1213, SEQ ID NO: 1226, SEQ ID NO: 1239, SEQ ID NO:
1317, SEQ ID NO: 1330, SEQ ID NO: 1382, SEQ ID NO: 1395, SEQ ID NO:
1408, and SEQ ID NO: 1421; and (e) as depicted in SEQ ID NO: 432,
SEQ ID NO: 448, SEQ ID NO: 414, SEQ ID NO: 406, SEQ ID NO: 602, and
SEQ ID NO: 992.
5. The antibody construct according to claim 2, wherein the first
binding domain comprises a VH region and a VL region selected from
the group consisting of: (1) pairs of a VH region and a VL region
as depicted in SEQ ID NOs: 362+418, SEQ ID NOs: 364+420, SEQ ID
NOs: 485+580, SEQ ID NOs: 486+581, SEQ ID NOs: 487+582, SEQ ID NOs:
492+587, SEQ ID NOs: 493+588, SEQ ID NOs: 494+589, SEQ ID NOs:
495+590, SEQ ID NOs: 1133+1135, SEQ ID NOs: 1172+1174, SEQ ID NOs:
1341+1343, SEQ ID NOs: 1354+1356, SEQ ID NOs: 1367+1369, SEQ ID
NOs: 1432+1434, and SEQ ID NOs: 1445+1447; (2) pairs of a VH region
and a VL region as depicted in SEQ ID NOs: 342+398, SEQ ID NOs:
366+422, SEQ ID NOs: 370+426, SEQ ID NOs: 344+400, SEQ ID NOs:
372+428, SEQ ID NOs: 368+424, SEQ ID NOs: 496+591, SEQ ID NOs:
497+592, SEQ ID NOs: 498+593, SEQ ID NOs: 499+594, SEQ ID NOs:
500+595, SEQ ID NOs: 508+603, SEQ ID NOs: 509+604, SEQ ID NOs:
510+605, SEQ ID NOs: 511+606, SEQ ID NOs: 512+607, SEQ ID NOs:
519+614, SEQ ID NOs: 520+615, SEQ ID NOs: 521+616, SEQ ID NOs:
522+617, SEQ ID NOs: 523+618, SEQ ID NOs: 524+619, SEQ ID NOs:
525+620, SEQ ID NOs: 526+621, SEQ ID NOs: 527+622, SEQ ID NOs:
528+623, SEQ ID NOs: 529+624, SEQ ID NOs: 530+625, SEQ ID NOs:
531+626, SEQ ID NOs: 532+627, SEQ ID NOs: 533+628, SEQ ID NOs:
534+629, SEQ ID NOs: 535+630, SEQ ID NOs: 536+631, SEQ ID NOs:
537+632, SEQ ID NOs: 538+633, SEQ ID NOs: 1016+1018, SEQ ID NOs:
1029+1031, SEQ ID NOs: 1042+1044, SEQ ID NOs: 1081+1083, SEQ ID
NOs: 1107+1109, SEQ ID NOs: 1120+1122, SEQ ID NOs: 1250+1252, SEQ
ID NOs: 1263+1265, SEQ ID NOs: 1276+1278, SEQ ID NOs: 1289+1291,
and SEQ ID NOs: 1302+1304; (3) pairs of a VH region and a VL region
as depicted in SEQ ID NOs: 338+394, SEQ ID NOs: 354+410, SEQ ID
NOs: 378+434, SEQ ID NOs: 356+412, SEQ ID NOs: 476+571, SEQ ID NOs:
477+572, SEQ ID NOs: 478+573, SEQ ID NOs: 479+574, SEQ ID NOs:
480+575, SEQ ID NOs: 481+576, SEQ ID NOs: 482+577, SEQ ID NOs:
483+578, SEQ ID NOs: 484+579, SEQ ID NOs: 501+596, SEQ ID NOs:
502+597, SEQ ID NOs: 503+598, SEQ ID NOs: 504+599, SEQ ID NOs:
505+600, SEQ ID NOs: 506+601, SEQ ID NOs: 517+612, SEQ ID NOs:
518+613, SEQ ID NOs: 1003+1005, SEQ ID NOs: 1055+1057, and SEQ ID
NOs: 1094+1096; (4) pairs of a VH region and a VL region as
depicted in SEQ ID NOs: 352+408, SEQ ID NOs: 360+416, SEQ ID NOs:
388+444, SEQ ID NOs: 386+442, SEQ ID NOs: 340+396, SEQ ID NOs:
346+402, SEQ ID NOs: 374+430, SEQ ID NOs: 348+404, SEQ ID NOs:
390+446, SEQ ID NOs: 463+558, SEQ ID NOs: 464+559, SEQ ID NOs:
465+560, SEQ ID NOs: 466+561, SEQ ID NOs: 467+562, SEQ ID NOs:
468+563, SEQ ID NOs: 469+564, SEQ ID NOs: 470+565, SEQ ID NOs:
471+566, SEQ ID NOs: 472+567, SEQ ID NOs: 473+568, SEQ ID NOs:
474+569, SEQ ID NOs: 475+570, SEQ ID NOs: 488+583, SEQ ID NOs:
489+584, SEQ ID NOs: 490+585, SEQ ID NOs: 491+586, SEQ ID NOs:
513+608, SEQ ID NOs: 514+609, SEQ ID NOs: 515+610, SEQ ID NOs:
516+611, SEQ ID NOs: 540+635, SEQ ID NOs: 541+636, SEQ ID NOs:
542+637, SEQ ID NOs: 543+638, SEQ ID NOs: 977+979, SEQ ID NOs:
1068+1070, SEQ ID NOs: 1146+1148, SEQ ID NOs: 1159+1161, SEQ ID
NOs: 1185+1187, SEQ ID NOs: 1198+1200, SEQ ID NOs: 1211+1213, SEQ
ID NOs: 1224+1226, SEQ ID NOs: 1237+1239, SEQ ID NOs: 1315+1317,
SEQ ID NOs: 1328+1330, SEQ ID NOs: 1380, +1382 SEQ ID NOs:
1393+1395, SEQ ID NOs: 1406+1408, and SEQ ID NOs: 1419+1421; and
(5) pairs of a VH region and a VL region as depicted in SEQ ID NOs:
376+432, SEQ ID NOs: 392+448, SEQ ID NOs: 358+414, SEQ ID NOs:
350+406, SEQ ID NOs: 507+602, and SEQ ID NOs: 990+992.
6. The antibody construct according to claim 2, wherein the
antibody construct is in a format selected from the group
consisting of (scFv).sub.2, (single domain mAb).sub.2, scFv-single
domain mAb, diabodies and oligomers thereof.
7. The antibody construct according to claim 6, wherein the first
binding domain comprises an amino acid sequence selected from the
group consisting of (a) as depicted in SEQ ID NO: 117, SEQ ID NO:
1137, SEQ ID NO: 1176, SEQ ID NO: 1345, SEQ ID NO: 1358, SEQ ID NO:
1371, SEQ ID NO: 1436, and SEQ ID NO: 1449; (b) as depicted in SEQ
ID NO: 1020, SEQ ID NO: 1033, SEQ ID NO: 1046, SEQ ID NO: 1085, SEQ
ID NO: 1111, SEQ ID NO: 1124, SEQ ID NO: 1254, SEQ ID NO: 1267, SEQ
ID NO: 1280, SEQ ID NO: 1293, and SEQ ID NO: 1306; (c) as depicted
in SEQ ID NO: 1007, SEQ ID NO: 1059, and SEQ ID NO: 1098; (d) as
depicted in SEQ ID NO: 981, SEQ ID NO: 1072, SEQ ID NO: 1150, SEQ
ID NO: 1163, SEQ ID NO: 1189, SEQ ID NO: 1202, SEQ ID NO: 1215, SEQ
ID NO: 1228, SEQ ID NO: 1241, SEQ ID NO: 1319, SEQ ID NO: 1332, SEQ
ID NO: 1384, SEQ ID NO: 1397, SEQ ID NO: 1410, and SEQ ID NO: 1423;
and (e) as depicted in SEQ ID NO: 994.
8. The antibody construct according to claim 2, wherein the second
binding domain is capable of binding to human and Callithrix
jacchus, Saguinus oedipus or Saimiri sciureus CD3 epsilon.
9. The antibody construct according claim 8, comprising the amino
acid sequence selected from the group consisting of (a) as depicted
in SEQ ID NO: 1138, SEQ ID NO: 1177, SEQ ID NO: 1346, SEQ ID NO:
1359, SEQ ID NO: 1372, SEQ ID NO: 1437, and SEQ ID NO: 1450; (b) as
depicted in SEQ ID NO: 1021, SEQ ID NO: 1034, SEQ ID NO: 1047, SEQ
ID NO: 1086, SEQ ID NO: 1112, SEQ ID NO: 1125, SEQ ID NO: 1255, SEQ
ID NO: 1268, SEQ ID NO: 1281, SEQ ID NO: 1294, and SEQ ID NO: 1307;
(c) as depicted in SEQ ID NO: 1008, SEQ ID NO: 1060, and SEQ ID NO:
1099; (d) as depicted in SEQ ID NO: 982, SEQ ID NO: 1073, SEQ ID
NO: 1151, SEQ ID NO: 1164, SEQ ID NO: 1190, SEQ ID NO: 1203, SEQ ID
NO: 1216, SEQ ID NO: 1229, SEQ ID NO: 1242, SEQ ID NO: 1320, SEQ ID
NO: 1333, SEQ ID NO: 1385, SEQ ID NO: 1398, SEQ ID NO: 1411, and
SEQ ID NO: 1424; and (e) as depicted in SEQ ID NO: 995.
10. A nucleic acid encoding the antibody construct of claim 1.
11. A vector comprising the nucleic acid of claim 10.
12. A host cell transformed or transfected with the nucleic acid of
claim 10.
13. A process for producing an antibody construct, said process
comprising culturing the host cell of claim 12 under conditions
allowing the expression of the antibody construct and recovering
the produced antibody construct from the culture.
14. A composition comprising the antibody construct of claim 1.
15. (canceled)
16. A method for treating or ameliorating a melanoma disease or
metastatic melanoma disease, comprising the step of administering
to a subject in need thereof the antibody construct according to
claim 1.
17. The method according to claim 16, wherein the melanoma disease
or metastatic melanoma disease is superficial spreading melanoma,
lentigo maligna, lentigo maligna melanoma, acral lentiginous
melanoma or nodular melanoma.
18. A kit comprising the antibody construct of claim 1 according to
any one of claims 1 to 9, or produced according to the process of
claim 13, a vector as defined in claim 11, and/or a host cell as
defined in claim 12.
Description
RELATED APPLICATIONS
[0001] This application is related to a U.S. provisional
application entitled "Antibodies targeting CDH19 for melanoma",
filed on Mar. 15, 2013, the same day as the present application is
filed. This related application is incorporated in its entirety by
reference.
FIELD OF THE INVENTION
[0002] The present invention relates to an antibody construct
comprising a first human binding domain capable of binding to human
CDH19 on the surface of a target cell and a second domain capable
of binding to human CD3 on the surface of a T cell. Moreover, the
invention provides a nucleic acid sequence encoding the antibody
construct, a vector comprising said nucleic acid sequence and a
host cell transformed or transfected with said vector. Furthermore,
the invention provides a process for the production of the antibody
construct of the invention, a medical use of said antibody
construct and a kit comprising said antibody construct.
BACKGROUND OF THE INVENTION
[0003] Melanoma is a skin cancer that is caused by the oncogenic
transformation of melanocytes, which are pigment producing skin
cells. As of 2009, Melanoma had a prevalence of more than 870,000
cases in the US alone (US National Institutes of Health). Each
year, over 75,000 new cases of melanoma are diagnosed in the US,
and approximately 25% of patients have advanced disease at the time
of diagnosis. Despite the fact that cases of primary melanoma can
be cured by surgery if they are detected early enough, melanoma is
the leading cause of death from skin disease in the US, responsible
for about 10,000 deaths per year in the US. Once the disease has
spread and became metastatic, the prognosis is poor, with a 5 year
relative survival of 15%.
[0004] There are four basic types of melanomas. Three types are
found in the top layers of the skin and the fourth one is invasive
and has penetrated deeper into the skin and may have spread to
other areas of the body.
[0005] Superficial spreading melanoma is the most common type of
melanoma which accounts for about 70% of all cases. It grows along
the top layer of the skin for a fairly long time before penetrating
more deeply. It first appears as a flat or slightly raised
discolored patch that has irregular borders and may be somewhat
asymmetrical in form. The color varies, and you may see areas of
tan, brown, black, red, blue or white. This type of melanoma can
occur in a previously benign mole and is found most often in young
people.
[0006] Lentigo maligna is similar to the superficial spreading
type, as it also remains close to the skin surface for quite a
while, and usually appears as a flat or mildly elevated mottled
tan, brown or dark brown discoloration. It is found most often in
the elderly. When this cancer becomes invasive, it is referred to
as lentigo maligna melanoma.
[0007] Acral lentiginous melanoma also spreads superficially before
penetrating more deeply. It is quite different from the others,
though, as it usually appears as a black or brown discoloration
under the nails or on the soles of the feet or palms of the hands.
This type of melanoma is sometimes found on dark-skinned people,
and can often advance more quickly than superficial spreading
melanoma and lentigo maligna.
[0008] Nodular melanoma is usually invasive at the time it is first
diagnosed. The malignancy is recognized when it becomes a bump. It
is usually black, but occasionally is blue, gray, white, brown,
tan, red or skin tone. This is the most aggressive of the
melanomas, and is found in 10 to 15 percent of cases.
[0009] Common treatments for metastatic melanoma include
chemotherapy, targeted therapies for eligible patients (e.g. BRAF
inhibitor treatment for patients with BRAF mutations) and
immunotherapy. Metastatic melanoma is a tumor type where
immunotherapy has been demonstrated to not only slow disease
progression, but to lead to cures in late stage patients.
Interleukin-2 was approved for the use in metastatic melanoma in
1998, and in 2011 an antibody targeting CTLA4, a member of a new
generation of immune checkpoint inhibitors, gained approval by the
FDA.
[0010] CDH19 is a type II cadherin transmembrane protein of unknown
function. The human gene was cloned in 2000 based on its sequence
similarity to CDH7 (Kools, P. et al. Genomics. 2000). Expressed
Sequence Tags (ESTs) for CDH19 were isolated from melanocyte cDNA
libraries, indicating that expression of CDH19 may be limited to
cells of neural crest origin (Kools, P. et al. Genomics. 2000). In
support of this notion, rat CDH19 was found to be expressed
primarily in nerve ganglia and in Schwann cells during rat
embryonic development (Takahashi, M. and Osumi, O. Devl Dynamics.
2005.).
[0011] Diagnostic antibodies detecting CDH19 in Western Blot,
immunohistochemitstry or flow cytometry are known in the art and
commercially available. Those antibodies comprise poly- and
monoclonal antibodies generated in animal hosts.
SUMMARY OF THE INVENTION
[0012] The present invention provides an isolated multispecific
antibody construct comprising a first human binding domain capable
of binding to human CDH19 on the surface of a target cell and a
second domain capable of binding to human CD3 on the surface of a T
cell.
[0013] In one embodiment the antibody construct of the invention
the first binding domain comprises a VH region comprising CDR-H1,
CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and
CDR-L3 selected from the group consisting of: [0014] (a) CDR-H1 as
depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53,
CDR-H3 as depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID
NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as
depicted in SEQ ID NO: 222, CDR-H1 as depicted in SEQ ID NO: 82,
CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID
NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in
SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 252, CDR-H1 as
depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83,
CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID
NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as
depicted in SEQ ID NO: 927, CDR-H1 as depicted in SEQ ID NO: 82,
CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID
NO: 909, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted
in SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927, CDR-H1
as depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53,
CDR-H3 as depicted in SEQ ID NO: 54, CDR-L1 as depicted in SEQ ID
NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as
depicted in SEQ ID NO: 926, CDR-H1 as depicted in SEQ ID NO: 52,
CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID
NO: 904, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted
in SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 926, [0015]
CDR-H1 as depicted in SEQ ID NO: 1126, CDR-H2 as depicted in SEQ ID
NO: 1127, CDR-H3 as depicted in SEQ ID NO: 1128, CDR-L1 as depicted
in SEQ ID NO: 1129, CDR-L2 as depicted in SEQ ID NO: 1130 and
CDR-L3 as depicted in SEQ ID NO: 1131, [0016] CDR-H1 as depicted in
SEQ ID NO: 1165, CDR-H2 as depicted in SEQ ID NO: 1166, CDR-H3 as
depicted in SEQ ID NO: 1167, CDR-L1 as depicted in SEQ ID NO: 1168,
CDR-L2 as depicted in SEQ ID NO: 1169 and CDR-L3 as depicted in SEQ
ID NO: 1170, [0017] CDR-H1 as depicted in SEQ ID NO: 1334, CDR-H2
as depicted in SEQ ID NO: 1335, CDR-H3 as depicted in SEQ ID NO:
1336, CDR-L1 as depicted in SEQ ID NO: 1337, CDR-L2 as depicted in
SEQ ID NO: 1338 and CDR-L3 as depicted in SEQ ID NO: 1339, [0018]
CDR-H1 as depicted in SEQ ID NO: 1347, CDR-H2 as depicted in SEQ ID
NO: 1348, CDR-H3 as depicted in SEQ ID NO: 1349, CDR-L1 as depicted
in SEQ ID NO: 1350, CDR-L2 as depicted in SEQ ID NO: 1351 and
CDR-L3 as depicted in SEQ ID NO: 1352, and [0019] CDR-H1 as
depicted in SEQ ID NO: 1360 CDR-H2 as depicted in SEQ ID NO: 1361,
CDR-H3 as depicted in SEQ ID NO: 1362, CDR-L1 as depicted in SEQ ID
NO: 1363, CDR-L2 as depicted in SEQ ID NO: 1364 and CDR-L3 as
depicted in SEQ ID NO: 1365, [0020] CDR-H1 as depicted in SEQ ID
NO: 1425 CDR-H2 as depicted in SEQ ID NO: 1426, CDR-H3 as depicted
in SEQ ID NO: 1427, CDR-L1 as depicted in SEQ ID NO: 1428, CDR-L2
as depicted in SEQ ID NO: 1429 and CDR-L3 as depicted in SEQ ID NO:
1430, [0021] CDR-H1 as depicted in SEQ ID NO: 1438 CDR-H2 as
depicted in SEQ ID NO: 1439, CDR-H3 as depicted in SEQ ID NO: 1440,
CDR-L1 as depicted in SEQ ID NO: 1441, CDR-L2 as depicted in SEQ ID
NO: 1442 and CDR-L3 as depicted in SEQ ID NO: 1443; [0022] (b)
CDR-H1 as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID
NO: 125, CDR-H3 as depicted in SEQ ID NO: 126, CDR-L1 as depicted
in SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3
as depicted in SEQ ID NO: 294, CDR-H1 as depicted in SEQ ID NO:
130, CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in
SEQ ID NO: 132, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as
depicted in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO:
300, CDR-H1 as depicted in SEQ ID NO: 136, CDR-H2 as depicted in
SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID NO: 138, CDR-L1 as
depicted in SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305
and CDR-L3 as depicted in SEQ ID NO: 306, CDR-H1 as depicted in SEQ
ID NO: 142, CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as
depicted in SEQ ID NO: 144, CDR-L1 as depicted in SEQ ID NO: 310,
CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ
ID NO: 312, CDR-H1 as depicted in SEQ ID NO: 148, CDR-H2 as
depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID NO: 150,
CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID
NO: 317 and CDR-L3 as depicted in SEQ ID NO: 318, CDR-H1 as
depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO: 167,
CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in SEQ ID
NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as
depicted in SEQ ID NO: 336, CDR-H1 as depicted in SEQ ID NO: 124,
CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID
NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted
in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 294, CDR-H1
as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO:
125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in
SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as
depicted in SEQ ID NO: 928, CDR-H1 as depicted in SEQ ID NO: 124,
CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID
NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted
in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 929, CDR-H1
as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO:
167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in
SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as
depicted in SEQ ID NO: 336, CDR-H1 as depicted in SEQ ID NO: 166,
CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID
NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted
in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 942, CDR-H1
as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO:
167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in
SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as
depicted in SEQ ID NO: 943, CDR-H1 as depicted in SEQ ID NO: 148,
CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID
NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted
in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 318, CDR-H1
as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO:
149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in
SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as
depicted in SEQ ID NO: 937, CDR-H1 as depicted in SEQ ID NO: 148,
CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID
NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted
in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 938, CDR-H1
as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO:
149, CDR-H3 as depicted in SEQ ID NO: 919, CDR-L1 as depicted in
SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as
depicted in SEQ ID NO: 938, CDR-H1 as depicted in SEQ ID NO: 142,
CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID
NO: 144, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted
in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 935, CDR-H1
as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO:
143, CDR-H3 as depicted in SEQ ID NO: 918, CDR-L1 as depicted in
SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as
depicted in SEQ ID NO: 935, CDR-H1 as depicted in SEQ ID NO: 142,
CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID
NO: 918, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted
in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 936, CDR-H1
as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO:
137, CDR-H3 as depicted in SEQ ID NO: 138, CDR-L1 as depicted in
SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as
depicted in SEQ ID NO: 933, CDR-H1 as depicted in SEQ ID NO: 136,
CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID
NO: 917, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted
in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 934, CDR-H1
as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO:
131, CDR-H3 as depicted in SEQ ID NO: 132, CDR-L1 as depicted in
SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as
depicted in SEQ ID NO: 930, CDR-H1 as depicted in SEQ ID NO: 130,
CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID
NO: 916, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted
in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 931, CDR-H1
as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO:
131, CDR-H3 as depicted in SEQ ID NO: 916, CDR-L1 as depicted in
SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as
depicted in SEQ ID NO: 932, CDR-H1 as depicted in SEQ ID NO: 1009,
CDR-H2 as depicted in SEQ ID NO: 1010, CDR-H3 as depicted in SEQ ID
NO: 1011, CDR-L1 as depicted in SEQ ID NO: 1012, CDR-L2 as depicted
in SEQ ID NO: 1013 and CDR-L3 as depicted in SEQ ID NO: 1014,
[0023] CDR-H1 as depicted in SEQ ID NO: 1022, CDR-H2 as depicted in
SEQ ID NO: 1023, CDR-H3 as depicted in SEQ ID NO: 1024, CDR-L1 as
depicted in SEQ ID NO: 1025, CDR-L2 as depicted in SEQ ID NO: 1026
and CDR-L3 as depicted in SEQ ID NO: 1027, [0024] CDR-H1 as
depicted in SEQ ID NO: 1035, CDR-H2 as depicted in SEQ ID NO: 1036,
CDR-H3 as depicted in SEQ ID NO: 1037, CDR-L1 as depicted in SEQ ID
NO: 1038, CDR-L2 as depicted in SEQ ID NO: 1039 and CDR-L3 as
depicted in SEQ ID NO: 1040, [0025] CDR-H1 as depicted in SEQ ID
NO: 1074, CDR-H2 as depicted in SEQ ID NO: 1075, CDR-H3 as depicted
in SEQ ID NO: 1076, CDR-L1 as depicted in SEQ ID NO: 1077, CDR-L2
as depicted in SEQ ID NO: 1078 and CDR-L3 as depicted in SEQ ID NO:
1079, [0026] CDR-H1 as depicted in SEQ ID NO: 1100, CDR-H2 as
depicted in SEQ ID NO: 1101, CDR-H3 as depicted in SEQ ID NO: 1102,
CDR-L1 as depicted in SEQ ID NO: 1103, CDR-L2 as depicted in SEQ ID
NO: 1104 and CDR-L3 as depicted in SEQ ID NO: 1105, [0027] CDR-H1
as depicted in SEQ ID NO: 1113, CDR-H2 as depicted in SEQ ID NO:
1114, CDR-H3 as depicted in SEQ ID NO: 1115, CDR-L1 as depicted in
SEQ ID NO: 1116, CDR-L2 as depicted in SEQ ID NO: 1117 and CDR-L3
as depicted in SEQ ID NO: 1118, [0028] CDR-H1 as depicted in SEQ ID
NO: 1243, CDR-H2 as depicted in SEQ ID NO: 1244, CDR-H3 as depicted
in SEQ ID NO: 1245, CDR-L1 as depicted in SEQ ID NO: 1246, CDR-L2
as depicted in SEQ ID NO: 1247 and CDR-L3 as depicted in SEQ ID NO:
1248, [0029] CDR-H1 as depicted in SEQ ID NO: 1256, CDR-H2 as
depicted in SEQ ID NO: 1257, CDR-H3 as depicted in SEQ ID NO: 1258,
CDR-L1 as depicted in SEQ ID NO: 1259, CDR-L2 as depicted in SEQ ID
NO: 1260 and CDR-L3 as depicted in SEQ ID NO: 1261, [0030] CDR-H1
as depicted in SEQ ID NO: 1269, CDR-H2 as depicted in SEQ ID NO:
1270, CDR-H3 as depicted in SEQ ID NO: 1271, CDR-L1 as depicted in
SEQ ID NO: 1272, CDR-L2 as depicted in SEQ ID NO: 1273 and CDR-L3
as depicted in SEQ ID NO: 1274, [0031] CDR-H1 as depicted in SEQ ID
NO: 1282, CDR-H2 as depicted in SEQ ID NO: 1283, CDR-H3 as depicted
in SEQ ID NO: 1284, CDR-L1 as depicted in SEQ ID NO: 1285, CDR-L2
as depicted in SEQ ID NO: 1286 and CDR-L3 as depicted in SEQ ID NO:
1287, and [0032] CDR-H1 as depicted in SEQ ID NO: 1295, CDR-H2 as
depicted in SEQ ID NO: 1296, CDR-H3 as depicted in SEQ ID NO: 1297,
CDR-L1 as depicted in SEQ ID NO: 1298, CDR-L2 as depicted in SEQ ID
NO: 1299 and CDR-L3 as depicted in SEQ ID NO: 1300; [0033] (c)
CDR-H1 as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID
NO: 95, CDR-H3 as depicted in SEQ ID NO: 96, CDR-L1 as depicted in
SEQ ID NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as
depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 100,
CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID
NO: 102, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted
in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1
as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO:
119, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in
SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as
depicted in SEQ ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 154,
CDR-H2 as depicted in SEQ ID NO: 155, CDR-H3 as depicted in SEQ ID
NO: 156, CDR-L1 as depicted in SEQ ID NO: 322, CDR-L2 as depicted
in SEQ ID NO: 323 and CDR-L3 as depicted in SEQ ID NO: 324, CDR-H1
as depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO:
101, CDR-H3 as depicted in SEQ ID NO: 912, CDR-L1 as depicted in
SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as
depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 100,
CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID
NO: 913, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted
in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1
as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95,
CDR-H3 as depicted in SEQ ID NO: 910, CDR-L1 as depicted in SEQ ID
NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as
depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 94,
CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID
NO: 911, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted
in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1
as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO:
119, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in
SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as
depicted in SEQ ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 118,
CDR-H2 as depicted in SEQ ID NO: 914, CDR-H3 as depicted in SEQ ID
NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted
in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, CDR-H1
as depicted in SEQ ID NO: 154, CDR-H2 as depicted in SEQ ID NO:
155, CDR-H3 as depicted in SEQ ID NO: 920, CDR-L1 as depicted in
SEQ ID NO: 322, CDR-L2 as depicted in SEQ ID NO: 323 and CDR-L3 as
depicted in SEQ ID NO: 324, [0034] CDR-H1 as depicted in SEQ ID NO:
996, CDR-H2 as depicted in SEQ ID NO: 997, CDR-H3 as depicted in
SEQ ID NO: 998, CDR-L1 as depicted in SEQ ID NO: 999, CDR-L2 as
depicted in SEQ ID NO: 1000 and CDR-L3 as depicted in SEQ ID NO:
1001, [0035] CDR-H1 as depicted in SEQ ID NO: 1048, CDR-H2 as
depicted in SEQ ID NO: 1049, CDR-H3 as depicted in SEQ ID NO: 1050,
CDR-L1 as depicted in SEQ ID NO: 1051, CDR-L2 as depicted in SEQ ID
NO: 1052 and CDR-L3 as depicted in SEQ ID NO: 1053, and [0036]
CDR-H1 as depicted in SEQ ID NO: 1087, CDR-H2 as depicted in SEQ ID
NO: 1088, CDR-H3 as depicted in SEQ ID NO: 1089, CDR-L1 as depicted
in SEQ ID NO: 1090, CDR-L2 as depicted in SEQ ID NO: 1091 and
CDR-L3 as depicted in SEQ ID NO: 1092; [0037] (d) CDR-H1 as
depicted in SEQ ID NO: 4, CDR-H2 as depicted in SEQ ID NO: 5,
CDR-H3 as depicted in SEQ ID NO: 6, CDR-L1 as depicted in SEQ ID
NO: 172, CDR-L2 as depicted in SEQ ID NO: 173 and CDR-L3 as
depicted in SEQ ID NO: 174, CDR-H1 as depicted in SEQ ID NO: 10,
CDR-H2 as depicted in SEQ ID NO: 11, CDR-H3 as depicted in SEQ ID
NO: 12, CDR-L1 as depicted in SEQ ID NO: 178, CDR-L2 as depicted in
SEQ ID NO: 179 and CDR-L3 as depicted in SEQ ID NO: 180, CDR-H1 as
depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as
depicted in SEQ ID NO: 198, CDR-H1 as depicted in SEQ ID NO: 34,
CDR-H2 as depicted in SEQ ID NO: 35, CDR-H3 as depicted in SEQ ID
NO: 36, CDR-L1 as depicted in SEQ ID NO: 202, CDR-L2 as depicted in
SEQ ID NO: 203 and CDR-L3 as depicted in SEQ ID NO: 204, CDR-H1 as
depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47,
CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID
NO: 214, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as
depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 58,
CDR-H2 as depicted in SEQ ID NO: 59, CDR-H3 as depicted in SEQ ID
NO: 60, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in
SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as
depicted in SEQ ID NO: 64, CDR-H2 as depicted in SEQ ID NO: 65,
CDR-H3 as depicted in SEQ ID NO: 66, CDR-L1 as depicted in SEQ ID
NO: 232, CDR-L2 as depicted in SEQ ID NO: 233 and CDR-L3 as
depicted in SEQ ID NO: 234, CDR-H1 as depicted in SEQ ID NO: 70,
CDR-H2 as depicted in SEQ ID NO: 71, CDR-H3 as depicted in SEQ ID
NO: 72, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in
SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as
depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161,
CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID
NO: 328, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 46,
CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID
NO: 48, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in
SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as
depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47,
CDR-H3 as depicted in SEQ ID NO: 902, CDR-L1 as depicted in SEQ ID
NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as
depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46,
CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID
NO: 903, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted
in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1
as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47,
CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID
NO: 925, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as
depicted in SEQ ID NO: 216, CDR-H1 as
depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907,
CDR-H3 as depicted in SEQ ID NO: 72, CDR-L1 as depicted in SEQ ID
NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as
depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 70,
CDR-H2 as depicted in SEQ ID NO: 907, CDR-H3 as depicted in SEQ ID
NO: 908, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted
in SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1
as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 901,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as
depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 58,
CDR-H2 as depicted in SEQ ID NO: 905, CDR-H3 as depicted in SEQ ID
NO: 906, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted
in SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1
as depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905,
CDR-H3 as depicted in SEQ ID NO: 60, CDR-L1 as depicted in SEQ ID
NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as
depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 160,
CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID
NO: 162, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted
in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1
as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO:
921, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in
SEQ ID NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 940, CDR-H1 as depicted in SEQ ID NO: 160,
CDR-H2 as depicted in SEQ ID NO: 161, CDR-H3 as depicted in SEQ ID
NO: 162, CDR-L1 as depicted in SEQ ID NO: 941, CDR-L2 as depicted
in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330, CDR-H1
as depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as
depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 28,
CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID
NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in
SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as
depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 901,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as
depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 28,
CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID
NO: 30, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted in
SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 330,
[0038] CDR-H1 as depicted in SEQ ID NO: 970, CDR-H2 as depicted in
SEQ ID NO: 971, CDR-H3 as depicted in SEQ ID NO: 972, CDR-L1 as
depicted in SEQ ID NO: 973, CDR-L2 as depicted in SEQ ID NO: 974
and CDR-L3 as depicted in SEQ ID NO: 975, CDR-H1 as depicted in SEQ
ID NO: 1061, CDR-H2 as depicted in SEQ ID NO: 1062, CDR-H3 as
depicted in SEQ ID NO: 1063, CDR-L1 as depicted in SEQ ID NO: 1064,
CDR-L2 as depicted in SEQ ID NO: 1065 and CDR-L3 as depicted in SEQ
ID NO: 1066, [0039] CDR-H1 as depicted in SEQ ID NO: 1139, CDR-H2
as depicted in SEQ ID NO: 1140, CDR-H3 as depicted in SEQ ID NO:
1141, CDR-L1 as depicted in SEQ ID NO: 1142, CDR-L2 as depicted in
SEQ ID NO: 1143 and CDR-L3 as depicted in SEQ ID NO: 1144, [0040]
CDR-H1 as depicted in SEQ ID NO: 1152, CDR-H2 as depicted in SEQ ID
NO: 1153, CDR-H3 as depicted in SEQ ID NO: 1154, CDR-L1 as depicted
in SEQ ID NO: 1155, CDR-L2 as depicted in SEQ ID NO: 1156 and
CDR-L3 as depicted in SEQ ID NO: 1157, [0041] CDR-H1 as depicted in
SEQ ID NO: 1178, CDR-H2 as depicted in SEQ ID NO: 1179, CDR-H3 as
depicted in SEQ ID NO: 1180, CDR-L1 as depicted in SEQ ID NO: 1181,
CDR-L2 as depicted in SEQ ID NO: 1182 and CDR-L3 as depicted in SEQ
ID NO: 1183, [0042] CDR-H1 as depicted in SEQ ID NO: 1191, CDR-H2
as depicted in SEQ ID NO: 1192, CDR-H3 as depicted in SEQ ID NO:
1193, CDR-L1 as depicted in SEQ ID NO: 1194, CDR-L2 as depicted in
SEQ ID NO: 1195 and CDR-L3 as depicted in SEQ ID NO: 1196, [0043]
CDR-H1 as depicted in SEQ ID NO: 1204, CDR-H2 as depicted in SEQ ID
NO: 1205, CDR-H3 as depicted in SEQ ID NO: 1206, CDR-L1 as depicted
in SEQ ID NO: 1207, CDR-L2 as depicted in SEQ ID NO: 1208 and
CDR-L3 as depicted in SEQ ID NO: 1209, [0044] CDR-H1 as depicted in
SEQ ID NO: 1217, CDR-H2 as depicted in SEQ ID NO: 1218, CDR-H3 as
depicted in SEQ ID NO: 1219, CDR-L1 as depicted in SEQ ID NO: 1220,
CDR-L2 as depicted in SEQ ID NO: 1221 and CDR-L3 as depicted in SEQ
ID NO: 1222, [0045] CDR-H1 as depicted in SEQ ID NO: 1230, CDR-H2
as depicted in SEQ ID NO: 1231, CDR-H3 as depicted in SEQ ID NO:
1232, CDR-L1 as depicted in SEQ ID NO: 1233, CDR-L2 as depicted in
SEQ ID NO: 1234 and CDR-L3 as depicted in SEQ ID NO: 1235, [0046]
CDR-H1 as depicted in SEQ ID NO: 1308, CDR-H2 as depicted in SEQ ID
NO: 1309, CDR-H3 as depicted in SEQ ID NO: 1310, CDR-L1 as depicted
in SEQ ID NO: 1311, CDR-L2 as depicted in SEQ ID NO: 1312 and
CDR-L3 as depicted in SEQ ID NO: 1313, [0047] CDR-H1 as depicted in
SEQ ID NO: 1321, CDR-H2 as depicted in SEQ ID NO: 1322, CDR-H3 as
depicted in SEQ ID NO: 1323, CDR-L1 as depicted in SEQ ID NO: 1324,
CDR-L2 as depicted in SEQ ID NO: 1325 and CDR-L3 as depicted in SEQ
ID NO: 1326, [0048] CDR-H1 as depicted in SEQ ID NO: 1373, CDR-H2
as depicted in SEQ ID NO: 1374, CDR-H3 as depicted in SEQ ID NO:
1375, CDR-L1 as depicted in SEQ ID NO: 1376, CDR-L2 as depicted in
SEQ ID NO: 1377 and CDR-L3 as depicted in SEQ ID NO: 1378, [0049]
CDR-H1 as depicted in SEQ ID NO: 1386, CDR-H2 as depicted in SEQ ID
NO: 1387, CDR-H3 as depicted in SEQ ID NO: 1388, CDR-L1 as depicted
in SEQ ID NO: 1389, CDR-L2 as depicted in SEQ ID NO: 1390 and
CDR-L3 as depicted in SEQ ID NO: 1391, [0050] CDR-H1 as depicted in
SEQ ID NO: 1399, CDR-H2 as depicted in SEQ ID NO: 1400, CDR-H3 as
depicted in SEQ ID NO: 1401, CDR-L1 as depicted in SEQ ID NO: 1402,
CDR-L2 as depicted in SEQ ID NO: 1403 and CDR-L3 as depicted in SEQ
ID NO: 1404, [0051] CDR-H1 as depicted in SEQ ID NO: 1412, CDR-H2
as depicted in SEQ ID NO: 1413, CDR-H3 as depicted in SEQ ID NO:
1414, CDR-L1 as depicted in SEQ ID NO: 1415, CDR-L2 as depicted in
SEQ ID NO: 1416 and CDR-L3 as depicted in SEQ ID NO: 1417; and
[0052] (e) CDR-H1 as depicted in SEQ ID NO: 76, CDR-H2 as depicted
in SEQ ID NO: 77, CDR-H3 as depicted in SEQ ID NO: 78, CDR-L1 as
depicted in SEQ ID NO: 244, CDR-L2 as depicted in SEQ ID NO: 245
and CDR-L3 as depicted in SEQ ID NO: 246, CDR-H1 as depicted in SEQ
ID NO: 88, CDR-H2 as depicted in SEQ ID NO: 89, CDR-H3 as depicted
in SEQ ID NO: 90, CDR-L1 as depicted in SEQ ID NO: 256, CDR-L2 as
depicted in SEQ ID NO: 257 and CDR-L3 as depicted in SEQ ID NO:
258, CDR-H1 as depicted in SEQ ID NO: 106, CDR-H2 as depicted in
SEQ ID NO: 107, CDR-H3 as depicted in SEQ ID NO: 108, CDR-L1 as
depicted in SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID NO: 275
and CDR-L3 as depicted in SEQ ID NO: 276, CDR-H1 as depicted in SEQ
ID NO: 112, CDR-H2 as depicted in SEQ ID NO: 113, CDR-H3 as
depicted in SEQ ID NO: 114, CDR-L1 as depicted in SEQ ID NO: 280,
CDR-L2 as depicted in SEQ ID NO: 281 and CDR-L3 as depicted in SEQ
ID NO: 282, CDR-H1 as depicted in SEQ ID NO: 106, CDR-H2 as
depicted in SEQ ID NO: 107, CDR-H3 as depicted in SEQ ID NO: 108,
CDR-L1 as depicted in SEQ ID NO: 274, CDR-L2 as depicted in SEQ ID
NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276, and [0053] CDR-H1
as depicted in SEQ ID NO: 983, CDR-H2 as depicted in SEQ ID NO:
984, CDR-H3 as depicted in SEQ ID NO: 985, CDR-L1 as depicted in
SEQ ID NO: 986, CDR-L2 as depicted in SEQ ID NO: 987 and CDR-L3 as
depicted in SEQ ID NO: 988.
[0054] In a further embodiment of the antibody construct of the
invention the first binding domain comprises a VH region selected
from the group consisting of VH regions [0055] (a) as depicted in
SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 485, SEQ ID NO: 486, SEQ
ID NO: 487, SEQ ID NO: 492, SEQ ID NO: 493, SEQ ID NO: 494, SEQ ID
NO: 495, SEQ ID NO: 1133, SEQ ID NO: 1172, SEQ ID NO: 1341, SEQ ID
NO: 1354, SEQ ID NO: 1367, SEQ ID NO: 1432, and SEQ ID NO: 1445;
[0056] (b) as depicted in SEQ ID NO: 342, SEQ ID NO: 366, SEQ ID
NO: 370, SEQ ID NO: 344, SEQ ID NO: 372, SEQ ID NO: 368, SEQ ID NO:
496, SEQ ID NO: 497, SEQ ID NO: 498, SEQ ID NO: 499, SEQ ID NO:
500, SEQ ID NO: 508, SEQ ID NO: 509, SEQ ID NO: 510, SEQ ID NO:
511, SEQ ID NO: 512, SEQ ID NO: 519, SEQ ID NO: 520, SEQ ID NO:
521, SEQ ID NO: 522, SEQ ID NO: 523, SEQ ID NO: 524, SEQ ID NO:
525, SEQ ID NO: 526, SEQ ID NO: 527, SEQ ID NO: 528, SEQ ID NO:
529, SEQ ID NO: 530, SEQ ID NO: 531, SEQ ID NO: 532, SEQ ID NO:
533, SEQ ID NO: 534, SEQ ID NO: 535, SEQ ID NO: 536, SEQ ID NO:
537, SEQ ID NO: 538, SEQ ID NO: 1016, SEQ ID NO: 1029, SEQ ID NO:
1042, SEQ ID NO: 1081, SEQ ID NO: 1107, SEQ ID NO: 1120, SEQ ID NO:
1250, SEQ ID NO: 1263, SEQ ID NO: 1276, SEQ ID NO: 1289, and SEQ ID
NO: 1302; [0057] (c) as depicted in SEQ ID NO: 338, SEQ ID NO: 354,
SEQ ID NO: 378, SEQ ID NO: 356, SEQ ID NO: 476, SEQ ID NO: 477, SEQ
ID NO: 478, SEQ ID NO: 479, SEQ ID NO: 480, SEQ ID NO: 481, SEQ ID
NO: 482, SEQ ID NO: 483, SEQ ID NO: 484, SEQ ID NO: 501, SEQ ID NO:
502, SEQ ID NO: 503, SEQ ID NO: 504, SEQ ID NO: 505, SEQ ID NO:
506, SEQ ID NO: 517, SEQ ID NO: 518, SEQ ID NO: 1003, SEQ ID NO:
1055, and SEQ ID NO: 1094; [0058] (d) as depicted in SEQ ID NO:
352, SEQ ID NO: 360, SEQ ID NO: 388, SEQ ID NO: 386, SEQ ID NO:
340, SEQ ID NO: 346, SEQ ID NO: 374, SEQ ID NO: 348, SEQ ID NO:
390, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO: 465, SEQ ID NO:
466, SEQ ID NO: 467, SEQ ID NO: 468, SEQ ID NO: 469, SEQ ID NO:
470, SEQ ID NO: 471, SEQ ID NO: 472, SEQ ID NO: 473, SEQ ID NO:
474, SEQ ID NO: 475, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO:
490, SEQ ID NO: 491, SEQ ID NO: 513, SEQ ID NO: 514, SEQ ID NO:
515, SEQ ID NO: 516, SEQ ID NO: 540, SEQ ID NO: 541, SEQ ID NO:
542, SEQ ID NO: 543, SEQ ID NO: 977, SEQ ID NO: 1068, SEQ ID NO:
1146, SEQ ID NO: 1159, SEQ ID NO: 1185, SEQ ID NO: 1198, SEQ ID NO:
1211, SEQ ID NO: 1224, SEQ ID NO: 1237, SEQ ID NO: 1315, SEQ ID NO:
1328, SEQ ID NO: 1380, SEQ ID NO: 1393, SEQ ID NO: 1406, and SEQ ID
NO: 1419; and [0059] (e) as depicted in SEQ ID NO: 376, SEQ ID NO:
392, SEQ ID NO: 358, SEQ ID NO: 350, SEQ ID NO: 507, and SEQ ID NO:
990.
[0060] In another embodiment of the antibody construct of the
invention the first binding domain comprises a VL region selected
from the group consisting of VL regions [0061] (a) as depicted in
SEQ ID NO: 418, SEQ ID NO: 420, SEQ ID NO: 580, SEQ ID NO: 581, SEQ
ID NO: 582, SEQ ID NO: 587, SEQ ID NO: 588, SEQ ID NO: 589, SEQ ID
NO: 590, SEQ ID NO: 1135, SEQ ID NO: 1174, SEQ ID NO: 1343, SEQ ID
NO: 1356, SEQ ID NO: 1369, SEQ ID NO: 1434, and SEQ ID NO: 1447;
[0062] (b) as depicted in SEQ ID NO: 398, SEQ ID NO: 422, SEQ ID
NO: 426, SEQ ID NO: 400, SEQ ID NO: 428, SEQ ID NO: 424, SEQ ID NO:
591, SEQ ID NO: 592, SEQ ID NO: 593, SEQ ID NO: 594, SEQ ID NO:
595, SEQ ID NO: 603, SEQ ID NO: 604, SEQ ID NO: 605, SEQ ID NO:
606, SEQ ID NO: 607, SEQ ID NO: 614, SEQ ID NO: 615, SEQ ID NO:
616, SEQ ID NO: 617, SEQ ID NO: 618, SEQ ID NO: 619, SEQ ID NO:
620, SEQ ID NO: 621, SEQ ID NO: 622, SEQ ID NO: 623, SEQ ID NO:
624, SEQ ID NO: 625, SEQ ID NO: 626, SEQ ID NO: 627, SEQ ID NO:
628, SEQ ID NO: 629, SEQ ID NO: 630, SEQ ID NO: 631, SEQ ID NO:
632, SEQ ID NO: 633, SEQ ID NO: 1018, SEQ ID NO: 1031, SEQ ID NO:
1044, SEQ ID NO: 1083, SEQ ID NO: 1109, SEQ ID NO: 1122, SEQ ID NO:
1252, SEQ ID NO: 1265, SEQ ID NO: 1278, SEQ ID NO: 1291, and SEQ ID
NO: 1304; [0063] (c) as depicted in SEQ ID NO: 394, SEQ ID NO: 410,
SEQ ID NO: 434, SEQ ID NO: 412, SEQ ID NO: 571, SEQ ID NO: 572, SEQ
ID NO: 573, SEQ ID NO: 574, SEQ ID NO: 575, SEQ ID NO: 576, SEQ ID
NO: 577, SEQ ID NO: 578, SEQ ID NO: 579, SEQ ID NO: 596, SEQ ID NO:
597, SEQ ID NO: 598, SEQ ID NO: 599, SEQ ID NO: 600, SEQ ID NO:
601, SEQ ID NO: 612, SEQ ID NO: 613, SEQ ID NO: 1005, SEQ ID NO:
1057, and SEQ ID NO: 1096; [0064] (d) as depicted in SEQ ID NO:
408, SEQ ID NO: 416, SEQ ID NO: 444, SEQ ID NO: 442, SEQ ID NO:
396, SEQ ID NO: 402, SEQ ID NO: 430, SEQ ID NO: 404, SEQ ID NO:
446, SEQ ID NO: 558, SEQ ID NO: 559, SEQ ID NO: 560, SEQ ID NO:
561, SEQ ID NO: 562, SEQ ID NO: 563, SEQ ID NO: 564, SEQ ID NO:
565, SEQ ID NO: 566, SEQ ID NO: 567, SEQ ID NO: 568, SEQ ID NO:
569, SEQ ID NO: 570, SEQ ID NO: 583, SEQ ID NO: 584, SEQ ID NO:
585, SEQ ID NO: 586, SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO:
610, SEQ ID NO: 611, SEQ ID NO: 635, SEQ ID NO: 636, SEQ ID NO:
637, SEQ ID NO: 638, SEQ ID NO: 979, SEQ ID NO: 1070, SEQ ID NO:
1148, SEQ ID NO: 1161, SEQ ID NO: 1187, SEQ ID NO: 1200, SEQ ID NO:
1213, SEQ ID NO: 1226, SEQ ID NO: 1239, SEQ ID NO: 1317, SEQ ID NO:
1330, SEQ ID NO: 1382, SEQ ID NO: 1395, SEQ ID NO: 1408, and SEQ ID
NO: 1421; and [0065] (e) as depicted in SEQ ID NO: 432, SEQ ID NO:
448, SEQ ID NO: 414, SEQ ID NO: 406, SEQ ID NO: 602, and SEQ ID NO:
992.
[0066] The invention further provides an embodiment of the antibody
construct of the invention, wherein the first binding domain
comprises a VH region and a VL region selected from the group
consisting of: [0067] (1) pairs of a VH region and a VL region as
depicted in SEQ ID NOs: 362+418, SEQ ID NOs: 364+420, SEQ ID NOs:
485+580, SEQ ID NOs: 486+581, SEQ ID NOs: 487+582, SEQ ID NOs:
492+587, SEQ ID NOs: 493+588, SEQ ID NOs: 494+589, SEQ ID NOs:
495+590, SEQ ID NOs: 1133+1135, SEQ ID NOs: 1172+1174, SEQ ID NOs:
1341+1343, SEQ ID NOs: 1354+1356, SEQ ID NOs: 1367+1369, SEQ ID
NOs: 1432+1434, and SEQ ID NOs: 1445+1447; [0068] (2) pairs of a VH
region and a VL region as depicted in SEQ ID NOs: 342+398, SEQ ID
NOs: 366+422, SEQ ID NOs: 370+426, SEQ ID NOs: 344+400, SEQ ID NOs:
372+428, SEQ ID NOs: 368+424, SEQ ID NOs: 496+591, SEQ ID NOs:
497+592, SEQ ID NOs: 498+593, SEQ ID NOs: 499+594, SEQ ID NOs:
500+595, SEQ ID NOs: 508+603, SEQ ID NOs: 509+604, SEQ ID NOs:
510+605, SEQ ID NOs: 511+606, SEQ ID NOs: 512+607, SEQ ID NOs:
519+614, SEQ ID NOs: 520+615, SEQ ID NOs: 521+616, SEQ ID NOs:
522+617, SEQ ID NOs: 523+618, SEQ ID NOs: 524+619, SEQ ID NOs:
525+620, SEQ ID NOs: 526+621, SEQ ID NOs: 527+622, SEQ ID NOs:
528+623, SEQ ID NOs: 529+624, SEQ ID NOs: 530+625, SEQ ID NOs:
531+626, SEQ ID NOs: 532+627, SEQ ID NOs: 533+628, SEQ ID NOs:
534+629, SEQ ID NOs: 535+630, SEQ ID NOs: 536+631, SEQ ID NOs:
537+632, SEQ ID NOs: 538+633, SEQ ID NOs: 1016+1018, SEQ ID NOs:
1029+1031, SEQ ID NOs: 1042+1044, SEQ ID NOs: 1081+1083, SEQ ID
NOs: 1107+1109, SEQ ID NOs: 1120+1122, SEQ ID NOs: 1250+1252, SEQ
ID NOs: 1263+1265, SEQ ID NOs: 1276+1278, SEQ ID NOs: 1289+1291,
and SEQ ID NOs: 1302+1304; [0069] (3) pairs of a VH region and a VL
region as depicted in SEQ ID NOs: 338+394, SEQ ID NOs: 354+410, SEQ
ID NOs: 378+434, SEQ ID NOs: 356+412, SEQ ID NOs: 476+571, SEQ ID
NOs: 477+572, SEQ ID NOs: 478+573, SEQ ID NOs: 479+574, SEQ ID NOs:
480+575, SEQ ID NOs: 481+576, SEQ ID NOs: 482+577, SEQ ID NOs:
483+578, SEQ ID NOs: 484+579, SEQ ID NOs: 501+596, SEQ ID NOs:
502+597, SEQ ID NOs: 503+598, SEQ ID NOs: 504+599, SEQ ID NOs:
505+600, SEQ ID NOs: 506+601, SEQ ID NOs: 517+612, SEQ ID NOs:
518+613, SEQ ID NOs: 1003+1005, SEQ ID NOs: 1055+1057, and SEQ ID
NOs: 1094+1096; [0070] (4) pairs of a VH region and a VL region as
depicted in SEQ ID NOs: 352+408, SEQ ID NOs: 360+416, SEQ ID NOs:
388+444, SEQ ID NOs: 386+442, SEQ ID NOs: 340+396, SEQ ID NOs:
346+402, SEQ ID NOs: 374+430, SEQ ID NOs: 348+404, SEQ ID NOs:
390+446, SEQ ID NOs: 463+558, SEQ ID NOs: 464+559, SEQ ID NOs:
465+560, SEQ ID NOs: 466+561, SEQ ID NOs: 467+562, SEQ ID NOs:
468+563, SEQ ID NOs: 469+564, SEQ ID NOs: 470+565, SEQ ID NOs:
471+566, SEQ ID NOs: 472+567, SEQ ID NOs: 473+568, SEQ ID NOs:
474+569, SEQ ID NOs: 475+570, SEQ ID NOs: 488+583, SEQ ID NOs:
489+584, SEQ ID NOs: 490+585, SEQ ID NOs: 491+586, SEQ ID NOs:
513+608, SEQ ID NOs: 514+609, SEQ ID NOs: 515+610, SEQ ID NOs:
516+611, SEQ ID NOs: 540+635, SEQ ID NOs: 541+636, SEQ ID NOs:
542+637, SEQ ID NOs: 543+638, SEQ ID NOs: 977+979, SEQ ID NOs:
1068+1070, SEQ ID NOs: 1146+1148, SEQ ID NOs: 1159+1161, SEQ ID
NOs: 1185+1187, SEQ ID NOs: 1198+1200, SEQ ID NOs: 1211+1213, SEQ
ID NOs: 1224+1226, SEQ ID NOs: 1237+1239, SEQ ID NOs: 1315+1317,
SEQ ID NOs: 1328+1330, SEQ ID NOs: 1380, +1382 SEQ ID NOs:
1393+1395, SEQ ID NOs: 1406+1408, and SEQ ID NOs: 1419+1421; and
[0071] (5) pairs of a VH region and a VL region as depicted in SEQ
ID NOs: 376+432, SEQ ID NOs: 392+448, SEQ ID NOs: 358+414, SEQ ID
NOs: 350+406, SEQ ID NOs: 507+602, and SEQ ID NOs: 990+992.
[0072] In a further embodiment of the invention the antibody
construct is in a format selected from the group consisting of
(scFv).sub.2, (single domain mAb).sub.2, scFv-single domain mAb,
diabodies and oligomers thereof.
[0073] In a preferred embodiment the first binding domain comprises
an amino acid sequence selected from the group consisting of [0074]
(a) as depicted in SEQ ID NO: 117, SEQ ID NO: 1137, SEQ ID NO:
1176, SEQ ID NO: 1345, SEQ ID NO: 1358, SEQ ID NO: 1371, SEQ ID NO:
1436, and SEQ ID NO: 1449; [0075] (b) as depicted in SEQ ID NO:
1020, SEQ ID NO: 1033, SEQ ID NO: 1046, SEQ ID NO: 1085, SEQ ID NO:
1111, SEQ ID NO: 1124, SEQ ID NO: 1254, SEQ ID NO: 1267, SEQ ID NO:
1280, SEQ ID NO: 1293, and SEQ ID NO: 1306; [0076] (c) as depicted
in SEQ ID NO: 1007, SEQ ID NO: 1059, and SEQ ID NO: 1098; [0077]
(d) as depicted in SEQ ID NO: 981, SEQ ID NO: 1072, SEQ ID NO:
1150, SEQ ID NO: 1163, SEQ ID NO: 1189, SEQ ID NO: 1202, SEQ ID NO:
1215, SEQ ID NO: 1228, SEQ ID NO: 1241, SEQ ID NO: 1319, SEQ ID NO:
1332, SEQ ID NO: 1384, SEQ ID NO: 1397, SEQ ID NO: 1410, and SEQ ID
NO: 1423; and [0078] (e) as depicted in SEQ ID NO: 994.
[0079] In another embodiment of the antibody construct of the
invention the second binding domain is capable of binding to human
and Callithrix jacchus, Saguinus oedipus or Saimiri sciureus CD3
epsilon.
[0080] In a preferred embodiment the antibody construct of the
invention has an amino acid sequence selected from the group
consisting of [0081] (a) as depicted in SEQ ID NO: 1138, SEQ ID NO:
1177, SEQ ID NO: 1346, SEQ ID NO: 1359, SEQ ID NO: 1372, SEQ ID NO:
1437, and SEQ ID NO: 1450; [0082] (b) as depicted in SEQ ID NO:
1021, SEQ ID NO: 1034, SEQ ID NO: 1047, SEQ ID NO: 1086, SEQ ID NO:
1112, SEQ ID NO: 1125, SEQ ID NO: 1255, SEQ ID NO: 1268, SEQ ID NO:
1281, SEQ ID NO: 1294, and SEQ ID NO: 1307; [0083] (c) as depicted
in SEQ ID NO: 1008, SEQ ID NO: 1060, and SEQ ID NO: 1099; [0084]
(d) as depicted in SEQ ID NO: 982, SEQ ID NO: 1073, SEQ ID NO:
1151, SEQ ID NO: 1164, SEQ ID NO: 1190, SEQ ID NO: 1203, SEQ ID NO:
1216, SEQ ID NO: 1229, SEQ ID NO: 1242, SEQ ID NO: 1320, SEQ ID NO:
1333, SEQ ID NO: 1385, SEQ ID NO: 1398, SEQ ID NO: 1411, and SEQ ID
NO: 1424; and [0085] (e) as depicted in SEQ ID NO: 995.
[0086] The invention further provides a nucleic acid sequence
encoding an antibody construct of the invention.
[0087] Furthermore, the invention provides a vector comprising a
nucleic acid sequence of the invention. Moreover, the invention
provides a host cell transformed or transfected with the nucleic
acid sequence of the invention.
[0088] In a further embodiment the invention provides a process for
the production of a antibody construct of the invention, said
process comprising culturing a host cell of the invention under
conditions allowing the expression of the antibody construct of the
invention and recovering the produced antibody construct from the
culture.
[0089] Moreover, the invention provides a pharmaceutical
composition comprising an antibody construct of the invention or
produced according to the process of the invention
[0090] In one embodiment the invention provides the antibody
construct of the invention or produced according to the process of
the invention for use in the prevention, treatment or amelioration
of a melanoma disease or metastatic melanoma disease.
[0091] The invention also provides a method for the treatment or
amelioration of a melanoma disease or metastatic melanoma disease,
comprising the step of administering to a subject in need thereof
the antibody construct of the invention or produced according to
the process of the invention.
[0092] In a preferred embodiment method of use of the invention the
melanoma disease or metastatic melanoma disease is selected from
the group consisting of superficial spreading melanoma, lentigo
maligna, lentigo maligna melanoma, acral lentiginous melanoma and
nodular melanoma.
[0093] In a further embodiment, the invention provides a kit
comprising an antibody construct of the invention, or produced
according to the process of the invention, a vector of the
invention, and/or a host cell of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0094] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawing(s) will be provided by the Office
upon request and payment of the necessary fee.
[0095] FIG. 1:
[0096] FIG. 1 depicts cell viability data of Colo-699 cells that
have been treated with fully human anti-CDH19 antibodies and a high
concentration of a goat anti-human Fc monovalent Fab conjugated
with DM1 (DM1-Fab) at a drug-antibody ratio (DAR) (.about.1.3).
[0097] FIG. 2:
[0098] FIG. 2 depicts the average cell viability data from a CHL-1
assay plotted against the average cell viability data from the
Colo-699 assay.
[0099] FIG. 3:
[0100] FIG. 3 shows the relative expression of CDH19 mRNA in
metastatic and primary melanoma samples.
[0101] FIG. 4:
[0102] FIG. 4 shows the expression of CDH19 protein in human tumor
samples by IHC.
[0103] FIG. 5:
[0104] FIG. 5 shows the results of the analysis of tumor cell lines
by flow cytometry and IHC to identify model systems with CDH19
expression similar to human tumors based on the number of CDH19
receptors present on the cell surface.
[0105] FIG. 6:
[0106] FACS analysis of CDH19/CD3 bispecific antibodies on
indicated cell lines:
[0107] 1) untransfected L1.2. 2) L1.2 cells stably transfected with
human CDH19, 3) melanoma cell line CHL-1, 4) melanoma cell line
A2058, 5) human CD3 positive human T cell line HBP-ALL, 6) macaque
T cell line 4119 LnPx. Negative controls [1) to 6)]: detection
antibodies without prior CDH19/CD3 bispecific antibody.
[0108] FIG. 7:
[0109] Cytotoxic activity of CDH19/CD3 bispecific antibodies as
measured in a 48-hour FACS-based cytotoxicity assay. Effector
cells: unstimulated human PBMC. Target cells: as indicated.
Effector to target cell (E:T)-ratio: 10:1.
[0110] FIG. 8:
[0111] Tumor growth in vivo inhibition of Colo699 cells by
administration of CDH19 BiTE 2G6. The bispecific antibody construct
inhibits growth of tumors at 0.5 mg/kg dose.
[0112] FIG. 9:
[0113] Tumor growth in vivo inhibition of CHL-1 cells by
administration of CDH19 BiTE 2G6. The bispecific antibody construct
inhibits growth of tumors at 0.5 mg/kg dose.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
[0114] It must be noted that as used herein, the singular forms
"a", "an", and "the", include plural references unless the context
clearly indicates otherwise. Thus, for example, reference to "a
reagent" includes one or more of such different reagents and
reference to "the method" includes reference to equivalent steps
and methods known to those of ordinary skill in the art that could
be modified or substituted for the methods described herein.
[0115] Unless otherwise indicated, the term "at least" preceding a
series of elements is to be understood to refer to every element in
the series. Those skilled in the art will recognize, or be able to
ascertain using no more than routine experimentation, many
equivalents to the specific embodiments of the invention described
herein. Such equivalents are intended to be encompassed by the
present invention.
[0116] The term "and/or" wherever used herein includes the meaning
of "and", "or" and "all or any other combination of the elements
connected by said term".
[0117] The term "about" or "approximately" as used herein means
within .+-.20%, preferably within .+-.15%, more preferably within
.+-.10%, and most preferably within .+-.5% of a given value or
range.
[0118] Throughout this specification and the claims which follow,
unless the context requires otherwise, the word "comprise", and
variations such as "comprises" and "comprising", will be understood
to imply the inclusion of a stated integer or step or group of
integers or steps but not the exclusion of any other integer or
step or group of integer or step. When used herein the term
"comprising" can be substituted with the term "containing" or
"including" or sometimes when used herein with the term
"having".
[0119] When used herein "consisting of" excludes any element, step,
or ingredient not specified in the claim element. When used herein,
"consisting essentially of" does not exclude materials or steps
that do not materially affect the basic and novel characteristics
of the claim.
[0120] In each instance herein any of the terms "comprising",
"consisting essentially of" and "consisting of" may be replaced
with either of the other two terms.
[0121] The definition of the term "antibody" includes embodiments
such as monoclonal, chimeric, single chain, humanized and human
antibodies, as well as antibody fragments, like, inter alia, Fab
fragments. Antibody fragments or derivatives further comprise
F(ab').sub.2, Fv, scFv fragments or single domain antibodies such
as domain antibodies or nanobodies, single variable domain
antibodies or immunoglobulin single variable domain comprising
merely one variable domain, which might be VHH, VH or VL, that
specifically bind an antigen or epitope independently of other V
regions or domains; see, for example, Harlow and Lane (1988) and
(1999), loc. cit.; Kontermann and Dubel, Antibody Engineering,
Springer, 2nd ed. 2010 and Little, Recombinant Antibodies for
Immunotherapy, Cambridge University Press 2009. Such immunoglobulin
single variable domain encompasses not only an isolated antibody
single variable domain polypeptide, but also larger polypeptides
that comprise one or more monomers of an antibody single variable
domain polypeptide sequence.
[0122] In line with this definition all above described embodiments
of the term antibody can be subsumed under the term "antibody
construct". Said term also includes diabodies or Dual-Affinity
Re-Targeting (DART) antibodies. Further envisaged are (bispecific)
single chain diabodies, tandem diabodies (Tandab's), "minibodies"
exemplified by a structure which is as follows: (VH-VL-CH3).sub.2,
(scFv-CH3).sub.2 or (scFv-CH3-scFv).sub.2, "Fc DART" antibodies and
"IgG DART" antibodies, and multibodies such as triabodies.
Immunoglobulin single variable domains encompass not only an
isolated antibody single variable domain polypeptide, but also
larger polypeptides that comprise one or more monomers of an
antibody single variable domain polypeptide sequence.
[0123] Various procedures are known in the art and may be used for
the production of such antibody constructs (antibodies and/or
fragments). Thus, (antibody) derivatives can be produced by
peptidomimetics. Further, techniques described for the production
of single chain antibodies (see, inter alia, U.S. Pat. No.
4,946,778, Kontermann and Dubel (2010), loc. cit. and Little
(2009), loc. cit.) can be adapted to produce single chain
antibodies specific for elected polypeptide(s). Also, transgenic
animals may be used to express humanized antibodies specific for
polypeptides and fusion proteins of this invention. For the
preparation of monoclonal antibodies, any technique, providing
antibodies produced by continuous cell line cultures can be used.
Examples for such techniques include the hybridoma technique
(Kohler and Milstein Nature 256 (1975), 495-497), the trioma
technique, the human B-cell hybridoma technique (Kozbor, Immunology
Today 4 (1983), 72) and the EBV-hybridoma technique to produce
human monoclonal antibodies (Cole et al., Monoclonal Antibodies and
Cancer Therapy, Alan R. Liss, Inc. (1985), 77-96). Surface plasmon
resonance as employed in the BIAcore system can be used to increase
the efficiency of phage antibodies which bind to an epitope of a
target polypeptide, such as CD3 epsilon (Schier, Human Antibodies
Hybridomas 7 (1996), 97-105; Malmborg, J. Immunol. Methods 183
(1995), 7-13). It is also envisaged in the context of this
invention that the term "antibody" comprises antibody constructs,
which may be expressed in a host as described herein below, e.g.
antibody constructs which may be transfected and/or transduced via,
inter alia, viruses or plasmid vectors.
[0124] Furthermore, the term "antibody" as employed in the
invention also relates to derivatives or variants of the antibodies
described herein which display the same specificity as the
described antibodies.
[0125] The terms "antigen-binding domain", "antigen-binding
fragment" and "antibody binding region" when used herein refer to a
part of an antibody molecule that comprises amino acids responsible
for the specific binding between antibody and antigen. The part of
the antigen that is specifically recognized and bound by the
antibody is referred to as the "epitope" as described herein above.
As mentioned above, an antigen-binding domain may typically
comprise an antibody light chain variable region (VL) and an
antibody heavy chain variable region (VH); however, it does not
have to comprise both. Fd fragments, for example, have two VH
regions and often retain some antigen-binding function of the
intact antigen-binding domain. Examples of antigen-binding
fragments of an antibody include (1) a Fab fragment, a monovalent
fragment having the VL, VH, CL and CH1 domains; (2) a F(ab').sub.2
fragment, a bivalent fragment having two Fab fragments linked by a
disulfide bridge at the hinge region; (3) a Fd fragment having the
two VH and CH1 domains; (4) a Fv fragment having the VL and VH
domains of a single arm of an antibody, (5) a dAb fragment (Ward et
al., (1989) Nature 341:544-546), which has a VH domain; (6) an
isolated complementarity determining region (CDR), and (7) a single
chain Fv (scFv). Although the two domains of the Fv fragment, VL
and VH are coded for by separate genes, they can be joined, using
recombinant methods, by a synthetic linker that enables them to be
made as a single protein chain in which the VL and VH regions pair
to form monovalent molecules (known as single chain Fv (scFv); see
e.g., Huston et al. (1988) Proc. Natl. Acad. Sci USA 85:5879-5883).
These antibody fragments are obtained using conventional techniques
known to those with skill in the art, and the fragments are
evaluated for function in the same manner as are intact
antibodies.
[0126] The term "monoclonal antibody" as used herein refers to an
antibody obtained from a population of substantially homogeneous
antibodies, i.e., the individual antibodies comprising the
population are identical except for possible naturally occurring
mutations and/or post-translation modifications (e.g.,
isomerizations, amidations) that may be present in minor amounts.
Monoclonal antibodies are highly specific, being directed against a
single antigenic site. Furthermore, in contrast to conventional
(polyclonal) antibody preparations which typically include
different antibodies directed against different determinants
(epitopes), each monoclonal antibody is directed against a single
determinant on the antigen. In addition to their specificity, the
monoclonal antibodies are advantageous in that they are synthesized
by the hybridoma culture, uncontaminated by other immunoglobulins.
The modifier "monoclonal" indicates the character of the antibody
as being obtained from a substantially homogeneous population of
antibodies, and is not to be construed as requiring production of
the antibody by any particular method. For example, the monoclonal
antibodies to be used in accordance with the present invention may
be made by the hybridoma method first described by Kohler et al.,
Nature, 256: 495 (1975), or may be made by recombinant DNA methods
(see, e.g., U.S. Pat. No. 4,816,567). The "monoclonal antibodies"
may also be isolated from phage antibody libraries using the
techniques described in Clackson et al., Nature, 352: 624-628
(1991) and Marks et al., J. Mol. Biol., 222: 581-597 (1991), for
example.
[0127] The term "human antibody" includes antibodies having
variable and constant regions corresponding substantially to human
germline immunoglobulin sequences known in the art, including, for
example, those described by Kabat et al. (See Kabat et al. (1991)
loc. cit.). The human antibodies of the invention may include amino
acid residues not encoded by human germline immunoglobulin
sequences (e.g., mutations introduced by random or site-specific
mutagenesis in vitro or by somatic mutation in vivo), for example
in the CDRs, and in particular, CDR3. The human antibody can have
at least one, two, three, four, five, or more positions replaced
with an amino acid residue that is not encoded by the human
germline immunoglobulin sequence. It is emphasized that the
definition of human antibodies as used herein also contemplates
fully human antibodies, which include only non-artificially and/or
genetically altered human sequences of antibodies as those can be
derived by using technologies using systems such as the
Xenomice.
[0128] Examples of "antibody variants" include humanized variants
of non-human antibodies, "affinity matured" antibodies (see, e.g.
Hawkins et al. J. Mol. Biol. 254, 889-896 (1992) and Lowman et al.,
Biochemistry 30, 10832-10837 (1991)) and antibody mutants with
altered effector function (s) (see, e.g., U.S. Pat. No. 5,648,260,
Kontermann and Dubel (2010), loc. cit. and Little (2009), loc.
cit.).
[0129] As used herein, "in vitro generated antibody" refers to an
antibody where all or part of the variable region (e.g., at least
one CDR) is generated in a non-immune cell selection (e.g., an in
vitro phage display, protein chip or any other method in which
candidate sequences can be tested for their ability to bind to an
antigen). This term thus preferably excludes sequences generated by
genomic rearrangement in an immune cell.
[0130] The pairing of a VH and VL together forms a single
antigen-binding site. The CH domain most proximal to VH is
designated as CH1. Each L chain is linked to an H chain by one
covalent disulfide bond, while the two H chains are linked to each
other by one or more disulfide bonds depending on the H chain
isotype. The VH and VL domains consist of four regions of
relatively conserved sequences called framework regions (FR1, FR2,
FR3, and FR4), which form a scaffold for three regions of
hypervariable sequences (complementarity determining regions,
CDRs). The CDRs contain most of the residues responsible for
specific interactions of the antibody with the antigen. CDRs are
referred to as CDR 1, CDR2, and CDR3. Accordingly, CDR constituents
on the heavy chain are referred to as H1, H2, and H3, while CDR
constituents on the light chain are referred to as L1, L2, and
L3.
[0131] The term "variable" refers to the portions of the
immunoglobulin domains that exhibit variability in their sequence
and that are involved in determining the specificity and binding
affinity of a particular antibody (i.e., the "variable domain(s)").
Variability is not evenly distributed throughout the variable
domains of antibodies; it is concentrated in sub-domains of each of
the heavy and light chain variable regions. These sub-domains are
called "hypervariable" regions or "complementarity determining
regions" (CDRs). The more conserved (i.e., non-hypervariable)
portions of the variable domains are called the "framework" regions
(FRM). The variable domains of naturally occurring heavy and light
chains each comprise four FRM regions, largely adopting a
.beta.-sheet configuration, connected by three hypervariable
regions, which form loops connecting, and in some cases forming
part of, the .beta.-sheet structure. The hypervariable regions in
each chain are held together in close proximity by the FRM and,
with the hypervariable regions from the other chain, contribute to
the formation of the antigen-binding site (see Kabat et al., loc.
cit.). The constant domains are not directly involved in antigen
binding, but exhibit various effector functions, such as, for
example, antibody-dependent, cell-mediated cytotoxicity and
complement activation.
[0132] The terms "CDR", and its plural "CDRs", refer to a
complementarity determining region (CDR) of which three make up the
binding character of a light chain variable region (CDRL1, CDRL2
and CDRL3) and three make up the binding character of a heavy chain
variable region (CDRH1, CDRH2 and CDRH3). CDRs contribute to the
functional activity of an antibody molecule and are separated by
amino acid sequences that comprise scaffolding or framework
regions. The exact definitional CDR boundaries and lengths are
subject to different classification and numbering systems. CDRs may
therefore be referred to by Kabat, Chothia, contact or any other
boundary definitions, including the numbering system described
herein. Despite differing boundaries, each of these systems has
some degree of overlap in what constitutes the so called
"hypervariable regions" within the variable sequences. CDR
definitions according to these systems may therefore differ in
length and boundary areas with respect to the adjacent framework
region. See for example Kabat, Chothia, and/or MacCallum (Kabat et
al., loc. cit.; Chothia et al., J. Mol. Biol, 1987, 196: 901; and
MacCallum et al., J. Mol. Biol, 1996, 262: 732). However, the
numbering in accordance with the so-called Kabat system is
preferred. The CDR3 of the light chain and, particularly, CDR3 of
the heavy chain may constitute the most important determinants in
antigen binding within the light and heavy chain variable regions.
In some antibody constructs, the heavy chain CDR3 appears to
constitute the major area of contact between the antigen and the
antibody. In vitro selection schemes in which CDR3 alone is varied
can be used to vary the binding properties of an antibody or
determine which residues contribute to the binding of an
antigen.
[0133] "Consisting essentially of" means that the amino acid
sequence can vary by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
13, 14, or 15% relative to the recited SEQ ID NO: sequence and
still retain biological activity, as described herein.
[0134] In some embodiments, the antibody constructs of the
invention are isolated proteins or substantially pure proteins. An
"isolated" protein is unaccompanied by at least some of the
material with which it is normally associated in its natural state,
for example constituting at least about 5%, or at least about 50%
by weight of the total protein in a given sample. It is understood
that the isolated protein may constitute from 5 to 99.9% by weight
of the total protein content depending on the circumstances. For
example, the protein may be made at a significantly higher
concentration through the use of an inducible promoter or high
expression promoter, such that the protein is made at increased
concentration levels. The definition includes the production of an
antigen binding protein in a wide variety of organisms and/or host
cells that are known in the art.
[0135] For amino acid sequences, sequence identity and/or
similarity is determined by using standard techniques known in the
art, including, but not limited to, the local sequence identity
algorithm of Smith and Waterman, 1981, Adv. Appl. Math. 2:482, the
sequence identity alignment algorithm of Needleman and Wunsch,
1970, J. Mol. Biol. 48:443, the search for similarity method of
Pearson and Lipman, 1988, Proc. Nat. Acad. Sci. U.S.A. 85:2444,
computerized implementations of these algorithms (GAP, BESTFIT,
FASTA, and TFASTA in the Wisconsin Genetics Software Package,
Genetics Computer Group, 575 Science Drive, Madison, Wis.), the
Best Fit sequence program described by Devereux et al., 1984, Nucl.
Acid Res. 12:387-395, preferably using the default settings, or by
inspection. Preferably, percent identity is calculated by FastDB
based upon the following parameters: mismatch penalty of 1; gap
penalty of 1; gap size penalty of 0.33; and joining penalty of 30,
"Current Methods in Sequence Comparison and Analysis,"
Macromolecule Sequencing and Synthesis, Selected Methods and
Applications, pp 127-149 (1988), Alan R. Liss, Inc.
[0136] An example of a useful algorithm is PILEUP. PILEUP creates a
multiple sequence alignment from a group of related sequences using
progressive, pairwise alignments. It can also plot a tree showing
the clustering relationships used to create the alignment. PILEUP
uses a simplification of the progressive alignment method of Feng
& Doolittle, 1987, J. Mol. Evol. 35:351-360; the method is
similar to that described by Higgins and Sharp, 1989, CABIOS
5:151-153. Useful PILEUP parameters including a default gap weight
of 3.00, a default gap length weight of 0.10, and weighted end
gaps.
[0137] Another example of a useful algorithm is the BLAST
algorithm, described in: Altschul et al., 1990, J. Mol. Biol.
215:403-410; Altschul et al., 1997, Nucleic Acids Res.
25:3389-3402; and Karin et al., 1993, Proc. Natl. Acad. Sci. U.S.A.
90:5873-5787. A particularly useful BLAST program is the WU-BLAST-2
program which was obtained from Altschul et al., 1996, Methods in
Enzymology 266:460-480. WU-BLAST-2 uses several search parameters,
most of which are set to the default values. The adjustable
parameters are set with the following values: overlap span=1,
overlap fraction=0.125, word threshold (T)=II. The HSP S and HSP S2
parameters are dynamic values and are established by the program
itself depending upon the composition of the particular sequence
and composition of the particular database against which the
sequence of interest is being searched; however, the values may be
adjusted to increase sensitivity.
[0138] An additional useful algorithm is gapped BLAST as reported
by Altschul et al., 1993, Nucl. Acids Res. 25:3389-3402. Gapped
BLAST uses BLOSUM-62 substitution scores; threshold T parameter set
to 9; the two-hit method to trigger ungapped extensions, charges
gap lengths of k a cost of 10+k; Xu set to 16, and Xg set to 40 for
database search stage and to 67 for the output stage of the
algorithms. Gapped alignments are triggered by a score
corresponding to about 22 bits.
[0139] Generally, the amino acid homology, similarity, or identity
between individual variant CDRs are at least 80% to the sequences
depicted herein, and more typically with preferably increasing
homologies or identities of at least 85%, 90%, 91%, 92%, 93%, 94%,
95%, 96%, 97%, 98%, 99%, and almost 100%. In a similar manner,
"percent (%) nucleic acid sequence identity" with respect to the
nucleic acid sequence of the binding proteins identified herein is
defined as the percentage of nucleotide residues in a candidate
sequence that are identical with the nucleotide residues in the
coding sequence of the antigen binding protein. A specific method
utilizes the BLASTN module of WU-BLAST-2 set to the default
parameters, with overlap span and overlap fraction set to 1 and
0.125, respectively.
[0140] Generally, the nucleic acid sequence homology, similarity,
or identity between the nucleotide sequences encoding individual
variant CDRs and the nucleotide sequences depicted herein are at
least 80%, and more typically with preferably increasing homologies
or identities of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,
88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, and
almost 100%.
[0141] Thus, a "variant CDR" is one with the specified homology,
similarity, or identity to the parent CDR of the invention, and
shares biological function, including, but not limited to, at least
80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%,
93%, 94%, 95%, 96%, 97%, 98%, or 99% of the specificity and/or
activity of the parent CDR.
[0142] While the site or region for introducing an amino acid
sequence variation is predetermined, the mutation per se need not
be predetermined. For example, in order to optimize the performance
of a mutation at a given site, random mutagenesis may be conducted
at the target codon or region and the expressed antigen binding
protein CDR variants screened for the optimal combination of
desired activity. Techniques for making substitution mutations at
predetermined sites in DNA having a known sequence are well known,
for example, M13 primer mutagenesis and PCR mutagenesis. Screening
of the mutants is done using assays of antigen binding protein
activities, such as CDH19 binding.
[0143] The term "amino acid" or "amino acid residue" typically
refers to an amino acid having its art recognized definition such
as an amino acid selected from the group consisting of: alanine
(Ala or A); arginine (Arg or R); asparagine (Asn or N); aspartic
acid (Asp or D); cysteine (Cys or C); glutamine (Gln or Q);
glutamic acid (Glu or E); glycine (Gly or G); histidine (His or H);
isoleucine (He or I): leucine (Leu or L); lysine (Lys or K);
methionine (Met or M); phenylalanine (Phe or F); pro line (Pro or
P); serine (Ser or S); threonine (Thr or T); tryptophan (Trp or W);
tyrosine (Tyr or Y); and valine (Val or V), although modified,
synthetic, or rare amino acids may be used as desired. Generally,
amino acids can be grouped as having a nonpolar side chain (e.g.,
Ala, Cys, He, Leu, Met, Phe, Pro, Val); a negatively charged side
chain (e.g., Asp, Glu); a positively charged sidechain (e.g., Arg,
His, Lys); or an uncharged polar side chain (e.g., Asn, Cys, Gln,
Gly, His, Met, Phe, Ser, Thr, Trp, and Tyr).
[0144] The term "hypervariable region" (also known as
"complementarity determining regions" or CDRs) when used herein
refers to the amino acid residues of an antibody which are (usually
three or four short regions of extreme sequence variability) within
the V-region domain of an immunoglobulin which form the
antigen-binding site and are the main determinants of antigen
specificity. There are at least two methods for identifying the CDR
residues: (1) An approach based on cross-species sequence
variability (i. e., Kabat et al., loc. cit.); and (2) An approach
based on crystallographic studies of antigen-antibody complexes
(Chothia, C. et al., J. Mol. Biol. 196: 901-917 (1987)). However,
to the extent that two residue identification techniques define
regions of overlapping, but not identical regions, they can be
combined to define a hybrid CDR. However, in general, the CDR
residues are preferably identified in accordance with the so-called
Kabat (numbering) system.
[0145] The term "framework region" refers to the art-recognized
portions of an antibody variable region that exist between the more
divergent (i.e., hypervariable) CDRs. Such framework regions are
typically referred to as frameworks 1 through 4 (FR1, FR2, FR3, and
FR4) and provide a scaffold for the presentation of the six CDRs
(three from the heavy chain and three from the light chain) in
three dimensional space, to form an antigen-binding surface.
[0146] Typically, CDRs form a loop structure that can be classified
as a canonical structure. The term "canonical structure" refers to
the main chain conformation that is adopted by the antigen binding
(CDR) loops. From comparative structural studies, it has been found
that five of the six antigen binding loops have only a limited
repertoire of available conformations. Each canonical structure can
be characterized by the torsion angles of the polypeptide backbone.
Correspondent loops between antibodies may, therefore, have very
similar three dimensional structures, despite high amino acid
sequence variability in most parts of the loops (Chothia and Lesk,
J. Mol. Biol., 1987, 196: 901; Chothia et al., Nature, 1989, 342:
877; Martin and Thornton, J. Mol. Biol, 1996, 263: 800, each of
which is incorporated by reference in its entirety). Furthermore,
there is a relationship between the adopted loop structure and the
amino acid sequences surrounding it. The conformation of a
particular canonical class is determined by the length of the loop
and the amino acid residues residing at key positions within the
loop, as well as within the conserved framework (i.e., outside of
the loop). Assignment to a particular canonical class can therefore
be made based on the presence of these key amino acid residues. The
term "canonical structure" may also include considerations as to
the linear sequence of the antibody, for example, as catalogued by
Kabat (Kabat et al., loc. cit.). The Kabat numbering scheme
(system) is a widely adopted standard for numbering the amino acid
residues of an antibody variable domain in a consistent manner and
is the preferred scheme applied in the present invention as also
mentioned elsewhere herein. Additional structural considerations
can also be used to determine the canonical structure of an
antibody. For example, those differences not fully reflected by
Kabat numbering can be described by the numbering system of Chothia
et al and/or revealed by other techniques, for example,
crystallography and two or three-dimensional computational
modeling. Accordingly, a given antibody sequence may be placed into
a canonical class which allows for, among other things, identifying
appropriate chassis sequences (e.g., based on a desire to include a
variety of canonical structures in a library). Kabat numbering of
antibody amino acid sequences and structural considerations as
described by Chothia et al., loc. cit. and their implications for
construing canonical aspects of antibody structure, are described
in the literature.
[0147] CDR3 is typically the greatest source of molecular diversity
within the antibody-binding site. H3, for example, can be as short
as two amino acid residues or greater than 26 amino acids. The
subunit structures and three-dimensional configurations of
different classes of immunoglobulins are well known in the art. For
a review of the antibody structure, see Antibodies: A Laboratory
Manual, Cold Spring Harbor Laboratory, eds. Harlow et al., 1988.
One of skill in the art will recognize that each subunit structure,
e.g., a CH, VH, CL, VL, CDR, FR structure, comprises active
fragments, e.g., the portion of the VH, VL, or CDR subunit the
binds to the antigen, i.e., the antigen-binding fragment, or, e.g.,
the portion of the CH subunit that binds to and/or activates, e.g.,
an Fc receptor and/or complement. The CDRs typically refer to the
Kabat CDRs, as described in Sequences of Proteins of immunological
Interest, US Department of Health and Human Services (1991), eds.
Kabat et al. Another standard for characterizing the antigen
binding site is to refer to the hypervariable loops as described by
Chothia. See, e.g., Chothia, et al. (1987; J. Mol. Biol.
227:799-817); and Tomlinson et al. (1995) EMBO J. 14: 4628-4638.
Still another standard is the AbM definition used by Oxford
Molecular's AbM antibody modeling software. See, generally, e.g.,
Protein Sequence and Structure Analysis of Antibody Variable
Domains. In: Antibody Engineering Lab Manual (Ed.: Duebel, S. and
Kontermann, R., Springer-Verlag, Heidelberg). Embodiments described
with respect to Kabat CDRs can alternatively be implemented using
similar described relationships with respect to Chothia
hypervariable loops or to the AbM-defined loops.
[0148] The sequence of antibody genes after assembly and somatic
mutation is highly varied, and these varied genes are estimated to
encode 10.sup.10 different antibody molecules (Immunoglobulin
Genes, 2.sup.nd ed., eds. Jonio et al., Academic Press, San Diego,
Calif., 1995). Accordingly, the immune system provides a repertoire
of immunoglobulins. The term "repertoire" refers to at least one
nucleotide sequence derived wholly or partially from at least one
sequence encoding at least one immunoglobulin. The sequence(s) may
be generated by rearrangement in vivo of the V, D, and J segments
of heavy chains, and the V and J segments of light chains.
Alternatively, the sequence(s) can be generated from a cell in
response to which rearrangement occurs, e.g., in vitro stimulation.
Alternatively, part or all of the sequence(s) may be obtained by
DNA splicing, nucleotide synthesis, mutagenesis, and other methods,
see, e.g., U.S. Pat. No. 5,565,332. A repertoire may include only
one sequence or may include a plurality of sequences, including
ones in a genetically diverse collection.
[0149] The term "binding molecule" or "antibody construct" in the
sense of the present disclosure indicates any molecule capable of
(specifically) binding to, interacting with or recognizing the
target molecules CDH19 and CD3. Such molecules or constructs may
include proteinaceous parts and non-proteinaceous parts (e.g.
chemical linkers or chemical cross-linking agents such as
glutaraldehyde).
[0150] In the event that a linker is used, this linker is
preferably of a length and sequence sufficient to ensure that each
of the first and second domains can, independently from one
another, retain their differential binding specificities. Most
preferably and as documented in the appended examples, the antibody
construct of the invention is a "bispecific single chain antibody
construct", more prefereably a bispecific single chain Fv (scFv).
Bispecific single chain molecules are known in the art and are
described in WO 99/54440, Mack, J. Immunol. (1997), 158, 3965-3970,
Mack, PNAS, (1995), 92, 7021-7025, Kufer, Cancer Immunol.
Immunother., (1997), 45, 193-197, Loffler, Blood, (2000), 95, 6,
2098-2103, Bruhl, Immunol., (2001), 166, 2420-2426, Kipriyanov, J.
Mol. Biol., (1999), 293, 41-56.
[0151] The said variable domains comprised in the herein described
antibody constructs may be connected by additional linker
sequences. The term "peptide linker" defines in accordance with the
present invention an amino acid sequence by which the amino acid
sequences of the first domain and the second domain of the antibody
construct of the invention are linked with each other. An essential
technical feature of such peptide linker is that said peptide
linker does not comprise any polymerization activity. Among the
suitable peptide linkers are those described in U.S. Pat. Nos.
4,751,180 and 4,935,233 or WO 88/09344. A preferred embodiment of a
peptide linker is characterized by the amino acid sequence
Gly-Gly-Gly-Gly-Ser, i.e. Gly4Ser, or polymers thereof, i.e.
(Gly4Ser)x, where x is an integer 1 or greater. The characteristics
of said peptide linker, which comprise the absence of the promotion
of secondary structures are known in the art and described e.g. in
Dall'Acqua et al. (Biochem. (1998) 37, 9266-9273), Cheadle et al.
(Mol Immunol (1992) 29, 21-30) and Raag and Whitlow (FASEB (1995)
9(1), 73-80). Peptide linkers which also do not promote any
secondary structures are preferred. The linkage of said domains to
each other can be provided by, e.g. genetic engineering, as
described in the examples. Methods for preparing fused and
operatively linked bispecific single chain constructs and
expressing them in mammalian cells or bacteria are well-known in
the art (e.g. WO 99/54440 or Sambrook et al., Molecular Cloning: A
Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring
Harbor, N.Y., 2001).
[0152] For peptide linkers, which connect the at least two binding
domains in the antibody construct of the invention peptide linkers
are preferred which comprise only a few number of amino acid
residues, e.g. 12 amino acid residues or less. Thus, peptide linker
of 12, 11, 10, 9, 8, 7, 6 or 5 amino acid residues are preferred.
An envisaged peptide linker with less than 5 amino acids comprises
4, 3, 2 or one amino acid(s) wherein Gly-rich linkers are
preferred. A particularly preferred "single" amino acid in context
of said "peptide linker" is Gly. Accordingly, said peptide linker
may consist of the single amino acid Gly.
[0153] The term "multispecific" as used herein refers to a binding
molecule which is an antibody construct and comprises at least a
first and a second binding domain, wherein the first binding domain
is capable of binding to one antigen or target, and the second
binding domain is capable of binding to another antigen or target.
Accordingly, antibody constructs according to the invention
comprise at least specificities for two different antigens or
targets and are at least bispecific. The "antibody construct" of
the invention also comprises multispecific binding molecules such
as e.g. trispecific binding molecules, the latter ones including
three binding domains.
[0154] It is also envisaged that the antibody construct of the
invention has, in addition to its function to bind to the target
molecules CDH19 and CD3, a further function. In this format, the
antibody construct is a tri- or multifunctional antibody construct
by targeting plasma cells through binding to CDH19, mediating
cytotoxic T cell activity through CD3 binding and providing a
further function such as a fully functional Fc constant domain
mediating antibody-dependent cellular cytotoxicity through
recruitment of effector cells like NK cells, a label (fluorescent
etc.), a therapeutic agent such as, e.g. a toxin or radionuclide,
and/or means to enhance serum half-life, etc.
[0155] The term "binding domain" characterizes in connection with
the present invention a domain which is capable of specifically
binding to/interacting with a given target epitope or a given
target site on the target molecules CDH19 and CD3.
[0156] Binding domains can be derived from a binding domain donor
such as for example an antibody. It is envisaged that a binding
domain of the present invention comprises at least said part of any
of the aforementioned binding domains that is required for binding
to/interacting with a given target epitope or a given target site
on the target molecules CDH19 and CD3.
[0157] It is envisaged that the binding domain of the
aforementioned binding domain donors is characterized by that part
of these donors that is responsible for binding the respective
target, i.e. when that part is removed from the binding domain
donor, said donor loses its binding capability. "Loses" means a
reduction of at least 50% of the binding capability when compared
with the binding donor. Methods to map these binding sites are well
known in the art--it is therefore within the standard knowledge of
the skilled person to locate/map the binding site of a binding
domain donor and, thereby, to "derive" said binding domain from the
respective binding domain donors.
[0158] The term "epitope" refers to a site on an antigen to which a
binding domain, such as an antibody or immunoglobulin or derivative
or fragment of an antibody or of an immunoglobulin, specifically
binds. An "epitope" is antigenic and thus the term epitope is
sometimes also referred to herein as "antigenic structure" or
"antigenic determinant". Thus, the binding domain is an
"antigen-interaction-site". Said binding/interaction is also
understood to define a "specific recognition". In one example, said
binding domain which (specifically) binds to/interacts with a given
target epitope or a given target site on the target molecules CDH19
and CD3 is an antibody or immunoglobulin, and said binding domain
is a VH and/or VL region of an antibody or of an
immunoglobulin.
[0159] "Epitopes" can be formed both by contiguous amino acids or
non-contiguous amino acids juxtaposed by tertiary folding of a
protein. A "linear epitope" is an epitope where an amino acid
primary sequence comprises the recognized epitope. A linear epitope
typically includes at least 3 or at least 4, and more usually, at
least 5 or at least 6 or at least 7, for example, about 8 to about
10 amino acids in a unique sequence.
[0160] A "conformational epitope", in contrast to a linear epitope,
is an epitope wherein the primary sequence of the amino acids
comprising the epitope is not the sole defining component of the
epitope recognized (e.g., an epitope wherein the primary sequence
of amino acids is not necessarily recognized by the binding
domain). Typically a conformational epitope comprises an increased
number of amino acids relative to a linear epitope. With regard to
recognition of conformational epitopes, the binding domain
recognizes a three-dimensional structure of the antigen, preferably
a peptide or protein or fragment thereof (in the context of the
present invention, the antigen for one of the binding domains is
comprised within the CDH19 protein). For example, when a protein
molecule folds to form a three-dimensional structure, certain amino
acids and/or the polypeptide backbone forming the conformational
epitope become juxtaposed enabling the antibody to recognize the
epitope. Methods of determining the conformation of epitopes
include, but are not limited to, x-ray crystallography,
two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy
and site-directed spin labelling and electron paramagnetic
resonance (EPR) spectroscopy. Moreover, the provided examples
describe a further method to characterize a given binding domain by
way of binning, which includes a test whether the given binding
domain binds to one or more epitope cluster(s) of a given protein,
in particular CDH19.
[0161] As used herein, the term "epitope cluster" denotes the
entirety of epitopes lying in a defined contiguous stretch of an
antigen. An epitope cluster can comprise one, two or more epitopes.
The concept of epitope cluster is also used in the characterization
of the features of the antibody constructs of the invention.
[0162] The terms "(capable of) binding to", "specifically
recognizing", "directed to" and "reacting with" mean in accordance
with this invention that a binding domain is capable of
specifically interacting with one or more, preferably at least two,
more preferably at least three and most preferably at least four
amino acids of an epitope.
[0163] As used herein, the terms "specifically interacting",
"specifically binding" or "specifically bind(s)" mean that a
binding domain exhibits appreciable affinity for a particular
protein or antigen and, generally, does not exhibit significant
reactivity with proteins or antigens other than CDH19 or CD3.
"Appreciable affinity" includes binding with an affinity of about
10.sup.-6M (KD) or stronger. Preferably, binding is considered
specific when binding affinity is about 10.sup.-12 to 10.sup.-8 M,
10.sup.-12 to 10.sup.-9 M, 10.sup.-12 to 10.sup.-10 M, 10.sup.-11
to 10.sup.-8 M, preferably of about 10.sup.-11 to 10.sup.-9 M.
Whether a binding domain specifically reacts with or binds to a
target can be tested readily by, inter alia, comparing the reaction
of said binding domain with a target protein or antigen with the
reaction of said binding domain with proteins or antigens other
than CDH19 or CD3. Preferably, a binding domain of the invention
does not essentially bind or is not capable of binding to proteins
or antigens other than CDH19 or CD3 (i.e. the first binding domain
is not capable of binding to proteins other than CDH19 and the
second binding domain is not capable of binding to proteins other
than CD3).
[0164] The term "does not essentially bind", or "is not capable of
binding" means that a binding domain of the present invention does
not bind another protein or antigen other than CDH19 or CD3, i.e.,
does not show reactivity of more than 30%, preferably not more than
20%, more preferably not more than 10%, particularly preferably not
more than 9%, 8%, 7%, 6% or 5% with proteins or antigens other than
CDH19 or CD3, whereby binding to CDH19 or CD3, respectively, is set
to be 100%.
[0165] Specific binding is believed to be effected by specific
motifs in the amino acid sequence of the binding domain and the
antigen. Thus, binding is achieved as a result of their primary,
secondary and/or tertiary structure as well as the result of
secondary modifications of said structures. The specific
interaction of the antigen-interaction-site with its specific
antigen may result in a simple binding of said site to the antigen.
Moreover, the specific interaction of the antigen-interaction-site
with its specific antigen may alternatively or additionally result
in the initiation of a signal, e.g. due to the induction of a
change of the conformation of the antigen, an oligomerization of
the antigen, etc.
[0166] Proteins (including fragments thereof, preferably
biologically active fragments, and peptides, usually having less
than 30 amino acids) comprise one or more amino acids coupled to
each other via a covalent peptide bond (resulting in a chain of
amino acids). The term "polypeptide" as used herein describes a
group of molecules, which consist of more than 30 amino acids.
Polypeptides may further form multimers such as dimers, trimers and
higher oligomers, i.e. consisting of more than one polypeptide
molecule. Polypeptide molecules forming such dimers, trimers etc.
may be identical or non-identical. The corresponding higher order
structures of such multimers are, consequently, termed homo- or
heterodimers, homo- or heterotrimers etc. An example for a
hereteromultimer is an antibody molecule, which, in its naturally
occurring form, consists of two identical light polypeptide chains
and two identical heavy polypeptide chains. The terms "polypeptide"
and "protein" also refer to naturally modified
polypeptides/proteins wherein the modification is effected e.g. by
post-translational modifications like glycosylation, acetylation,
phosphorylation and the like. A "polypeptide" when referred to
herein may also be chemically modified such as pegylated. Such
modifications are well known in the art.
[0167] "Isolated" when used to describe the antibody construct
disclosed herein, means a antibody construct that has been
identified, separated and/or recovered from a component of its
production environment. Preferably, the isolated antibody construct
is free of association with all other components from its
production environment. Contaminant components of its production
environment, such as that resulting from recombinant transfected
cells, are materials that would typically interfere with diagnostic
or therapeutic uses for the polypeptide, and may include enzymes,
hormones, and other proteinaceous or non-proteinaceous solutes. In
preferred embodiments, the antibody construct will be purified (1)
to a degree sufficient to obtain at least 15 residues of N-terminal
or internal amino acid sequence by use of a spinning cup
sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or
reducing conditions using Coomassie blue or, preferably, silver
stain. Ordinarily, however, an isolated antibody will be prepared
by at least one purification step.
[0168] Amino acid sequence modifications of the antibody constructs
described herein are contemplated. For example, it may be desirable
to improve the binding affinity and/or other biological properties
of the antibody. Amino acid sequence variants of the antibody
constructs are prepared by introducing appropriate nucleotide
changes into the antibody constructs nucleic acid, or by peptide
synthesis.
[0169] Such modifications include, for example, deletions from,
and/or insertions into, and/or substitutions of, residues within
the amino acid sequences of the antibody constructs. Any
combination of deletion, insertion, and substitution is made to
arrive at the final construct, provided that the final construct
possesses the desired characteristics. The amino acid changes also
may alter post-translational processes of the antibody constructs,
such as changing the number or position of glycosylation sites.
Preferably, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids may be
substituted in a CDR, while 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
13, 14, 15, 16, 17, 18, 19, 20, or 25 amino acids may be
substituted in the framework regions (FRs). The substitutions are
preferably conservative substitutions as described herein.
Additionally or alternatively, 1, 2, 3, 4, 5, or 6 amino acids may
be inserted or deleted in each of the CDRs (of course, dependent on
their length), while 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 16, 17, 18, 19, 20, or 25 amino acids may be inserted or
deleted in each of the FRs.
[0170] A useful method for identification of certain residues or
regions of the antibody constructs that are preferred locations for
mutagenesis is called "alanine scanning mutagenesis" as described
by Cunningham and Wells in Science, 244: 1081-1085 (1989). Here, a
residue or group of target residues within the antibody construct
is/are identified (e.g. charged residues such as arg, asp, his,
lys, and glu) and replaced by a neutral or negatively charged amino
acid (most preferably alanine or polyalanine) to affect the
interaction of the amino acids with the epitope.
[0171] Those amino acid locations demonstrating functional
sensitivity to the substitutions then are refined by introducing
further or other variants at, or for, the sites of substitution.
Thus, while the site for introducing an amino acid sequence
variation is predetermined, the nature of the mutation per se needs
not to be predetermined. For example, to analyze the performance of
a mutation at a given site, ala scanning or random mutagenesis is
conducted at a target codon or region and the expressed antibody
construct variants are screened for the desired activity.
[0172] Preferably, amino acid sequence insertions include amino-
and/or carboxyl-terminal fusions ranging in length from 1, 2, 3, 4,
5, 6, 7, 8, 9 or 10 residues to polypeptides containing a hundred
or more residues, as well as intrasequence insertions of single or
multiple amino acid residues. An insertional variant of the
antibody construct includes the fusion to the N- or C-terminus of
the antibody to an enzyme or a fusion to a polypeptide which
increases the serum half-life of the antibody.
[0173] Another type of variant is an amino acid substitution
variant. These variants have preferably at least 1, 2, 3, 4, 5, 6,
7, 8, 9 or 10 amino acid residues in the antibody construct
replaced by a different residue. The sites of greatest interest for
substitutional mutagenesis include the CDRs of the heavy and/or
light chain, in particular the hypervariable regions, but FR
alterations in the heavy and/or light chain are also
contemplated.
[0174] For example, if a CDR sequence encompasses 6 amino acids, it
is envisaged that one, two or three of these amino acids are
substituted. Similarly, if a CDR sequence encompasses 15 amino
acids it is envisaged that one, two, three, four, five or six of
these amino acids are substituted.
[0175] Generally, if amino acids are substituted in one or more or
all of the CDRs of the heavy and/or light chain, it is preferred
that the then-obtained "substituted" sequence is at least 60%, more
preferably 65%, even more preferably 70%, particularly preferably
75%, more particularly preferably 80% identical to the "original"
CDR sequence. This means that it is dependent of the length of the
CDR to which degree it is identical to the "substituted" sequence.
For example, a CDR having 5 amino acids is preferably 80% identical
to its substituted sequence in order to have at least one amino
acid substituted. Accordingly, the CDRs of the antibody construct
may have different degrees of identity to their substituted
sequences, e.g., CDRL1 may have 80%, while CDRL3 may have 90%.
[0176] Preferred substitutions (or replacements) are conservative
substitutions. However, any substitution (including
non-conservative substitution or one or more from the "exemplary
substitutions" listed in Table 1, below) is envisaged as long as
the antibody construct retains its capability to bind to CDH19 via
the first binding domain and to CD3 epsilon via the second binding
domain and/or its CDRs have an identity to the then substituted
sequence (at least 60%, more preferably 65%, even more preferably
70%, particularly preferably 75%, more particularly preferably 80%
identical to the "original" CDR sequence).
[0177] Conservative substitutions are shown in Table 1 under the
heading of "preferred substitutions". If such substitutions result
in a change in biological activity, then more substantial changes,
denominated "exemplary substitutions" in Table 1, or as further
described below in reference to amino acid classes, may be
introduced and the products screened for a desired
characteristic.
TABLE-US-00001 TABLE 1 Amino Acid Substitutions Original Exemplary
Substitutions Preferred Substitutions Ala (A) val, leu, ile val Arg
(R) lys, gin, asn lys Asn (N) gin, his, asp, lys, arg gln Asp (D)
glu, asn glu Cys (C) ser, ala ser Gln (Q) asn, glu asn Glu (E) asp,
gin asp Gly (G) ala ala His (H) asn, gin, lys, arg arg Ile (I) leu,
val, met, ala, phe leu Leu (L) norleucine, ile, val, met, ala ile
Lys (K) arg, gin, asn arg Met (M) leu, phe, ile leu Phe (F) leu,
val, ile, ala, tyr tyr Pro (P) ala ala Ser (S) thr thr Thr (T) ser
ser Trp (W) tyr, phe tyr Tyr (Y) trp, phe, thr, ser phe Val (V)
ile, leu, met, phe, ala leu
[0178] Substantial modifications in the biological properties of
the antibody construct of the present invention are accomplished by
selecting substitutions that differ significantly in their effect
on maintaining (a) the structure of the polypeptide backbone in the
area of the substitution, for example, as a sheet or helical
conformation, (b) the charge or hydrophobicity of the molecule at
the target site, or (c) the bulk of the side chain. Naturally
occurring residues are divided into groups based on common
side-chain properties: (1) hydrophobic: norleucine, met, ala, val,
leu, ile; (2) neutral hydrophilic: cys, ser, thr; (3) acidic: asp,
glu; (4) basic: asn, gin, his, lys, arg; (5) residues that
influence chain orientation: gly, pro; and (6) aromatic: trp, tyr,
phe.
[0179] Non-conservative substitutions will entail exchanging a
member of one of these classes for another class. Any cysteine
residue not involved in maintaining the proper conformation of the
antibody construct may be substituted, generally with serine, to
improve the oxidative stability of the molecule and prevent
aberrant crosslinking. Conversely, cysteine bond(s) may be added to
the antibody to improve its stability (particularly where the
antibody is an antibody fragment such as an Fv fragment).
[0180] A particularly preferred type of substitutional variant
involves substituting one or more hypervariable region residues of
a parent antibody (e. g. a humanized or human antibody). Generally,
the resulting variant(s) selected for further development will have
improved biological properties relative to the parent antibody from
which they are generated. A convenient way for generating such
substitutional variants involves affinity maturation using phage
display. Briefly, several hypervariable region sites (e. g. 6-7
sites) are mutated to generate all possible amino acid
substitutions at each site. The antibody variants thus generated
are displayed in a monovalent fashion from filamentous phage
particles as fusions to the gene III product of M13 packaged within
each particle. The phage-displayed variants are then screened for
their biological activity (e. g. binding affinity) as herein
disclosed. In order to identify candidate hypervariable region
sites for modification, alanine scanning mutagenesis can be
performed to identify hypervariable region residues contributing
significantly to antigen binding. Alternatively, or additionally,
it may be beneficial to analyze a crystal structure of the
antigen-antibody complex to identify contact points between the
binding domain and, e.g., human CDH19. Such contact residues and
neighbouring residues are candidates for substitution according to
the techniques elaborated herein. Once such variants are generated,
the panel of variants is subjected to screening as described herein
and antibodies with superior properties in one or more relevant
assays may be selected for further development.
[0181] Other modifications of the antibody construct are
contemplated herein. For example, the antibody construct may be
linked to one of a variety of non-proteinaceous polymers, e.g.,
polyethylene glycol, polypropylene glycol, polyoxyalkylenes, or
copolymers of polyethylene glycol and polypropylene glycol. The
antibody construct may also be entrapped in microcapsules prepared,
for example, by coacervation techniques or by interfacial
polymerization (for example, hydroxymethylcellulose or
gelatine-microcapsules and poly (methylmethacylate) microcapsules,
respectively), in colloidal drug delivery systems (for example,
liposomes, albumin microspheres, microemulsions, nanoparticles and
nanocapsules), or in macroemulsions. Such techniques are disclosed
in Remington's Pharmaceutical Sciences, 16th edition, Oslo, A.,
Ed., (1980).
[0182] The antibody constructs disclosed herein may also be
formulated as immuno-liposomes. A "liposome" is a small vesicle
composed of various types of lipids, phospholipids and/or
surfactant which is useful for delivery of a drug to a mammal. The
components of the liposome are commonly arranged in a bilayer
formation, similar to the lipid arrangement of biological
membranes. Liposomes containing the antibody are prepared by
methods known in the art, such as described in Epstein et al.,
Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc.
Natl Acad. Sci. USA, 77: 4030 (1980); U.S. Pat. Nos. 4,485,045 and
4,544,545; and WO 97/38731 published Oct. 23, 1997. Liposomes with
enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.
Particularly useful liposomes can be generated by the reverse phase
evaporation method with a lipid composition comprising
phosphatidylcholine, cholesterol and PEG-derivatized
phosphatidylethanolamine (PEG-PE). Liposomes are extruded through
filters of defined pore size to yield liposomes with the desired
diameter. Fab' fragments of the antibody of the present invention
can be conjugated to the liposomes as described in Martin et al. J.
Biol. Chem. 257: 286-288 (1982) via a disulfide interchange
reaction. A chemotherapeutic agent is optionally contained within
the liposome. See Gabizon et al. J. National Cancer Inst. 81 (19)
1484 (1989).
[0183] When using recombinant techniques, the antibody construct
can be produced intracellularly, in the periplasmic space, or
directly secreted into the medium. If the antibody construct is
produced intracellularly, as a first step, the particulate debris,
either host cells or lysed fragments, are removed, for example, by
centrifugation or ultrafiltration. Carter et al., Bio/Technology
10: 163-167 (1992) describe a procedure for isolating antibodies
which are secreted to the periplasmic space of E. coli.
[0184] The antibody construct composition prepared from the cells
can be purified using, for example, hydroxylapatite chromatography,
gel electrophoresis, dialysis, and affinity chromatography, with
affinity chromatography being the preferred purification
technique.
[0185] The term "nucleic acid" is well known to the skilled person
and encompasses DNA (such as cDNA) and RNA (such as mRNA). The
nucleic acid can be double stranded and single stranded, linear and
circular. Said nucleic acid molecule is preferably comprised in a
vector which is preferably comprised in a host cell. Said host cell
is, e.g. after transformation or transfection with the nucleic acid
sequence of the invention, capable of expressing the antibody
construct. For that purpose the nucleic acid molecule is
operatively linked with control sequences.
[0186] A vector is a nucleic acid molecule used as a vehicle to
transfer (foreign) genetic material into a cell. The term "vector"
encompasses--but is not restricted to--plasmids, viruses, cosmids
and artificial chromosomes. In general, engineered vectors comprise
an origin of replication, a multicloning site and a selectable
marker. The vector itself is generally a nucleotide sequence,
commonly a DNA sequence, that comprises an insert (transgene) and a
larger sequence that serves as the "backbone" of the vector. Modern
vectors may encompass additional features besides the transgene
insert and a backbone: promoter, genetic marker, antibiotic
resistance, reporter gene, targeting sequence, protein purification
tag. Vectors called expression vectors (expression constructs)
specifically are for the expression of the transgene in the target
cell, and generally have control sequences such as a promoter
sequence that drives expression of the transgene. Insertion of a
vector into the target cell is usually called "transformation" for
bacteria, "transfection" for eukaryotic cells, although insertion
of a viral vector is also called "transduction".
[0187] As used herein, the term "host cell" is intended to refer to
a cell into which a nucleic acid encoding the antibody construct of
the invention is introduced by way of transformation, transfection
and the like. It should be understood that such terms refer not
only to the particular subject cell but to the progeny or potential
progeny of such a cell. Because certain modifications may occur in
succeeding generations due to either mutation or environmental
influences, such progeny may not, in fact, be identical to the
parent cell, but are still included within the scope of the term as
used herein.
[0188] As used herein, the term "expression" includes any step
involved in the production of a antibody construct of the invention
including, but not limited to, transcription, post-transcriptional
modification, translation, post-translational modification, and
secretion.
[0189] The term "control sequences" refers to DNA sequences
necessary for the expression of an operably linked coding sequence
in a particular host organism. The control sequences that are
suitable for prokaryotes, for example, include a promoter,
optionally an operator sequence, and a ribosome binding site.
Eukaryotic cells are known to utilize promoters, polyadenylation
signals, and enhancers.
[0190] A nucleic acid is "operably linked" when it is placed into a
functional relationship with another nucleic acid sequence. For
example, DNA for a presequence or secretory leader is operably
linked to DNA for a polypeptide if it is expressed as a preprotein
that participates in the secretion of the polypeptide; a promoter
or enhancer is operably linked to a coding sequence if it affects
the transcription of the sequence; or a ribosome binding site is
operably linked to a coding sequence if it is positioned so as to
facilitate translation. Generally, "operably linked" means that the
DNA sequences being linked are contiguous, and, in the case of a
secretory leader, contiguous and in reading phase. However,
enhancers do not have to be contiguous. Linking is accomplished by
ligation at convenient restriction sites. If such sites do not
exist, the synthetic oligonucleotide adaptors or linkers are used
in accordance with conventional practice.
[0191] The terms "host cell," "target cell" or "recipient cell" are
intended to include any individual cell or cell culture that can be
or has/have been recipients for vectors or the incorporation of
exogenous nucleic acid molecules, polynucleotides and/or proteins.
It also is intended to include progeny of a single cell, and the
progeny may not necessarily be completely identical (in morphology
or in genomic or total DNA complement) to the original parent cell
due to natural, accidental, or deliberate mutation. The cells may
be prokaryotic or eukaryotic, and include but are not limited to
bacteria, yeast cells, animal cells, and mammalian cells, e.g.,
murine, rat, macaque or human.
[0192] Suitable host cells include prokaryotes and eukaryotic host
cells including yeasts, fungi, insect cells and mammalian
cells.
[0193] The antibody construct of the invention can be produced in
bacteria. After expression, the antibody construct of the
invention, preferably the antibody construct is isolated from the
E. coli cell paste in a soluble fraction and can be purified
through, e.g., affinity chromatography and/or size exclusion. Final
purification can be carried out similar to the process for
purifying antibody expressed e. g, in CHO cells.
[0194] In addition to prokaryotes, eukaryotic microbes such as
filamentous fungi or yeast are suitable cloning or expression hosts
for the antibody construct of the invention. Saccharomyces
cerevisiae, or common baker's yeast, is the most commonly used
among lower eukaryotic host microorganisms. However, a number of
other genera, species, and strains are commonly available and
useful herein, such as Schizosaccharomyces pombe, Kluyveromyces
hosts such as, e.g., K. lactis, K. fragilis (ATCC 12424), K.
bulgaricus (ATCC 16045), K. wickeramii (ATCC 24178), K. waltii
(ATCC 56500), K. drosophilarum (ATCC 36906), K. thermotolerans, and
K. marxianus; yarrowia (EP 402 226); Pichia pastoris (EP 183 070);
Candida; Trichoderma reesia (EP 244 234); Neurospora crassa;
Schwanniomyces such as Schwanniomyces occidentalis; and filamentous
fungi such as, e.g., Neurospora, Penicillium, Tolypocladium, and
Aspergillus hosts such as A. nidulans and A. niger.
[0195] Suitable host cells for the expression of glycosylated
antibody construct of the invention, preferably antibody derived
antibody constructs are derived from multicellular organisms.
Examples of invertebrate cells include plant and insect cells.
Numerous baculoviral strains and variants and corresponding
permissive insect host cells from hosts such as Spodoptera
frugiperda (caterpillar), Aedes aegypti (mosquito), Aedes
albopictus (mosquito), Drosophila melanogaster (fruit fly), and
Bombyx mori have been identified. A variety of viral strains for
transfection are publicly available, e. g., the L-1 variant of
Autographa californica NPV and the Bm-5 strain of Bombyx mori NPV,
and such viruses may be used as the virus herein according to the
present invention, particularly for transfection of Spodoptera
frugperda cells.
[0196] Plant cell cultures of cotton, corn, potato, soybean,
petunia, tomato, Arabidopsis and tobacco can also be utilized as
hosts. Cloning and expression vectors useful in the production of
proteins in plant cell culture are known to those of skill in the
art. See e.g. Hiatt et al., Nature (1989) 342: 76-78, Owen et al.
(1992) Bio/Technology 10: 790-794, Artsaenko et al. (1995) The
Plant J 8: 745-750, and Fecker et al. (1996) Plant Mol Biol 32:
979-986.
[0197] However, interest has been greatest in vertebrate cells, and
propagation of vertebrate cells in culture (tissue culture) has
become a routine procedure. Examples of useful mammalian host cell
lines are monkey kidney CV1 line transformed by SV40 (COS-7, ATCC
CRL 1651); human embryonic kidney line (293 or 293 cells subcloned
for growth in suspension culture, Graham et al., J. Gen Virol. 36:
59 (1977)); baby hamster kidney cells (BHK, ATCC CCL 10); Chinese
hamster ovary cells/-DHFR (CHO, Urlaub et al., Proc. Natl. Acad.
Sci. USA 77: 4216 (1980)); mouse sertoli cells (TM4, Mather, Biol.
Reprod. 23: 243-251 (1980)); monkey kidney cells (CVI ATCC CCL 70);
African green monkey kidney cells (VERO-76, ATCC CRL1587); human
cervical carcinoma cells (HELA, ATCC CCL 2); canine kidney cells
(MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3A, ATCC CRL
1442); human lung cells (W138, ATCC CCL 75); human liver cells (Hep
G2,1413 8065); mouse mammary tumor (MMT 060562, ATCC CCLS 1); TRI
cells (Mather et al., Annals N. Y Acad. Sci. 383: 44-68 (1982));
MRC 5 cells; FS4 cells; and a human hepatoma line (Hep G2).
[0198] When using recombinant techniques, the antibody construct of
the invention can be produced intracellularly, in the periplasmic
space, or directly secreted into the medium. If the antibody
construct is produced intracellularly, as a first step, the
particulate debris, either host cells or lysed fragments, are
removed, for example, by centrifugation or ultrafiltration. Carter
et al., Bio/Technology 10: 163-167 (1992) describe a procedure for
isolating antibodies which are secreted to the periplasmic space of
E. coli. Briefly, cell paste is thawed in the presence of sodium
acetate (pH 3.5), EDTA, and phenylmethylsulfonylfluoride (PMSF)
over about 30 min. Cell debris can be removed by centrifugation.
Where the antibody is secreted into the medium, supernatants from
such expression systems are generally first concentrated using a
commercially available protein concentration filter, for example,
an Amicon or Millipore Pellicon ultrafiltration unit. A protease
inhibitor such as PMSF may be included in any of the foregoing
steps to inhibit proteolysis and antibiotics may be included to
prevent the growth of adventitious contaminants.
[0199] The antibody construct of the invention prepared from the
host cells can be purified using, for example, hydroxylapatite
chromatography, gel electrophoresis, dialysis, and affinity
chromatography, with affinity chromatography being the preferred
purification technique.
[0200] The matrix to which the affinity ligand is attached is most
often agarose, but other matrices are available. Mechanically
stable matrices such as controlled pore glass or poly
(styrenedivinyl) benzene allow for faster flow rates and shorter
processing times than can be achieved with agarose. Where the
antibody construct of the invention comprises a CH3 domain, the
Bakerbond ABXMresin (J. T. Baker, Phillipsburg, N.J.) is useful for
purification. Other techniques for protein purification such as
fractionation on an ion-exchange column, ethanol precipitation,
Reverse Phase HPLC, chromatography on silica, chromatography on
heparin SEPHAROSE.TM. chromatography on an anion or cation exchange
resin (such as a polyaspartic acid column), chromato-focusing,
SDS-PAGE, and ammonium sulfate precipitation are also available
depending on the antibody to be recovered.
[0201] The term "culturing" refers to the in vitro maintenance,
differentiation, growth, proliferation and/or propagation of cells
under suitable conditions in a medium.
[0202] As used herein, the term "pharmaceutical composition"
relates to a composition for administration to a patient,
preferably a human patient. The particular preferred pharmaceutical
composition of this invention comprises the antibody construct of
the invention. Preferably, the pharmaceutical composition comprises
suitable formulations of carriers, stabilizers and/or excipients.
In a preferred embodiment, the pharmaceutical composition comprises
a composition for parenteral, transdermal, intraluminal,
intraarterial, intrathecal and/or intranasal administration or by
direct injection into tissue. It is in particular envisaged that
said composition is administered to a patient via infusion or
injection. Administration of the suitable compositions may be
effected by different ways, e.g., by intravenous, intraperitoneal,
subcutaneous, intramuscular, topical or intradermal administration.
In particular, the present invention provides for an uninterrupted
administration of the suitable composition. As a non-limiting
example, uninterrupted, i.e. continuous administration may be
realized by a small pump system worn by the patient for metering
the influx of therapeutic agent into the body of the patient. The
pharmaceutical composition comprising the antibody construct of the
invention can be administered by using said pump systems. Such pump
systems are generally known in the art, and commonly rely on
periodic exchange of cartridges containing the therapeutic agent to
be infused. When exchanging the cartridge in such a pump system, a
temporary interruption of the otherwise uninterrupted flow of
therapeutic agent into the body of the patient may ensue. In such a
case, the phase of administration prior to cartridge replacement
and the phase of administration following cartridge replacement
would still be considered within the meaning of the pharmaceutical
means and methods of the invention together make up one
"uninterrupted administration" of such therapeutic agent.
[0203] The continuous or uninterrupted administration of these
antibody constructs of the invention may be intravenous or
subcutaneous by way of a fluid delivery device or small pump system
including a fluid driving mechanism for driving fluid out of a
reservoir and an actuating mechanism for actuating the driving
mechanism. Pump systems for subcutaneous administration may include
a needle or a cannula for penetrating the skin of a patient and
delivering the suitable composition into the patient's body. Said
pump systems may be directly fixed or attached to the skin of the
patient independently of a vein, artery or blood vessel, thereby
allowing a direct contact between the pump system and the skin of
the patient. The pump system can be attached to the skin of the
patient for 24 hours up to several days. The pump system may be of
small size with a reservoir for small volumes. As a non-limiting
example, the volume of the reservoir for the suitable
pharmaceutical composition to be administered can be between 0.1
and 50 ml.
[0204] The continuous administration may be transdermal by way of a
patch worn on the skin and replaced at intervals. One of skill in
the art is aware of patch systems for drug delivery suitable for
this purpose. It is of note that transdermal administration is
especially amenable to uninterrupted administration, as exchange of
a first exhausted patch can advantageously be accomplished
simultaneously with the placement of a new, second patch, for
example on the surface of the skin immediately adjacent to the
first exhausted patch and immediately prior to removal of the first
exhausted patch. Issues of flow interruption or power cell failure
do not arise.
[0205] The inventive compositions may further comprise a
pharmaceutically acceptable carrier. Examples of suitable
pharmaceutical carriers are well known in the art and include
solutions, e.g. phosphate buffered saline solutions, water,
emulsions, such as oil/water emulsions, various types of wetting
agents, sterile solutions, liposomes, etc. Compositions comprising
such carriers can be formulated by well known conventional methods.
Formulations can comprise carbohydrates, buffer solutions, amino
acids and/or surfactants. Carbohydrates may be non-reducing sugars,
preferably trehalose, sucrose, octasulfate, sorbitol or xylitol. In
general, as used herein, "pharmaceutically acceptable carrier"
means any and all solvents, dispersion media, coatings,
antibacterial and antifungal agents, isotonic and absorption
delaying agents, compatible with pharmaceutical administration. The
use of such media and agents for pharmaceutically active substances
is well known in the art. Acceptable carriers, excipients, or
stabilizers are nontoxic to recipients at the dosages and
concentrations employed and include: additional buffering agents;
preservatives; co-solvents; antioxidants, including ascorbic acid
and methionine; chelating agents such as EDTA; metal complexes
(e.g., Zn-protein complexes); biodegradable polymers, such as
polyesters; salt-forming counter-ions, such as sodium, polyhydric
sugar alcohols; amino acids, such as alanine, glycine, asparagine,
2-phenylalanine, and threonine; sugars or sugar alcohols, such as
trehalose, sucrose, octasulfate, sorbitol or xylitol stachyose,
mannose, sorbose, xylose, ribose, myoinisitose, galactose,
lactitol, ribitol, myoinisitol, galactitol, glycerol, cyclitols
(e.g., inositol), polyethylene glycol; sulfur containing reducing
agents, such as glutathione, thioctic acid, sodium thioglycolate,
thioglycerol, [alpha]-monothioglycerol, and sodium thio sulfate;
low molecular weight proteins, such as human serum albumin, bovine
serum albumin, gelatin, or other immunoglobulins; and hydrophilic
polymers, such as polyvinylpyrrolidone. Such formulations may be
used for continuous administrations which may be intravenuous or
subcutaneous with and/or without pump systems. Amino acids may be
charged amino acids, preferably lysine, lysine acetate, arginine,
glutamate and/or histidine. Surfactants may be detergents,
preferably with a molecular weight of >1.2 KD and/or a
polyether, preferably with a molecular weight of >3 KD.
Non-limiting examples for preferred detergents are Tween 20, Tween
40, Tween 60, Tween 80 or Tween 85. Non-limiting examples for
preferred polyethers are PEG 3000, PEG 3350, PEG 4000 or PEG 5000.
Buffer systems used in the present invention can have a preferred
pH of 5-9 and may comprise citrate, succinate, phosphate, histidine
and acetate.
[0206] The compositions of the present invention can be
administered to the subject at a suitable dose which can be
determined e.g. by dose escalating studies by administration of
increasing doses of the polypeptide of the invention exhibiting
cross-species specificity described herein to non-chimpanzee
primates, for instance macaques. As set forth above, the antibody
construct of the invention exhibiting cross-species specificity
described herein can be advantageously used in identical form in
preclinical testing in non-chimpanzee primates and as drug in
humans. These compositions can also be administered in combination
with other proteinaceous and non-proteinaceous drugs. These drugs
may be administered simultaneously with the composition comprising
the polypeptide of the invention as defined herein or separately
before or after administration of said polypeptide in timely
defined intervals and doses. The dosage regimen will be determined
by the attending physician and clinical factors. As is well known
in the medical arts, dosages for any one patient depend upon many
factors, including the patient's size, body surface area, age, the
particular compound to be administered, sex, time and route of
administration, general health, and other drugs being administered
concurrently.
[0207] Preparations for parenteral administration include sterile
aqueous or non-aqueous solutions, suspensions, and emulsions.
Examples of non-aqueous solvents are propylene glycol, polyethylene
glycol, vegetable oils such as olive oil, and injectable organic
esters such as ethyl oleate. Aqueous carriers include water,
alcoholic/aqueous solutions, emulsions or suspensions, including
saline and buffered media. Parenteral vehicles include sodium
chloride solution, Ringer's dextrose, dextrose and sodium chloride,
lactated Ringer's, or fixed oils. Intravenous vehicles include
fluid and nutrient replenishers, electrolyte replenishers (such as
those based on Ringer's dextrose), and the like. Preservatives and
other additives may also be present such as, for example,
antimicrobials, anti-oxidants, chelating agents, inert gases and
the like. In addition, the composition of the present invention
might comprise proteinaceous carriers, like, e.g., serum albumin or
immunoglobulin, preferably of human origin. It is envisaged that
the composition of the invention might comprise, in addition to the
polypeptide of the invention defined herein, further biologically
active agents, depending on the intended use of the composition.
Such agents might be drugs acting on the gastro-intestinal system,
drugs acting as cytostatica, drugs preventing hyperurikemia, drugs
inhibiting immunoreactions (e.g. corticosteroids), drugs modulating
the inflammatory response, drugs acting on the circulatory system
and/or agents such as cytokines known in the art. It is also
envisaged that the antibody construct of the present invention is
applied in a co-therapy, i.e., in combination with another
anti-cancer medicament.
[0208] The biological activity of the pharmaceutical composition
defined herein can be determined for instance by cytotoxicity
assays, as described in the following examples, in WO 99/54440 or
by Schlereth et al. (Cancer Immunol. Immunother. 20 (2005), 1-12).
"Efficacy" or "in vivo efficacy" as used herein refers to the
response to therapy by the pharmaceutical composition of the
invention, using e.g. standardized NCI response criteria. The
success or in vivo efficacy of the therapy using a pharmaceutical
composition of the invention refers to the effectiveness of the
composition for its intended purpose, i.e. the ability of the
composition to cause its desired effect, i.e. depletion of
pathologic cells, e.g. tumor cells. The in vivo efficacy may be
monitored by established standard methods for the respective
disease entities including, but not limited to white blood cell
counts, differentials, Fluorescence Activated Cell Sorting, bone
marrow aspiration. In addition, various disease specific clinical
chemistry parameters and other established standard methods may be
used. Furthermore, computer-aided tomography, X-ray, nuclear
magnetic resonance tomography (e.g. for National Cancer
Institute-criteria based response assessment [Cheson B D, Horning S
J, Coiffier B, Shipp M A, Fisher R I, Connors J M, Lister T A, Vose
J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D,
Hiddemann W, Castellino R, Harris N L, Armitage J O, Carter W,
Hoppe R, Canellos G P. Report of an international workshop to
standardize response criteria for non-Hodgkin's lymphomas. NCI
Sponsored International Working Group. J Clin Oncol. 1999 April;
17(4):1244]), positron-emission tomography scanning, white blood
cell counts, differentials, Fluorescence Activated Cell Sorting,
bone marrow aspiration, lymph node biopsies/histologies, and
various lymphoma specific clinical chemistry parameters (e.g.
lactate dehydrogenase) and other established standard methods may
be used.
[0209] Another major challenge in the development of drugs such as
the pharmaceutical composition of the invention is the predictable
modulation of pharmacokinetic properties. To this end, a
pharmacokinetic profile of the drug candidate, i.e. a profile of
the pharmacokinetic parameters that affect the ability of a
particular drug to treat a given condition, can be established.
Pharmacokinetic parameters of the drug influencing the ability of a
drug for treating a certain disease entity include, but are not
limited to: half-life, volume of distribution, hepatic first-pass
metabolism and the degree of blood serum binding. The efficacy of a
given drug agent can be influenced by each of the parameters
mentioned above.
[0210] "Half-life" means the time where 50% of an administered drug
are eliminated through biological processes, e.g. metabolism,
excretion, etc.
[0211] By "hepatic first-pass metabolism" is meant the propensity
of a drug to be metabolized upon first contact with the liver, i.e.
during its first pass through the liver.
[0212] "Volume of distribution" means the degree of retention of a
drug throughout the various compartments of the body, like e.g.
intracellular and extracellular spaces, tissues and organs, etc.
and the distribution of the drug within these compartments.
[0213] "Degree of blood serum binding" means the propensity of a
drug to interact with and bind to blood serum proteins, such as
albumin, leading to a reduction or loss of biological activity of
the drug.
[0214] Pharmacokinetic parameters also include bioavailability, lag
time (Tlag), Tmax, absorption rates, more onset and/or Cmax for a
given amount of drug administered. "Bioavailability" means the
amount of a drug in the blood compartment. "Lag time" means the
time delay between the administration of the drug and its detection
and measurability in blood or plasma.
[0215] "Tmax" is the time after which maximal blood concentration
of the drug is reached, and "Cmax" is the blood concentration
maximally obtained with a given drug. The time to reach a blood or
tissue concentration of the drug which is required for its
biological effect is influenced by all parameters. Pharmacokinetic
parameters of bispecific single chain antibodies exhibiting
cross-species specificity, which may be determined in preclinical
animal testing in non-chimpanzee primates as outlined above, are
also set forth e.g. in the publication by Schlereth et al. (Cancer
Immunol. Immunother. 20 (2005), 1-12).
[0216] The term "toxicity" as used herein refers to the toxic
effects of a drug manifested in adverse events or severe adverse
events. These side events might refer to a lack of tolerability of
the drug in general and/or a lack of local tolerance after
administration. Toxicity could also include teratogenic or
carcinogenic effects caused by the drug.
[0217] The term "safety", "in vivo safety" or "tolerability" as
used herein defines the administration of a drug without inducing
severe adverse events directly after administration (local
tolerance) and during a longer period of application of the drug.
"Safety", "in vivo safety" or "tolerability" can be evaluated e.g.
at regular intervals during the treatment and follow-up period.
Measurements include clinical evaluation, e.g. organ
manifestations, and screening of laboratory abnormalities. Clinical
evaluation may be carried out and deviations to normal findings
recorded/coded according to NCI-CTC and/or MedDRA standards. Organ
manifestations may include criteria such as allergy/immunology,
blood/bone marrow, cardiac arrhythmia, coagulation and the like, as
set forth e.g. in the Common Terminology Criteria for adverse
events v3.0 (CTCAE). Laboratory parameters which may be tested
include for instance hematology, clinical chemistry, coagulation
profile and urine analysis and examination of other body fluids
such as serum, plasma, lymphoid or spinal fluid, liquor and the
like. Safety can thus be assessed e.g. by physical examination,
imaging techniques (i.e. ultrasound, x-ray, CT scans, Magnetic
Resonance Imaging (MRI), other measures with technical devices
(i.e. electrocardiogram), vital signs, by measuring laboratory
parameters and recording adverse events. For example, adverse
events in non-chimpanzee primates in the uses and methods according
to the invention may be examined by histopathological and/or
histochemical methods.
[0218] The term "effective dose" or "effective dosage" is defined
as an amount sufficient to achieve or at least partially achieve
the desired effect. The term "therapeutically effective dose" is
defined as an amount sufficient to cure or at least partially
arrest the disease and its complications in a patient already
suffering from the disease. Amounts effective for this use will
depend upon the severity of the infection and the general state of
the subject's own immune system. The term "patient" includes human
and other mammalian subjects that receive either prophylactic or
therapeutic treatment.
[0219] The term "effective and non-toxic dose" as used herein
refers to a tolerable dose of an inventive antibody construct which
is high enough to cause depletion of pathologic cells, tumor
elimination, tumor shrinkage or stabilization of disease without or
essentially without major toxic effects. Such effective and
non-toxic doses may be determined e.g. by dose escalation studies
described in the art and should be below the dose inducing severe
adverse side events (dose limiting toxicity, DLT).
[0220] The above terms are also referred to e.g. in the Preclinical
safety evaluation of biotechnology-derived pharmaceuticals S6; ICH
Harmonised Tripartite Guideline; ICH Steering Committee meeting on
Jul. 16, 1997.
[0221] The appropriate dosage, or therapeutically effective amount,
of the antibody construct of the invention will depend on the
condition to be treated, the severity of the condition, prior
therapy, and the patient's clinical history and response to the
therapeutic agent. The proper dose can be adjusted according to the
judgment of the attending physician such that it can be
administered to the patient one time or over a series of
administrations. The pharmaceutical composition can be administered
as a sole therapeutic or in combination with additional therapies
such as anti-cancer therapies as needed.
[0222] The pharmaceutical compositions of this invention are
particularly useful for parenteral administration, i.e.,
subcutaneously, intramuscularly, intravenously, intra-articular
and/or intra-synovial. Parenteral administration can be by bolus
injection or continuous infusion.
[0223] If the pharmaceutical composition has been lyophilized, the
lyophilized material is first reconstituted in an appropriate
liquid prior to administration. The lyophilized material may be
reconstituted in, e.g., bacteriostatic water for injection (BWFI),
physiological saline, phosphate buffered saline (PBS), or the same
formulation the protein had been in prior to lyophilization.
[0224] In an internal analysis of proprietary mRNA expression data
it has been surprisingly found that CDH19 expression is elevated in
both primary and metastatic melanoma tumors compared to normal,
untransformed tissues. Internal analysis also confirmed that
expression of CDH19 in normal tissues is limited to neural crest
derived peripheral nerve ganglia and nerve fibers. The differential
CDH19 expression in normal and tumor tissues makes this protein
attractive for cell-surface targeting therapeutics. Although CDH 19
was discussed as one marker as part of long lists of markers
associated with some cancer types (see e.g. WO2009/055937) or
Parkinson's disease (see e.g. WO2005/067391) CDH19 was never
discussed as a prognostic marker or a drug target in connection
with melanoma tumors.
[0225] As stated above, the present invention provides an isolated
multispecific antibody construct comprising a first human binding
domain capable of binding to human CDH19 on the surface of a target
cell and a second domain capable of binding to human CD3 on the
surface of a T cell.
[0226] The "CDH19 extracellular domain" or "CDH19 ECD" refers to a
form of CDH19 which is essentially free of transmembrane and
cytoplasmic domains of CDH19. It will be understood by the skilled
artisan that the transmembrane domain identified for the CDH19
polypeptide of the present invention is identified pursuant to
criteria routinely employed in the art for identifying that type of
hydrophobic domain. The exact boundaries of a transmembrane domain
may vary but most likely by no more than about 5 amino acids at
either end of the domain specifically mentioned herein. A preferred
human CDH19 ECD is shown in SEQ ID NO: 948. In this context it is
understood that the CDH19 ECD represents the part of CDH19 on the
surface of a target cell.
[0227] The T cell CD3 receptor complex is a protein complex and is
composed of four distinct chains. In mammals, the complex contains
a CD3.gamma. chain, a CD3.delta. chain, and two CD3c (epsilon)
chains. These chains associate with a molecule known as the T cell
receptor (TCR) and the .zeta. chain to generate an activation
signal in T lymphocytes.
[0228] The redirected lysis of target cells via the recruitment of
T cells by a multispecific, at least bispecific, antibody construct
involves cytolytic synapse formation and delivery of perforin and
granzymes. The engaged T cells are capable of serial target cell
lysis, and are not affected by immune escape mechanisms interfering
with peptide antigen processing and presentation, or clonal T cell
differentiation; see, for example, WO 2007/042261.
[0229] The affinity of the first binding domain for human CDH19 is
preferably .ltoreq.15 nM, more preferably .ltoreq.10 nM, even more
preferably .ltoreq.5 nM, even more preferably .ltoreq.1 nM, even
more preferably .ltoreq.0.5 nM, even more preferably .ltoreq.0.1
nM, and most preferably .ltoreq.0.05 nM. The affinity of the first
binding domain for macaque CDH19 is preferably .ltoreq.15 nM, more
preferably .ltoreq.10 nM, even more preferably nM, even more
preferably .ltoreq.1 nM, even more preferably .ltoreq.0.5 nM, even
more preferably .ltoreq.0.1 nM, and most preferably .ltoreq.0.05 nM
or even .ltoreq.0.01 nM. The affinity can be measured for example
in a Biacore assay or in a Scatchard assay, e.g. as described in
the Examples. The affinity gap for binding to macaque CDH19 versus
human CDH19 is preferably [1:10-1:5] or [5:1-10:1], more preferably
[1:5-5:1], and most preferably [1:2-3:1] or even [1:1-3:1]. Other
methods of determining the affinity are well-known to the skilled
person.
[0230] Human antibodies, respectively human antibody constructs,
avoid some of the problems associated with antibodies/antibody
constructs that possess murine or rat variable and/or constant
regions. The presence of such murine or rat derived proteins can
lead to the rapid clearance of the antibodies/antibody constructs
or can lead to the generation of an immune response against the
antibody/antibody construct by a patient. In order to avoid the
utilization of murine or rat derived antibodies/antibody
constructs, human or fully human antibodies can be generated
through the introduction of human antibody function into a rodent
so that the rodent produces fully human antibodies.
[0231] The ability to clone and reconstruct megabase-sized human
loci in YACs and to introduce them into the mouse germline provides
a powerful approach to elucidating the functional components of
very large or crudely mapped loci as well as generating useful
models of human disease. Furthermore, the utilization of such
technology for substitution of mouse loci with their human
equivalents could provide unique insights into the expression and
regulation of human gene products during development, their
communication with other systems, and their involvement in disease
induction and progression.
[0232] An important practical application of such a strategy is the
"humanization" of the mouse humoral immune system. Introduction of
human immunoglobulin (Ig) loci into mice in which the endogenous Ig
genes have been inactivated offers the opportunity to study the
mechanisms underlying programmed expression and assembly of
antibodies as well as their role in B-cell development.
Furthermore, such a strategy could provide an ideal source for
production of fully human monoclonal antibodies (mAbs)--an
important milestone towards fulfilling the promise of antibody
therapy in human disease. Fully human antibodies/antibody
constructs are expected to minimize the immunogenic and allergic
responses intrinsic to mouse or mouse-derivatized mAbs and thus to
increase the efficacy and safety of the administered
antibodies/antibody constructs. The use of fully human
antibodies/antibody constructs can be expected to provide a
substantial advantage in the treatment of chronic and recurring
human diseases, such as inflammation, autoimmunity, and cancer,
which require repeated compound administrations.
[0233] One approach towards this goal was to engineer mouse strains
deficient in mouse antibody production with large fragments of the
human Ig loci in anticipation that such mice would produce a large
repertoire of human antibodies in the absence of mouse antibodies.
Large human Ig fragments would preserve the large variable gene
diversity as well as the proper regulation of antibody production
and expression. By exploiting the mouse machinery for antibody
diversification and selection and the lack of immunological
tolerance to human proteins, the reproduced human antibody
repertoire in these mouse strains should yield high affinity
antibodies against any antigen of interest, including human
antigens. Using the hybridoma technology, antigen-specific human
mAbs with the desired specificity could be readily produced and
selected. This general strategy was demonstrated in connection with
our generation of the first XenoMouse mouse strains, as published
in 1994. (See Green et al. Nature Genetics 7:13-21 (1994)) The
XenoMouse strains were engineered with yeast artificial chromosomes
(YACs) containing 245 kb and 190 kb-sized germline configuration
fragments of the human heavy chain locus and kappa light chain
locus, respectively, which contained core variable and constant
region sequences. Id. The human Ig containing YACs proved to be
compatible with the mouse system for both rearrangement and
expression of antibodies and were capable of substituting for the
inactivated mouse Ig genes. This was demonstrated by their ability
to induce B-cell development, to produce an adult-like human
repertoire of fully human antibodies, and to generate
antigen-specific human mAbs. These results also suggested that
introduction of larger portions of the human Ig loci containing
greater numbers of V genes, additional regulatory elements, and
human Ig constant regions might recapitulate substantially the full
repertoire that is characteristic of the human humoral response to
infection and immunization. The work of Green et al. was recently
extended to the introduction of greater than approximately 80% of
the human antibody repertoire through introduction of megabase
sized, germline configuration YAC fragments of the human heavy
chain loci and kappa light chain loci, respectively. See Mendez et
al. Nature Genetics 15:146-156 (1997) and U.S. patent application
Ser. No. 08/759,620, filed Dec. 3, 1996, the disclosures of which
are hereby incorporated by reference.
[0234] The production of the XenoMouse mice is further discussed
and delineated in U.S. patent application Ser. No. 07/466,008,
filed Jan. 12, 1990, Ser. No. 07/610,515, filed Nov. 8, 1990, Ser.
No. 07/919,297, filed Jul. 24, 1992, Ser. No. 07/922,649, filed
Jul. 30, 1992, filed Ser. No. 08/031,801, filed Mar. 15, 1993, Ser.
No. 08/112,848, filed Aug. 27, 1993, Ser. No. 08/234,145, filed
Apr. 28, 1994, Ser. No. 08/376,279, filed Jan. 20, 1995, Ser. No.
08/430,938, Apr. 27, 1995, Ser. No. 08/464,584, filed Jun. 5, 1995,
Ser. No. 08/464,582, filed Jun. 5, 1995, Ser. No. 08/463,191, filed
Jun. 5, 1995, Ser. No. 08/462,837, filed Jun. 5, 1995, Ser. No.
08/486,853, filed Jun. 5, 1995, Ser. No. 08/486,857, filed Jun. 5,
1995, Ser. No. 08/486,859, filed Jun. 5, 1995, Ser. No. 08/462,513,
filed Jun. 5, 1995, Ser. No. 08/724,752, filed Oct. 2, 1996, and
Ser. No. 08/759,620, filed Dec. 3, 1996 and U.S. Pat. Nos.
6,162,963, 6,150,584, 6,114,598, 6,075,181, and 5,939,598 and
Japanese Patent Nos. 3 068 180 B2, 3 068 506 B2, and 3 068 507 B2.
See also Mendez et al. Nature Genetics 15:146-156 (1997) and Green
and Jakobovits J. Exp. Med. 188:483-495 (1998). See also European
Patent No., EP 0 463151 B1, grant published Jun. 12, 1996,
International Patent Application No., WO 94/02602, published Feb.
3, 1994, International Patent Application No., WO 96/34096,
published Oct. 31, 1996, WO 98/24893, published Jun. 11, 1998, WO
00/76310, published Dec. 21, 2000, WO 03/47336. The disclosures of
each of the above-cited patents, applications, and references are
hereby incorporated by reference in their entirety.
[0235] In an alternative approach, others, including GenPharm
International, Inc., have utilized a "minilocus" approach. In the
minilocus approach, an exogenous Ig locus is mimicked through the
inclusion of pieces (individual genes) from the Ig locus. Thus, one
or more V.sub.H genes, one or more D.sub.H genes, one or more
J.sub.H genes, a mu constant region, and a second constant region
(preferably a gamma constant region) are formed into a construct
for insertion into an animal. This approach is described in U.S.
Pat. No. 5,545,807 to Surani et al. and U.S. Pat. Nos. 5,545,806,
5,625,825, 5,625,126, 5,633,425, 5,661,016, 5,770,429, 5,789,650,
5,814,318, 5,877,397, 5,874,299, and 6,255,458 each to Lonberg and
Kay, U.S. Pat. Nos. 5,591,669 and 6,023,010 to Krimpenfort and
Berns, U.S. Pat. Nos. 5,612,205, 5,721,367, and 5,789,215 to Berns
et al., and U.S. Pat. No. 5,643,763 to Choi and Dunn, and GenPharm
International U.S. patent application Ser. No. 07/574,748, filed
Aug. 29, 1990, Ser. No. 07/575,962, filed Aug. 31, 1990, Ser. No.
07/810,279, filed Dec. 17, 1991, Ser. No. 07/853,408, filed Mar.
18, 1992, Ser. No. 07/904,068, filed Jun. 23, 1992, Ser. No.
07/990,860, filed Dec. 16, 1992, Ser. No. 08/053,131, filed Apr.
26, 1993, Ser. No. 08/096,762, filed Jul. 22, 1993, Ser. No.
08/155,301, filed Nov. 18, 1993, Ser. No. 08/161,739, filed Dec. 3,
1993, Ser. No. 08/165,699, filed Dec. 10, 1993, Ser. No.
08/209,741, filed Mar. 9, 1994, the disclosures of which are hereby
incorporated by reference. See also European Patent No. 0 546 073 B
1, International Patent Application Nos. WO 92/03918, WO 92/22645,
WO 92/22647, WO 92/22670, WO 93/12227, WO 94/00569, WO 94/25585, WO
96/14436, WO 97/13852, and WO 98/24884 and U.S. Pat. No. 5,981,175,
the disclosures of which are hereby incorporated by reference in
their entirety. See further Taylor et al., 1992, Chen et al., 1993,
Tuaillon et al., 1993, Choi et al., 1993, Lonberg et al., (1994),
Taylor et al., (1994), and Tuaillon et al., (1995), Fishwild et
al., (1996), the disclosures of which are hereby incorporated by
reference in their entirety.
[0236] Kirin has also demonstrated the generation of human
antibodies from mice in which, through microcell fusion, large
pieces of chromosomes, or entire chromosomes, have been introduced.
See European Patent Application Nos. 773 288 and 843 961, the
disclosures of which are hereby incorporated by reference. Xenerex
Biosciences is developing a technology for the potential generation
of human antibodies. In this technology, SCID mice are
reconstituted with human lymphatic cells, e.g., B and/or T cells.
Mice are then immunized with an antigen and can generate an immune
response against the antigen. See U.S. Pat. Nos. 5,476,996,
5,698,767, and 5,958,765.
[0237] Human anti-mouse antibody (HAMA) responses have led the
industry to prepare chimeric or otherwise humanized antibodies.
While chimeric antibodies have a human constant region and a murine
variable region, it is expected that certain human anti-chimeric
antibody (HACA) responses will be observed, particularly in chronic
or multi-dose utilizations of the antibody. Thus, it would be
desirable to provide fully human antibodies against EGFRvIII in
order to vitiate concerns and/or effects of HAMA or HACA
response.
[0238] Cytotoxicity mediated by CDH19/CD3 bispecific antibody
constructs can be measured in various ways. Effector cells can be
e.g. stimulated enriched (human) CD8 positive T cells or
unstimulated (human) peripheral blood mononuclear cells (PBMC). If
the target cells are of macaque origin or express or are
transfected with macaque CDH19, the effector cells should also be
of macaque origin such as a macaque T cell line, e.g. 4119LnPx. The
target cells should express (at least the extracellular domain of)
CDH19, e.g. human or macaque CDH19. Target cells can be a cell line
(such as CHO) which is stably or transiently transfected with
CDH19, e.g. human or macaque CDH19. Alternatively, the target cells
can be a CDH19 positive natural expresser cell line, such as the
human myeloma cell line CHL-1 or Colo-699. Usually EC50-values are
expected to be lower with target cell lines expressing higher
levels of CDH19 on the cell surface. The effector to target cell
(E:T) ratio is usually about 10:1, but can also vary. Cytotoxic
activity of CDH19/CD3 bispecific antibody constructs can be
measured in an 51-chromium release assay (incubation time of about
18 hours) or in a in a FACS-based cytotoxicity assay (incubation
time of about 48 hours). Modifications of the assay incubation time
(cytotoxic reaction) are also possible. Other methods of measuring
cytotoxicity are well-known to the skilled person and comprise MTT
or MTS assays, ATP-based assays including bioluminescent assays,
the sulforhodamine B (SRB) assay, WST assay, clonogenic assay and
the ECIS technology.
[0239] The cytotoxic activity mediated by CDH19/CD3 bispecific
antibody constructs of the present invention is preferably measured
in a cell-based cytotoxicity assay. It is represented by the
EC.sub.50 value, which corresponds to the half maximal effective
concentration (concentration of the antibody construct which
induces a cytotoxic response halfway between the baseline and
maximum). Preferably, the EC.sub.50 value of the CDH19/CD3
bispecific antibody constructs is .ltoreq.20.000 pg/ml, more
preferably .ltoreq.5000 pg/ml, even more preferably .ltoreq.1000
pg/ml, even more preferably .ltoreq.500 pg/ml, even more preferably
.ltoreq.350 pg/ml, even more preferably .ltoreq.320 pg/ml, even
more preferably .ltoreq.250 pg/ml, even more preferably .ltoreq.100
pg/ml, even more preferably .ltoreq.50 pg/ml, even more preferably
.ltoreq.10 pg/ml, and most preferably .ltoreq.5 pg/ml.
[0240] Any of the above given EC.sub.50 values can be combined with
any one of the indicated scenarios of a cell-based cytotoxicity
assay. For example, when (human) CD8 positive T cells or a macaque
T cell line are used as effector cells, the EC.sub.50 value of the
CDH19/CD3 bispecific antibody construct is preferably .ltoreq.1000
pg/ml, more preferably .ltoreq.500 pg/ml, even more preferably
.ltoreq.250 pg/ml, even more preferably .ltoreq.100 pg/ml, even
more preferably .ltoreq.50 pg/ml, even more preferably .ltoreq.10
pg/ml, and most preferably .ltoreq.5 pg/ml. If in this assay the
target cells are (human or macaque) CDH19 transfected cells such as
CHO cells, the EC.sub.50 value of the CDH19/CD3 bispecific antibody
construct is preferably .ltoreq.150 pg/ml, more preferably
.ltoreq.100 pg/ml, even more preferably .ltoreq.50 pg/ml, even more
preferably .ltoreq.30 pg/ml, even more preferably .ltoreq.10 pg/ml,
and most preferably .ltoreq.5 pg/ml.
[0241] If the target cells are a CDH19positive natural expresser
cell line, then the EC.sub.50 value is preferably .ltoreq.350
pg/ml, more preferably .ltoreq.320 pg/ml, even more preferably
.ltoreq.250 pg/ml, even more preferably .ltoreq.200 pg/ml, even
more preferably .ltoreq.100 pg/ml, even more preferably .ltoreq.150
pg/ml, even more preferably .ltoreq.100 pg/ml, and most preferably
.ltoreq.50 pg/ml, or lower. When (human) PBMCs are used as effector
cells, the EC.sub.50 value of the CDH19/CD3 bispecific antibody
construct is preferably .ltoreq.1000 pg/ml, more preferably
.ltoreq.750 pg/ml, more preferably .ltoreq.500 pg/ml, even more
preferably .ltoreq.350 pg/ml, even more preferably .ltoreq.320
pg/ml, even more preferably .ltoreq.250 pg/ml, even more preferably
.ltoreq.100 pg/ml, and most preferably .ltoreq.50 pg/ml, or
lower.
[0242] The difference in cytotoxic activity between the monomeric
and the dimeric isoform of individual CDH19/CD3 bispecific antibody
constructs is referred to as "potency gap". This potency gap can
e.g. be calculated as ratio between EC.sub.50 values of the
molecule's monomeric and dimeric form. Potency gaps of the
CDH19/CD3 bispecific antibody constructs of the present invention
are preferably .ltoreq.5, more preferably 54, even more preferably
.ltoreq.3, even more preferably .ltoreq.2 and most preferably
.ltoreq.1.
[0243] The antibody construct of the invention is a fusion protein
comprising at least two binding domains, with or without peptide
linkers (spacer peptides). Among the suitable peptide linkers are
those described in U.S. Pat. Nos. 4,751,180 and 4,935,233 or WO
88/09344.
[0244] Another method for preparing oligomeric antibody constuct
derivatives involves use of a leucine zipper. Leucine zipper
domains are peptides that promote oligomerization of the proteins
in which they are found. Leucine zippers were originally identified
in several DNA-binding proteins (Landschulz et al., 1988, Science
240:1759), and have since been found in a variety of different
proteins. Among the known leucine zippers are naturally occurring
peptides and derivatives thereof that dimerize or trimerize.
Examples of leucine zipper domains suitable for producing soluble
oligomeric proteins are described in PCT application WO 94/10308,
and the leucine zipper derived from lung surfactant protein D (SPD)
described in Hoppe et al., 1994, FEBS Letters 344:191, hereby
incorporated by reference. The use of a modified leucine zipper
that allows for stable trimerization of a heterologous protein
fused thereto is described in Fanslow et al., 1994, Semin. Immunol.
6:267-78. In one approach, recombinant fusion proteins comprising
CDH19 antibody fragment or derivative fused to a leucine zipper
peptide are expressed in suitable host cells, and the soluble
oligomeric CDH19 antibody fragments or derivatives that form are
recovered from the culture supernatant.
[0245] Covalent modifications of antigen binding proteins are
included within the scope of this invention, and are generally, but
not always, done post-translationally. For example, several types
of covalent modifications of the antigen binding protein are
introduced into the molecule by reacting specific amino acid
residues of the antigen binding protein with an organic
derivatizing agent that is capable of reacting with selected side
chains or the N- or C-terminal residues.
[0246] Cysteinyl residues most commonly are reacted with
.alpha.-haloacetates (and corresponding amines), such as
chloroacetic acid or chloroacetamide, to give carboxymethyl or
carboxyamidomethyl derivatives. Cysteinyl residues also are
derivatized by reaction with bromotrifluoroacetone,
.alpha.-bromo-.beta.-(5-imidozoyl)propionic acid, chloroacetyl
phosphate, N-alkylmaleimides, 3-nitro-2-pyridyl disulfide, methyl
2-pyridyl disulfide, p-chloromercuribenzoate,
2-chloromercuri-4-nitrophenol, or
chloro-7-nitrobenzo-2-oxa-1,3-diazole.
[0247] Histidyl residues are derivatized by reaction with
diethylpyrocarbonate at pH 5.5-7.0 because this agent is relatively
specific for the histidyl side chain. Para-bromophenacyl bromide
also is useful; the reaction is preferably performed in 0.1M sodium
cacodylate at pH 6.0. Lysinyl and amino terminal residues are
reacted with succinic or other carboxylic acid anhydrides.
Derivatization with these agents has the effect of reversing the
charge of the lysinyl residues. Other suitable reagents for
derivatizing alpha-amino-containing residues include imidoesters
such as methyl picolinimidate; pyridoxal phosphate; pyridoxal;
chloroborohydride; trinitrobenzenesulfonic acid; O-methylisourea;
2,4-pentanedione; and transaminase-catalyzed reaction with
glyoxylate.
[0248] Arginyl residues are modified by reaction with one or
several conventional reagents, among them phenylglyoxal,
2,3-butanedione, 1,2-cyclohexanedione, and ninhydrin.
Derivatization of arginine residues requires that the reaction be
performed in alkaline conditions because of the high pKa of the
guanidine functional group. Furthermore, these reagents may react
with the groups of lysine as well as the arginine epsilon-amino
group.
[0249] The specific modification of tyrosyl residues may be made,
with particular interest in introducing spectral labels into
tyrosyl residues by reaction with aromatic diazonium compounds or
tetranitromethane. Most commonly, N-acetylimidizole and
tetranitromethane are used to form O-acetyl tyrosyl species and
3-nitro derivatives, respectively. Tyrosyl residues are iodinated
using .sup.125I or .sup.131I to prepare labeled proteins for use in
radioimmunoassay, the chloramine T method described above being
suitable.
[0250] Carboxyl side groups (aspartyl or glutamyl) are selectively
modified by reaction with carbodiimides (R'--N.dbd.C.dbd.N--R'),
where R and R' are optionally different alkyl groups, such as
1-cyclohexyl-3-(2-morpholinyl-4-ethyl) carbodiimide or
1-ethyl-3-(4-azonia-4,4-dimethylpentyl) carbodiimide. Furthermore,
aspartyl and glutamyl residues are converted to asparaginyl and
glutaminyl residues by reaction with ammonium ions.
[0251] Derivatization with bifunctional agents is useful for
crosslinking antigen binding proteins to a water-insoluble support
matrix or surface for use in a variety of methods. Commonly used
crosslinking agents include, e.g.,
1,1-bis(diazoacetyl)-2-phenylethane, glutaraldehyde,
N-hydroxysuccinimide esters, for example, esters with
4-azidosalicylic acid, homobifunctional imidoesters, including
disuccinimidyl esters such as
3,3'-dithiobis(succinimidylpropionate), and bifunctional maleimides
such as bis-N-maleimido-1,8-octane. Derivatizing agents such as
methyl-3-[(p-azidophenyl)dithio]propioimidate yield
photoactivatable intermediates that are capable of forming
crosslinks in the presence of light. Alternatively, reactive
water-insoluble matrices such as cyanogen bromide-activated
carbohydrates and the reactive substrates described in U.S. Pat.
Nos. 3,969,287; 3,691,016; 4,195,128; 4,247,642; 4,229,537; and
4,330,440 are employed for protein immobilization.
[0252] Glutaminyl and asparaginyl residues are frequently
deamidated to the corresponding glutamyl and aspartyl residues,
respectively. Alternatively, these residues are deamidated under
mildly acidic conditions. Either form of these residues falls
within the scope of this invention.
[0253] Other modifications include hydroxylation of proline and
lysine, phosphorylation of hydroxyl groups of seryl or threonyl
residues, methylation of the .alpha.-amino groups of lysine,
arginine, and histidine side chains (T. E. Creighton, Proteins:
Structure and Molecular Properties, W. H. Freeman & Co., San
Francisco, 1983, pp. 79-86), acetylation of the N-terminal amine,
and amidation of any C-terminal carboxyl group.
[0254] Another type of covalent modification of the antigen binding
protein included within the scope of this invention comprises
altering the glycosylation pattern of the protein. As is known in
the art, glycosylation patterns can depend on both the sequence of
the protein (e.g., the presence or absence of particular
glycosylation amino acid residues, discussed below), or the host
cell or organism in which the protein is produced. Particular
expression systems are discussed below.
[0255] Glycosylation of polypeptides is typically either N-linked
or O-linked. N-linked refers to the attachment of the carbohydrate
moiety to the side chain of an asparagine residue. The tri-peptide
sequences asparagine-X-serine and asparagine-X-threonine, where X
is any amino acid except proline, are the recognition sequences for
enzymatic attachment of the carbohydrate moiety to the asparagine
side chain. Thus, the presence of either of these tri-peptide
sequences in a polypeptide creates a potential glycosylation site.
O-linked glycosylation refers to the attachment of one of the
sugars N-acetylgalactosamine, galactose, or xylose, to a
hydroxyamino acid, most commonly serine or threonine, although
5-hydroxyproline or 5-hydroxylysine may also be used.
[0256] Addition of glycosylation sites to the antigen binding
protein is conveniently accomplished by altering the amino acid
sequence such that it contains one or more of the above-described
tri-peptide sequences (for N-linked glycosylation sites). The
alteration may also be made by the addition of, or substitution by,
one or more serine or threonine residues to the starting sequence
(for O-linked glycosylation sites). For ease, the antigen binding
protein amino acid sequence is preferably altered through changes
at the DNA level, particularly by mutating the DNA encoding the
target polypeptide at preselected bases such that codons are
generated that will translate into the desired amino acids.
[0257] Another means of increasing the number of carbohydrate
moieties on the antigen binding protein is by chemical or enzymatic
coupling of glycosides to the protein. These procedures are
advantageous in that they do not require production of the protein
in a host cell that has glycosylation capabilities for N- and
O-linked glycosylation. Depending on the coupling mode used, the
sugar(s) may be attached to (a) arginine and histidine, (b) free
carboxyl groups, (c) free sulfhydryl groups such as those of
cysteine, (d) free hydroxyl groups such as those of serine,
threonine, or hydroxyproline, (e) aromatic residues such as those
of phenylalanine, tyrosine, or tryptophan, or (f) the amide group
of glutamine. These methods are described in WO 87/05330 published
Sep. 11, 1987, and in Aplin and Wriston, 1981, CRC Crit. Rev.
Biochem., pp. 259-306.
[0258] Removal of carbohydrate moieties present on the starting
antigen binding protein may be accomplished chemically or
enzymatically. Chemical deglycosylation requires exposure of the
protein to the compound trifluoromethanesulfonic acid, or an
equivalent compound. This treatment results in the cleavage of most
or all sugars except the linking sugar (N-acetylglucosamine or
N-acetylgalactosamine), while leaving the polypeptide intact.
Chemical deglycosylation is described by Hakimuddin et al., 1987,
Arch. Biochem. Biophys. 259:52 and by Edge et al., 1981, Anal.
Biochem. 118:131. Enzymatic cleavage of carbohydrate moieties on
polypeptides can be achieved by the use of a variety of endo- and
exo-glycosidases as described by Thotakura et al., 1987, Meth.
Enzymol. 138:350. Glycosylation at potential glycosylation sites
may be prevented by the use of the compound tunicamycin as
described by Duskin et al., 1982, J. Biol. Chem. 257:3105.
Tunicamycin blocks the formation of protein-N-glycoside
linkages.
[0259] Another type of covalent modification of the antigen binding
protein comprises linking the antigen binding protein to various
non-proteinaceous polymers, including, but not limited to, various
polyols such as polyethylene glycol, polypropylene glycol or
polyoxyalkylenes, in the manner set forth in U.S. Pat. No.
4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337.
In addition, as is known in the art, amino acid substitutions may
be made in various positions within the antigen binding protein to
facilitate the addition of polymers such as PEG.
[0260] In some embodiments, the covalent modification of the
antigen binding proteins of the invention comprises the addition of
one or more labels.
[0261] The term "labelling group" means any detectable label.
Examples of suitable labelling groups include, but are not limited
to, the following: radioisotopes or radionuclides (e.g., .sup.3H,
.sup.14C, .sup.15N, .sup.35S, .sup.90Y, .sup.99Tc, .sup.111In,
.sup.125I, .sup.131I), fluorescent groups (e.g., FITC, rhodamine,
lanthanide phosphors), enzymatic groups (e.g., horseradish
peroxidase, .beta.-galactosidase, luciferase, alkaline
phosphatase), chemiluminescent groups, biotinyl groups, or
predetermined polypeptide epitopes recognized by a secondary
reporter (e.g., leucine zipper pair sequences, binding sites for
secondary antibodies, metal binding domains, epitope tags). In some
embodiments, the labelling group is coupled to the antigen binding
protein via spacer arms of various lengths to reduce potential
steric hindrance. Various methods for labelling proteins are known
in the art and may be used in performing the present invention.
[0262] In general, labels fall into a variety of classes, depending
on the assay in which they are to be detected: a) isotopic labels,
which may be radioactive or heavy isotopes; b) magnetic labels
(e.g., magnetic particles); c) redox active moieties; d) optical
dyes; enzymatic groups (e.g. horseradish peroxidase,
.beta.-galactosidase, luciferase, alkaline phosphatase); e)
biotinylated groups; and f) predetermined polypeptide epitopes
recognized by a secondary reporter (e.g., leucine zipper pair
sequences, binding sites for secondary antibodies, metal binding
domains, epitope tags, etc.). In some embodiments, the labelling
group is coupled to the antigen binding protein via spacer arms of
various lengths to reduce potential steric hindrance. Various
methods for labelling proteins are known in the art and may be used
in performing the present invention.
[0263] Specific labels include optical dyes, including, but not
limited to, chromophores, phosphors and fluorophores, with the
latter being specific in many instances. Fluorophores can be either
"small molecule" fluores, or proteinaceous fluores.
[0264] By "fluorescent label" is meant any molecule that may be
detected via its inherent fluorescent properties. Suitable
fluorescent labels include, but are not limited to, fluorescein,
rhodamine, tetramethylrhodamine, eosin, erythrosin, coumarin,
methyl-coumarins, pyrene, Malacite green, stilbene, Lucifer Yellow,
Cascade BlueJ, Texas Red, IAEDANS, EDANS, BODIPY FL, LC Red 640, Cy
5, Cy 5.5, LC Red 705, Oregon green, the Alexa-Fluor dyes (Alexa
Fluor 350, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 546, Alexa
Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 660, Alexa
Fluor 680), Cascade Blue, Cascade Yellow and R-phycoerythrin (PE)
(Molecular Probes, Eugene, Oreg.), FITC, Rhodamine, and Texas Red
(Pierce, Rockford, Ill.), Cy5, Cy5.5, Cy7 (Amersham Life Science,
Pittsburgh, Pa.). Suitable optical dyes, including fluorophores,
are described in Molecular Probes Handbook by Richard P. Haugland,
hereby expressly incorporated by reference.
[0265] Suitable proteinaceous fluorescent labels also include, but
are not limited to, green fluorescent protein, including a Renilla,
Ptilosarcus, or Aequorea species of GFP (Chalfie et al., 1994,
Science 263:802-805), EGFP (Clontech Laboratories, Inc., Genbank
Accession Number U55762), blue fluorescent protein (BFP, Quantum
Biotechnologies, Inc. 1801 de Maisonneuve Blvd. West, 8th Floor,
Montreal, Quebec, Canada H3H 1J9; Stauber, 1998, Biotechniques
24:462-471; Heim et al., 1996, Curr. Biol. 6:178-182), enhanced
yellow fluorescent protein (EYFP, Clontech Laboratories, Inc.),
luciferase (Ichiki et al., 1993, J. Immunol. 150:5408-5417), .beta.
galactosidase (Nolan et al., 1988, Proc. Natl. Acad. Sci. U.S.A.
85:2603-2607) and Renilla (WO92/15673, WO95/07463, WO98/14605,
WO98/26277, WO99/49019, U.S. Pat. Nos. 5,292,658, 5,418,155,
5,683,888, 5,741,668, 5,777,079, 5,804,387, 5,874,304, 5,876,995,
5,925,558). All of the above-cited references are expressly
incorporated herein by reference.
[0266] The antibody construct of the invention may also comprise
additional domains, which e.g. are helpful in the isolation of the
molecule or relate to an adapted pharmacokinetic profile of the
molecule.
[0267] Domains helpful for the isolation of an antibody construct
may be elected from peptide motives or secondarily introduced
moieties, which can be captured in an isolation method, e.g. an
isolation column. A non-limiting embodiments of such additional
domains comprise peptide motives known as Myc-tag, HAT-tag, HA-tag,
TAP-tag, GST-tag, chitin binding domain (CBD-tag), maltose binding
protein (MBP-tag), Flag-tag, Strep-tag and variants thereof (e.g.
StrepII-tag) and His-tag. All herein disclosed antibody constructs
characterized by the identified CDRs are preferred to comprise a
His-tag domain, which is generally known as a repeat of consecutive
His residues in the amino acid sequence of a molecule, preferably
of six His residues.
[0268] As described in appended example 2 a broad number of CDH19
specific binder has been characterized with respect to identified
binding characteristics and those binders were grouped into five
different bins, which refers to five different subgroups of CDH19
specific binding domains. Accordingly, in one embodiment the
antibody construct of the invention the first binding domain
comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL
region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group
consisting of: [0269] (a) CDR-H1 as depicted in SEQ ID NO: 52,
CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID
NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in
SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 222, CDR-H1 as
depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83,
CDR-H3 as depicted in SEQ ID NO: 84, CDR-L1 as depicted in SEQ ID
NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as
depicted in SEQ ID NO: 252, CDR-H1 as depicted in SEQ ID NO: 82,
CDR-H2 as depicted in SEQ ID NO: 83, CDR-H3 as depicted in SEQ ID
NO: 84, CDR-L1 as depicted in SEQ ID NO: 250, CDR-L2 as depicted in
SEQ ID NO: 251 and CDR-L3 as depicted in SEQ ID NO: 927, CDR-H1 as
depicted in SEQ ID NO: 82, CDR-H2 as depicted in SEQ ID NO: 83,
CDR-H3 as depicted in SEQ ID NO: 909, CDR-L1 as depicted in SEQ ID
NO: 250, CDR-L2 as depicted in SEQ ID NO: 251 and CDR-L3 as
depicted in SEQ ID NO: 927, CDR-H1 as depicted in SEQ ID NO: 52,
CDR-H2 as depicted in SEQ ID NO: 53, CDR-H3 as depicted in SEQ ID
NO: 54, CDR-L1 as depicted in SEQ ID NO: 220, CDR-L2 as depicted in
SEQ ID NO: 221 and CDR-L3 as depicted in SEQ ID NO: 926, CDR-H1 as
depicted in SEQ ID NO: 52, CDR-H2 as depicted in SEQ ID NO: 53,
CDR-H3 as depicted in SEQ ID NO: 904, CDR-L1 as depicted in SEQ ID
NO: 220, CDR-L2 as depicted in SEQ ID NO: 221 and CDR-L3 as
depicted in SEQ ID NO: 926, [0270] CDR-H1 as depicted in SEQ ID NO:
1126, CDR-H2 as depicted in SEQ ID NO: 1127, CDR-H3 as depicted in
SEQ ID NO: 1128, CDR-L1 as depicted in SEQ ID NO: 1129, CDR-L2 as
depicted in SEQ ID NO: 1130 and CDR-L3 as depicted in SEQ ID NO:
1131, [0271] CDR-H1 as depicted in SEQ ID NO: 1165, CDR-H2 as
depicted in SEQ ID NO: 1166, CDR-H3 as depicted in SEQ ID NO: 1167,
CDR-L1 as depicted in SEQ ID NO: 1168, CDR-L2 as depicted in SEQ ID
NO: 1169 and CDR-L3 as depicted in SEQ ID NO: 1170, [0272] CDR-H1
as depicted in SEQ ID NO: 1334, CDR-H2 as depicted in SEQ ID NO:
1335, CDR-H3 as depicted in SEQ ID NO: 1336, CDR-L1 as depicted in
SEQ ID NO: 1337, CDR-L2 as depicted in SEQ ID NO: 1338 and CDR-L3
as depicted in SEQ ID NO: 1339, [0273] CDR-H1 as depicted in SEQ ID
NO: 1347, CDR-H2 as depicted in SEQ ID NO: 1348, CDR-H3 as depicted
in SEQ ID NO: 1349, CDR-L1 as depicted in SEQ ID NO: 1350, CDR-L2
as depicted in SEQ ID NO: 1351 and CDR-L3 as depicted in SEQ ID NO:
1352, and [0274] CDR-H1 as depicted in SEQ ID NO: 1360 CDR-H2 as
depicted in SEQ ID NO: 1361, CDR-H3 as depicted in SEQ ID NO: 1362,
CDR-L1 as depicted in SEQ ID NO: 1363, CDR-L2 as depicted in SEQ ID
NO: 1364 and CDR-L3 as depicted in SEQ ID NO: 1365, [0275] CDR-H1
as depicted in SEQ ID NO: 1425 CDR-H2 as depicted in SEQ ID NO:
1426, CDR-H3 as depicted in SEQ ID NO: 1427, CDR-L1 as depicted in
SEQ ID NO: 1428, CDR-L2 as depicted in SEQ ID NO: 1429 and CDR-L3
as depicted in SEQ ID NO: 1430, [0276] CDR-H1 as depicted in SEQ ID
NO: 1438 CDR-H2 as depicted in SEQ ID NO: 1439, CDR-H3 as depicted
in SEQ ID NO: 1440, CDR-L1 as depicted in SEQ ID NO: 1441, CDR-L2
as depicted in SEQ ID NO: 1442 and CDR-L3 as depicted in SEQ ID NO:
1443; [0277] which all characterize binding domains for CDH19
grouped into bin 1; [0278] (b) CDR-H1 as depicted in SEQ ID NO:
124, CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in
SEQ ID NO: 126, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as
depicted in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO:
294, CDR-H1 as depicted in SEQ ID NO: 130, CDR-H2 as depicted in
SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID NO: 132, CDR-L1 as
depicted in SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299
and CDR-L3 as depicted in SEQ ID NO: 300, CDR-H1 as depicted in SEQ
ID NO: 136, CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as
depicted in SEQ ID NO: 138, CDR-L1 as depicted in SEQ ID NO: 304,
CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ
ID NO: 306, CDR-H1 as depicted in SEQ ID NO: 142, CDR-H2 as
depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID NO: 144,
CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID
NO: 311 and CDR-L3 as depicted in SEQ ID NO: 312, CDR-H1 as
depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO: 149,
CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in SEQ ID
NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as
depicted in SEQ ID NO: 318, CDR-H1 as depicted in SEQ ID NO: 166,
CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID
NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted
in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 336, CDR-H1
as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO:
125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in
SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as
depicted in SEQ ID NO: 294, CDR-H1 as depicted in SEQ ID NO: 124,
CDR-H2 as depicted in SEQ ID NO: 125, CDR-H3 as depicted in SEQ ID
NO: 915, CDR-L1 as depicted in SEQ ID NO: 292, CDR-L2 as depicted
in SEQ ID NO: 293 and CDR-L3 as depicted in SEQ ID NO: 928, CDR-H1
as depicted in SEQ ID NO: 124, CDR-H2 as depicted in SEQ ID NO:
125, CDR-H3 as depicted in SEQ ID NO: 915, CDR-L1 as depicted in
SEQ ID NO: 292, CDR-L2 as depicted in SEQ ID NO: 293 and CDR-L3 as
depicted in SEQ ID NO: 929, CDR-H1 as depicted in SEQ ID NO: 166,
CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID
NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted
in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 336, CDR-H1
as depicted in SEQ ID NO: 166, CDR-H2 as depicted in SEQ ID NO:
167, CDR-H3 as depicted in SEQ ID NO: 168, CDR-L1 as depicted in
SEQ ID NO: 334, CDR-L2 as depicted in SEQ ID NO: 335 and CDR-L3 as
depicted in SEQ ID NO: 942, CDR-H1 as depicted in SEQ ID NO: 166,
CDR-H2 as depicted in SEQ ID NO: 167, CDR-H3 as depicted in SEQ ID
NO: 168, CDR-L1 as depicted in SEQ ID NO: 334, CDR-L2 as depicted
in SEQ ID NO: 335 and CDR-L3 as depicted in SEQ ID NO: 943, CDR-H1
as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO:
149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in
SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as
depicted in SEQ ID NO: 318, CDR-H1 as depicted in SEQ ID NO: 148,
CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID
NO: 150, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted
in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 937, CDR-H1
as depicted in SEQ ID NO: 148, CDR-H2 as depicted in SEQ ID NO:
149, CDR-H3 as depicted in SEQ ID NO: 150, CDR-L1 as depicted in
SEQ ID NO: 316, CDR-L2 as depicted in SEQ ID NO: 317 and CDR-L3 as
depicted in SEQ ID NO: 938, CDR-H1 as depicted in SEQ ID NO: 148,
CDR-H2 as depicted in SEQ ID NO: 149, CDR-H3 as depicted in SEQ ID
NO: 919, CDR-L1 as depicted in SEQ ID NO: 316, CDR-L2 as depicted
in SEQ ID NO: 317 and CDR-L3 as depicted in SEQ ID NO: 938, CDR-H1
as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO:
143, CDR-H3 as depicted in SEQ ID NO: 144, CDR-L1 as depicted in
SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as
depicted in SEQ ID NO: 935, CDR-H1 as depicted in SEQ ID NO: 142,
CDR-H2 as depicted in SEQ ID NO: 143, CDR-H3 as depicted in SEQ ID
NO: 918, CDR-L1 as depicted in SEQ ID NO: 310, CDR-L2 as depicted
in SEQ ID NO: 311 and CDR-L3 as depicted in SEQ ID NO: 935, CDR-H1
as depicted in SEQ ID NO: 142, CDR-H2 as depicted in SEQ ID NO:
143, CDR-H3 as depicted in SEQ ID NO: 918, CDR-L1 as depicted in
SEQ ID NO: 310, CDR-L2 as depicted in SEQ ID NO: 311 and CDR-L3 as
depicted in SEQ ID NO: 936, CDR-H1 as depicted in SEQ ID NO: 136,
CDR-H2 as depicted in SEQ ID NO: 137, CDR-H3 as depicted in SEQ ID
NO: 138, CDR-L1 as depicted in SEQ ID NO: 304, CDR-L2 as depicted
in SEQ ID NO: 305 and CDR-L3 as depicted in SEQ ID NO: 933, CDR-H1
as depicted in SEQ ID NO: 136, CDR-H2 as depicted in SEQ ID NO:
137, CDR-H3 as depicted in SEQ ID NO: 917, CDR-L1 as depicted in
SEQ ID NO: 304, CDR-L2 as depicted in SEQ ID NO: 305 and CDR-L3 as
depicted in SEQ ID NO: 934, CDR-H1 as depicted in SEQ ID NO: 130,
CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID
NO: 132, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted
in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 930, CDR-H1
as depicted in SEQ ID NO: 130, CDR-H2 as depicted in SEQ ID NO:
131, CDR-H3 as depicted in SEQ ID NO: 916, CDR-L1 as depicted in
SEQ ID NO: 298, CDR-L2 as depicted in SEQ ID NO: 299 and CDR-L3 as
depicted in SEQ ID NO: 931, CDR-H1 as depicted in SEQ ID NO: 130,
CDR-H2 as depicted in SEQ ID NO: 131, CDR-H3 as depicted in SEQ ID
NO: 916, CDR-L1 as depicted in SEQ ID NO: 298, CDR-L2 as depicted
in SEQ ID NO: 299 and CDR-L3 as depicted in SEQ ID NO: 932, CDR-H1
as depicted in SEQ ID NO: 1009, CDR-H2 as depicted in SEQ ID NO:
1010, CDR-H3 as depicted in SEQ ID NO: 1011, CDR-L1 as depicted in
SEQ ID NO: 1012, CDR-L2 as depicted in SEQ ID NO: 1013 and CDR-L3
as depicted in SEQ ID NO: 1014, [0279] CDR-H1 as depicted in SEQ ID
NO: 1022, CDR-H2 as depicted in SEQ ID NO: 1023, CDR-H3 as depicted
in SEQ ID NO: 1024, CDR-L1 as depicted in SEQ ID NO: 1025, CDR-L2
as depicted in SEQ ID NO: 1026 and CDR-L3 as depicted in SEQ ID NO:
1027, CDR-H1 as depicted in SEQ ID NO: 1035, CDR-H2 as depicted in
SEQ ID NO: 1036, CDR-H3 as depicted in SEQ ID NO: 1037, CDR-L1 as
depicted in SEQ ID NO: 1038, CDR-L2 as depicted in SEQ ID NO: 1039
and CDR-L3 as depicted in SEQ ID NO: 1040, [0280] CDR-H1 as
depicted in SEQ ID NO: 1074, CDR-H2 as depicted in SEQ ID NO: 1075,
CDR-H3 as depicted in SEQ ID NO: 1076, CDR-L1 as depicted in SEQ ID
NO: 1077, CDR-L2 as depicted in SEQ ID NO: 1078 and CDR-L3 as
depicted in SEQ ID NO: 1079, [0281] CDR-H1 as depicted in SEQ ID
NO: 1100, CDR-H2 as depicted in SEQ ID NO: 1101, CDR-H3 as depicted
in SEQ ID NO: 1102, CDR-L1 as depicted in SEQ ID NO: 1103, CDR-L2
as depicted in SEQ ID NO: 1104 and CDR-L3 as depicted in SEQ ID NO:
1105, [0282] CDR-H1 as depicted in SEQ ID NO: 1113, CDR-H2 as
depicted in SEQ ID NO: 1114, CDR-H3 as depicted in SEQ ID NO: 1115,
CDR-L1 as depicted in SEQ ID NO: 1116, CDR-L2 as depicted in SEQ ID
NO: 1117 and CDR-L3 as depicted in SEQ ID NO: 1118, [0283] CDR-H1
as depicted in SEQ ID NO: 1243, CDR-H2 as depicted in SEQ ID NO:
1244, CDR-H3 as depicted in SEQ ID NO: 1245, CDR-L1 as depicted in
SEQ ID NO: 1246, CDR-L2 as depicted in SEQ ID NO: 1247 and CDR-L3
as depicted in SEQ ID NO: 1248, [0284] CDR-H1 as depicted in SEQ ID
NO: 1256, CDR-H2 as depicted in SEQ ID NO: 1257, CDR-H3 as depicted
in SEQ ID NO: 1258, CDR-L1 as depicted in SEQ ID NO: 1259, CDR-L2
as depicted in SEQ ID NO: 1260 and CDR-L3 as depicted in SEQ ID NO:
1261, [0285] CDR-H1 as depicted in SEQ ID NO: 1269, CDR-H2 as
depicted in SEQ ID NO: 1270, CDR-H3 as depicted in SEQ ID NO: 1271,
CDR-L1 as depicted in SEQ ID NO: 1272, CDR-L2 as depicted in SEQ ID
NO: 1273 and CDR-L3 as depicted in SEQ ID NO: 1274, [0286] CDR-H1
as depicted in SEQ ID NO: 1282, CDR-H2 as depicted in SEQ ID NO:
1283, CDR-H3 as depicted in SEQ ID NO: 1284, CDR-L1 as depicted in
SEQ ID NO: 1285, CDR-L2 as depicted in SEQ ID NO: 1286 and CDR-L3
as depicted in SEQ ID NO: 1287, and [0287] CDR-H1 as depicted in
SEQ ID NO: 1295, CDR-H2 as depicted in SEQ ID NO: 1296, CDR-H3 as
depicted in SEQ ID NO: 1297, CDR-L1 as depicted in SEQ ID NO: 1298,
CDR-L2 as depicted in SEQ ID NO: 1299 and CDR-L3 as depicted in SEQ
ID NO: 1300; [0288] which all characterize binding domains for
CDH19 grouped into bin 2; [0289] (c) CDR-H1 as depicted in SEQ ID
NO: 94, CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in
SEQ ID NO: 96, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as
depicted in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO:
264, CDR-H1 as depicted in SEQ ID NO: 100, CDR-H2 as depicted in
SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID NO: 102, CDR-L1 as
depicted in SEQ ID NO: 268, CDR-L2 as depicted in SEQ ID NO: 269
and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ
ID NO: 118, CDR-H2 as depicted in SEQ ID NO: 119, CDR-H3 as
depicted in SEQ ID NO: 120, CDR-L1 as depicted in SEQ ID NO: 286,
CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ
ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 154, CDR-H2 as
depicted in SEQ ID NO: 155, CDR-H3 as depicted in SEQ ID NO: 156,
CDR-L1 as depicted in SEQ ID NO: 322, CDR-L2 as depicted in SEQ ID
NO: 323 and CDR-L3 as depicted in SEQ ID NO: 324, CDR-H1 as
depicted in SEQ ID NO: 100, CDR-H2 as depicted in SEQ ID NO: 101,
CDR-H3 as depicted in SEQ ID NO: 912, CDR-L1 as depicted in SEQ ID
NO: 268, CDR-L2 as depicted in SEQ ID NO: 269 and CDR-L3 as
depicted in SEQ ID NO: 270, CDR-H1 as depicted in SEQ ID NO: 100,
CDR-H2 as depicted in SEQ ID NO: 101, CDR-H3 as depicted in SEQ ID
NO: 913, CDR-L1 as depicted in SEQ ID NO: 268, CDR-L2 as depicted
in SEQ ID NO: 269 and CDR-L3 as depicted in SEQ ID NO: 270, CDR-H1
as depicted in SEQ ID NO: 94, CDR-H2 as depicted in SEQ ID NO: 95,
CDR-H3 as depicted in SEQ ID NO: 910, CDR-L1 as depicted in SEQ ID
NO: 262, CDR-L2 as depicted in SEQ ID NO: 263 and CDR-L3 as
depicted in SEQ ID NO: 264, CDR-H1 as depicted in SEQ ID NO: 94,
CDR-H2 as depicted in SEQ ID NO: 95, CDR-H3 as depicted in SEQ ID
NO: 911, CDR-L1 as depicted in SEQ ID NO: 262, CDR-L2 as depicted
in SEQ ID NO: 263 and CDR-L3 as depicted in SEQ ID NO: 264, CDR-H1
as depicted in SEQ ID NO: 118, CDR-H2 as depicted in SEQ ID NO:
119, CDR-H3 as depicted in SEQ ID NO: 120, CDR-L1 as depicted in
SEQ ID NO: 286, CDR-L2 as depicted in SEQ ID NO: 287 and CDR-L3 as
depicted in SEQ ID NO: 288, CDR-H1 as depicted in SEQ ID NO: 118,
CDR-H2 as depicted in SEQ ID NO: 914, CDR-H3 as depicted in SEQ ID
NO: 120, CDR-L1 as depicted in SEQ ID NO: 286, CDR-L2 as depicted
in SEQ ID NO: 287 and CDR-L3 as depicted in SEQ ID NO: 288, CDR-H1
as depicted in SEQ ID NO: 154, CDR-H2 as depicted in SEQ ID NO:
155, CDR-H3 as depicted in SEQ ID NO: 920, CDR-L1 as depicted in
SEQ ID NO: 322, CDR-L2 as depicted in SEQ ID NO: 323 and CDR-L3 as
depicted in SEQ ID NO: 324, CDR-H1 as depicted in SEQ ID NO: 996,
CDR-H2 as depicted in SEQ ID NO: 997, CDR-H3 as depicted in SEQ ID
NO: 998, CDR-L1 as depicted in SEQ ID NO: 999, CDR-L2 as depicted
in SEQ ID NO: 1000 and CDR-L3 as depicted in SEQ ID NO: 1001,
[0290] CDR-H1 as depicted in SEQ ID NO: 1048, CDR-H2 as depicted in
SEQ ID NO: 1049, CDR-H3 as depicted in SEQ ID NO: 1050, CDR-L1 as
depicted in SEQ ID NO: 1051, CDR-L2 as depicted in SEQ ID NO: 1052
and CDR-L3 as depicted in SEQ ID NO: 1053, and
[0291] CDR-H1 as depicted in SEQ ID NO: 1087, CDR-H2 as depicted in
SEQ ID NO: 1088, CDR-H3 as depicted in SEQ ID NO: 1089, CDR-L1 as
depicted in SEQ ID NO: 1090, CDR-L2 as depicted in SEQ ID NO: 1091
and CDR-L3 as depicted in SEQ ID NO: 1092; [0292] which all
characterize binding domains for CDH19 grouped into bin 3; [0293]
(d) CDR-H1 as depicted in SEQ ID NO: 4, CDR-H2 as depicted in SEQ
ID NO: 5, CDR-H3 as depicted in SEQ ID NO: 6, CDR-L1 as depicted in
SEQ ID NO: 172, CDR-L2 as depicted in SEQ ID NO: 173 and CDR-L3 as
depicted in SEQ ID NO: 174, CDR-H1 as depicted in SEQ ID NO: 10,
CDR-H2 as depicted in SEQ ID NO: 11, CDR-H3 as depicted in SEQ ID
NO: 12, CDR-L1 as depicted in SEQ ID NO: 178, CDR-L2 as depicted in
SEQ ID NO: 179 and CDR-L3 as depicted in SEQ ID NO: 180, CDR-H1 as
depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 196, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as
depicted in SEQ ID NO: 198, CDR-H1 as depicted in SEQ ID NO: 34,
CDR-H2 as depicted in SEQ ID NO: 35, CDR-H3 as depicted in SEQ ID
NO: 36, CDR-L1 as depicted in SEQ ID NO: 202, CDR-L2 as depicted in
SEQ ID NO: 203 and CDR-L3 as depicted in SEQ ID NO: 204, CDR-H1 as
depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47,
CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID
NO: 214, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as
depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 58,
CDR-H2 as depicted in SEQ ID NO: 59, CDR-H3 as depicted in SEQ ID
NO: 60, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in
SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as
depicted in SEQ ID NO: 64, CDR-H2 as depicted in SEQ ID NO: 65,
CDR-H3 as depicted in SEQ ID NO: 66, CDR-L1 as depicted in SEQ ID
NO: 232, CDR-L2 as depicted in SEQ ID NO: 233 and CDR-L3 as
depicted in SEQ ID NO: 234, CDR-H1 as depicted in SEQ ID NO: 70,
CDR-H2 as depicted in SEQ ID NO: 71, CDR-H3 as depicted in SEQ ID
NO: 72, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in
SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as
depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161,
CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID
NO: 328, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 46,
CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID
NO: 48, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted in
SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1 as
depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47,
CDR-H3 as depicted in SEQ ID NO: 902, CDR-L1 as depicted in SEQ ID
NO: 924, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as
depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 46,
CDR-H2 as depicted in SEQ ID NO: 47, CDR-H3 as depicted in SEQ ID
NO: 903, CDR-L1 as depicted in SEQ ID NO: 924, CDR-L2 as depicted
in SEQ ID NO: 215 and CDR-L3 as depicted in SEQ ID NO: 216, CDR-H1
as depicted in SEQ ID NO: 46, CDR-H2 as depicted in SEQ ID NO: 47,
CDR-H3 as depicted in SEQ ID NO: 48, CDR-L1 as depicted in SEQ ID
NO: 925, CDR-L2 as depicted in SEQ ID NO: 215 and CDR-L3 as
depicted in SEQ ID NO: 216, CDR-H1 as depicted in SEQ ID NO: 70,
CDR-H2 as depicted in SEQ ID NO: 907, CDR-H3 as depicted in SEQ ID
NO: 72, CDR-L1 as depicted in SEQ ID NO: 238, CDR-L2 as depicted in
SEQ ID NO: 239 and CDR-L3 as depicted in SEQ ID NO: 240, CDR-H1 as
depicted in SEQ ID NO: 70, CDR-H2 as depicted in SEQ ID NO: 907,
CDR-H3 as depicted in SEQ ID NO: 908, CDR-L1 as depicted in SEQ ID
NO: 238, CDR-L2 as depicted in SEQ ID NO: 239 and CDR-L3 as
depicted in SEQ ID NO: 240, CDR-H1 as depicted in SEQ ID NO: 28,
CDR-H2 as depicted in SEQ ID NO: 901, CDR-H3 as depicted in SEQ ID
NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in
SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as
depicted in SEQ ID NO: 58, CDR-H2 as depicted in SEQ ID NO: 905,
CDR-H3 as depicted in SEQ ID NO: 906, CDR-L1 as depicted in SEQ ID
NO: 226, CDR-L2 as depicted in SEQ ID NO: 227 and CDR-L3 as
depicted in SEQ ID NO: 228, CDR-H1 as depicted in SEQ ID NO: 58,
CDR-H2 as depicted in SEQ ID NO: 905, CDR-H3 as depicted in SEQ ID
NO: 60, CDR-L1 as depicted in SEQ ID NO: 226, CDR-L2 as depicted in
SEQ ID NO: 227 and CDR-L3 as depicted in SEQ ID NO: 228, CDR-H1 as
depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO: 161,
CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in SEQ ID
NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 160,
CDR-H2 as depicted in SEQ ID NO: 921, CDR-H3 as depicted in SEQ ID
NO: 162, CDR-L1 as depicted in SEQ ID NO: 939, CDR-L2 as depicted
in SEQ ID NO: 329 and CDR-L3 as depicted in SEQ ID NO: 940, CDR-H1
as depicted in SEQ ID NO: 160, CDR-H2 as depicted in SEQ ID NO:
161, CDR-H3 as depicted in SEQ ID NO: 162, CDR-L1 as depicted in
SEQ ID NO: 941, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 28,
CDR-H2 as depicted in SEQ ID NO: 29, CDR-H3 as depicted in SEQ ID
NO: 30, CDR-L1 as depicted in SEQ ID NO: 196, CDR-L2 as depicted in
SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as
depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 922, CDR-L2 as depicted in SEQ ID NO: 197 and CDR-L3 as
depicted in SEQ ID NO: 923, CDR-H1 as depicted in SEQ ID NO: 28,
CDR-H2 as depicted in SEQ ID NO: 901, CDR-H3 as depicted in SEQ ID
NO: 30, CDR-L1 as depicted in SEQ ID NO: 922, CDR-L2 as depicted in
SEQ ID NO: 197 and CDR-L3 as depicted in SEQ ID NO: 923, CDR-H1 as
depicted in SEQ ID NO: 28, CDR-H2 as depicted in SEQ ID NO: 29,
CDR-H3 as depicted in SEQ ID NO: 30, CDR-L1 as depicted in SEQ ID
NO: 939, CDR-L2 as depicted in SEQ ID NO: 329 and CDR-L3 as
depicted in SEQ ID NO: 330, CDR-H1 as depicted in SEQ ID NO: 970,
CDR-H2 as depicted in SEQ ID NO: 971, CDR-H3 as depicted in SEQ ID
NO: 972, CDR-L1 as depicted in SEQ ID NO: 973, CDR-L2 as depicted
in SEQ ID NO: 974 and CDR-L3 as depicted in SEQ ID NO: 975, CDR-H1
as depicted in SEQ ID NO: 1061, CDR-H2 as depicted in SEQ ID NO:
1062, CDR-H3 as depicted in SEQ ID NO: 1063, CDR-L1 as depicted in
SEQ ID NO: 1064, CDR-L2 as depicted in SEQ ID NO: 1065 and CDR-L3
as depicted in SEQ ID NO: 1066, [0294] CDR-H1 as depicted in SEQ ID
NO: 1139, CDR-H2 as depicted in SEQ ID NO: 1140, CDR-H3 as depicted
in SEQ ID NO: 1141, CDR-L1 as depicted in SEQ ID NO: 1142, CDR-L2
as depicted in SEQ ID NO: 1143 and CDR-L3 as depicted in SEQ ID NO:
1144, [0295] CDR-H1 as depicted in SEQ ID NO: 1152, CDR-H2 as
depicted in SEQ ID NO: 1153, CDR-H3 as depicted in SEQ ID NO: 1154,
CDR-L1 as depicted in SEQ ID NO: 1155, CDR-L2 as depicted in SEQ ID
NO: 1156 and CDR-L3 as depicted in SEQ ID NO: 1157, [0296] CDR-H1
as depicted in SEQ ID NO: 1178, CDR-H2 as depicted in SEQ ID NO:
1179, CDR-H3 as depicted in SEQ ID NO: 1180, CDR-L1 as depicted in
SEQ ID NO: 1181, CDR-L2 as depicted in SEQ ID NO: 1182 and CDR-L3
as depicted in SEQ ID NO: 1183, [0297] CDR-H1 as depicted in SEQ ID
NO: 1191, CDR-H2 as depicted in SEQ ID NO: 1192, CDR-H3 as depicted
in SEQ ID NO: 1193, CDR-L1 as depicted in SEQ ID NO: 1194, CDR-L2
as depicted in SEQ ID NO: 1195 and CDR-L3 as depicted in SEQ ID NO:
1196, [0298] CDR-H1 as depicted in SEQ ID NO: 1204, CDR-H2 as
depicted in SEQ ID NO: 1205, CDR-H3 as depicted in SEQ ID NO: 1206,
CDR-L1 as depicted in SEQ ID NO: 1207, CDR-L2 as depicted in SEQ ID
NO: 1208 and CDR-L3 as depicted in SEQ ID NO: 1209, [0299] CDR-H1
as depicted in SEQ ID NO: 1217, CDR-H2 as depicted in SEQ ID NO:
1218, CDR-H3 as depicted in SEQ ID NO: 1219, CDR-L1 as depicted in
SEQ ID NO: 1220, CDR-L2 as depicted in SEQ ID NO: 1221 and CDR-L3
as depicted in SEQ ID NO: 1222, [0300] CDR-H1 as depicted in SEQ ID
NO: 1230, CDR-H2 as depicted in SEQ ID NO: 1231, CDR-H3 as depicted
in SEQ ID NO: 1232, CDR-L1 as depicted in SEQ ID NO: 1233, CDR-L2
as depicted in SEQ ID NO: 1234 and CDR-L3 as depicted in SEQ ID NO:
1235, [0301] CDR-H1 as depicted in SEQ ID NO: 1308, CDR-H2 as
depicted in SEQ ID NO: 1309, CDR-H3 as depicted in SEQ ID NO: 1310,
CDR-L1 as depicted in SEQ ID NO: 1311, CDR-L2 as depicted in SEQ ID
NO: 1312 and CDR-L3 as depicted in SEQ ID NO: 1313, [0302] CDR-H1
as depicted in SEQ ID NO: 1321, CDR-H2 as depicted in SEQ ID NO:
1322, CDR-H3 as depicted in SEQ ID NO: 1323, CDR-L1 as depicted in
SEQ ID NO: 1324, CDR-L2 as depicted in SEQ ID NO: 1325 and CDR-L3
as depicted in SEQ ID NO: 1326, [0303] CDR-H1 as depicted in SEQ ID
NO: 1373, CDR-H2 as depicted in SEQ ID NO: 1374, CDR-H3 as depicted
in SEQ ID NO: 1375, CDR-L1 as depicted in SEQ ID NO: 1376, CDR-L2
as depicted in SEQ ID NO: 1377 and CDR-L3 as depicted in SEQ ID NO:
1378, [0304] CDR-H1 as depicted in SEQ ID NO: 1386, CDR-H2 as
depicted in SEQ ID NO: 1387, CDR-H3 as depicted in SEQ ID NO: 1388,
CDR-L1 as depicted in SEQ ID NO: 1389, CDR-L2 as depicted in SEQ ID
NO: 1390 and CDR-L3 as depicted in SEQ ID NO: 1391, [0305] CDR-H1
as depicted in SEQ ID NO: 1399, CDR-H2 as depicted in SEQ ID NO:
1400, CDR-H3 as depicted in SEQ ID NO: 1401, CDR-L1 as depicted in
SEQ ID NO: 1402, CDR-L2 as depicted in SEQ ID NO: 1403 and CDR-L3
as depicted in SEQ ID NO: 1404, [0306] CDR-H1 as depicted in SEQ ID
NO: 1412, CDR-H2 as depicted in SEQ ID NO: 1413, CDR-H3 as depicted
in SEQ ID NO: 1414, CDR-L1 as depicted in SEQ ID NO: 1415, CDR-L2
as depicted in SEQ ID NO: 1416 and CDR-L3 as depicted in SEQ ID NO:
1417; [0307] which all characterize binding domains for CDH19
grouped into bin 4; and [0308] (e) CDR-H1 as depicted in SEQ ID NO:
76, CDR-H2 as depicted in SEQ ID NO: 77, CDR-H3 as depicted in SEQ
ID NO: 78, CDR-L1 as depicted in SEQ ID NO: 244, CDR-L2 as depicted
in SEQ ID NO: 245 and CDR-L3 as depicted in SEQ ID NO: 246, CDR-H1
as depicted in SEQ ID NO: 88, CDR-H2 as depicted in SEQ ID NO: 89,
CDR-H3 as depicted in SEQ ID NO: 90, CDR-L1 as depicted in SEQ ID
NO: 256, CDR-L2 as depicted in SEQ ID NO: 257 and CDR-L3 as
depicted in SEQ ID NO: 258, CDR-H1 as depicted in SEQ ID NO: 106,
CDR-H2 as depicted in SEQ ID NO: 107, CDR-H3 as depicted in SEQ ID
NO: 108, CDR-L1 as depicted in SEQ ID NO: 274, CDR-L2 as depicted
in SEQ ID NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276, CDR-H1
as depicted in SEQ ID NO: 112, CDR-H2 as depicted in SEQ ID NO:
113, CDR-H3 as depicted in SEQ ID NO: 114, CDR-L1 as depicted in
SEQ ID NO: 280, CDR-L2 as depicted in SEQ ID NO: 281 and CDR-L3 as
depicted in SEQ ID NO: 282, CDR-H1 as depicted in SEQ ID NO: 106,
CDR-H2 as depicted in SEQ ID NO: 107, CDR-H3 as depicted in SEQ ID
NO: 108, CDR-L1 as depicted in SEQ ID NO: 274, CDR-L2 as depicted
in SEQ ID NO: 275 and CDR-L3 as depicted in SEQ ID NO: 276, and
[0309] CDR-H1 as depicted in SEQ ID NO: 983, CDR-H2 as depicted in
SEQ ID NO: 984, CDR-H3 as depicted in SEQ ID NO: 985, CDR-L1 as
depicted in SEQ ID NO: 986, CDR-L2 as depicted in SEQ ID NO: 987
and CDR-L3 as depicted in SEQ ID NO: 988, which all characterize
binding domains for CDH19 grouped into bin 5.
[0310] In a further embodiment of the antibody construct of the
invention the first binding domain comprises a VH region selected
from the group consisting of VH regions [0311] (a) as depicted in
SEQ ID NO: 362, SEQ ID NO: 364, SEQ ID NO: 485, SEQ ID NO: 486, SEQ
ID NO: 487, SEQ ID NO: 492, SEQ ID NO: 493, SEQ ID NO: 494, SEQ ID
NO: 495, SEQ ID NO: 1133, SEQ ID NO: 1172, SEQ ID NO: 1341, SEQ ID
NO: 1354, SEQ ID NO: 1367, SEQ ID NO: 1432, and SEQ ID NO: 1445
grouped into bin 1; [0312] (b) as depicted in SEQ ID NO: 342, SEQ
ID NO: 366, SEQ ID NO: 370, SEQ ID NO: 344, SEQ ID NO: 372, SEQ ID
NO: 368, SEQ ID NO: 496, SEQ ID NO: 497, SEQ ID NO: 498, SEQ ID NO:
499, SEQ ID NO: 500, SEQ ID NO: 508, SEQ ID NO: 509, SEQ ID NO:510,
SEQ ID NO:511, SEQ ID NO:512, SEQ ID NO:519, SEQ ID NO: 520, SEQ ID
NO: 521, SEQ ID NO: 522, SEQ ID NO: 523, SEQ ID NO: 524, SEQ ID NO:
525, SEQ ID NO: 526, SEQ ID NO: 527, SEQ ID NO: 528, SEQ ID NO:
529, SEQ ID NO: 530, SEQ ID NO: 531, SEQ ID NO: 532, SEQ ID NO:
533, SEQ ID NO: 534, SEQ ID NO: 535, SEQ ID NO: 536, SEQ ID NO:
537, SEQ ID NO: 538, SEQ ID NO: 1016, SEQ ID NO: 1029, SEQ ID NO:
1042, SEQ ID NO: 1081, SEQ ID NO: 1107, SEQ ID NO: 1120, SEQ ID NO:
1250, SEQ ID NO: 1263, SEQ ID NO: 1276, SEQ ID NO: 1289, and SEQ ID
NO: 1302; [0313] grouped into bin 2; [0314] (c) as depicted in SEQ
ID NO: 338, SEQ ID NO: 354, SEQ ID NO: 378, SEQ ID NO: 356, SEQ ID
NO: 476, SEQ ID NO: 477, SEQ ID NO: 478, SEQ ID NO: 479, SEQ ID
NO:480, SEQ ID NO:481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO:
484, SEQ ID NO:501, SEQ ID NO:502, SEQ ID NO: 503, SEQ ID NO:504,
SEQ ID NO: 505, SEQ ID NO: 506, SEQ ID NO: 517, SEQ ID NO: 518, SEQ
ID NO: 1003, SEQ ID NO: 1055, and SEQ ID NO: 1094; [0315] grouped
into bin 3; [0316] (d) as depicted in SEQ ID NO: 352, SEQ ID NO:
360, SEQ ID NO: 388, SEQ ID NO: 386, SEQ ID NO: 340, SEQ ID NO:
346, SEQ ID NO: 374, SEQ ID NO: 348, SEQ ID NO: 390, SEQ ID NO:
463, SEQ ID NO: 464, SEQ ID NO: 465, SEQ ID NO: 466, SEQ ID NO:
467, SEQ ID NO: 468, SEQ ID NO: 469, SEQ ID NO: 470, SEQ ID NO:
471, SEQ ID NO: 472, SEQ ID NO: 473, SEQ ID NO: 474, SEQ ID NO:
475, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO: 490, SEQ ID NO:
491, SEQ ID NO: 513, SEQ ID NO: 514, SEQ ID NO: 515, SEQ ID NO:
516, SEQ ID NO: 540, SEQ ID NO:541, SEQ ID NO:542, SEQ ID NO: 543,
SEQ ID NO:977, SEQ ID NO: 1068, SEQ ID NO: 1146, SEQ ID NO: 1159,
SEQ ID NO: 1185, SEQ ID NO: 1198, SEQ ID NO: 1211, SEQ ID NO: 1224,
SEQ ID NO: 1237, SEQ ID NO: 1315, SEQ ID NO: 1328, SEQ ID NO: 1380,
SEQ ID NO: 1393, SEQ ID NO: 1406, and SEQ ID NO: 1419; [0317]
grouped into bin 4; and [0318] (e) as depicted in SEQ ID NO: 376,
SEQ ID NO: 392, SEQ ID NO: 358, SEQ ID NO: 350, SEQ ID NO: 507, and
SEQ ID NO: 990 [0319] grouped into bin 5.
[0320] In another embodiment of the antibody construct of the
invention the first binding domain comprises a VL region selected
from the group consisting of VL regions [0321] (a) as depicted in
SEQ ID NO: 418, SEQ ID NO: 420, SEQ ID NO: 580, SEQ ID NO: 581, SEQ
ID NO: 582, SEQ ID NO: 587, SEQ ID NO: 588, SEQ ID NO: 589, SEQ ID
NO: 590, SEQ ID NO: 1135, SEQ ID NO: 1174, SEQ ID NO: 1343, SEQ ID
NO: 1356, SEQ ID NO: 1369, SEQ ID NO: 1434, and SEQ ID NO: 1447;
[0322] grouped into bin 1; [0323] (b) as depicted in SEQ ID NO:
398, SEQ ID NO: 422, SEQ ID NO: 426, SEQ ID NO: 400, SEQ ID NO:
428, SEQ ID NO: 424, SEQ ID NO: 591, SEQ ID NO: 592, SEQ ID NO:
593, SEQ ID NO: 594, SEQ ID NO: 595, SEQ ID NO: 603, SEQ ID NO:
604, SEQ ID NO: 605, SEQ ID NO: 606, SEQ ID NO: 607, SEQ ID NO:
614, SEQ ID NO: 615, SEQ ID NO: 616, SEQ ID NO: 617, SEQ ID NO:
618, SEQ ID NO: 619, SEQ ID NO:620, SEQ ID NO:621, SEQ ID NO: 622,
SEQ ID NO:623, SEQ ID NO: 624, SEQ ID NO: 625, SEQ ID NO: 626, SEQ
ID NO: 627, SEQ ID NO: 628, SEQ ID NO:629, SEQ ID NO:630, SEQ ID
NO: 631, SEQ ID NO:632, SEQ ID NO: 633, SEQ ID NO: 1018, SEQ ID NO:
1031, SEQ ID NO: 1044, SEQ ID NO: 1083, SEQ ID NO: 1109, SEQ ID NO:
1122, SEQ ID NO: 1252, SEQ ID NO: 1265, SEQ ID NO: 1278, SEQ ID NO:
1291, and SEQ ID NO: 1304; [0324] grouped into bin 2; [0325] (c) as
depicted in SEQ ID NO: 394, SEQ ID NO: 410, SEQ ID NO: 434, SEQ ID
NO: 412, SEQ ID NO: 571, SEQ ID NO: 572, SEQ ID NO: 573, SEQ ID NO:
574, SEQ ID NO: 575, SEQ ID NO: 576, SEQ ID NO: 577, SEQ ID NO:
578, SEQ ID NO: 579, SEQ ID NO: 596, SEQ ID NO: 597, SEQ ID NO:
598, SEQ ID NO: 599, SEQ ID NO: 600, SEQ ID NO: 601, SEQ ID NO:
612, SEQ ID NO: 613, SEQ ID NO: 1005, SEQ ID NO: 1057, and SEQ ID
NO: 1096; [0326] grouped into bin 3; [0327] (d) as depicted in SEQ
ID NO: 408, SEQ ID NO: 416, SEQ ID NO: 444, SEQ ID NO: 442, SEQ ID
NO: 396, SEQ ID NO: 402, SEQ ID NO: 430, SEQ ID NO: 404, SEQ ID NO:
446, SEQ ID NO: 558, SEQ ID NO: 559, SEQ ID NO: 560, SEQ ID NO:
561, SEQ ID NO: 562, SEQ ID NO: 563, SEQ ID NO: 564, SEQ ID NO:
565, SEQ ID NO: 566, SEQ ID NO: 567, SEQ ID NO: 568, SEQ ID NO:
569, SEQ ID NO: 570, SEQ ID NO: 583, SEQ ID NO: 584, SEQ ID NO:
585, SEQ ID NO: 586, SEQ ID NO:608, SEQ ID NO:609, SEQ ID NO:610,
SEQ ID NO:611, SEQ ID NO:635, SEQ ID NO: 636, SEQ ID NO: 637, SEQ
ID NO: 638, SEQ ID NO: 979, SEQ ID NO: 1070, SEQ ID NO: 1148, SEQ
ID NO: 1161, SEQ ID NO: 1187, SEQ ID NO: 1200, SEQ ID NO: 1213, SEQ
ID NO: 1226, SEQ ID NO: 1239, SEQ ID NO: 1317, SEQ ID NO: 1330, SEQ
ID NO: 1382, SEQ ID NO: 1395, SEQ ID NO: 1408, and SEQ ID NO: 1421
[0328] grouped into bin 4; and [0329] (e) as depicted in SEQ ID NO:
432, SEQ ID NO: 448, SEQ ID NO: 414, SEQ ID NO: 406, SEQ ID NO:
602, and SEQ ID NO: 992 [0330] grouped into bin 5.
[0331] The invention further provides an embodiment of the antibody
construct of the invention, wherein the first binding domain
comprises a VH region and a VL region selected from the group
consisting of: [0332] (1) pairs of a VH region and a VL region as
depicted in SEQ ID NOs: 362+418, SEQ ID NOs: 364+420, SEQ ID NOs:
485+580, SEQ ID NOs: 486+581, SEQ ID NOs: 487+582, SEQ ID NOs:
492+587, SEQ ID NOs: 493+588, SEQ ID NOs: 494+589, SEQ ID NOs:
495+590, SEQ ID NOs: 1133+1135, SEQ ID NOs: 1172+1174, SEQ ID NOs:
1341+1343, SEQ ID NOs: 1354+1356, SEQ ID NOs: 1367+1369, SEQ ID
NOs: 1432+1434, and SEQ ID NOs: 1445+1447; [0333] all pairs grouped
into bin 1; [0334] (2) pairs of a VH region and a VL region as
depicted in SEQ ID NOs: 342+398, SEQ ID NOs: 366+422, SEQ ID NOs:
370+426, SEQ ID NOs: 344+400, SEQ ID NOs: 372+428, SEQ ID NOs:
368+424, SEQ ID NOs: 496+591, SEQ ID NOs: 497+592, SEQ ID NOs:
498+593, SEQ ID NOs: 499+594, SEQ ID NOs: 500+595, SEQ ID NOs:
508+603, SEQ ID NOs: 509+604, SEQ ID NOs: 510+605, SEQ ID NOs:
511+606, SEQ ID NOs: 512+607, SEQ ID NOs: 519+614, SEQ ID NOs:
520+615, SEQ ID NOs: 521+616, SEQ ID NOs: 522+617, SEQ ID NOs:
523+618, SEQ ID NOs: 524+619, SEQ ID NOs: 525+620, SEQ ID NOs:
526+621, SEQ ID NOs: 527+622, SEQ ID NOs: 528+623, SEQ ID NOs:
529+624, SEQ ID NOs: 530+625, SEQ ID NOs: 531+626, SEQ ID NOs:
532+627, SEQ ID NOs: 533+628, SEQ ID NOs: 534+629, SEQ ID NOs:
535+630, SEQ ID NOs: 536+631, SEQ ID NOs: 537+632, SEQ ID NOs:
538+633, SEQ ID NOs: 1016+1018, SEQ ID NOs: 1029+1031, SEQ ID NOs:
1042+1044, SEQ ID NOs: 1081+1083, SEQ ID NOs: 1107+1109, SEQ ID
NOs: 1120+1122, SEQ ID NOs: 1250+1252, SEQ ID NOs: 1263+1265, SEQ
ID NOs: 1276+1278, SEQ ID NOs: 1289+1291, and SEQ ID NOs:
1302+1304; [0335] all pairs grouped into bin 2; [0336] (3) pairs of
a VH region and a VL region as depicted in SEQ ID NOs: 338+394, SEQ
ID NOs: 354+410, SEQ ID NOs: 378+434, SEQ ID NOs: 356+412, SEQ ID
NOs: 476+571, SEQ ID NOs: 477+572, SEQ ID NOs: 478+573, SEQ ID NOs:
479+574, SEQ ID NOs: 480+575, SEQ ID NOs: 481+576, SEQ ID NOs:
482+577, SEQ ID NOs: 483+578, SEQ ID NOs: 484+579, SEQ ID NOs:
501+596, SEQ ID NOs: 502+597, SEQ ID NOs: 503+598, SEQ ID NOs:
504+599, SEQ ID NOs: 505+600, SEQ ID NOs: 506+601, SEQ ID NOs:
517+612, SEQ ID NOs: 518+613, SEQ ID NOs: 1003+1005, SEQ ID NOs:
1055+1057, and SEQ ID NOs: 1094+1096; [0337] all pairs grouped into
bin 3; [0338] (4) pairs of a VH region and a VL region as depicted
in SEQ ID NOs: 352+408, SEQ ID NOs: 360+416, SEQ ID NOs: 388+444,
SEQ ID NOs: 386+442, SEQ ID NOs: 340+396, SEQ ID NOs: 346+402, SEQ
ID NOs: 374+430, SEQ ID NOs: 348+404, SEQ ID NOs: 390+446, SEQ ID
NOs: 463+558, SEQ ID NOs: 464+559, SEQ ID NOs: 465+560, SEQ ID NOs:
466+561, SEQ ID NOs: 467+562, SEQ ID NOs: 468+563, SEQ ID NOs:
469+564, SEQ ID NOs: 470+565, SEQ ID NOs: 471+566, SEQ ID NOs:
472+567, SEQ ID NOs: 473+568, SEQ ID NOs: 474+569, SEQ ID NOs:
475+570, SEQ ID NOs: 488+583, SEQ ID NOs: 489+584, SEQ ID NOs:
490+585, SEQ ID NOs: 491+586, SEQ ID NOs: 513+608, SEQ ID NOs:
514+609, SEQ ID NOs: 515+610, SEQ ID NOs: 516+611, SEQ ID NOs:
540+635, SEQ ID NOs: 541+636, SEQ ID NOs: 542+637, SEQ ID NOs:
543+638, SEQ ID NOs: 977+979, SEQ ID NOs: 1068+1070, SEQ ID NOs:
1146+1148, SEQ ID NOs: 1159+1161, SEQ ID NOs: 1185+1187, SEQ ID
NOs: 1198+1200, SEQ ID NOs: 1211+1213, SEQ ID NOs: 1224+1226, SEQ
ID NOs: 1237+1239, SEQ ID NOs: 1315+1317, SEQ ID NOs: 1328+1330,
SEQ ID NOs: 1380, +1382 SEQ ID NOs: 1393+1395, SEQ ID NOs:
1406+1408, and SEQ ID NOs: 1419+1421; [0339] all pairs grouped into
bin 4; and [0340] (5) pairs of a VH region and a VL region as
depicted in SEQ ID NOs: 376+432, SEQ ID NOs: 392+448, SEQ ID NOs:
358+414, SEQ ID NOs: 350+406, SEQ ID NOs: 507+602, and SEQ ID NOs:
990+992 [0341] all pairs grouped into bin 5.
[0342] In a further embodiment of the invention the antibody
construct is in a format selected from the group consisting of
(scFv).sub.2, (single domain mAb).sub.2, scFv-single domain mAb,
diabodies and oligomers thereof.
[0343] In a preferred embodiment the first binding domain comprises
an amino acid selected from the group consisting of [0344] (a) as
depicted in SEQ ID NO: 117, SEQ ID NO: 1137, SEQ ID NO: 1176, SEQ
ID NO: 1345, SEQ ID NO: 1358, SEQ ID NO: 1371, SEQ ID NO: 1436, and
SEQ ID NO: 1449; [0345] all binders grouped into bin 1; [0346] (b)
as depicted in SEQ ID NO: 1020, SEQ ID NO: 1033, SEQ ID NO: 1046,
SEQ ID NO: 1085, SEQ ID NO: 1111, SEQ ID NO: 1124, SEQ ID NO: 1254,
SEQ ID NO: 1267, SEQ ID NO: 1280, SEQ ID NO: 1293, and SEQ ID NO:
1306; [0347] all binders grouped into bin 2; [0348] (c) as depicted
in SEQ ID NO: 1007, SEQ ID NO: 1059, and SEQ ID NO: 1098; all
binders grouped into bin 3; [0349] (d) as depicted in SEQ ID NO:
981, SEQ ID NO: 1072, SEQ ID NO: 1150, SEQ ID NO: 1163, SEQ ID NO:
1189, SEQ ID NO: 1202, SEQ ID NO: 1215, SEQ ID NO: 1228, SEQ ID NO:
1241, SEQ ID NO: 1319, SEQ ID NO: 1332, SEQ ID NO: 1384, SEQ ID NO:
1397, SEQ ID NO: 1410, and SEQ ID NO: 1423; [0350] all binders
grouped into bin 4; and [0351] (e) as depicted in SEQ ID NO: 994
grouped into bin 5.
[0352] In one aspect of the invention, the second binding domain is
capable of binding to to human CD3 and to macaque CD3, preferably
to human CD3 epsilon and to macaque CD3 epsilon. Additionally or
alternatively, the second binding domain is capable of binding to
Callithrix jacchus, Saguinus oedipus and/or Saimiri sciureus CD3
epsilon. According to these embodiments, one or both binding
domains of the antibody construct of the invention are preferably
cross-species specific for members of the mammalian order of
primates. Cross-species specific CD3 binding domains are, for
example, described in WO 2008/119567.
[0353] It is particularly preferred for the antibody construct of
the present invention that the second binding domain capable of
binding to the T cell CD3 receptor complex comprises a VL region
comprising CDR-L1, CDR-L2 and CDR-L3 selected from: [0354] (a)
CDR-L1 as depicted in SEQ ID NO: 27 of WO 2008/119567, CDR-L2 as
depicted in SEQ ID NO: 28 of WO 2008/119567 and CDR-L3 as depicted
in SEQ ID NO: 29 of WO 2008/119567; [0355] (b) CDR-L1 as depicted
in SEQ ID NO: 117 of WO 2008/119567, CDR-L2 as depicted in SEQ ID
NO: 118 of WO 2008/119567 and CDR-L3 as depicted in SEQ ID NO: 119
of WO 2008/119567; and [0356] (c) CDR-L1 as depicted in SEQ ID NO:
153 of WO 2008/119567, CDR-L2 as depicted in SEQ ID NO: 154 of WO
2008/119567 and CDR-L3 as depicted in SEQ ID NO: 155 of WO
2008/119567.
[0357] In an alternatively preferred embodiment of the antibody
construct of the present invention, the second binding domain
capable of binding to the T cell CD3 receptor complex comprises a
VH region comprising CDR-H 1, CDR-H2 and CDR-H3 selected from:
[0358] (a) CDR-H1 as depicted in SEQ ID NO: 12 of WO 2008/119567,
CDR-H2 as depicted in SEQ ID NO: 13 of WO 2008/119567 and CDR-H3 as
depicted in SEQ ID NO: 14 of WO 2008/119567; [0359] (b) CDR-H1 as
depicted in SEQ ID NO: 30 of WO 2008/119567, CDR-H2 as depicted in
SEQ ID NO: 31 of WO 2008/119567 and CDR-H3 as depicted in SEQ ID
NO: 32 of WO 2008/119567; [0360] (c) CDR-H1 as depicted in SEQ ID
NO: 48 of WO 2008/119567, CDR-H2 as depicted in SEQ ID NO: 49 of WO
2008/119567 and CDR-H3 as depicted in SEQ ID NO: 50 of WO
2008/119567; [0361] (d) CDR-H1 as depicted in SEQ ID NO: 66 of WO
2008/119567, CDR-H2 as depicted in SEQ ID NO: 67 of WO 2008/119567
and CDR-H3 as depicted in SEQ ID NO: 68 of WO 2008/119567; [0362]
(e) CDR-H1 as depicted in SEQ ID NO: 84 of WO 2008/119567, CDR-H2
as depicted in SEQ ID NO: 85 of WO 2008/119567 and CDR-H3 as
depicted in SEQ ID NO: 86 of WO 2008/119567; [0363] (f) CDR-H1 as
depicted in SEQ ID NO: 102 of WO 2008/119567, CDR-H2 as depicted in
SEQ ID NO: 103 of WO2008/119567 and CDR-H3 as depicted in SEQ ID
NO: 104 of WO 2008/119567; [0364] (g) CDR-H1 as depicted in SEQ ID
NO: 120 of WO 2008/119567, CDR-H2 as depicted in SEQ ID NO: 121 of
WO2008/119567 and CDR-H3 as depicted in SEQ ID NO: 122 of WO
2008/119567; [0365] (h) CDR-H1 as depicted in SEQ ID NO: 138 of WO
2008/119567, CDR-H2 as depicted in SEQ ID NO: 139 of WO2008/119567
and CDR-H3 as depicted in SEQ ID NO: 140 of WO 2008/119567; [0366]
(i) CDR-H1 as depicted in SEQ ID NO: 156 of WO 2008/119567, CDR-H2
as depicted in SEQ ID NO: 157 of WO2008/119567 and CDR-H3 as
depicted in SEQ ID NO: 158 of WO 2008/119567; and [0367] (j) CDR-H1
as depicted in SEQ ID NO: 174 of WO 2008/119567, CDR-H2 as depicted
in SEQ ID NO: 175 of WO2008/119567 and CDR-H3 as depicted in SEQ ID
NO: 176 of WO 2008/119567.
[0368] It is further preferred for the antibody construct of the
present invention that the second binding domain capable of binding
to the T cell CD3 receptor complex comprises a VL region selected
from the group consisting of a VL region as depicted in SEQ ID NO:
35, 39, 125, 129, 161 or 165 of WO 2008/119567.
[0369] It is alternatively preferred that the second binding domain
capable of binding to the T cell CD3 receptor complex comprises a
VH region selected from the group consisting of a VH region as
depicted in SEQ ID NO: 15, 19, 33, 37, 51, 55, 69, 73, 87, 91, 105,
109, 123, 127, 141, 145, 159, 163, 177 or 181 of WO
2008/119567.
[0370] More preferably, the antibody construct of the present
invention is characterized by the second binding domain capable of
binding to the T cell CD3 receptor complex comprising a VL region
and a VH region selected from the group consisting of: [0371] (a) a
VL region as depicted in SEQ ID NO: 17 or 21 of WO 2008/119567 and
a VH region as depicted in SEQ ID NO: 15 or 19 of WO 2008/119567;
[0372] (b) a VL region as depicted in SEQ ID NO: 35 or 39 of WO
2008/119567 and a VH region as depicted in SEQ ID NO: 33 or 37 of
WO 2008/119567; [0373] (c) a VL region as depicted in SEQ ID NO: 53
or 57 of WO 2008/119567 and a VH region as depicted in SEQ ID NO:
51 or 55 of WO 2008/119567; [0374] (d) a VL region as depicted in
SEQ ID NO: 71 or 75 of WO 2008/119567 and a VH region as depicted
in SEQ ID NO: 69 or 73 of WO 2008/119567; [0375] (e) a VL region as
depicted in SEQ ID NO: 89 or 93 of WO 2008/119567 and a VH region
as depicted in SEQ ID NO: 87 or 91 of WO 2008/119567; [0376] (f) a
VL region as depicted in SEQ ID NO: 107 or 111 of WO 2008/119567
and a VH region as depicted in SEQ ID NO: 105 or 109 of WO
2008/119567; [0377] (g) a VL region as depicted in SEQ ID NO: 125
or 129 of WO 2008/119567 and a VH region as depicted in SEQ ID NO:
123 or 127 of WO 2008/119567; [0378] (h) a VL region as depicted in
SEQ ID NO: 143 or 147 of WO 2008/119567 and a VH region as depicted
in SEQ ID NO: 141 or 145 of WO 2008/119567; [0379] (i) a VL region
as depicted in SEQ ID NO: 161 or 165 of WO 2008/119567 and a VH
region as depicted in SEQ ID NO: 159 or 163 of WO 2008/119567; and
[0380] (j) a VL region as depicted in SEQ ID NO: 179 or 183 of WO
2008/119567 and a VH region as depicted in SEQ ID NO: 177 or 181 of
WO 2008/119567.
[0381] According to a preferred embodiment of the antibody
construct of the present invention, in particular the second
binding domain capable of binding to the T cell CD3 receptor
complex, the pairs of VH-regions and VL-regions are in the format
of a single chain antibody (scFv). The VH and VL regions are
arranged in the order VH-VL or VL-VH. It is preferred that the
VH-region is positioned N-terminally to a linker sequence. The
VL-region is positioned C-terminally of the linker sequence.
[0382] A preferred embodiment of the above described antibody
construct of the present invention is characterized by the second
binding domain capable of binding to the T cell CD3 receptor
complex comprising an amino acid sequence selected from the group
consisting of SEQ ID NOs: 23, 25, 41, 43, 59, 61, 77, 79, 95, 97,
113, 115, 131, 133, 149, 151, 167, 169, 185 or 187 of WO
2008/119567.
[0383] In a preferred embodiment the antibody construct of the
invention has an amino acid sequence selected from the group
consisting of [0384] (a) as depicted in SEQ ID NO: 1138, SEQ ID NO:
1177, SEQ ID NO: 1346, SEQ ID NO: 1359, SEQ ID NO: 1372, SEQ ID NO:
1437, and SEQ ID NO: 1450; [0385] (b) as depicted in SEQ ID NO:
1021, SEQ ID NO: 1034, SEQ ID NO: 1047, SEQ ID NO: 1086, SEQ ID NO:
1112, SEQ ID NO: 1125, SEQ ID NO: 1255, SEQ ID NO: 1268, SEQ ID NO:
1281, SEQ ID NO: 1294, and SEQ ID NO: 1307; [0386] (c) as depicted
in SEQ ID NO: 1008, SEQ ID NO: 1060, and SEQ ID NO: 1099; [0387]
(d) as depicted in SEQ ID NO: 982, SEQ ID NO: 1073, SEQ ID NO:
1151, SEQ ID NO: 1164, SEQ ID NO: 1190, SEQ ID NO: 1203, SEQ ID NO:
1216, SEQ ID NO: 1229, SEQ ID NO: 1242, SEQ ID NO: 1320, SEQ ID NO:
1333, SEQ ID NO: 1385, SEQ ID NO: 1398, SEQ ID NO: 1411, and SEQ ID
NO: 1424; and [0388] (e) as depicted in SEQ ID NO: 995.
[0389] The invention further provides a nucleic acid sequence
encoding an antibody construct of the invention.
[0390] Furthermore, the invention provides a vector comprising a
nucleic acid sequence of the invention. Moreover, the invention
provides a host cell transformed or transfected with the nucleic
acid sequence of the invention.
[0391] In a further embodiment the invention provides a process for
the production of a antibody construct of the invention, said
process comprising culturing a host cell of the invention under
conditions allowing the expression of the antibody construct of the
invention and recovering the produced antibody construct from the
culture.
[0392] Moreover, the invention provides a pharmaceutical
composition comprising an antibody construct of the invention or
produced according to the process of the invention
[0393] The formulations described herein are useful as
pharmaceutical compositions in the treatment, amelioration and/or
prevention of the pathological medical condition as described
herein in a patient in need thereof. The term "treatment" refers to
both therapeutic treatment and prophylactic or preventative
measures. Treatment includes the application or administration of
the formulation to the body, an isolated tissue, or cell from a
patient who has a disease/disorder, a symptom of a
disease/disorder, or a predisposition toward a disease/disorder,
with the purpose to cure, heal, alleviate, relieve, alter, remedy,
ameliorate, improve, or affect the disease, the symptom of the
disease, or the predisposition toward the disease.
[0394] Those "in need of treatment" include those already with the
disorder, as well as those in which the disorder is to be
prevented. The term "disease" is any condition that would benefit
from treatment with the protein formulation described herein. This
includes chronic and acute disorders or diseases including those
pathological conditions that predispose the mammal to the disease
in question. Non-limiting examples of diseases/disorders to be
treated herein include proliferative disease, a tumorous disease,
or an immunological disorder.
[0395] In some embodiments, the invention provides a pharmaceutical
composition comprising a therapeutically effective amount of one or
a plurality of the antibody construct of the invention together
with a pharmaceutically effective diluents, carrier, solubilizer,
emulsifier, preservative, and/or adjuvant. Pharmaceutical
compositions of the invention include, but are not limited to,
liquid, frozen, and lyophilized compositions.
[0396] Preferably, formulation materials are nontoxic to recipients
at the dosages and concentrations employed. In specific
embodiments, pharmaceutical compositions comprising a
therapeutically effective amount of an antibody construct of the
invention.
[0397] In certain embodiments, the pharmaceutical composition may
contain formulation materials for modifying, maintaining or
preserving, for example, the pH, osmolarity, viscosity, clarity,
color, isotonicity, odor, sterility, stability, rate of dissolution
or release, adsorption or penetration of the composition. In such
embodiments, suitable formulation materials include, but are not
limited to, amino acids (such as glycine, glutamine, asparagine,
arginine, proline, or lysine); antimicrobials; antioxidants (such
as ascorbic acid, sodium sulfite or sodium hydrogen-sulfite);
buffers (such as borate, bicarbonate, Tris-HCl, citrates,
phosphates or other organic acids); bulking agents (such as
mannitol or glycine); chelating agents (such as ethylenediamine
tetraacetic acid (EDTA)); complexing agents (such as caffeine,
polyvinylpyrrolidone, beta-cyclodextrin or
hydroxypropyl-beta-cyclodextrin); fillers; monosaccharides;
disaccharides; and other carbohydrates (such as glucose, mannose or
dextrins); proteins (such as serum albumin, gelatin or
immunoglobulins); coloring, flavoring and diluting agents;
emulsifying agents; hydrophilic polymers (such as
polyvinylpyrrolidone); low molecular weight polypeptides;
salt-forming counterions (such as sodium); preservatives (such as
benzalkonium chloride, benzoic acid, salicylic acid, thimerosal,
phenethyl alcohol, methylparaben, propylparaben, chlorhexidine,
sorbic acid or hydrogen peroxide); solvents (such as glycerin,
propylene glycol or polyethylene glycol); sugar alcohols (such as
mannitol or sorbitol); suspending agents; surfactants or wetting
agents (such as pluronics, PEG, sorbitan esters, polysorbates such
as polysorbate 20, polysorbate, triton, tromethamine, lecithin,
cholesterol, tyloxapal); stability enhancing agents (such as
sucrose or sorbitol); tonicity enhancing agents (such as alkali
metal halides, preferably sodium or potassium chloride, mannitol
sorbitol); delivery vehicles; diluents; excipients and/or
pharmaceutical adjuvants. See, REMINGTON'S PHARMACEUTICAL SCIENCES,
18" Edition, (A. R. Genrmo, ed.), 1990, Mack Publishing
Company.
[0398] In certain embodiments, the optimal pharmaceutical
composition will be determined by one skilled in the art depending
upon, for example, the intended route of administration, delivery
format and desired dosage. See, for example, REMINGTON'S
PHARMACEUTICAL SCIENCES, supra. In certain embodiments, such
compositions may influence the physical state, stability, rate of
in vivo release and rate of in vivo clearance of the antigen
binding proteins of the invention. In certain embodiments, the
primary vehicle or carrier in a pharmaceutical composition may be
either aqueous or non-aqueous in nature. For example, a suitable
vehicle or carrier may be water for injection, physiological saline
solution or artificial cerebrospinal fluid, possibly supplemented
with other materials common in compositions for parenteral
administration. Neutral buffered saline or saline mixed with serum
albumin are further exemplary vehicles. In specific embodiments,
pharmaceutical compositions comprise Tris buffer of about pH
7.0-8.5, or acetate buffer of about pH 4.0-5.5, and may further
include sorbitol or a suitable substitute therefore. In certain
embodiments of the invention, human antibody or antigen binding
fragment thereof of the invention or the antibody construct of the
invention compositions may be prepared for storage by mixing the
selected composition having the desired degree of purity with
optional formulation agents (REMINGTON'S PHARMACEUTICAL SCIENCES,
supra) in the form of a lyophilized cake or an aqueous solution.
Further, in certain embodiments, the human antibody or antigen
binding fragment thereof of the invention or the antibody construct
of the invention may be formulated as a lyophilizate using
appropriate excipients such as sucrose.
[0399] The pharmaceutical compositions of the invention can be
selected for parenteral delivery. Alternatively, the compositions
may be selected for inhalation or for delivery through the
digestive tract, such as orally. Preparation of such
pharmaceutically acceptable compositions is within the skill of the
art. The formulation components are present preferably in
concentrations that are acceptable to the site of administration.
In certain embodiments, buffers are used to maintain the
composition at physiological pH or at a slightly lower pH,
typically within a pH range of from about 5 to about 8.
[0400] When parenteral administration is contemplated, the
therapeutic compositions for use in this invention may be provided
in the form of a pyrogen-free, parenterally acceptable aqueous
solution comprising the desired human antibody or antigen binding
fragment thereof of the invention or the antibody construct of the
invention in a pharmaceutically acceptable vehicle. A particularly
suitable vehicle for parenteral injection is sterile distilled
water in which the antibody construct of the invention is
formulated as a sterile, isotonic solution, properly preserved. In
certain embodiments, the preparation can involve the formulation of
the desired molecule with an agent, such as injectable
microspheres, bio-erodible particles, polymeric compounds (such as
polylactic acid or polyglycolic acid), beads or liposomes, that may
provide controlled or sustained release of the product which can be
delivered via depot injection. In certain embodiments, hyaluronic
acid may also be used, having the effect of promoting sustained
duration in the circulation. In certain embodiments, implantable
drug delivery devices may be used to introduce the desired antigen
binding protein.
[0401] Additional pharmaceutical compositions will be evident to
those skilled in the art, including formulations involving h the
antibody construct of the invention in sustained- or
controlled-delivery formulations. Techniques for formulating a
variety of other sustained- or controlled-delivery means, such as
liposome carriers, bio-erodible microparticles or porous beads and
depot injections, are also known to those skilled in the art. See,
for example, International Patent Application No. PCT/US93/00829,
which is incorporated by reference and describes controlled release
of porous polymeric microparticles for delivery of pharmaceutical
compositions. Sustained-release preparations may include
semipermeable polymer matrices in the form of shaped articles,
e.g., films, or microcapsules. Sustained release matrices may
include polyesters, hydrogels, polylactides (as disclosed in U.S.
Pat. No. 3,773,919 and European Patent Application Publication No.
EP 058481, each of which is incorporated by reference), copolymers
of L-glutamic acid and gamma ethyl-L-glutamate (Sidman et al.,
1983, Biopolymers 2:547-556), poly (2-hydroxyethyl-methacrylate)
(Langer et al., 1981, J. Biomed. Mater. Res. 15:167-277 and Langer,
1982, Chem. Tech. 12:98-105), ethylene vinyl acetate (Langer et
al., 1981, supra) or poly-D(-)-3-hydroxybutyric acid (European
Patent Application Publication No. EP 133,988). Sustained release
compositions may also include liposomes that can be prepared by any
of several methods known in the art. See, e.g., Eppstein et al.,
1985, Proc. Natl. Acad. Sci. U.S.A. 82:3688-3692; European Patent
Application Publication Nos. EP 036,676; EP 088,046 and EP 143,949,
incorporated by reference.
[0402] Pharmaceutical compositions used for in vivo administration
are typically provided as sterile preparations. Sterilization can
be accomplished by filtration through sterile filtration membranes.
When the composition is lyophilized, sterilization using this
method may be conducted either prior to or following lyophilization
and reconstitution. Compositions for parenteral administration can
be stored in lyophilized form or in a solution. Parenteral
compositions generally are placed into a container having a sterile
access port, for example, an intravenous solution bag or vial
having a stopper pierceable by a hypodermic injection needle.
[0403] Aspects of the invention includes self-buffering antibody
construct of the invention formulations, which can be used as
pharmaceutical compositions, as described in international patent
application WO 06138181A2 (PCT/US2006/022599), which is
incorporated by reference in its entirety herein.
[0404] As discussed above, certain embodiments provide antibody
construct of the invention protein compositions, particularly
pharmaceutical compositions of the invention, that comprise, in
addition to the antibody construct of the invention, one or more
excipients such as those illustratively described in this section
and elsewhere herein. Excipients can be used in the invention in
this regard for a wide variety of purposes, such as adjusting
physical, chemical, or biological properties of formulations, such
as adjustment of viscosity, and or processes of the invention to
improve effectiveness and or to stabilize such formulations and
processes against degradation and spoilage due to, for instance,
stresses that occur during manufacturing, shipping, storage,
pre-use preparation, administration, and thereafter. A variety of
expositions are available on protein stabilization and formulation
materials and methods useful in this regard, such as Arakawa et
al., "Solvent interactions in pharmaceutical formulations," Pharm
Res. 8(3): 285-91 (1991); Kendrick et al., "Physical stabilization
of proteins in aqueous solution," in: RATIONAL DESIGN OF STABLE
PROTEIN FORMULATIONS: THEORY AND PRACTICE, Carpenter and Manning,
eds. Pharmaceutical Biotechnology. 13: 61-84 (2002), and Randolph
et al., "Surfactant-protein interactions," Pharm Biotechnol. 13:
159-75 (2002), each of which is herein incorporated by reference in
its entirety, particularly in parts pertinent to excipients and
processes of the same for self-buffering protein formulations in
accordance with the current invention, especially as to protein
pharmaceutical products and processes for veterinary and/or human
medical uses.
[0405] Salts may be used in accordance with certain embodiments of
the invention to, for example, adjust the ionic strength and/or the
isotonicity of a formulation and/or to improve the solubility
and/or physical stability of a protein or other ingredient of a
composition in accordance with the invention.
[0406] As is well known, ions can stabilize the native state of
proteins by binding to charged residues on the protein's surface
and by shielding charged and polar groups in the protein and
reducing the strength of their electrostatic interactions,
attractive, and repulsive interactions. Ions also can stabilize the
denatured state of a protein by binding to, in particular, the
denatured peptide linkages (--CONH) of the protein. Furthermore,
ionic interaction with charged and polar groups in a protein also
can reduce intermolecular electrostatic interactions and, thereby,
prevent or reduce protein aggregation and insolubility.
[0407] Ionic species differ significantly in their effects on
proteins. A number of categorical rankings of ions and their
effects on proteins have been developed that can be used in
formulating pharmaceutical compositions in accordance with the
invention. One example is the Hofmeister series, which ranks ionic
and polar non-ionic solutes by their effect on the conformational
stability of proteins in solution. Stabilizing solutes are referred
to as "kosmotropic." Destabilizing solutes are referred to as
"chaotropic." Kosmotropes commonly are used at high concentrations
(e.g., >1 molar ammonium sulfate) to precipitate proteins from
solution ("salting-out"). Chaotropes commonly are used to denture
and/or to solubilize proteins ("salting-in"). The relative
effectiveness of ions to "salt-in" and "salt-out" defines their
position in the Hofmeister series.
[0408] Free amino acids can be used in the antibody construct of
the invention formulations in accordance with various embodiments
of the invention as bulking agents, stabilizers, and antioxidants,
as well as other standard uses. Lysine, proline, serine, and
alanine can be used for stabilizing proteins in a formulation.
Glycine is useful in lyophilization to ensure correct cake
structure and properties. Arginine may be useful to inhibit protein
aggregation, in both liquid and lyophilized formulations.
Methionine is useful as an antioxidant.
[0409] Polyols include sugars, e.g., mannitol, sucrose, and
sorbitol and polyhydric alcohols such as, for instance, glycerol
and propylene glycol, and, for purposes of discussion herein,
polyethylene glycol (PEG) and related substances. Polyols are
kosmotropic. They are useful stabilizing agents in both liquid and
lyophilized formulations to protect proteins from physical and
chemical degradation processes. Polyols also are useful for
adjusting the tonicity of formulations.
[0410] Among polyols useful in select embodiments of the invention
is mannitol, commonly used to ensure structural stability of the
cake in lyophilized formulations. It ensures structural stability
to the cake. It is generally used with a lyoprotectant, e.g.,
sucrose. Sorbitol and sucrose are among preferred agents for
adjusting tonicity and as stabilizers to protect against
freeze-thaw stresses during transport or the preparation of bulks
during the manufacturing process. Reducing sugars (which contain
free aldehyde or ketone groups), such as glucose and lactose, can
glycate surface lysine and arginine residues. Therefore, they
generally are not among preferred polyols for use in accordance
with the invention. In addition, sugars that form such reactive
species, such as sucrose, which is hydrolyzed to fructose and
glucose under acidic conditions, and consequently engenders
glycation, also is not among preferred polyols of the invention in
this regard. PEG is useful to stabilize proteins and as a
cryoprotectant and can be used in the invention in this regard.
[0411] Embodiments of the antibody construct of the invention
formulations further comprise surfactants. Protein molecules may be
susceptible to adsorption on surfaces and to denaturation and
consequent aggregation at air-liquid, solid-liquid, and
liquid-liquid interfaces. These effects generally scale inversely
with protein concentration. These deleterious interactions
generally scale inversely with protein concentration and typically
are exacerbated by physical agitation, such as that generated
during the shipping and handling of a product.
[0412] Surfactants routinely are used to prevent, minimize, or
reduce surface adsorption. Useful surfactants in the invention in
this regard include polysorbate 20, polysorbate 80, other fatty
acid esters of sorbitan polyethoxylates, and poloxamer 188.
[0413] Surfactants also are commonly used to control protein
conformational stability. The use of surfactants in this regard is
protein-specific since, any given surfactant typically will
stabilize some proteins and destabilize others.
[0414] Polysorbates are susceptible to oxidative degradation and
often, as supplied, contain sufficient quantities of peroxides to
cause oxidation of protein residue side-chains, especially
methionine. Consequently, polysorbates should be used carefully,
and when used, should be employed at their lowest effective
concentration. In this regard, polysorbates exemplify the general
rule that excipients should be used in their lowest effective
concentrations.
[0415] Embodiments of the antibody construct of the invention
formulations further comprise one or more antioxidants. To some
extent deleterious oxidation of proteins can be prevented in
pharmaceutical formulations by maintaining proper levels of ambient
oxygen and temperature and by avoiding exposure to light.
Antioxidant excipients can be used as well to prevent oxidative
degradation of proteins. Among useful antioxidants in this regard
are reducing agents, oxygen/free-radical scavengers, and chelating
agents. Antioxidants for use in therapeutic protein formulations in
accordance with the invention preferably are water-soluble and
maintain their activity throughout the shelf life of a product.
EDTA is a preferred antioxidant in accordance with the invention in
this regard.
[0416] Antioxidants can damage proteins. For instance, reducing
agents, such as glutathione in particular, can disrupt
intramolecular disulfide linkages. Thus, antioxidants for use in
the invention are selected to, among other things, eliminate or
sufficiently reduce the possibility of themselves damaging proteins
in the formulation.
[0417] Formulations in accordance with the invention may include
metal ions that are protein co-factors and that are necessary to
form protein coordination complexes, such as zinc necessary to form
certain insulin suspensions. Metal ions also can inhibit some
processes that degrade proteins. However, metal ions also catalyze
physical and chemical processes that degrade proteins.
[0418] Magnesium ions (10-120 mM) can be used to inhibit
isomerization of aspartic acid to isoaspartic acid. Ca+2 ions (up
to 100 mM) can increase the stability of human deoxyribonuclease.
Mg+2, Mn+2, and Zn+2, however, can destabilize rhDNase. Similarly,
Ca+2 and Sr+2 can stabilize Factor VIII, it can be destabilized by
Mg+2, Mn+2 and Zn+2, Cu+2 and Fe+2, and its aggregation can be
increased by Al+3 ions.
[0419] Embodiments of the antibody construct of the invention
formulations further comprise one or more preservatives.
Preservatives are necessary when developing multi-dose parenteral
formulations that involve more than one extraction from the same
container. Their primary function is to inhibit microbial growth
and ensure product sterility throughout the shelf-life or term of
use of the drug product. Commonly used preservatives include benzyl
alcohol, phenol and m-cresol. Although preservatives have a long
history of use with small-molecule parenterals, the development of
protein formulations that includes preservatives can be
challenging. Preservatives almost always have a destabilizing
effect (aggregation) on proteins, and this has become a major
factor in limiting their use in multi-dose protein formulations. To
date, most protein drugs have been formulated for single-use only.
However, when multi-dose formulations are possible, they have the
added advantage of enabling patient convenience, and increased
marketability. A good example is that of human growth hormone (hGH)
where the development of preserved formulations has led to
commercialization of more convenient, multi-use injection pen
presentations. At least four such pen devices containing preserved
formulations of hGH are currently available on the market.
Norditropin (liquid, Novo Nordisk), Nutropin AQ (liquid, Genentech)
& Genotropin (lyophilized--dual chamber cartridge, Pharmacia
& Upjohn) contain phenol while Somatrope (Eli Lilly) is
formulated with m-cresol. Several aspects need to be considered
during the formulation and development of preserved dosage forms.
The effective preservative concentration in the drug product must
be optimized. This requires testing a given preservative in the
dosage form with concentration ranges that confer anti-microbial
effectiveness without compromising protein stability.
[0420] As might be expected, development of liquid formulations
containing preservatives are more challenging than lyophilized
formulations. Freeze-dried products can be lyophilized without the
preservative and reconstituted with a preservative containing
diluent at the time of use. This shortens the time for which a
preservative is in contact with the protein, significantly
minimizing the associated stability risks. With liquid
formulations, preservative effectiveness and stability should be
maintained over the entire product shelf-life (about 18 to 24
months). An important point to note is that preservative
effectiveness should be demonstrated in the final formulation
containing the active drug and all excipient components.
[0421] The antibody construct of the invention generally will be
designed for specific routes and methods of administration, for
specific administration dosages and frequencies of administration,
for specific treatments of specific diseases, with ranges of
bio-availability and persistence, among other things. Formulations
thus may be designed in accordance with the invention for delivery
by any suitable route, including but not limited to orally,
aurally, opthalmically, rectally, and vaginally, and by parenteral
routes, including intravenous and intraarterial injection,
intramuscular injection, and subcutaneous injection.
[0422] Once the pharmaceutical composition has been formulated, it
may be stored in sterile vials as a solution, suspension, gel,
emulsion, solid, crystal, or as a dehydrated or lyophilized powder.
Such formulations may be stored either in a ready-to-use form or in
a form (e.g., lyophilized) that is reconstituted prior to
administration. The invention also provides kits for producing a
single-dose administration unit. The kits of the invention may each
contain both a first container having a dried protein and a second
container having an aqueous formulation. In certain embodiments of
this invention, kits containing single and multi-chambered
pre-filled syringes (e.g., liquid syringes and lyosyringes) are
provided. The therapeutically effective amount of an antibody
construct of the invention protein-containing pharmaceutical
composition to be employed will depend, for example, upon the
therapeutic context and objectives. One skilled in the art will
appreciate that the appropriate dosage levels for treatment will
vary depending, in part, upon the molecule delivered, the
indication for which the antibody construct of the invention is
being used, the route of administration, and the size (body weight,
body surface or organ size) and/or condition (the age and general
health) of the patient. In certain embodiments, the clinician may
titer the dosage and modify the route of administration to obtain
the optimal therapeutic effect. A typical dosage may range from
about 0.1 pg/kg to up to about 30 mg/kg or more, depending on the
factors mentioned above. In specific embodiments, the dosage may
range from 1.0 pg/kg up to about 20 mg/kg, optionally from 10 pg/kg
up to about 10 mg/kg or from 100 pg/kg up to about 5 mg/kg.
[0423] A therapeutic effective amount of an antibody construct of
the invention preferably results in a decrease in severity of
disease symptoms, in increase in frequency or duration of disease
symptom-free periods or a prevention of impairment or disability
due to the disease affliction. For treating CDH19-expressing
tumors, a therapeutically effective amount of the antibody
construct of the invention, e.g. an anti-CDH19/CD3 antibody
construct, preferably inhibits cell growth or tumor growth by at
least about 20%, at least about 40%, at least about 50%, at least
about 60%, at least about 70%, at least about 80%, or at least
about 90% relative to untreated patients. The ability of a compound
to inhibit tumor growth may be evaluated in an animal model
predictive of efficacy in human tumors.
[0424] Pharmaceutical compositions may be administered using a
medical device. Examples of medical devices for administering
pharmaceutical compositions are described in U.S. Pat. Nos.
4,475,196; 4,439,196; 4,447,224; 4,447, 233; 4,486,194; 4,487,603;
4,596,556; 4,790,824; 4,941,880; 5,064,413; 5,312,335; 5,312,335;
5,383,851; and 5,399,163, all incorporated by reference herein.
[0425] In one embodiment the invention provides the antibody
construct of the invention or produced according to the process of
the invention for use in the prevention, treatment or amelioration
of a melanoma disease or metastatic melanoma disease.
[0426] The invention also provides a method for the treatment or
amelioration of a melanoma disease or metastatic melanoma disease,
comprising the step of administering to a subject in need thereof
the antibody construct of the invention or produced according to
the process of the invention.
[0427] In a preferred embodiment method of use of the invention the
melanoma disease or metastatic melanoma disease is selected from
the group consisting of superficial spreading melanoma, lentigo
maligna, lentigo maligna melanoma, acral lentiginous melanoma and
nodular melanoma.
[0428] In a further embodiment, the invention provides a kit
comprising an antibody construct of the invention, or produced
according to the process of the invention, a vector of the
invention, and/or a host cell of the invention.
[0429] It should be understood that the inventions herein are not
limited to particular methodology, protocols, or reagents, as such
can vary. The discussion and examples provided herein are presented
for the purpose of describing particular embodiments only and are
not intended to limit the scope of the present invention, which is
defined solely by the claims. All publications and patents cited
throughout the text of this specification (including all patents,
patent applications, scientific publications, manufacturer's
specifications, instructions, etc.), whether supra or infra, are
hereby incorporated by reference in their entirety. Nothing herein
is to be construed as an admission that the invention is not
entitled to antedate such disclosure by virtue of prior invention.
To the extent the material incorporated by reference contradicts or
is inconsistent with this specification, the specification will
supersede any such material.
EXAMPLES
[0430] The following examples are provided for the purpose of
illustrating specific embodiments or features of the present
invention. These examples should not be construed as to limit the
scope of this invention. The examples are included for purposes of
illustration, and the present invention is limited only by the
claims.
Example 1--Fully Human Monoclonal Antibodies Against CDH19
[0431] 1.1 Immunization:
[0432] Fully human antibodies to Cadherin-19 (CDH19) were generated
using XENOMOUSE.RTM. technology, transgenic mice engineered to
express diverse repertoires of fully human IgG.kappa. and
IgG.lamda. antibodies of the corresponding isotype. (U.S. Pat. Nos.
6,114,598; 6,162,963; 6,833,268; 7,049,426; 7,064,244, which are
incorporated herein by reference in their entirety; Green et al.,
1994, Nature Genetics 7:13-21; Mendez et al., 1997, Nature Genetics
15:146-156; Green and Jakobovitis, 1998, J. Ex. Med. 188:483-495;
Kellermann and Green, Current Opinion in Biotechnology 13, 593-597,
2002).
[0433] Mice were immunized with multiple forms of Cadherin-19
immunogen, including: (1) full length human and cynomologous
("cyno") monkey cadherin-19, (2) secreted Cadherin-19 ecto-domain
(amino acids 1-596), and (3) a truncated membrane bound form of
human cadherin-19 (amino acids 1-624). Mice were immunized over a
period of 8 to 10 weeks with a range of 16-18 boosts.
[0434] Sera were collected at approximately 5 and 9 weeks after the
first injection and specific titers were determined by FACs
staining of recombinant Cadherin-19 receptor transiently expressed
on CHO-S cells. A total of 37 animals were identified with specific
immune responses, these animals were pooled into 3 groups and
advanced to antibody generation.
[0435] 1.2 Preparation of Monoclonal Antibodies
[0436] Animals exhibiting suitable titers were identified, and
lymphocytes were obtained from draining lymph nodes and, if
necessary, pooled for each cohort. Lymphocytes were dissociated
from lymphoid tissue by grinding in a suitable medium (for example,
Dulbecco's Modified Eagle Medium (DMEM); obtainable from
Invitrogen, Carlsbad, Calif.) to release the cells from the
tissues, and suspended in DMEM. B cells were selected and/or
expanded using standard methods, and fused with suitable fusion
partner using techniques that were known in the art.
[0437] After several days of culture, the hybridoma supernatants
were collected and subjected to screening assays as detailed in the
examples below, including confirmation of binding to human and
cynomologous monkey as well as the ability to kill cell lines in
secondary antibody-drug conjugate Bioassays. Hybridoma lines that
were identified to have the binding and functional properties of
interest were then further selected and subjected to standard
cloning and subcloning techniques. Clonal lines were expanded in
vitro, and the secreted human antibodies obtained for analysis and
V gene sequencing was performed.
[0438] 1.3 Selection of Cadherin-19 Receptor Specific Binding
Antibodies by FMAT
[0439] After 14 days of culture, hybridoma supernatants were
screened for CDH19-specific monoclonal antibodies by Fluorometric
Microvolume Assay Technology (FMAT) (Applied Biosystems, Foster
City, Calif.). The supernatants were screened against adherent CHO
cells transiently transfected with human Cadherin-19 and counter
screened against CHO cells transiently transfected with the same
expression plasmid that did not contain the Cadherin-19 gene.
[0440] After multiple screening campaigns, a panel of 1570
anti-Cadherin-19 binding hybridoma lines were identified and
advanced to further characterization assays.
Example 2--Assessment of Fully Human Monoclonal Antibodies Against
CDH19
[0441] 2.1 Additional Binding Characterization by Flow Cytometry
(FACs)
[0442] FACS binding assays were performed to evaluate the binding
of the anti-Cadherin-19 receptor specific antibodies to endogenous
Cadherin-19 receptor expressed on the CHL-1 tumor cell lines. In
addition, cross-reactive binding to murine and cynomologous monkey
Cadherin-19 orthologues was also evaluated by FACs using
recombinant forms of the various receptors transiently expressed on
293T cells.
[0443] FACs assays were performed by incubating hybridoma
supernatants with 10,000 to 25,000 cells in PBS/2% Fetal bovine
serum/2 mM Calcium Chloride at 4.degree. C. for one hour followed
by two washes with PBS/2% Fetal bovine serum/2 mM Calcium Chloride.
Cells were then treated with florochrome-labeled secondary
antibodies at 4.degree. C. followed by one wash. The cells were
resuspended in 50 .mu.l of PBS/2% FBS and antibody binding was
analyzed using a FACSCalibur.TM. instrument.
[0444] 2.2 Antibody Drug Conjugate Screening of Fully Human
Antibodies Derived from XenoMouse.RTM. Hybridomas
[0445] Cell killing through antibody drug conjugates requires the
delivery of the conjugate into a cell through internalization and
the catabolism of the drug-conjugate into a form that it is toxic
to the cell. To identify antibodies with these properties,
CDH19-positive cell lines (Colo-699 or CHL-1) were seeded at low
cell densities and allowed to adhere overnight in a 384 well plate.
XENOMOUSE.RTM. hybridoma samples containing fully human anti-CDH19
antibodies were then added to these cells in the presence of a high
concentration of a goat anti-human Fc monovalent Fab conjugated
with DM1 (DM1-Fab) at a relatively low drug-antibody ratio (DAR)
(.about.1.3). The cells were incubated for 96 hours at 37.degree.
C. and 5% CO.sub.2 in the presence of the antibody samples and the
DM1-Fab. At the end of this time, the cell viability was assessed
using the CellTiter-Glo.RTM. Luminescent Cell Viability reagent
(Promega) according to manufacturer's recommendations.
[0446] An example of the cell viability data with the Colo-699
cells is shown in FIG. 1 and FIG. 2. The antibodies capable of
delivering the DM1-Fab to the cells and inhibiting the cell growth
read out with a lower luminescent signal (RLU). The top antibodies
of interest from this screen are observed in the lower left corner
of FIG. 1 and are denoted as open circles. These antibodies were
taken forward into a cell viability assay on CHL-1 cells. The
average cell viability data from the CHL-1 assay is plotted against
the average cell viability data from the Colo-699 assay (FIG. 2).
The antibodies that had activity on both the Colo-699 and the CHL-1
cells are denoted as open circles on the left-hand side of the FIG.
2.
[0447] This assay was run concurrently with the FACs antibody
binding assay above (2.2), and the results from these two studies
were used to select the antibodies for further characterization. In
total, 1570 antibodies were run through these cell based viability
assays and approximately 44 antibodies were selected on the bases
of in vitro cell killing and/or antibody binding for sub-cloning, V
gene sequencing and expressed in recombinant form for further
characterization assays as described below.
[0448] These 44 antibodies were again assayed as in Example 2 and
19 antibodies were selected that contained unique sequences. Of
these 19 antibodies, 18 antibodies were analyzed and their
properties characterized in Table 2 below. The data in this table
was generated using FACs binding on recombinant human and
cynomologous CDH-19, +/-Calcium (Ca.sup.+2) binding data on
293/CDH-19 transfectants, binding to endogenous CDH-19 on CHL-1 and
Colo699 tumor cells and competition with the antibody designated as
4A9 in the table. These experiments provided the further
characterizations for the grouping of these antibodies into 5
groups or bins.
TABLE-US-00002 TABLE 2 Binning of Lead panel using Antibody Binding
Information Bin LMR Sequence/ Clone ID Ab ID ID Bin Characteristics
1 13589 4A9 High Endogenous binding, Calcium 13591 4F7 insensitive,
sequence clustered, moderate cyno complete 4A9 competitor 2 13885
19B5 High Endogenous binding, Calcium 13880 25F8 insensitive,
sequence clustered, Good cyno, 13882 26D1 partial 4A9 competitor
13881 26F12=27B3 13878 16H2=20D3=23E7 13879 22D1 3 13877 22G10 High
Endogenous binding, moderate 293 13874 17H8=23B6=28D10 binding,
Calcium insensitive, 2 sequence 13883 25G10 clusters, moderate
cyno, partial 13875 16C1 4A9 competitor, 22G10 best binder in bin.
4 13590 4B10 Low Endogenous and recombinant binding, 13586 4F3
Calcium sensitive, sequence diverse group, 13592 4A2 comparable
cyno, No 4A9 competition 13884 23A10 13588 2G6 5 13876 16A4 Best
endogenous binder, moderate recombinant binder, calcium
insensitive, very weak cyno, No 4A9 competition.
[0449] Of these 18 antibodies. 8 antibodies were selected for
further analysis of their epitope binding as described below. At
least one representative antibody from each bin was selected for
further analysis.
Example 3--Epitope Prediction
[0450] Epitope Prediction by 4A9 Antibody Competition and by
Human/Mouse Cadherin-19 Chimeras
[0451] A 4A9 binding competition method was developed to identify
antibodies that compete with 4A9 binding. In 96-well V-bottom
plates (Sarstedt #82.1583.001), 50,000 transiently transfected 293T
cells were incubated with 5 ug/ml of purified anti-CDH19 antibodies
for 1 hr at 4.degree. C. followed by one wash with PBS/2% FBS. 25
.mu.l of 5 pg/ml Alexa647-labelled 4A9 was then added to each well
and the plates incubated for 1 hour at 4.degree. C. Cells were then
washed two times and the amount of cell associated
Alexa647-labelled 4A9 was quantitated by flow cytometry.
[0452] The experiments included negative controls consisting of
PBS/2% FBS only. The average signal observed in these negative
control experiments was adopted as the maximum possible signal for
the assay. Antibodies were compared to this maximum signal and a
percent inhibition was calculated for each well (%
Inhibition=(1-(FL4 Geomean with the anti-CDH19 antibodies/Maximum
FL4 Geomean signal)).
[0453] Domain binding was determined by flow cytometry as above on
293T cells transiently transfected with plasmids consisting of
single or dual human CDH19 cadherin repeat domain replacements into
the mouse Cadherin19 backbone cloned into the pTT5 expression
vector immediately preceded by native human or murine CDH19 leader
sequences and a Flag tag (SEQ ID NO: 968). The experiment included
assaying the anti-CDH19 antibodies against mouse Cadherin19 to
determine suitability for binning on these human/mouse
chimeras.
[0454] The data from these experiments are presented in the Table
below entitled as follows:
TABLE-US-00003 TABLE 3 Calcium Sensitive Binding and Epitope
Prediction Summary Hu Hu Hu Hu Mu Ca2+ Competes EC1- Hu EC1- Hu
EC2- Hu EC4- Hu EC1- Predicted Clone Sensitive with 4A9 5 EC1 2 EC2
3 EC3 5 EC5 5 Epitope ID Ab ID Bin Binding (13589) A B C D E F G H
I Region 4A9 13589 1 No Yes + + + - - - - - - 44-141 14056 1 No Yes
+ + + - - - - - - 14057 1 No Yes + + + - - - - - - 25F8 13880 2 No
Yes + + + - - - - - - 14094 2 No Yes + + + - - - - - - 14096 2 No
Yes + + + - - - - - - 26D1 13882 2 No Yes + + + - - - - - - 14088 2
No Yes + + + - - - - - - 17H8 13874 3 No Yes + + + - - - - - -
14045 3 No Yes + + + - - - - - - 14048 3 No Yes + + + - - - - - -
4A2 13592 4 Yes No + - - - + + - - - 250-364 14026 4 Yes No + - - -
+ + - - - 4B10 13590 4 Yes No + - - - + + - - - 14055 4 Yes No + -
- - + + - - - 14054 4 Yes No + - - - + + - - - 2G6 13588 4 Yes No +
+ + + + + + + + un- 14304 4 Yes No + + + + + + + + + assignable
14039 4 Yes No + + + + + + + + + 16A4 13876 5 No No + + + - - - - -
- Unassigned 14071 5 No No + + + - - - - - - complex epitope Rat
anti-FLAG + + + + + + + + + Legend Table 3 Human and/or murine
chimera constructs A = huCDH19(44-772) (see SEQ ID NO: 944) B =
huCDH19(44-141)::muCDH19(140-770) (see SEQ ID NO: 952) C =
huCDH19(44-249)::muCDH19(248-770) (see SEQ ID NO: 954) D =
muCDH19(44-139)::huCDH19(142-249)::muCDH19(248-770) (see SEQ ID NO:
956) E = muCDH19(44-139)::huCDH19(142-364)::muCDH19(363-770) (see
SEQ ID NO: 958) F =
muCDH19(44-247)::huCDH19(250-364)::muCDH19(363-770) (see SEQ ID NO:
960) G = muCDH19(44-362)::huCDH19(365-772) (see SEQ ID NO: 962) H =
muCDH19(44-461)::huCDH19(464-772) (see SEQ ID NO: 964) I =
muCDH19(44-770) (see SEQ ID NO: 966)
Epitope Prediction by Human/Chicken Cadherin-19 Chimeras
[0455] Domain binding was determined by flow cytometry on 293T
cells transiently transfected with plasmids consisting of single
human CDH19 cadherin repeat domain replacements into the chicken
Cadherin19 backbone cloned into the pTT5 expression vector
immediately preceded by native human or chicken CDH19 leader
sequences and a Flag tag. The experiment included assaying a subset
of anti-CDH19 antibodies against chicken Cadherin19 to determine
suitability for binning on these human/chicken chimeras.
[0456] The following binding assay was completed in presence of 2
mM CaCl2). In 96-well V-bottom plates (Costar 3897), 50,000
transiently transfected 293T cells were incubated with 5 ug/ml of
purified anti-CDH19 antibodies for 1 hr at 4.degree. C. followed by
two washes with PBS/2% FBS. 50 .mu.l of 5 pg/ml Alexa647-labelled
anti-human IgG secondary antibody (Jackson Immuno 109-605-098) and
2 ug/ml 7AAD (Sigma A9400) was then added to each well and the
plates incubated for 15 minutes at 4.degree. C. Cells were then
washed one time and the amount of cell associated Alexa647-labelled
Ab was quantitated by flow cytometry. The experiments included mock
transfected controls. The data from these experiments are presented
in the Table below, n.d.=not determined.
TABLE-US-00004 TABLE 4 Antibody Bin C Epitope Prediction Summary Hu
Ck Hu Hu Hu Hu EC1-5 EC1-5 EC1 EC2 EC3 EC5 Predicted Clone ID Ab.
ID Bin A J K L M O Epitope Region 4A9 13589 1 + - + - - - 44-141
26F12 13881 2 + - + - - - Bin A 25F8 14096 2 + - + - - - 26D1 13882
2 + - + - - - 17H8 13874 3 + - + - - - 16A4 14071 5 + - + - - - 4A2
13592 4 + - - - + - 250-364 4B10 13590 4 + - - - + - Bin B 2G6
13588 4 + - - - + - 23A10 14077 4 + - - - + - Rat anti-FLAG + + + +
+ + control Positive Binding (+) Negative Binding (-) Legend Table
4 Human and/or chicken chimera constructs A = huCDH19(44-772) (see
SEQ ID NO: 944) J = ckCDH19(44-776) (see SEQ ID NO: 1451) K =
huCDH19(44-141)::ckCDH19(142-776) (see SEQ ID NO: 1452) L =
ckCDH19(44-141)::huCDH19(142-249)::ckCDH19(250-776) (see SEQ ID NO:
1453) M = ckCDH19(44-249)::huCDH19(250-364)::ckCDH19(365-776) (see
SEQ ID NO: 1454) N =
ckCDH19(44-364)::huCDH19(365-463)::ckCDH19(469-776) (see SEQ ID NO:
1455) O = ckCDH19(44-468)::huCDH19(464-772) (see SEQ ID NO:
1456)
Epitope Prediction by Macaque/Dog or Rat/Macaque Cadherin-19
Chimeras
[0457] Domain binding was determined by flow cytometry on 293T
cells transiently transfected with plasmids consisting of rhesus
macaque CDH19 cadherin repeat domain 1 or segments domain 1
(designated EC1a, EC1b, EC1c) replacements into the dog Cadherin19
backbone, or rat CDH19 cadherin repeat domain 2 replacement into
the rhesus Cadherin19 backbone cloned into the pTT5 expression
vector immediately preceded by native rhesus or canine CDH19 leader
sequences and a Flag tag. The experiment included assaying a subset
of anti-CDH19 antibodies against dog, rat and macaque Cadherin19 to
determine suitability for binning on these macaque/dog and
rat/rhesus chimeras.
[0458] The following binding assay was completed in presence of 2
mM CaCl2. In 96-well V-bottom plates (Costar 3897), 50,000
transiently transfected 293T cells were incubated with 5 ug/ml of
purified anti-CDH19 antibodies for 1 hr at 4.degree. C. followed by
two washes with PBS/2% FBS. 50 .mu.l of 5 pg/ml Alexa647-labelled
anti-human IgG secondary antibody (Jackson Immuno 109-605-098) and
2 ug/ml 7AAD (Sigma A9400) was then added to each well and the
plates incubated for 15 minutes at 4.degree. C. Cells were then
washed one time and the amount of cell associated Alexa647-labelled
Ab was quantitated by flow cytometry. The experiments included mock
transfected controls. The data from these experiments are presented
in the Table below, n.d.=not determined.
TABLE-US-00005 TABLE 5 Antibody BinA Epitope prediction Summary Rh
Ca rh rh rh ra Ra Predicted EC1-5 EC1-5 EC1 EC1a EC1b EC2 EC1-5
Epitope Clone ID Ab. ID Bin P Q R S T V W Region 4A9 13589 1 + - +
- - - - 44-141 Bin A.1 26F12 13881 2 + - + + + - - 44-141 25F8
14096 2 + - + + + - - Bin A.2 26D1 13882 2 + - + + + - - (44-114)
17H8 13874 3 + - + + - - - 44-141 16A4 14071 5 + - + + - n.d. + Bin
A.3 (44-65) 4A2 13592 4 + - n.d. n.d. n.d. n.d. + 250-364 4B10
13590 4 + + n.d. n.d. n.d. n.d. + Bin B 2G6 13588 4 + + n.d. n.d.
n.d. n.d. + 23A10 14077 4 + + n.d. n.d. n.d. n.d. + Rat anti-FLAG +
+ + + + + + Positive Binding (+) Negative Binding (-) Not
Determined (n.d.) Legend Table 5 Rhesus macaque, dog, and/or rat
chimera constructs P = rhCDH19(44-772) (see SEQ ID NO: 1457) Q =
caCDH19(44-770) (see SEQ ID NO: 1458) R =
rhCDH19(44-141)::caCDH19(141-770) (see SEQ ID NO: 1459) S =
rhCDH19(44-65)::caCDH19(65-770) (see SEQ ID NO: 1460) T =
caCDH19(44-87)::rhCDH19(89-114)::caCDH19(115-770) (see SEQ ID NO:
1461) U = caCDH19(44-120)::rhCDH19(122-137)::caCDH19(137-770) (see
SEQ ID NO: 1462) V =
rhCDH19(44-141)::raCDH19(140-247)::rhCDH19(250-772) (see SEQ ID NO:
1463) W = raCDH19(44-770) (see SEQ ID NO: 1464)
[0459] The data summarized in table 5 allowed for segregating the
binder of Bin A 44-141 into the following subgroups:
Bin A.1 44-141
Bin A.2 44-141 (44-114)
Bin A.3 44-141 (44-65)
Epitope Prediction by Rat/Mouse or Human/Mouse Cadherin-19
Chimeras
[0460] Domain binding was determined by flow cytometry on 293T
cells transiently transfected with plasmids consisting of rat CDH19
cadherin repeat domain 3 substitutions (designated EC3a, EC3b) or
human CDH19 cadherin repeat domain 3 substitution (designated EC3c)
into the mouse Cadherin19 backbone cloned into the pTT5 expression
vector immediately preceded by native mouse CDH19 leader sequence
and a Flag tag. The experiment included assaying a subset of
anti-CDH19 antibodies against human, rat and mouse Cadherin19 to
determine suitability for binning on these rat/mouse and
human/mouse chimeras.
[0461] The following binding assay was completed in presence of 2
mM CaCl2). In 96-well V-bottom plates (Costar 3897), 50,000
transiently transfected 293T cells were incubated with 5 ug/ml of
purified anti-CDH19 antibodies for 1 hr at 4.degree. C. followed by
two washes with PBS/2% FBS. 50 .mu.l of 5 pg/ml Alexa647-labelled
anti-human IgG secondary antibody (Jackson Immuno 109-605-098) and
2 ug/ml 7AAD (Sigma A9400) was then added to each well and the
plates incubated for 15 minutes at 4.degree. C. Cells were then
washed one time and the amount of cell associated Alexa647-labelled
Ab was quantitated by flow cytometry. The experiments included mock
transfected controls. The data from these experiments are presented
in the Table below, n.d.=not determined.
TABLE-US-00006 TABLE 6 Antibody Bin B Epitope Prediction Summary Hu
Mo Ra Ra Ra Hu Predicted EC1-5 EC1-5 EC1-5 EC3c EC3b EC3a Epitope
Clone ID Ab. ID Bin A I W X Y Z Region 4A9 13589 1 + - - n.d. n.d.
n.d. 44-141 26F12 13881 2 + - - n.d. n.d. n.d. Bin A 25F8 14096 2 +
- - n.d. n.d. n.d. 26D1 13882 2 + - - n.d. n.d. n.d. 17H8 13874 3 +
- - n.d. n.d. n.d. 16A4 14071 5 + - + n.d. n.d. n.d. 4A2 13592 4 +
- + + - - 250-364 4B10 13590 4 + - + + - - (324-327) Bin B.2 2G6
13588 4 + + + + + + 250-364 23A10 14077 4 + + + n.d. n.d. n.d. Bin
B.1 Rat anti-FLAG + + + + + + control Positive Binding (+) Negative
Binding (-) Not Determined (n.d.) Legend Table 6 Rat/mouse or
human/mouse chimera constructs A = huCDH19(44-772) (see SEQ ID NO:
944) I = muCDH19(44-770) (see SEQ ID NO: 966) W = raCDH19(44-770)
(see SEQ ID NO: 1464) X =
muCDH19(44-323)::raCDH19(324-327)::muCDH19(328-770) (see SEQ ID NO:
1465) Y = muCDH19(44-770)::raCDH19(290, 299, 308) (see SEQ ID NO:
1466) Z = muCDH19(44-770)::huCDH19(271) (see SEQ ID NO: 1467)
[0462] The data summarized in table 6 allowed for segregating the
binder of Bin B 250-364 into the following subgroups:
Bin B.1 250-364
[0463] Bin B.2 250-364 (324-327) by rodent numeration as referenced
in table 6, corresponding to residues (326-329) within human and
macaque CDH19
Example 4--Hotspot/Covariant Mutants
[0464] A total of 18 antibodies were analyzed for potential
hotspots and covariance violations. The designed variants (shown
below) outline amino acid substitutions capable of reducing and/or
avoiding isomerization, deamidation, oxidation, covariance
violations, and the like. The 80 engineered variants together with
the 15 parental antibodies, thus totaling 95 sequences, were taken
forward to the cloning, expression, and purification processes.
Site-directed mutagenesis was performed on the engineered variants
in a 96-well format. The parental antibodies and engineered
variants were expressed by high throughput transient transfection
in HEK 293-6E cells, purified using a modified AKTA auto-sampler
and assayed for activity and biophysical characteristics. The 3
parental antibodies that had either free (unpaired) Cys or
N-glycosylation site were not taken forward in this process. Those
were replaced with the engineered version of the parental
antibodies. The designed variants outline amino acid substitutions
capable of reducing and/or avoiding isomerization, deamidation,
oxidation, covariance violations, immunogenicity and the like. It
will be appreciated that these variant sequences are examples of
engineered antibodies within the meaning of the present application
but single point and/or multiple point mutations can be combined in
any combinatorial manner in order to arrive at a final desired
antigen binding molecule or antibody.
Example 5--CDH19 mRNA Expression Pattern
[0465] RNA was extracted from individual patient tissues
representing tumor (>70% tumor content by cell count) or normal
(0% tumor content by cell count). Individual tissues were
homogenized using TisssueLyzer (Qiagen, Valencia, Calif.) and total
RNA extracted and purified by the mirVana total RNA extraction kit
(Life Technologies, Foster City, Calif.). RNA quality and quantity
checked by NanoDrop (NanoDrop, Wilmington, Del.) spectrophotometer
readings and Bioanalyzer RNA profiling (Agilient Technologies,
Santa Clara, Calif.). RNA was DNAse treated with DNA-free kit (Life
Technologies, Foster City, Calif.) and reverse transcribed
according to manufacturer's specifications using random hexamers in
the High Capacity cDNA Reverse Transcription Kit (Life
Technologies, Foster City, Calif.). Quantitative Real Time
Polymerase Chain Reaction (qRT-PCR) was performed on cDNA using
primers to CDH19, probeset Hs00253534_m1, (Life Technologies,
Foster City, Calif.) or the housekeeping gene human ACTB (primers
CCT GGC ACC CAG CAC AA; GCC GAT CCA CAC GGA GTA CT; probe ATC AAG
ATC ATT GCT CCT CCT GAG CG). 10 .mu.L qRT-PCR reaction components;
1.0 ng/.mu.L cDNA, 2.times.Universal PCR Master Mix (Life
Technologies, Foster City, Calif.), gene expression assay (ACTB; 75
nM primers, 150 nM probe. EPOR; 300 nM primers, 250 nM probe)
Following the qRT-PCR amplification program: (1) activation at
50.degree. C. for 2 min; (2) denaturation at 95.degree. C. for 10
min; (3) amplification 40 cycles at 95.degree. C. for 15 s and
60.degree. C. for 1 min with fluorescence capture at each step (ABI
PRISM 7900HT Sequence Detection Systems, Applied Biosystems).
Threshold cycle values (C.sub.T) were determined, using Sequence
Detector software version 2.3 (Applied Biosystems) and transformed
to 2.sup.-.DELTA.CT for relative expression of CDH19 specific
transcript to ACTB. The results are shown in FIG. 3. Of 54 unique
metastatic and primary melanoma samples, the majority can be seen
to overexpress CDH19 mRNA relative to the expression in samples
from normal tissue.
Example 6--CDH19 Protein Expression
[0466] Expression of CDH19 protein was analyzed in human tumor
samples by IHC and the results are shown in FIG. 4. Samples were
fixed in 10% neutral buffered formalin for 24 hours, dehydrated and
paraffin embedded. 4 .mu.m sections were cut. Sections were
deparaffinized first and then heated in DIVA Decloaker solution
(Biocare) for 40 minutes for antigen retrieval. Remaining IHC steps
were performed at room temperature in a DAKO Autostainer. Sections
were incubated for 10 minutes with Peroxidazed 1 (Biocare) to block
endogenous peroxidase, followed by incubation for 10 minutes with
background sniper (Biocare) to reduce nonspecific background.
Section were incubated for 60 minutes with CDH19 antibody (Novo
Biologicals, Catalog # H00028513-B01P) at 5 pg/ml, then incubated
for 30 minutes with Envision+ HRP anti-mouse polymer (DAKO),
followed by DAB+(DAKO) for 5 minutes. Sections were counterstained
with hematoxylin (DAKO) approximately for 1 minute. CDH19
expression could be detected in 62% of tumors examined (staining
intensity .gtoreq.1+ in 101 of 162 samples). 51% of the tumor
samples demonstrated medium to high expression (staining intensity
of 2+ to 3+ in 83 of 162 samples). CDH19 showed dense and distinct
membrane staining in many samples, although in some tumors
heterogeneity was noted.
Example 7--Selection of Model Cell Lines
[0467] Tumor cell lines were analyzed by flow cytometry and IHC to
identify model systems with CDH19 expression similar to human
tumors. Human anti-huCDH19 IgG4 antibody 4A2 was purified directly
from hybridoma conditioned media. For flow cytometry,
2.times.10.sup.5 cells were incubated with 200 nM of the CDH19 4A2
antibody that was conjugated to PE at a 1:1 ratio. The incubation
and subsequent wash steps were performed in the presence of 1.2 mM
calcium. A tube of QuantiBRITE PE lyophilized beads with four
levels of PE (BD, cat #340495) was simultaneously prepared
according to the manufacturer's instructions. The beads were
analyzed by flow cytometry to generate a standard curve. The PE
median values obtained from the melanoma lines after FACS analysis
were then calibrated against the standard curve to calculate the
antibodies bound per cell (ABC), which provides an estimate of the
number of receptors on each cell. IHC was performed as described in
Example 6 and the results are provided in FIG. 5. The melanoma cell
line CHL-1 expresses about 10,000 CDH19 molecules on the cell
surface, while Colo699 cells express about 5,000 receptors.
[0468] Both cell lines represent tumors with medium to high
expression levels based on IHC. Expression in A2058 is very low,
while LOX cells do not express any detectable CDH19 protein.
Example 8
[0469] Bispecific Binding and Interspecies Cross-Reactivity
[0470] For confirmation of binding to human CDH19 and to human and
macaque CD3, bispecific antibodies were tested by flow cytometry
using indicated cell lines. L1.2 transfected with human CDH19, the
human melanoma cell lines CHL-1 and A2058 expressing native human
CDH19, CD3-expressing human T cell leukemia cell line HPB-ALL
(DSMZ, Braunschweig, ACC483) and the CD3-expressing macaque T cell
line 4119LnPx (Knappe A, et al., Blood, 2000, 95, 3256-3261) were
used as antigen positive cell lines. Moreover, untransfected L1.2
cells were used as negative control.
[0471] For flow cytometry 200,000 cells of the respective cell
lines were incubated for 30 min on ice with 50 .mu.l of purified
bispecific antibody at a concentration of 5 pg/ml. The cells were
washed twice in PBS/2% FCS and binding of the constructs was
detected with a murine PentaHis antibody (Qiagen; diluted 1:20 in
50 .mu.l PBS/2% FCS). After washing, bound PentaHis antibodies were
detected with an Fc gamma-specific antibody (Dianova) conjugated to
phycoerythrin, diluted 1:100 in PBS/2% FCS. Samples were measured
by flow cytometry on a FACSCanto II instrument and analyzed by
FACSDiva software (both from Becton Dickinson).
[0472] The CDH19/CD3 bispecific antibodies stained L1.2 cells
transfected with human CDH19, the human CDH19-expressing melanoma
cell lines CHL-1 and A2058 as well as human and macaque T cells.
Moreover, there was no staining of untransfected L1.2 cells (see
FIG. 6).
Example 9
[0473] Cytotoxic Activity
[0474] FACS-Based Cytotoxicity Assay with Unstimulated Human
PBMC
[0475] Isolation of Effector Cells
[0476] Human peripheral blood mononuclear cells (PBMC) were
prepared by Ficoll density gradient centrifugation from enriched
lymphocyte preparations (e.g. buffy coats), a side product of blood
banks collecting blood for transfusions. Buffy coats were supplied
by a local blood bank and PBMC were prepared on the same day of
blood collection. After Ficoll density centrifugation and extensive
washes with Dulbecco's PBS (Gibco), remaining erythrocytes were
removed from PBMC via incubation with erythrocyte lysis buffer (155
mM NH.sub.4Cl, 10 mM KHCO.sub.3, 100 .mu.M EDTA). Platelets were
removed via the supernatant upon centrifugation of PBMC at
100.times.g. Remaining lymphocytes mainly encompass B and T
lymphocytes, NK cells and monocytes. PBMC were kept in culture at
37.degree. C./5% CO.sub.2 in RPMI medium (Gibco) with 10% FCS
(Gibco).
[0477] Depletion of CD14.sup.+ and CD56.sup.+ Cells
[0478] For depletion of CD14.sup.+ cells, human CD14 MicroBeads
(Milteny Biotec, MACS, #130-050-201) were used, for depletion of NK
cells human CD56 MicroBeads (MACS, #130-050-401). PBMC were counted
and centrifuged for 10 min at room temperature with 300.times.g.
The supernatant was discarded and the cell pellet resuspended in
MACS isolation buffer [80 .mu.L/10.sup.7 cells; PBS (Invitrogen,
#20012-043), 0.5% (v/v) FBS (Gibco, #10270-106), 2 mM EDTA
(Sigma-Aldrich, # E-6511)]. CD14 MicroBeads and CD56 MicroBeads (20
.mu.L/10.sup.7 cells) were added and incubated for 15 min at
4-8.degree. C. The cells were washed with MACS isolation buffer
(1-2 mL/10.sup.7 cells). After centrifugation (see above),
supernatant was discarded and cells resuspended in MACS isolation
buffer (500 .mu.L/10.sup.8 cells). CD14/CD56 negative cells were
then isolated using LS Columns (Miltenyi Biotec, #130-042-401).
PBMC w/o CD14+/CD56+ cells were cultured in RPMI complete medium
i.e. RPMI1640 (Biochrom AG, # FG1215) supplemented with 10% FBS
(Biochrom AG, # S0115), 1.times. non-essential amino acids
(Biochrom AG, # K0293), 10 mM Hepes buffer (Biochrom AG, # L1613),
1 mM sodium pyruvate (Biochrom AG, # L0473) and 100 U/mL
penicillin/streptomycin (Biochrom AG, # A2213) at 37.degree. C. in
an incubator until needed.
[0479] Target Cell Labeling
[0480] For the analysis of cell lysis in flow cytometry assays, the
fluorescent membrane dye DiOC.sub.18 (DiO) (Molecular Probes, #
V22886) was used to label human CDH19- as target cells and
distinguish them from effector cells. Briefly, cells were
harvested, washed once with PBS and adjusted to 10.sup.6 cell/mL in
PBS containing 2% (v/v) FBS and the membrane dye DiO (5
.mu.L/10.sup.6 cells). After incubation for 3 min at 37.degree. C.,
cells were washed twice in complete RPMI medium and the cell number
adjusted to 1.25.times.10.sup.5 cells/mL. The vitality of cells was
determined using 0.5% (v/v) isotonic EosinG solution (Roth,
#45380).
[0481] Flow Cytometry Based Analysis
[0482] This assay was designed to quantify the lysis of human
CDH19-transfected CHO cells in the presence of serial dilutions of
CDH19 bispecific antibodies.
[0483] Equal volumes of DiO-labeled target cells and effector cells
(i.e., PBMC w/o CD14.sup.+ cells) were mixed, resulting in an E:T
cell ratio of 10:1. 160 .mu.L of this suspension were transferred
to each well of a 96-well plate. 40 .mu.L of serial dilutions of
the CDH19 bispecific antibodies and a negative control bispecific
(an CD3-based bispecific antibody recognizing an irrelevant target
antigen) or RPMI complete medium as an additional negative control
were added. The bispecific antibody-mediated cytotoxic reaction
proceeded for 48 hours in a 7% CO.sub.2 humidified incubator. Then
cells were transferred to a new 96-well plate and loss of target
cell membrane integrity was monitored by adding propidium iodide
(PI) at a final concentration of 1 pg/mL. PI is a membrane
impermeable dye that normally is excluded from viable cells,
whereas dead cells take it up and become identifiable by
fluorescent emission.
[0484] Samples were measured by flow cytometry on a FACSCanto II
instrument and analyzed by FACSDiva software (both from Becton
Dickinson).
[0485] Target cells were identified as DiO-positive cells.
PI-negative target cells were classified as living target cells.
Percentage of cytotoxicity was calculated according to the
following formula:
Cytotoxicity [ % ] = n dead target cells n target cells .times. 100
##EQU00001## n = number of events ##EQU00001.2##
[0486] Using GraphPad Prism 5 software (Graph Pad Software, San
Diego), the percentage of cytotoxicity was plotted against the
corresponding bispecific antibody concentrations. Dose response
curves were analyzed with the four parametric logistic regression
models for evaluation of sigmoid dose response curves with fixed
hill slope and EC50 values were calculated. The results are shown
in FIG. 7.
Example 10
[0487] In Vivo Tumor Growth Inhibition Experiments
[0488] 5 million Colo699 or CHL-1 tumor cells were admixed with 2.5
million freshly isolated peripheral blood mononuclear cells (PBMC)
and injected subcutaneously in the left flank of female athymic
nude mice on Day 0. The same day, mice were treated
intraperitoneally with either CDH19 BiTE 2G6 or non-specific
control BiTE (MEC14) at the indicated doses. Dosing continued daily
for the first 10 days post-tumor inoculation.
[0489] Tumor volumes and body weights were measured twice per week
using calipers and an analytical scale, respectively.
[0490] The results of experiments with Colo699 or CHL-1 tumor cells
are shown in FIGS. 8 and 9.
SEQUENCE TABLE
TABLE-US-00007 [0491] TABLE Ia HEAVY CHAIN CDRs Ab Type CDR 1 CDR 2
CDR 3 1D10 NA AGCTATGGCATGCAC GTTATATGGTATGATGGAAGT
AGGGCCGGTATAATAGGAAC 2C12 SEQ ID NO: 1 AATAAATACTATGCAGACTCC
TACAGGCTACTACTACGGTA GTGAAGGGC TGGACGTC SEQ ID NO: 2 SEQ ID NO: 3
AA SYGMH VIWYDGSNKYYADSVKG RAGIIGTTGYYYGMDV SEQ ID NO: 4 SEQ ID NO:
5 SEQ ID NO: 6 1F10 NA AGTGGTGGTTACTACT TACATCTATTACAGTGGGAGC
GATGGAAGCAGTGGCTGGTA GGAGC ACCTACTACAACCCGTCCCTC CTTCCAGCAC SEQ ID
NO: 7 ACGAGT SEQ ID NO: 9 SEQ ID NO: 8 AA SGGYYWS YIYYSGSTYYNPSLTS
DGSSGWYFQH SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 2C12_LC#1 NA
AGCTATGGCATGCAC GTTATATGGTATGATGGAAGT AGGGCCGGTATAATAGGAAC SEQ ID
NO: 13 AATAAATACTATGCAGACTCC TACAGGCTACTACTACGGTA GTGAAGGGC
TGGACGTC SEQ ID NO: 14 SEQ ID NO: 15 AA SYGMH VIWYDGSNKYYADSVKG
RAGIIGTTGYYYGMDV SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 2G6_LC#1
NA AGCTATGGCATGCAC TTTATATGGTATGATGGAAGT AGGGCCGGTATAATAGGAAC SEQ
ID NO: 19 AATAAATACTATGCAGACTCC TATAGGCTACTACTACGGTA GTGAAGGAC
TGGACGTC SEQ ID NO: 20 SEQ ID NO: 21 AA SYGMH FIWYDGSNKYYADSVKD
RAGIIGTIGYYYGMDV SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 2G6 NA
AGCTATGGCATGCAC TTTATATGGTATGATGGAAGT AGGGCCGGTATAATAGGAAC SEQ ID
NO: 25 AATAAATACTATGCAGACTCC TATAGGCTACTACTACGGTA GTGAAGGAC
TGGACGTC SEQ ID NO: 26 SEQ ID NO: 27 AA SYGMH FIWYDGSNKYYADSVKD
RAGIIGTIGYYYGMDV SEQ ID NO: 28 SEQ ID NO: 29 SEQ ID NO: 30 2H12 NA
AGCTATGGCATGCAC GTTATATGGTATGATGGAAGT AGGGCCGGTATAATAGGAAC SEQ ID
NO: 31 AATAAATACTATACAGACTCC TACAGGCTACTACTACGGTA GTGAAGGGC
TGGACGTC SEQ ID NO: 32 SEQ ID NO: 33 AA SYGMH VIWYDGSNKYYTDSVKG
RAGIIGTTGYYYGMDV SEQ ID NO: 34 SEQ ID NO: 35 SEQ ID NO: 36
2H12_LC#2 NA AGCTATGGCATGCAC GTTATATGGTATGATGGAAGT
AGGGCCGGTATAATAGGAAC SEQ ID NO: 37 AATAAATACTATACAGACTCC
TACAGGCTACTACTACGGTA GTGAAGGGC TGGACGTC SEQ ID NO: 38 SEQ ID NO: 39
AA SYGMH VIWYDGSNKYYTDSVKG RAGIIGTTGYYYGMDV SEQ ID NO: 40 SEQ ID
NO: 41 SEQ ID NO: 42 4A2 NA AGTAGTGGTTACTACT TACATCTATTACACTGGGAGC
GATGGAAGCAGTGGCTGGTA 5B4 GGAGC GCCTACTACAACCCGTCCCTC CTTCCAGTAT 5C5
SEQ ID NO: 43 AAGAGT SEQ ID NO: 45 SEQ ID NO: 44 AA SSGYYWS
YIYYTGSAYYNPSLKS DGSSGWYFQY SEQ ID NO: 46 SEQ ID NO: 47 SEQ ID NO:
48 4A9 NA GGTTACTACTGGAGC TATTTCTCTTACAGTGGGAGC
AACTGGGCCTTCCACTTTGA SEQ ID NO: 49 ACCAACTACAACCCCTCCCTC CTTC
AAGAGT SEQ ID NO: 51 SEQ ID NO: 50 AA GYYWS YFSYSGSTNYNPSLKS
NWAFHFDF SEQ ID NO: 52 SEQ ID NO: 53 SEQ ID NO: 54 4B10 NA
AGCTATGACATGCAC GTTATATCATATGATGGAACT GAACGATATTTTGACTGGTC 4C2 SEQ
ID NO: 55 AATGAATACTATGCAGACTCC TTTTGACTAC GTGAAGGGC SEQ ID NO: 57
SEQ ID NO: 56 AA SYDMH VISYDGTNEYYADSVKG ERYFDWSFDY SEQ ID NO: 58
SEQ ID NO: 59 SEQ ID NO: 60 4D2 NA AGTTATGACATGCAC
GTTATATCATATGATGGAACT GAACGATATTTTGACTGGTC SEQ ID NO: 61
AATGAATACTATGCAGACTCC TTTTGACTAC GTGAAGGGC SEQ ID NO: 63 SEQ ID NO:
62 AA SYDMH VISYDGTNEYYADSVKG ERYFDWSFDY SEQ ID NO: 64 SEQ ID NO:
65 SEQ ID NO: 66 4D3 NA AGCTATGACATGGAC GTTATATGGTATGATGGAAGT
GAAACTGGGGAGGgCTGGTA 4F3 SEQ ID NO: 67 AATAAAtacTATGCAGACTCC
CTTCGAtctc GTGAGGGGC SEQ ID NO: 69 SEQ ID NO: 68 AA SYDMD
VIWYDGSNKYYADSVRG ETGEGWYFDL SEQ ID NO: 70 SEQ ID NO: 71 SEQ ID NO:
72 4E10 NA AGCTATGACATGCAC GTTATATGGTATGATGGAAGT
GAGTATAGGTACAGCTGGTA SEQ ID NO: 73 AATAAATACTATGCAGACTCC CTTTGACTAC
GTGAAGGGC SEQ ID NO: 75 SEQ ID NO: 74 AA SYDMH VIWYDGSNKYYADSVKG
EYRYSWYFDY SEQ ID NO: 76 SEQ ID NO: 77 SEQ ID NO: 78 4F7 NA
AGTTACTCCTGGAGC TATATCTATTACAGTGGGAGC AACTGGGCCTTCCACTTTGA SEQ ID
NO: 79 ACCAACTACAACCCCTCCCTC CTAC AAGAGT SEQ ID NO: 81 SEQ ID NO:
80 AA SYSWS YIYYSGSTNYNPSLKS NWAFHFDY SEQ ID NO: 82 SEQ ID NO: 83
SEQ ID NO: 84 5E3 NA AGCTATAGCATGCAC TCCATTAGTAGTAGTAGTAGT
GGGGAAACTGGAACTAACTA SEQ ID NO: 85 TACATATACTACGCAGACTCA
CTACTACTACGGTATGGACG GTGAAGGGC TC SEQ ID NO: 86 SEQ ID NO: 87 AA
SYSMH SISSSSSYIYYADSVKG GETGTNYYYYGMDV SEQ ID NO: 88 SEQ ID NO: 89
SEQ ID NO: 90 17H8 NA AGTTACTACTGGAGC TATATCTATTACATTGGGAGC
GATTCCCGGTATAGAAGTGG 23B6 SEQ ID NO: 91 ACCAACTACAACCCCTCCCTC
CTGGTACGATGCTTTTGATA 28D10 AAGAGT TC SEQ ID NO: 92 SEQ ID NO: 93 AA
SYYWS YIYYIGSTNYNPSLKS DSRYRSGWYDAFDI SEQ ID NO: 94 SEQ ID NO: 95
SEQ ID NO: 96 16C1 NA GGTTACTACTGGAGC TATATCTATTACATTGGGAGC
GATGGGAGCAGTGGCTGGTA SEQ ID NO: 97 ACCAACTACAACCCCTCCCTC
CCGGTGGTTCGACCCC AAGAGT SEQ ID NO: 99 SEQ ID NO: 98 AA GYYWS
YIYYIGSTNYNPSLKS DGSSGWYRWFDP SEQ ID NO: 100 SEQ ID NO: 101 SEQ ID
NO: 102 16A4 NA AGTTACTACTGGAGC TATATCTATTACAGTGGGAGC
GATCAAAGGCGGATAGCAGC SEQ ID NO: 103 ACCAATTACAACCCCTCCCTC
AGCTGGTACCCACTTCTACG AAGAGT GTATGGACGTC SEQ ID NO: 104 SEQ ID NO:
105 AA SYYWS YIYYSGSTNYNPSLKS DQRRIAAAGTHFYGMDV SEQ ID NO: 106 SEQ
ID NO: 107 SEQ ID NO: 108 16E2 NA AGCTATGGCATGCAC
GTGATATGGTATGATGGAAGT GACGGGTGGGAGCTGTCCTT 17E10 SEQ ID NO: 109
AATAAATACTATGCAGACTCC TGACTAC 20B12 GTGAAGGGC SEQ ID NO: 111 SEQ ID
NO: 110 AA SYGMH VIWYDGSNKYYADSVKG DGWELSFDY SEQ ID NO: 112 SEQ ID
NO: 113 SEQ ID NO: 114 22G10 NA AGTTATGCCATGAAC
ACTATTAGTGGTGGTGGTGCT GGGGGAATGGGGGGATACTA SEQ ID NO: 115
AACACATACTACGCAGACTCC CTACGGTATGGACGTC GTGAAGGGC SEQ ID NO: 117 SEQ
ID NO: 116 AA SYAMN TISGGGANTYYADSVKG GGMGGYYYGMDV SEQ ID NO: 118
SEQ ID NO: 119 SEQ ID NO: 120 16H2 NA AGCTACTTTATTCAC
ATAATCAACCCTATTAGTGTT GGGGGGATACAGCTATGGTT 20D3 SEQ ID NO: 121
AGCACAAGCTACGCACAGAAG ACATTTTGACTAC 23E7 TTCCAGGGC SEQ ID NO: 123
SEQ ID NO: 122 AA SYFIH IINPISVSTSYAQKFQG GGIQLWLHFDY SEQ ID NO:
124 SEQ ID NO: 125 SEQ ID NO: 126 22D1 NA AGCTACTTTATTCAC
ATAATCAACCCTATTAGTGTT GGGGGGATACAGCTATGGTT SEQ ID NO: 127
AGCACAAGCTACGCACAGAAG ACATTTGGACTAC TTCCAGGGC SEQ ID NO: 129 SEQ ID
NO: 128 AA SYFIH IINPISVSTSYAQKFQG GGIQLWLHLDY SEQ ID NO: 130 SEQ
ID NO: 131 SEQ ID NO: 132 25F8 NA AGCTACTATATTCAC
ATAATCAACCCCAGTGGTGGT GGGGGAATACAGCTATGGTT SEQ ID NO: 133
AGCACAAGGTACGCACAGAAG ACATTttGACTAC TTCCAGGGC SEQ ID NO: 135 SEQ ID
NO 134 AA SYYIH IINPSGGSTRYAQKFQG GGIQLWLHFDY SEQ ID NO: 136 SEQ ID
NO: 137 SEQ ID NO: 138 26F12 NA AACTACTATATGTCC
ATAATCAACCCTAGTGGTGGT GGGGGGATACAACTATGGTT 27B3 SEQ ID NO: 139
GACTCAACCTACGCACAGAAG ACATTTTGACTAC TTCCAGGGC SEQ ID NO: 141 SEQ ID
NO: 140 AA NYYMS IINPSGGDSTYAQKFQG GGIQLWLHFDY SEQ ID NO: 142 SEQ
ID NO: 143 SEQ ID NO: 144 26D1 NA AGCTACTATATGTCC
ATAATCCACCCTAGTGGTGGT GGGGGGATAAAACTATGGTT SEQ ID NO: 145
GACACAACCTACGCACAGAAG ACATTTTGACTAT TTCCAGGGC SEQ ID NO: 147 SEQ ID
NO: 146 AA SYYMS IIHPSGGDTTYAQKFQG GGIKLWLHFDY SEQ ID NO: 148 SEQ
ID NO: 149 SEQ ID NO: 150 25G10 NA GGTTACTACTGGAGC
TATATCTATTACATTGGGAGC GATGGGAGCAGTGGCTGGTA SEQ ID NO: 151
ACCAACTACAACCCCTCCCTC CCGGTGGTTCGACCCC AAGAGT SEQ ID NO: 153 SEQ ID
NO: 152 AA GYYWS YIYYIGSTNYNPSLKS DGSSGWYRWFDP SEQ ID NO: 154 SEQ
ID NO: 155 SEQ ID NO: 156 23A10 NA CGCTATGGCATACAC
GTTATATGGTATGATGGAAGT AGGGCCGGTATACCTGGAAC SEQ ID NO: 157
AATAAATACTATGCAGACTCC TACGGGCTACTACTATGGTA GTGAAGGGC TGGACGTC SEQ
ID NO: 158 SEQ ID NO: 159 AA RYGIH VIWYDGSNKYYADSVKG
RAGIPGTTGYYYGMDV SEQ ID NO: 160 SEQ ID NO: 161 SEQ ID NO: 162 19B5
NA AGCTACTTTATTCAC ATTATCAACCCTATTAGTGTT GGGGGGATACAGCTATGGTT SEQ
ID NO: 163 AGCACAAGCTACGCACAGAAG ACATTTGGACTAC TTCCAGGGC SEQ ID NO:
165 SEQ ID NO: 164 AA SYFIH IINPISVSTSYAQKFQG GGIQLWLHLDY SEQ ID
NO: 166 SEQ ID NO: 167 SEQ ID NO: 168
TABLE-US-00008 TABLE Ib LIGHT CHAIN CDRs Ab Type CDR 1 CDR 2 CDR 3
1D10 NA TCTGGAGATAGATTGG CAAGATACCAAGCGGCCCTCA CAGGCGTGGGACAGCAGCAC
2C12 GGGAAAAATATACTTG SEQ ID NO: 170 TGTGGTA C SEQ ID NO: 171 SEQ
ID NO: 169 AA SGDRLGEKYTC QDTKRPS QAWDSSTVV SEQ ID NO: 172 SEQ ID
NO: 173 SEQ ID NO: 174 1F10 NA AGGGCCAGTCGGAGTA
GGTCCATCCAGCAGGGCCACT CAGCAGTATGGTAGCTCATT TTAGCAGCAGCTACTT SEQ ID
NO: 176 CACT AGCC SEQ ID NO: 177 SEQ ID NO: 175 AA RASRSISSSYLA
GPSSRAT QQYGSSFT SEQ ID NO: 178 SEQ ID NO: 179 SEQ ID NO: 180
2C12_LC#1 NA AGGtCTAGTCAAAGcc AAGGTTTCTAACTGGGactct
ATGCAAGGTATAGTGTGGCC tcgtaTACAGTGATGG SEQ ID NO: 182 GTGCAGT
AAACAcctACTTGAAT SEQ ID NO: 183 SEQ ID NO: 181 AA RSSQSLVYSDGNTYLN
KVSNWDS MQGIVWPCS SEQ ID NO: 184 SEQ ID NO: 185 SEQ ID NO: 186
2G6_LC#1 NA AGGTCTAGTCAAAGCC CAGGTTTCTAACTGGGACTCT
ATGCAAGATACACTGTGGCC TCGTATACAGTGATGG SEQ ID NO: 188 GTGCAGT
AAACACCTACTTGAAT SEQ ID NO: 189 SEQ ID NO: 187 AA RSSQSLVYSDGNTYLN
QVSNWDS MQDTLWPCS SEQ ID NO: 190 SEQ ID NO: 191 SEQ ID NO: 192 2G6
NA TCTGGAGATAGGTTGG CAAGATACCAAGCGGCCCTCA CAGGCGTGGGACAGCAGCAC
GGGAAAAATATACTTG SEQ ID NO: 194 TGTGGTA C SEQ ID NO: 195 SEQ ID NO:
193 AA SGDRLGEKYTC QDTKRPS QAWDSSTVV SEQ ID NO: 196 SEQ ID NO: 197
SEQ ID NO: 198 2H12 NA TCTGGAGATAGATTGG CAAGATACCAAGCGGCCCTCA
CAGGCGTGGGACAGCAGCAC GGGAAAAATATACTTG SEQ ID NO: 200 TGTGGTA C SEQ
ID NO: 201 SEQ ID NO: 199 AA SGDRLGEKYTC QDTKRPS QAWDSSTVV SEQ ID
NO: 202 SEQ ID NO: 203 SEQ ID NO: 204 2H12_LC#2 NA AGGTCTAGTCAAAGCC
AAGGTTTCTAACTGGGACTCT ATGCAAGATACACTGTGGCC TCGTATACAGTGATGG SEQ ID
NO: 206 GTGCAGT AAACACCTACTTGAAT SEQ ID NO: 207 SEQ ID NO: 205 AA
RSSQSLVYSDGNTYLN KVSNWDS MQDTLWPCS SEQ ID NO: 208 SEQ ID NO: 209
SEQ ID NO: 210 4A2 NA AGGgcCAGTCGGAATA GGTCCATCCAGCAGGGccaCT
CAGCAGTATGGtagctCATT 5B4 TTAGCAGCAGCTACtt SEQ ID NO: 212 CACT 5C5
aGCC SEQ ID NO: 213 SEQ ID NO: 211 AA RASRNISSSYLA GPSSRAT QQYGSSFT
SEQ ID NO: 214 SEQ ID NO: 215 SEQ ID NO: 216 4A9 NA
ACTGGGAGCAGCTCCA GGTAACAACAATCGGCCCTCA CAGTCCTATGACAGCagACT
ACATCGGGACAGGTTA SEQ ID NO: 218 GAGTGGTTGGGTG TGCTGTACAC SEQ ID NO:
219 SEQ ID NO: 217 AA TGSSSNIGTGYAVH GNNNRPS QSYDSRLSGWV SEQ ID NO:
220 SEQ ID NO: 221 SEQ ID NO: 222 4B10 NA AGGGCCAGTCAGAGTG
GGTGCATCCAGCAGGGCCACT CAGCAGTACAGTAACTCgtg 4C2 TTAGCAACACCTACTT SEQ
ID NO: 224 GACG AGCC SEQ ID NO: 225 SEQ ID NO: 223 AA RASQSVSNTYLA
GASSRAT QQYSNSWT SEQ ID NO: 226 SEQ ID NO: 227 SEQ ID NO: 228 4D2
NA AGGGCCAGTCAGAGTG GGTGCATCCAGCAGGGCCGCT CagcagTATAGTAacTcgtg
TTAGCAACACCTACTT SEQ ID NO: 230 GACG AGCC SEQ ID NO: 231 SEQ ID NO:
229 AA RASQSVSNTYLA GASSRAA QQYSNSWT SEQ ID NO: 232 SEQ ID NO: 233
SEQ ID NO: 234 4D3 NA AGGGCCAGTCAGAGTG GGTGCATCCAGCAGGGCCACT
CAGCAGTATGGTAGCTCGTG 4F3 TTAGCAGCAGCTACTT SEQ ID NO: 236 GACG AGCC
SEQ ID NO: 237 SEQ ID NO: 235 AA RASQSVSSSYLA GASSRAT QQYGSSWT SEQ
ID NO: 238 SEQ ID NO: 239 SEQ ID NO: 240 4E10 NA AGGGCCAGTCAGAGTG
GGTGCATCCAGCAGGGTCACT CAGCAATATAGTAACTCGTG TTGGCAGCAGCTACTT SEQ ID
NO: 242 GACG AGCC SEQ ID NO: 243 SEQ ID NO: 241 AA RASQSVGSSYLA
GASSRVT QQYSNSWT SEQ ID NO: 244 SEQ ID NO: 245 SEQ ID NO: 246 4F7
NA ACTGGGAGCAGCTCCA GGTAACAGCAATCGGCCCTCA CAGTCCTATGACAGCAGTCT
ATATCGGGACAGGTTA SEQ ID NO: 248 GAGTGGTTGGGTG TGATGTACAC SEQ ID NO:
249 SEQ ID NO: 247 AA TGSSSNIGTGYDVH GNSNRPS QSYDSSLSGWV SEQ ID NO:
250 SEQ ID NO: 251 SEQ ID NO: 252 5E3 NA TCTGGAGATAAATTGG
CAAGATAGCAAGCGGCCCTCA CAGGCGTGGGACAGCAGCAC GGGATGAATATGCTTG SEQ ID
NO: 254 TGTGGTA C SEQ ID NO: 255 SEQ ID NO: 253 AA SGDKLGDEYAC
QDSKRPS QAWDSSTVV SEQ ID NO: 256 SEQ ID NO: 257 SEQ ID NO: 258 17H8
NA AGGGCCAGTCAGAGTG GGTGCATCCAGCAGGGCCACT CAGCAGTATGGTAAATCACC 23B6
TTGCCGGCAGCTACCT SEQ ID NO: 260 GATCACC 28D10 AGCC SEQ ID NO: 261
SEQ ID NO: 259 AA RASQSVAGSYLA GASSRAT QQYGKSPIT SEQ ID NO: 262 SEQ
ID NO: 263 SEQ ID NO: 264 16C1 NA AGGGCCAGCCAGAGTG
GGTGCATCCAGCAGGGCCACT CAGCAGTATGGTAACTCACC TTAGCAGCAGCTACTT SEQ ID
NO: 266 GCTCACT AGCC SEQ ID NO: 267 SEQ ID NO: 265 AA RASQSVSSSYLA
GASSRAT QQYGNSPLT SEQ ID NO: 268 SEQ ID NO: 269 SEQ ID NO: 270 16A4
NA AGGGCCAGTCAGAGTG GGTACATCCAGCAGGGCCACT CAGCAGTACGGTAGCTCACC
TTAGCAGCAGTTATTT SEQ ID NO: 272 TTTCACT AGCC SEQ ID NO: 273 SEQ ID
NO: 271 AA RASQSVSSSYLA GTSSRAT QQYGSSPFT SEQ ID NO: 274 SEQ ID NO:
275 SEQ ID NO: ***276 16E2 NA CGGGCGAGTCAGGGCA
GCTGCATCCAGTTTGCAAAGT CAACACTATTTTACTTACCC 17E10 TTAGCAATTATTTAGC
SEQ ID NO: 278 TCGGACG 20B12 C SEQ ID NO: 279 SEQ ID NO: 277 AA
RASQGISNYLA AASSLQS QHYFTYPRT SEQ ID NO: 280 SEQ ID NO: 281 SEQ ID
NO: 282 22G10 NA AGGGCCAGTCAGAGTA GGTGCATTTACCAGGGCCACT
CAGCAGTATAATTACTGGCC TTAGCAGCAACTTAGC SEQ ID NO: 284 GCTCACT C SEQ
ID NO: 285 SEQ ID NO: 283 AA RASQSISSNLA GAFTRAT QQYNYWPLT SEQ ID
NO: 286 SEQ ID NO: 287 SEQ ID NO: 288 16H2 NA TCTGGAAGCAGCTCCA
ACTAATAATCAGCGGCCCTCA GCAACATGGGATGACAGCCT 20D3 ACATCGGAAGTAATTT
SEQ ID NO: 290 GAATGGTTGGGTG 23E7 TGTAAAC SEQ ID NO: 291 SEQ ID NO:
289 AA SGSSSNIGSNFVN TNNQRPS ATWDDSLNGWV SEQ ID NO: 292 SEQ ID NO:
293 SEQ ID NO: 294 22D1 NA TCTGGAAGCAGCTCCA ACTAATAATCAGCGGCCCTCA
GCAACATGGGATGACAGTAT ACATCGGAAGCAATTT SEQ ID NO: 296 GAATGGTTGGGTG
TGTAAAC SEQ ID NO: 297 SEQ ID NO: 295 AA SGSSSNIGSNEVN TNNQRPS
ATWDDSMNGWV SEQ ID NO: 298 SEQ ID NO: 299 SEQ ID NO: 300 25F8 NA
TCTGGAAGCAGCTCCA ACTAATAATCAGCGGCCCTCA GCAGCATGGGATGACAGCCT
ACATCGGAAGGAATTT SEQ ID NO: 302 GAATGGTTGGGTG TGTAAAC SEQ ID NO:
303 SEQ ID NO: 301 AA SGSSSNIGRNEVN TNNQRPS AAWDDSLNGWV SEQ ID NO:
304 SEQ ID NO: 305 SEQ ID NO: 306 26F12 NA TCTGGAAGCCGCTCCA
ACTAATTATCAGCGGCCCTCA GCAGTATGGGATGACAGCCT 27B3 ACATCGGAAGTAATTT
SEQ ID NO: 308 GAATGGTTGGGTG TGTAAAC SEQ ID NO: 309 SEQ ID NO: 307
AA SGSRSNIGSNEVN TNYQRPS AVWDDSLNGWV SEQ ID NO: 310 SEQ ID NO: 311
SEQ ID NO: 312 26D1 NA TCTGGAAGCCGCTCCA ACTAATAATCAGCGGCCCTCA
GCAGTATGGGATGACAGCCT ACATCGGAAGTAATTT SEQ ID NO: 314 GAATGGTTGGGTG
TGTAAAC SEQ ID NO: 315 SEQ ID NO: 313 AA SGSRSNIGSNEVN TNNQRPS
AVWDDSLNGWV SEQ ID NO: 316 SEQ ID NO: 317 SEQ ID NO: 318 25G10 NA
AGGGCCAGTCAGAGTG GGTGCATCCAGCAGGGCCACT CAGCAGTATGGTAACTCACC
TTAGCAGCAGCTACTT SEQ ID NO: 320 GCTCACT AGCC SEQ ID NO: 321 SEQ ID
NO: 319 AA RASQSVSSSYLA GASSRAT QQYGNSPLT SEQ ID NO: 322 SEQ ID NO:
323 SEQ ID NO: 324 23A10 NA TCTGGAGATAGATTGG CAAGATAATAAGTGGCCCTCA
CAGGCGTGGGACAGCAGcac GGGAGAAATATGTTTG SEQ ID NO: 326 TGTGGTA C SEQ
ID NO: 327 SEQ ID NO: 325 AA SGDRLGEKYVC QDNKWPS QAWDSSTVV SEQ ID
NO: 328 SEQ ID NO: 329 SEQ ID NO: 330 19B5 NA TCTGGAAGCAGGTCCA
ACTAATAATCAGCGGCCCTCA GCAACATGGGATGACAGTAT ACATCGGAAGCAATTT SEQ ID
NO: 332 GAATGGTTGGGTG TGTAAAC SEQ ID NO: 333 SEQ ID NO: 331 AA
SGSRSNIGSNEVN TNNQRPS ATWDDSMNGWV SEQ ID NO: 334 SEQ ID NO: 335 SEQ
ID NO: 336
[0492] Anti-CDH19 Variable Region Amino Acid Sequences and
Polynucleotide Sequences
TABLE-US-00009 TABLE IIa Heavy Chain Variable Region Polynucleotide
and Amino acid Sequences SEQ ID NO. DESIGNATION SOURCE TYPE
SEQUENCE 337 17H8 artificial nt
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT 23B6
CGGAGACCCTGTCCCTCACGTGCACTGTCTCTGGTGGCTCCAT 28D10
CAATAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGCGTCACCATATCAGTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCCTGTATTACTGTGCGAGAGATTCCCGGT
ATAGAAGTGGCTGGTACGATGCTTTTGATATCTGGGGCCAAGG GACAATGGTCACCGTCTCTTCA
338 17H8 artificial aa QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGK
23B6 GLEWIGYIYYIGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVT 28D10
AADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSS 339 4A2 artificial nt
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT 5B4
CACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT 5C5
CAGCAGTAGTGGTTACTACTGGAGCTGGATCCGCCAGCACCCA
GGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACACTGGGA
GCGCCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATATC
AGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCT
GTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGATG
GAAGCAGTGGCTGGTACTTCCAGTATTGGGGCCAGGGCACCCT GGTCACCGTCTCCTCA 340
4A2 artificial aa QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHP 5B4
GKGLEWIGYIYYTGSAYYNPSLKSRVTISVDTSKNQFSLKLSS 5C5
VTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS 341 16H2 artificial nt
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG 20D3
GGGCCTCAGTGAAGGTTTCCTGCAAGGTTTCTGGATACACCTT 23E7
CACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGAATAATCAACCCTATTAGTGTTAGCA
CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
TACAGCTATGGTTACATTTTGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 342
16H2 artificial aa QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ 20D3
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL 23E7
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS 343 26F12 artificial nt
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG 27B3
GGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTAGATACACCTT
CACCAACTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTGACT
CAACCTACGCACAGAAGTTCCAGGGCAGACTCACCATGACCGG
GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGA
TACAACTATGGTTACATTTTGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 344
26F12 artificial aa QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQ
27B3 GLEWMGIINPSGGDSTYAQKFQGRLTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS 345 4B10 artificial nt
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 4C2
GGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
CAGTAGCTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAATG
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACACTTCCAAGAACACGCTGTATTTGCAAATGAACAGCCTG
AGAGCTGAGGACACGGCTGTATATTACTGTGCGAGAGAACGAT
ATTTTGACTGGTCTTTTGACTACTGGGGCCAGGGAACCCTGGT CAGTGTCTCCTCA 346 4B10
artificial aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK 4C2
GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS 347 4D3 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 4F3
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCTCCTT
CAGTAGCTATGACATGGACTGGGTCCGCCAGACTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAGGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTTTCTGCAAATGAACAGCCTG
AGAGTCGAGGACACGGCTGTGTATTACTGTGCGAGAGAAACTG
GGGAGGGCTGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGT CACTGTCTCCTCA 348 4D3
artificial aa QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGK 4F3
GLEWVAVIWYDGSNKYYADSVRGRFTISRDNSKNTLFLQMNSL
RVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS 349 16E2 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 17E10
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCATCTT 20B12
CAGTAGCTATGGCATGCACTGGGTCCGCCAGACTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTGATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACATTTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
AGAGTCGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGGT
GGGAGCTGTCCTTTGACTACTGGGGCCAGGGAACCCTGGTCAC CGTCTCCTCA 350 16E2
artificial aa QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYGMHWVRQTPGK 17E10
GLEWVAVIWYDGSNKYYADSVKGRFTISRDISKNTLYLQMNSL 20B12
RVEDTAVYYCARDGWELSFDYWGQGTLVTVSS 351 1D10 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 2C12
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGTCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGCGCGAGAAGGGCCG
GTATAATAGGAACTACAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 352 1D10 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK 2C12
GLEWVSVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTTGYYYGMDVWGQGTTVTVSS 353 16C1 artificial nt
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
CGGAGACCCTGTCCCTCACTTGTACTGTCTCTGGTGGCTCCAT
CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATGTCAATAGA
CACGTCCAAGAACCAGTTCTCCCTGACGCTGAGCTCTTTGACC
GCTGCGGACACGGCCGTGTATTTCTGTGCGAGAGATGGGAGCA
GTGGCTGGTACCGGTGGTTCGACCCCTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 354
16C1 artificial aa QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK
GLEWIGYIYYIGSTNYNPSLKSRVTMSIDTSKNQFSLTLSSLT
AADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS 355 25G10 artificial nt
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATGTCAGTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGAGATGGGAGCA
GTGGCTGGTACCGGTGGTTCGACCCCTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 356
25G10 artificial aa QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK
GLEWIGYIYYIGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVT
AADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSS 357 16A4 artificial nt
CAGGTGCAGCTGCAGGAGTCgGGCCCAGGACTGGCGAAgcctt
cGGAGACcctgtccctcacctgCACTGTCTCTGGTGACTCCAT
CACTAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
ATTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGTTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGAGATCAAAGGC
GGATAGCAGCAGCTGGTACCCACTTCTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 358 16A4 artificial aa
QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGK
GLEWIGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVT
AADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTTVTVSS 359 1F10 artificial nt
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
CACAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGCAGTGGTGGTTACTACTGGAGCTGGATCCGCCAGCACCCA
GGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACAGTGGGA
GCACCTACTACAACCCGTCCCTCACGAGTCGAGTTACCATATC
AGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCT
GTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGATG
GAAGCAGTGGCTGGTACTTCCAGCACTGGGGCCAGGGCACCCT GGTCACCGTCTCCTCA 360
1F10 artificial aa QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHP
GKGLEWIGYIYYSGSTYYNPSLTSRVTISVDTSKNQFSLKLSS
VTAADTAVYYCARDGSSGWYFQHWGQGTLVTVSS 361 4A9 artificial nt
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGAAAG
GGACTGGAGTGGTTTGCATATTTCTCTTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCTTATCAGTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTC CTCA 362 4A9 artificial
aa QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK
GLEWFAYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSS 363 4F7 artificial nt
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCATTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC CTCA 364 4F7 artificial
aa QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSS 365 22D1 artificial nt
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
GGGCCTCAGTGAGGGTTTCCTGCAAGGTTTCTGGATACACCTT
CACCAGCTACTTTATTCACTGGGTACGCCAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGAATAATCAACCCTATTAGTGTTAGCA
CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
TACAGCTATGGTTACATTTGGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 366
22D1 artificial aa QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQ
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS 367 19B5 artificial nt
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
GGGCCTCAGTGAAGGTTTCCTGCAAGGTTTCTGGATACACCTT
CACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGGCTTGAATGGATGGGAATTATCAACCCTATTAGTGTTAGCA
CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGcCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
TACAGCTATGGTTACATTTGGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 368
19B5 artificial aa QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS 369 25F8 artificial nt
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
GGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTT
CACCAGCTACTATATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGACTTGAGTGGATGGGAATAATCAACCCCAGTGGTGGTAGCA
CAAGGTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCagcctG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGAA
TACAGCTATGGTTACATTttGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 370
25F8 artificial aa QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ
GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS 371 26D1 artificial nt
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG
GGGCCTCAGTGAAGGTTTCCTGTAAGGCATCTAGATACACCTT
CACCAGCTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGAATAATCCACCCTAGTGGTGGTGACA
CAACCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCGG
GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGA
TAAAACTATGGTTACATTTTGACTATTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 372
26D1 artificial aa QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQ
GLEWMGIIHPSGGDTTYAQKFQGRVTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS 373 4D2 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
GGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
CAGTAGTTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAATG
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACACTTCCAAGAACACGCTGTATTTGCAAATGAACAGCCTG
AGAGCTGAGGACACGGCTGTATATTACTGTGCGAGAGAACGAT
ATTTTGACTGGTCTTTTGACTACTGGGGCCAGGGAACCCTGGT CAGTGTCTCCTCA 374 4D2
artificial aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK
GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS 375 4E10 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCACGAACACGCTGCATCTGCAAATGAACAGCCCG
AGAGCCGAGGACACGGCTGTGTACTACTGTGCGAGAGAGTATA
GGTACAGCTGGTACTTTGACTACTGGGGCCAGGGAACCCTGGT CACCGTCTCCTCA 376 4E10
artificial aa QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSTNTLHLQMNSP
RAEDTAVYYCAREYRYSWYFDYWGQGTLVTVSS 377 22G10 artificial nt
GAGGTGCAACTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTG
GGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
TAGCAGTTATGCCATGAACTGGGTCCGCCAGGCTCCAGGGAAG
GGGCTGGAGTGGGTCTCAACTATTAGTGGTGGTGGTGCTAACA
CATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAG
TGACAATTCCAAGAGCACGCTGTATCTGCAAATGAACAGCCTG
AGAGCCGCGGACACGGCCGTATATCACTGTGCGAAAGGGGGAA
TGGGGGGATACTACTACGGTATGGACGTCTGGGGCCAAGGGAC CACGGTCACCGTCTCCTCA 378
22G10 artificial aa EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGK
GLEWVSTISGGGANTYYADSVKGRFTISSDNSKSTLYLQMNSL
RAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS 379 2C12_LC#1 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGTCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGCGCGAGAAGGGCCG
GTATAATAGGAACTACAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 380 2C12_LC#1 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
GLEWVSVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTTGYYYGMDVWGQGTTVTVSS 381 2H12_LC#2 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATACAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTACAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 382 2H12_LC#2 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
GLEWVAVIWYDGSNKYYTDSVKGRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTTGYYYGMDVWGQGTTVTVSS 383 2G6_LC#1 artificial nt
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 384 2G6_LC#1 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS 385 2H12 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATACAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTACAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 386 2H12 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
GLEWVAVIWYDGSNKYYTDSVKGRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTTGYYYGMDVWGQGTTVTVSS 387 2G6 artificial nt
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 388 2G6 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS 389 23A10 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCTAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 390 23A10 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLLMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS 391 5E3 artificial nt
GAGGTGCAGTTGGTGGAGTCTGGGGGAGGCCTGGTCAAGCCTG
GGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
CAGTAGCTATAGCATGCACTGGGTCCGCCAGGCTCCAGGGAAG
GGGCTGGAGTGGGTCTCATCCATTAGTAGTAGTAGTAGTTACA
TATACTACGCAGACTCAGTGAAGGGCCGATTCACCATCTCCAG
AGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTG
AGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGGGAAA
CTGGAACTAACTACTACTACTACGGTATGGACGTCTGGGGCCA
AGGGACCACGGTCACCGTCTCCTCA 392 5E3 artificial aa
EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMHWVRQAPGK
GLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSL
RAEDTAVYYCARGETGTNYYYYGMDVWGQGTTVTVSS
TABLE-US-00010 TABLE IIB Light Chain Variable Region Polynucleotide
and Amino acid Sequences SEQ ID NO. DESIGNATION SOURCE TYPE
SEQUENCE 393 17H8 artificial nt
GACATTGTATTGACGCAGtctCCAGGCACCCTGTCTTTGTCTC 23B6
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT 28D10
TGCCGGCAGCTACCTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTCTGGTGCATCCAGCAGGGCCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
TATTACTGTCAGCAGTATGGTAAATCACCGATCACCTTCGGCC
AAGGGACACGACTGGAGATGAAAGGA 394 17H8 artificial aa
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQ 23B6
APRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV 28D10
YYCQQYGKSPITFGQGTRLEMKG 395 4A2 artificial nt
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC 5B4
CAGGGGAAAGAGCCACCCTCTCTTGCAGGGCCAGTCGGAATAT 5C5
TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTCCATCCAGCAGGGCCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTACAGTG
TATTACTGTCAGCAGTATGGTAGCTCATTCACTTTCGGCCCTG GGACCAAAGTGGATATCAAACGA
396 4A2 artificial aa EIVLTQSPGTLSLSPGERATLSCRASRNISSSYLAWYQQKPGQ
5B4 APRLLIYGPSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFTV 5C5
YYCQQYGSSFTFGPGTKVDIKR 397 16H2 artificial nt
CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCG 20D3
GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACAT 23E7
CGGAAGTAATTTTGTAAACTGGTACAAACAACTCCCAGGAACG
GCCCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGAT
TATTACTGTGCAACATGGGATGACAGCCTGAATGGTTGGGTGT
TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 398 16H2 artificial aa
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGT 20D3
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD 23E7
YYCATWDDSLNGWVFGGGTKLTVLG 399 26F12 artificial nt
CAGTCTGTGCTGACTCAGTCACCCTCAGCGTCTGGGACCCCCG 27B3
GGCAGAAGGTCACCATCTCTTGTTCTGGAAGCCGCTCCAACAT
CGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACG
GCCCCCAAACTCCTCATCTATACTAATTATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
TATTACTGTGCAGTATGGGATGACAGCCTGAATGGTTGGGTGT
TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 400 26F12 artificial aa
QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGT 27B3
APKLLIYTNYQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCAVWDDSLNGWVFGGGTKLTVLG 401 4B10 artificial nt
GAAATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC 4C2
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
TAGCAACACCTACTTAGCCTGGTACCATCAGAGACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTG
GCATCCCAGACAGATTCAGTGGCAGTGGGTCTGGGACAGACTT
CGCTCTCACCATCAGCAGTCTGGAGCCTGAAGATTTTGCAGTG
TATTACTGTCAGCAGTACAGTAACTCgtgGACGTTCGGCCAAG GGACCAAGGTGGAAATCAaacGA
402 4B10 artificial aa EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQ
4C2 APRLLIYGASSRATGIPDRFSGSGSGTDFALTISSLEPEDFAV
YYCQQYSNSWTFGQGTKVEIKR 403 4D3 artificial nt
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC 4F3
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCAGACTGGAACCTGAGGATTTTGCAGTG
TATTACTGTCAGCAGTATGGTAGCTCGTGGACGTTCGGCCAAG GGACCAAGGTGGAAATCAAACGA
404 4D3 artificial aa EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ
4F3 APRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV
YYCQQYGSSWTFGQGTKVEIKR 405 16E2 artificial nt
GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATCTG 17E10
TAGGAGACAGAGTCACCATCACTTGTCGGGCGAGTCAGGGCAT 20B12
TAGCAATTATTTAGCCTGGTTACAGCAGAAACCAGGGAAAGCC
CCTAAGTCCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGG
TCCCATCAAAGTTCAGCGGCAGTGGATCTGGGACAGATTTCAC
TCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTAT
TACTGCCAACACTATTTTACTTACCCTCGGACGTTCGGCCAAG GGACCAAGGTGGAAATCAAACGA
406 16E2 artificial aa DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWLQQKPGKA
17E10 PKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATY 20B12
YCQHYFTYPRTFGQGTKVEIKR 407 1D10 artificial nt
TCCTATGCGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 2C12
GACAGACAGCCAGCCTCACCTGCTCTGGAGATAGATTGGGGGA
AAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCACCTCTGGTAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGA CCAAGCTGACCGTCCTAGGT
408 1D10 artificial aa SYALTQPPSVSVSPGQTASLTCSGDRLGEKYTCWYQQRPGQSP
2C12 LLVIYQDTKRPSGIPERFSGSTSGNTATLTISGTQAMDEADYY
CQAWDSSTVVFGGGTKLTVLG 409 16C1 artificial nt
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGCCAGAGTGT
TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGCCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCGGACTGGAGCCTGAAGATTTTGCAGTG
TATCACTGTCAGCAGTATGGTAACTCACCGCTCACTTTCGGCG
GAGGGACCAAGGTGGAGATCAAACGA 410 16C1 artificial aa
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ
APRLLIFGASSRATGIPDRFSGSGSGTDFTLTISGLEPEDFAV YHCQQYGNSPLTFGGGTKVEIKR
411 25G10 artificial nt GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGCCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGactT
CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
TATCACTGTCAGCAGTATGGTAACTCACCGCTCACTTTCGGCG
GAGGGACCAAGGTGGAGATCAAACGA 412 25G10 artificial aa
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ
APRLLIFGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV YHCQQYGNSPLTFGGGTKVEIKR
413 16A4 artificial nt GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
CAGGGGAAAGAGCCACCCtCTCCTGCAGGGCCAGTCAGAGTGT
TAGCAGCAGTTATTTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTACATCCAGCAGGGCCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
TATTATTGTCAGCAGTACGGTAGCTCACCTTTCACTTTCGGCG
GAGGGACCAAGGTGGAGATCAAACGA 414 16A4 artificial aa
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ
APRLLIYGTSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV YYCQQYGSSPFTFGGGTKVEIKR
415 1F10 artificial nt GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCGGAGTAT
TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTCCATCCAGCAGGGCCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
TATTACTGTCAGCAGTATGGTAGCTCATTCACTTTCGGCCCTG GGACCAAAGTGGATATCAAACGA
416 1F10 artificial aa EIVLTQSPGTLSLSPGERATLSCRASRSISSSYLAWYQQKPGQ
APRLLIYGPSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV YYCQQYGSSFTFGPGTKVDIKR
417 4A9 artificial nt CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG
GACAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAACAT
CGGGACAGGTTATGCTGTACACTGGTACCAGCAGTTTCCAGGA
ACAGCCCCCAAACTCCTCATCTATGGTAACAACAATCGGCCCT
CAGGGGTTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
GATTATTACTGCCAGTCCTATGACAGCAGACTGAGTGGTTGGG
TGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 418 4A9 artificial aa
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQFPG
TAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSRLSGWVFGGGTKLTVLG 419 4F7 artificial nt
CAGTCTGTgcTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG
GGCAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAATAT
CGGGACAGGTTATGATGTACACTGGTATCAGCAGcttcCAGGA
ACAGCCCCCAAACTCCTCATCCATGGTAACAGCAATCGGCCCT
CAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
GATTATTACTGCCAGTCCTATGACAGCAGTCTGAGTGGTTGGG
TGTTCGGCGGAGGGACCAGGTTGACCGTCCTAGGT 420 4F7 artificial aa
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPG
TAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSSLSGWVFGGGTRLTVLG 421 22D1 artificial nt
CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCG
GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACAT
CGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACG
GCCCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGAT
TATTACTGTGCAACATGGGATGACAGTATGAATGGTTGGGTGT
TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 422 22D1 artificial aa
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGT
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
YYCATWDDSMNGWVFGGGTKLTVLG 423 19B5 artificial nt
CAGTCTGCGCTGACTCAGCCACCCTCAACGACTGGGACCCCCG
GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGGTCCAACAT
CGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACG
GCCCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGAT
TATTACTGCGCAACATGGGATGACAGTATGAATGGTTGGGTGT
TCGGCGGAGGGACCAAACTGACCGTCCTAGGT 424 19B5 artificial aa
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYKQLPGT
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
YYCATWDDSMNGWVFGGGTKLTVLG 425 25F8 artificial nt
CAGTCTGCGCTGactCAGCCACCCTCAGCGACTGGGACCCCCG
GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACAT
CGGAAGGAATTTTGTAAACTGGTATAAGCAGCTCCCAGGAACG
GCCCCCAAAGTCCTCATTTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGAT
TATTACTGTGCAGCATGGGATGACAGCCTGAATGGTTGGGTGT
TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 426 25F8 artificial aa
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYKQLPGT
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
YYCAAWDDSLNGWVFGGGTKLTVLG 427 26D1 artificial nt
CACTCTGTGCTGACTCAGTCACCCTCAGCGTCTGGGACCCCCG
GACAGAGGGTCACCATCTCTTGTTCTGGAAGCCGCTCCAACAT
CGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACG
GCCCCCAAACTCCTCATCTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
TATTACTGTGCAGTATGGGATGACAGCCTGAATGGTTGGGTGT
TCGGCGGAGGGACCAAGCTGACCGTCCTAGGT 428 26D1 artificial aa
HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGT
APKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCAVWDDSLNGWVFGGGTKLTVLG 429 4D2 artificial nt
GAAATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
TAGCAACACCTACTTAGCCTGGTACCATCAGAGACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCGCTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
TATTACTGTCAGCAGTATAGTAACTCGTGGACGTTCGGCCAAG
GGACCAAGGTGGAAATCAAACGA
430 4D2 artificial aa EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQ
APRLLIYGASSRAAGIPDRFSGSGSGTDFTLTISRLEPEDFAV YYCQQYSNSWTFGQGTKVEIKR
431 4E10 artificial nt GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
TGGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGTCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGATTT
CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
TATTACTGTCAGCAATATAGTAACTCGTGGACGTTCGGCCAAG GGACCAAGGTGGAAATCAAACGA
432 4E10 artificial aa EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQ
APRLLIYGASSRVTGIPDRFSGSGSGTDFTLTISRLEPEDFAV YYCQQYSNSWTFGQGTKVEIKR
433 22G10 artificial nt GAAATAGTGATGACGCAGTCTCCAGTCACCCTGTCTCTGTCTC
TAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTAT
TAGCAGCAACTTAGCCTGGTTCCAGCAGAAACCTGGCCAGGCT
CCCAGACTCCTCATCTATGGTGCATTTACCAGGGCCACTGGTA
TCCCAGCCAGGGTCAGTGGCAGTGGGTCTGGGACAGAGTTCAC
TCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTTTAT
TACTGTCAGCAGTATAATTACTGGCCGCTCACTTTCGGCGGAG GGACCAAGGTGGAGATCAAGCGA
434 22G10 artificial aa EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQA
PRLLIYGAFTRATGIPARVSGSGSGTEFTLTISSLQSEDFAVY YCQQYNYWPLTFGGGTKVEIKR
435 2C12_LC#1 artificial nt
GATGTTGTGATGactCAGtCTccActctccctgcCCGTCACCC
TTGGACAGCCGGcctCCAtctcctgCAGGtCTAGTCAAAGcct
cgtaTACAGTGATGGAAACAcctACTTGAATTGGTTTCAGCAG
AGGCCAGGCCAATCTCCAAGGcgcctaATTTATAAGGTTTCTA
ACTGGGactctGGGGtCCCAGACAGATTCAGCgGCAGTGGGTC
AGGCActGATTTCACactGAAAAtCAGCAGGGTGGaggctgaG
GATGTTGGGGTTTATTactgCATGCAAGGTATAGTGTGGCCGT
GCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAaCgA 436 2C12_LC#1 artificial aa
DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQ
RPGQSPRRLIYKVSNWDSGVPDRFSGSGSGTDFTLKISRVEAE
DVGVYYCMQGIVWPCSFGQGTKLEIKR 437 2H12_LC#2 artificial nt
GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCC
TTGGACAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAAAGCCT
CGTATACAGTGATGGAAACACCTACTTGAATTGGTTTCAGCAG
AGGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGTTTCTA
ACTGGGACTCTGGGGTCCCAGACAGAATCAGCGGCAGTGGGTC
AGGCACCGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAG
GATGTTGGGGTTTATTACTGCATGCAAGATACACTGTGGCCGT
GCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGA 438 2H12_LC#2 artificial aa
DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQ
RPGQSPRRLIYKVSNWDSGVPDRISGSGSGTDFTLKISRVEAE
DVGVYYCMQDTLWPCSFGQGTKLEIKR 439 2G6_LC#1 artificial nt
GaTGTTGTGATGACTCagtctccACTCTCCCTGCCCGTCACCC
ttggacaGCCGGCCTccaTCTCCTGCAGGTCTAGTCAAAGCCT
CGTATACAGTGATGGAAACACCTACTTGAATTGGTTTCAGCAG
AGGCCAGGCCAATCTCCACGGCGCCTAATTTATCAGGTTTCTA
ACTGGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTC
AGGCACTGATTTCACACTGAAAATCAGCAGGGTGGAGGCTGAG
GATGTTGGGATTTATTACTGCATGCAAGATACACTGTGGCCGT
GCAGTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGA 440 2G6_LC#1 artificial aa
DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYLNWFQQ
RPGQSPRRLIYQVSNWDSGVPDRFSGSGSGTDFTLKISRVEAE
DVGIYYCMQDTLWPCSFGQGTKLEIKR 441 2H12 artificial nt
TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
AAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGTAACACAGCCACTCT
GACCATCAGCGGGACCCAGCCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGA CCAAGCTGACCGTCCtAGGT
442 2H12 artificial aa SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSP
LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQPMDEADYY CQAWDSSTVVFGGGTKLTVLG
443 2G6 artificial nt TCCTATGAACTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGGTTGGGGGA
AAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGTAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGA CCAAGCTGACCGTCCTAGGT
444 2G6 artificial aa SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSP
LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWDSSTVVFGGGTKLTVLG
445 23A10 artificial nt TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
GAAATATGTTTGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
ATACTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGGGGGA CCAAGCTGACCGTCCTAGGT
446 23A10 artificial aa SYELTQPPSVSVSPGQTASITCSGDRLGEKYVCWYQQKPGQSP
ILVIYQDNKWPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWDSSTVVFGGGTKLTVLG
447 5E3 artificial nt TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG
GACAGACAGCCAGCATCACCTGCTCTGGAGATAAATTGGGGGA
TGAATATGCTTGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
GTGCTGGTCATCTATCAAGATAGCAAGCGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGA CCAAGCTGACCGTCCTAGGT
448 5E3 artificial aa SYELTQPPSVSVSPGQTASITCSGDKLGDEYACWYQQKPGQSP
VLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY
CQAWDSSTVVFGGGTKLTVLG
TABLE-US-00011 TABLE IIc Heavy Chain Variable Region Polynucleotide
and Amino acid Sequences 13586_HC [hu anti-<huCDH19> 4F3 VH]
QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS SEQ ID NO:
449 13589_HC [hu anti-<huCDH19> 4A9 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSS SEQ ID NO: 450
13590_HC [hu anti-<huCDH19> 4B10 VH]
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS SEQ ID NO: 451
13874_HC [hu anti-<huCDH19> 17H8.2 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSS SEQ ID NO: 452
13875_HC [hu anti-<huCDH19> 16C1.1 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS SEQ ID NO: 453
13876_HC [hu anti-<huCDH19> 16A4.1 VH]
QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTTVTVSS SEQ ID NO:
454 13877_HC [hu anti-<huCDH19> 22G10.1 VH]
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS SEQ ID NO:
455 13878_HC [hu anti-<huCDH19> 20D3.1 VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO: 456
13879_HC [hu anti-<huCDH19> 22D1.1 VH]
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS SEQ ID NO: 457
13880_HC [hu anti-<huCDH19> 25F8.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
458 13881_HC [hu anti-<huCDH19> 26F12.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
459 13882_HC [hu anti-<huCDH19> 26D1.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS SEQ ID NO:
460 13883_HC [hu anti-<huCDH19> 25G10.1 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
VDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSS SEQ ID NO: 461
13885_HC [hu anti-<huCDH19> 19B5.1 VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS SEQ ID NO: 462
14022_HC [hu anti-<huCDH19> 4A2 VH]
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV
TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS SEQ ID NO: 463
14024_HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E, 1147P) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT
ISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS SEQ ID NO: 464
14025_HC [hu anti-<huCDH19> 4A2 VH]
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV
TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS SEQ ID NO: 465
14026_HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E, 1147P) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT
ISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS SEQ ID NO: 466
14027_HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E, H47P, D111E)
VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT
ISVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGWYFQYWGQGTLVTVSS SEQ ID NO: 467
14028_HC [hu anti-<huCDH19> 4A2 (1-472)(Q17E, H47P, D111E,
W134Y) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT
ISVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGYYFQYWGQGTLVTVSS SEQ ID NO: 468
14029_HC [hu anti-<huCDH19> 4A2 VH]
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV
TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS SEQ ID NO: 469
14030_HC [hu anti-<huCDH19> 4F3 (1-471)(R17G) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS SEQ ID NO:
470 14031_HC [hu anti-<huCDH19> 4F3 (1-471)(R17G, T47A) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS SEQ ID NO:
471 14032_HC [hu anti-<huCDH19> 4F3 (1-471)(R17G, T47A,
R141Q) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGQGTLVTVSS SEQ ID NO:
472 14033_HC [hu anti-<huCDH19> 4F3 (1-471)(R17G, T47A, D61E,
D72E, R141Q) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYEGSNKYYAESVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGQGTLVTVSS SEQ ID NO:
473 14034_HC [hu anti-<huCDH19> 4F3 (1-471)(R17G, T47A, D61E,
D72E, W134Y, R141Q) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYEGSNKYYAESVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGYYFDLWGQGTLVTVSS SEQ ID NO:
474 14039_HC [hu anti-<huCDH19> 2G6 (1-477)(R17G, D61E, D72E,
K94N) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYEGSNKYYAESVKD
RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 475 14040_HC [hu anti-<huCDH19> 16C1.1 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS SEQ ID NO: 476
14041_HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS SEQ ID NO: 477
14042_HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K, D109E) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLKLSSLTAADTAVYFCAREGSSGWYRWFDPWGQGTLVTVSS SEQ ID NO: 478
14043_HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K, W132Y,
W135Y) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGYYRYFDPWGQGTLVTVSS SEQ ID NO: 479
14044_HC [hu anti-<huCDH19> 16C1.1 (1-469)(T92K) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSS SEQ ID NO: 480
14045_HC [hu anti-<huCDH19> 17H8.2 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSS SEQ ID NO: 481
14046_HC [hu anti-<huCDH19> 17H8.2 (1-471)(D109E) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARESRYRSGWYDAFDIWGQGTMVTVSS SEQ ID NO: 482
14047_HC [hu anti-<huCDH19> 17H8.2 (1-471)(D109E, W132Y) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARESRYRSGYYDAFDIWGQGTMVTVSS SEQ ID NO: 483
14048_HC [hu anti-<huCDH19> 17H8.2 (1-471)(D109E) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARESRYRSGWYDAFDIWGQGTMVTVSS SEQ ID NO: 484
14049_HC [hu anti-<huCDH19> 4F7 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSS SEQ ID NO: 485
14050_HC [hu anti-<huCDH19> 4F7 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSS SEQ ID NO: 486
14051_HC [hu anti-<huCDH19> 4F7 (1-468)(W113Y) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNYAFHFDYWGQGTLVTVSS SEQ ID NO: 487
14052_HC [hu anti-<huCDH19> 4B10 (1-471)(R17G, D61E, D72E,
W134Y) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYEGTNEYYAESVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDYSFDYWGQGTLVSVSS SEQ ID NO: 488
14053_HC [hu anti-<huCDH19> 4B10 VH]
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS SEQ ID NO: 489
14054_HC [hu anti-<huCDH19> 4B10 (1-471)(R17G) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKG
RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS SEQ ID NO:
490 14055_HC [hu anti-<huCDH19> 4B10 (1-471)(R17G, D61E,
D72E) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYEGTNEYYAESVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS SEQ ID NO: 491
14056_HC [hu anti-<huCDH19> 4A9 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSS SEQ ID NO: 492
14057_HC [hu anti-<huCDH19> 4A9 (1-468)(F55I, A56G) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSS SEQ ID NO: 493
14058_HC [hu anti-<huCDH19> 4A9 (1-468)(F55I, A56G) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSS SEQ ID NO: 494
14059_HC [hu anti-<huCDH19> 4A9 (1-468)(F55I, A56G, W113Y)
VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNYAFHFDFWGQGTLVTVSS SEQ ID NO: 495
14060_HC [hu anti-<huCDH19> 20D3.1 VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
496
14061_HC [hu anti-<huCDH19> 20D3.1 VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO: 497
14062_HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS SEQ ID NO: 498
14063_HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS SEQ ID NO: 499
14064_HC [hu anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS SEQ ID NO: 500
14065_HC [hu anti-<huCDH19> 22G10.1 (1-470)(S82R, A99E) VH]
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISRDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS SEQ ID NO:
501 14066_HC [hu anti-<huCDH19> 22G10.1 (1-470)(A99E, H105Y)
VH]
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAEDTAVYYCAKGGMGGYYYGMDVWGQGTTVTVSS SEQ ID NO:
502 14067_HC [hu anti-<huCDH19> 22G10.1 (1-470)(A99E) VH]
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS SEQ ID NO:
503 14068_HC [hu anti-<huCDH19> 22G10.1 (1-470)(A99E) VH]
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS SEQ ID NO:
504 14069_HC [hu anti-<huCDH19> 22G10.1 (1-470)(D72E, A99E)
VH]
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYAESVKGRF
TISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS SEQ ID NO:
505 14070_HC [hu anti-<huCDH19> 22G10.1 (1-470)(H105Y) VH]
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAADTAVYYCAKGGMGGYYYGMDVWGQGTTVTVSS SEQ ID NO:
506 14071_HC [hu anti-<huCDH19> 16A4.1 (1-474)(T144L) VH]
QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTLVTVSS SEQ ID NO:
507 14072_HC [hu anti-<huCDH19> 19B5.1 VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS SEQ ID NO: 508
14073_HC [hu anti-<huCDH19> 19B5.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSS SEQ ID NO: 509
14074_HC [hu anti-<huCDH19> 19B5.1 VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS SEQ ID NO: 510
14075_HC [hu anti-<huCDH19> 19B5.1 VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS SEQ ID NO: 511
14076_HC [hu anti-<huCDH19> 19B5.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSS SEQ ID NO: 512
14077_HC [hu anti-<huCDH19> 23A10.3 (1-474)(L920) VH]
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGR
FTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 513 14078_HC [hu anti-<huCDH19> 23A10.3 (1-474)(R17G,
L92Q) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG
RFTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 514 14079_HC [hu anti-<huCDH19> 23A10.3 (1-474)(R17G,
D61E, D72E, L92Q) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYEGSNKYYAESVKGR
FTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 515 14080_HC [hu anti-<huCDH19> 23A10.3 VH]
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGR
FTISRDNSKNTLYLLMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 516 14081_HC [hu anti-<huCDH19> 25G10.1 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
VDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSS SEQ ID NO: 517
14082_HC [hu anti-<huCDH19> 25G10.1 (1-469)(D109E, W132Y,
W135Y) VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
VDTSKNQFSLKLSSVTAADTAVYYCAREGSSGYYRYFDPWGQGTLVTVSS SEQ ID NO: 518
14083_HC [hu anti-<huCDH19> 26D1.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS SEQ ID NO:
519 14084_HC [hu anti-<huCDH19> 26D1.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS SEQ ID NO:
520 14085_HC [hu anti-<huCDH19> 26D1.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS SEQ ID NO:
521 14086_HC [hu anti-<huCDH19> 26D1.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS SEQ ID NO:
522 14087_HC [hu anti-<huCDH19> 26D1.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLYLHFDYWGQGTLVTVSS SEQ ID NO:
523 14088_HC [hu anti-<huCDH19> 26D1.1 (1-469)(R27G, G82R)
VH]
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS SEQ ID NO:
524 14089_HC [hu anti-<huCDH19> 26F12.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
525 14090_HC [hu anti-<huCDH19> 26F12.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
526 14091_HC [hu anti-<huCDH19> 26F12.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS SEQ ID NO:
527 14092_HC [hu anti-<huCDH19> 26F12.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS SEQ ID NO:
528 14093_HC [hu anti-<huCDH19> 25F8.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
529 14094_HC [hu anti-<huCDH19> 25F8.1 VH]
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
530 14095_HC [hu anti-<huCDH19> 25F8.1 (1-469)(F90Y) VH]
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
531 14096_HC [hu anti-<huCDH19> 25F8.1 (1-469)(F90Y) VH]
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS SEQ ID NO:
532 14097_HC [hu anti-<huCDH19> 25F8.1 (1-469)(F90Y, W133Y)
VH]
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSS SEQ ID NO:
533 14098_HC [hu anti-<huCDH19> 22D1.1 VH]
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS SEQ ID NO: 534
14099_HC [hu anti-<huCDH19> 22D1.1 VH]
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS SEQ ID NO: 535
14100_HC [hu anti-<huCDH19> 22D1.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSS SEQ ID NO: 536
14101_HC [hu anti-<huCDH19> 22D1.1 (1-469)(W133Y) VH]
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSS SEQ ID NO: 537
14102_HC [hu anti-<huCDH19> 22D1.1 (1-469)(F90Y) VH]
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS SEQ ID NO: 538
13591_HC [hu anti-<huCDH19> 4F7 VH]
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSS SEQ ID NO: 539
14301_HC [hu anti-<huCDH19> 2G6 VH]
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD
RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 540 14302_HC [hu anti-<huCDH19> 2G6 (1-477)(R17G, K94N)
VH]
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD
RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 541 14303_HC [hu anti-<huCDH19> 2G6 (1-477)(D61E, D72E)
VH]
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYEGSNKYYAESVKD
RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 542 14304_HC [hu anti-<huCDH19> 2G6 (1-477)(R17G) VH]
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD
RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS SEQ ID
NO: 543
TABLE-US-00012 TABLE IId Light Chain Variable Region Amino acid
Sequences 13586_LC [hu anti-<huCDH19> 4F3 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR SEQ ID NO: 544 13589_LC [hu
anti-<huCDH19> 4A9 VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQFPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLG SEQ ID NO: 545 13590_LC
[hu anti-<huCDH19> 4B10 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FALTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR SEQ ID NO: 546 13874_LC [hu
anti-<huCDH19> 17H8.2 VL]
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKG SEQ ID NO: 547 13875_LC [hu
anti-<huCDH19> 16C1.1 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKR SEQ ID NO: 548 13876_LC [hu
anti-<huCDH19> 16A4.1 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSPFTFGGGTKVEIKR SEQ ID NO: 549 13877_LC [hu
anti-<huCDH19> 22G10.1 VL]
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKR SEQ ID NO: 552 13878_LC [hu
anti-<huCDH19> 20D3.1 VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 554 13879_LC
[hu anti-<huCDH19> 22D1.1 VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLG SEQ ID NO: 555 13880_LC
[hu anti-<huCDH19> 25F8.1 VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 556 13881_LC
[hu anti-<huCDH19> 26F12.1 VL]
QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 557 13882_LC
[hu anti-<huCDH19> 26D1.1 VL]
HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 555 13883_LC
[hu anti-<huCDH19> 25G10.1 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKR SEQ ID NO: 556 13885_LC [hu
anti-<huCDH19> 19B5.1 VIA
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLG SEQ ID NO: 557 14022_LC
[hu anti-<huCDH19> 4A2 (1-236)(N30Q) VL]
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKR SEQ ID NO: 558 14024_LC [hu
anti-<huCDH19> 4A2 (1-236)(N30Q, T102A, P141Q) VL]
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKR SEQ ID NO: 559 14025_LC [hu
anti-<huCDH19> 4A2 (1-236)(N30Q, T102A) VL]
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGPGTKVDIKR SEQ ID NO: 560 14026_LC [hu
anti-<huCDH19> 4A2 (1-236)(N30Q, T102A) VL]
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGPGTKVDIKR SEQ ID NO: 561 14027_LC [hu
anti-<huCDH19> 4A2 (1-236)(N30Q, T102A, P141Q) VL]
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKR SEQ ID NO: 562 14028_LC [hu
anti-<huCDH19> 4A2 (1-236)(N30Q, T102A, P141Q) VL]
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKR SEQ ID NO: 563 14029_LC [hu
anti-<huCDH19> 4A2 (1-236)(R29Q, N30S) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKR SEQ ID NO: 564 14030_LC [hu
anti-<huCDH19> 4F3 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR SEQ ID NO: 565 14031_LC [hu
anti-<huCDH19> 4F3 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR SEQ ID NO: 566 14032_LC [hu
anti-<huCDH19> 4F3 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR SEQ ID NO: 567 14033_LC [hu
anti-<huCDH19> 4F3 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR SEQ ID NO: 568 14034_LC [hu
anti-<huCDH19> 4F3 VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKR SEQ ID NO: 569 14039_LC [hu
anti-<huCDH19> 2G6 (1-234)(C42S, D110E) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG SEQ ID NO: 570 14040_LC [hu
anti-<huCDH19> 16C1.1 (1-235)(H105Y) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR SEQ ID NO: 571 14041_LC [hu
anti-<huCDH19> 16C1.1 (1-235)(H105Y) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR SEQ ID NO: 572 14042_LC [hu
anti-<huCDH19> 16C1.1 (1-235)(H105Y) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSS
SYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR SEQ ID NO: 573 14043_LC [hu
anti-<huCDH19> 16C1.1 (1-235)(H105Y) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSS
SYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR SEQ ID NO: 574 14044_LC [hu
anti-<huCDH19> 16C1.1 (1-235)(G95R, H105Y, G141Q) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGNSPLTFGQGTKVEIKR SEQ ID NO: 575 14045_LC [hu
anti-<huCDH19> 17H8.2 (1-235)(G149R) VL]
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKR SEQ ID NO: 576 14046_LC [hu
anti-<huCDH19> 17H8.2 (1-235)(G149R) VL]
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKR SEQ ID NO: 577 14047_LC [hu
anti-<huCDH19> 17H8.2 (1-235)(G149R) VL]
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKR SEQ ID NO: 578 14048_LC [hu
anti-<huCDH19> 17H8.2 (1-235)(S57Y, G149R) VL]
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKR SEQ ID NO: 579 14049_LC [hu
anti-<huCDH19> 4F7 (1-239)(H57Y) VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTRLTVLG SEQ ID NO: 580 14050_LC
[hu anti-<huCDH19> 4F7 (1-239)(H57Y, D110E) VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYESSLSGWVFGGGTRLTVLG SEQ ID NO: 581 14051_LC
[hu anti-<huCDH19> 4F7 (1-239)(D110E) VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYESSLSGWVFGGGTRLTVLG SEQ ID NO: 582 14052_LC
[hu anti-<huCDH19> 4B10 (1-236)(H450, A90T) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR SEQ ID NO: 583 14053_LC [hu
anti-<huCDH19> 4B10 (1-236)(H45Q, A90T) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR SEQ ID NO: 584 14054_LC [hu
anti-<huCDH19> 4B10 (1-236)(H45Q, A90T) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR SEQ ID NO: 585 14055_LC [hu
anti-<huCDH19> 4B10 (1-236)(H45Q, A90T) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKR SEQ ID NO: 586 14056_LC [hu
anti-<huCDH19> 4A9 (1-239)(F47L) VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLG SEQ ID NO: 587 14057_LC
[hu anti-<huCDH19> 4A9 (1-239)(F47L) VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLG SEQ ID NO: 588 14058_LC
[hu anti-<huCDH19> 4A9 (1-239)(F47L, D110E) VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYESRLSGWVFGGGTKLTVLG SEQ ID NO: 589 14059_LC
[hu anti-<huCDH19> 4A9 (1-239)(F47L, D110E) VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYESRLSGWVFGGGTKLTVLG SEQ ID NO: 590 14060_LC
[hu anti-<huCDH19> 20D3.1 (1-235)(S102A) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 591 14061_LC
[hu anti-<huCDH19> 20D3.1 (1-235)(K45Q, S102A) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 592
14062_LC [hu anti-<huCDH19> 20D3.1 (1-235)(K45Q, S102A) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 593 14063_LC
[hu anti-<huCDH19> 20D3.1 (1-235)(K45Q, S102A, D111E, N135Q)
VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDESLQGWVFGGGTKLTVLG SEQ ID NO: 594 14064_LC
[hu anti-<huCDH19> 20D3.1 (1-235)(W109Y) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATYDDSLNGWVFGGGTKLTVLG SEQ ID NO: 595 14065_LC
[hu anti-<huCDH19> 22G10.1 VL]
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKR SEQ ID NO: 596 14066_LC [hu
anti-<huCDH19> 22G10.1 VL]
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKR SEQ ID NO: 597 14067_LC [hu
anti-<huCDH19> 22G10.1 (1-234)(Q97E, S98P) VL]
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKR SEQ ID NO: 598 14068_LC [hu
anti-<huCDH19> 22G10.1 (1-234)(V78F, Q97E, S98P) VL]
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARFSGSGSGTEF
TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKR SEQ ID NO: 599 14069_LC [hu
anti-<huCDH19> 22G10.1 (1-234)(V78F, Q97E, S98P) VL]
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARFSGSGSGTEF
TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKR SEQ ID NO: 600 14070_LC [hu
anti-<huCDH19> 22G10.1 VL]
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKR SEQ ID NO: 601 14071_LC [hu
anti-<huCDH19> 16A4.1 (1-235)(G1410) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSPFTFGQGTKVEIKR SEQ ID NO: 602 14072_LC [hu
anti-<huCDH19> 19B5.1 (1-235)(K45Q, S102A) VL]
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG SEQ ID NO: 603 14073_LC
[hu anti-<huCDH19> 19B5.1 (1-235)(K45Q, S102A) VL]
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG SEQ ID NO: 604 14074_LC
[hu anti-<huCDH19> 19B5.1 (1-235)(T11V, K45Q, S102A) VL]
QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG SEQ ID NO: 605 14075_LC
[hu anti-<huCDH19> 19B5.1 (1-235)(T11V, K45Q, S102A, D111E,
N135Q) VL]
QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCATWDESMQGWVFGGGTKLTVLG SEQ ID NO: 606 14076_LC
[hu anti-<huCDH19> 19B5.1 (1-235)(T11V, K45Q, S102A, W109Y,
D111E, N135Q) VL]
QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCATYDESMQGWVFGGGTKLTVLG SEQ ID NO: 607 14077_LC
[hu anti-<huCDH19> 23A10.3 (1-231)(C42S) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLG SEQ ID NO: 608 14078_LC [hu
anti-<huCDH19> 23A10.3 (1-231)(C42S) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLG SEQ ID NO: 609 14079_LC [hu
anti-<huCDH19> 23A10.3 (1-231)(C42S, D110E) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG SEQ ID NO: 610 14080_LC [hu
anti-<huCDH19> 23A10.3 (1-231)(C42Y) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVYWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLG SEQ ID NO: 611 14081_LC [hu
anti-<huCDH19> 25G10.1 (1-235)(H105Y) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR SEQ ID NO: 612 14082_LC [hu
anti-<huCDH19> 25G10.1 (1-235)(H105Y) VL]
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKR SEQ ID NO: 613 14083_LC [hu
anti-<huCDH19> 26D1.1 (1-235)(S7P) VL]
HSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 614 14084_LC
[hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P) VL]
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 615 14085_LC
[hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P, W109Y) VL]
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVYDDSLNGWVFGGGTKLTVLG SEQ ID NO: 616 14086_LC
[hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P, W109Y, D111E,
N135Q) VL]
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLG SEQ ID NO: 617 14087_LC
[hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P, W109Y, D111E
,N135Q) VL]
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLG SEQ ID NO: 618 14088_LC
[hu anti-<huCDH19> 26D1.1 (1-235)(H1Q, S7P) VL]
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 619 14089_LC
[hu anti-<huCDH19> 26F12.1 (1-235)(S7P) VL]
QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 620 14090_LC
[hu anti-<huCDH19> 26F12.1 (1-235)(S7P, D111E) VL]
QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDESLNGWVFGGGTKLTVLG SEQ ID NO: 621 14091_LC
[hu anti-<huCDH19> 26F12.1 (1-235)(S7P, D111E) VL]
QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDESLNGWVFGGGTKLTVLG SEQ ID NO: 622 14092_LC
[hu anti-<huCDH19> 26F12.1 (1-235)(S7P, W109Y, D111E, N135Q)
VL]
QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLG SEQ ID NO: 623 14093_LC
[hu anti-<huCDH19> 25F8.1 (1-235)(K45Q) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 624 14094_LC
[hu anti-<huCDH19> 25F8.1 (1-235)(K45Q, S102A) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 625 14095_LC
[hu anti-<huCDH19> 25F8.1 (1-235)(K45Q, S102A) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGTKLTVLG SEQ ID NO: 626 14096_LC
[hu anti-<huCDH19> 25F8.1 (1-235)(K45Q, S102A, D111E) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCAAWDESLNGWVFGGGTKLTVLG SEQ ID NO: 627 14097_LC
[hu anti-<huCDH19> 25F8.1 (1-235)(K45Q, S102A, D111E, N135Q)
VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCAAWDESLQGWVFGGGTKLTVLG SEQ ID NO: 628 14098_LC
[hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG SEQ ID NO: 629 14099_LC
[hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A, D111E, N135Q)
VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDESMQGWVFGGGTKLTVLG SEQ ID NO: 630 14100_LC
[hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A, W109Y, D111E,
N135Q) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATYDESMQGWVFGGGTKLTVLG SEQ ID NO: 631 14101_LC
[hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A, W109Y) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATYDDSMNGWVFGGGTKLTVLG SEQ ID NO: 632 14102_LC
[hu anti-<huCDH19> 22D1.1 (1-235)(K45Q, S102A) VL]
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLG SEQ ID NO: 633 13591_LC
[hu anti-<huCDH19> 4F7 VL]
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTRLTVLG SEQ ID NO: 634 14301_LC
[hu anti-<huCDH19> 2G6 (1-234)(D110E) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG SEQ ID NO: 635 14302_LC [hu
anti-<huCDH19> 2G6 (1-234)(C42S, D110E) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG SEQ ID NO: 636 14303_LC [hu
anti-<huCDH19> 2G6 (1-234)(C42S, D110E) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLG SEQ ID NO: 637 14304_LC [hu
anti-<huCDH19> 23A10.3 (1-231)(C42S) VL]
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLG SEQ ID NO: 638
[0493] Anti-CDH19 Variable and Constant Region Polynucleotide and
Amino Acid Sequences
TABLE-US-00013 TABLE IIIa Heavy Chain Variable and Contant Region
Polynucleotide and Amino acid Sequences 2G6
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
GCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
CTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGAC
CGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTGAGAGCT
GAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCGGTATAATAGGAACTATAGGCTACTACTAC
GGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCG
GTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC
AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCAC
ACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCA
GCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAC
AAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTC
CTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACC
CCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTAC
GTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGT
ACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCA
AGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCT
GACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGC
CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCA
AGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG
GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO:
639
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD
RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 640 4A2
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGC
ACTGTCTCTGGTGGCTCCATCAGCAGTAGTGGTTACTACTGGAGCTGGATCCGCCAGCACCCAGGG
AAGGGCCTGGAGTGGATTGGGTACATCTATTACACTGGGAGCGCCTACTACAACCCGTCCCTCAAG
AGTCGAGTTACCATATCAGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACT
GCCGCGGACACGGCCGTGTATTACTGTGCGAGAGATGGAAGCAGTGGCTGGTACTTCCAGTATTGG
GGCCAGGGCACCCTGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCA
CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC
GAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC
CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC
CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCC
CAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTC
AGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGA
GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG
TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA
GCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAA
AGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACA
AGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACT
ACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 641
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV
TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 642 4A9
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
ACTGTCTCTGGTGGCTCCATCAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGAAAGGGA
CTGGAGTGGTTTGCATATTTCTCTTACAGTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA
GTCACCTTATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCG
GACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCTTCCACTTTGACTTCTGGGGCCAGGGAACC
CTGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGA
GCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG
TGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAG
GACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCT
GCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGAC
AAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGAC
GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCC
CCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCC
CAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTC
CCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGC
AGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGA
GCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 643
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT
AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 644 4B10
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTCAGTAGCTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGG
CTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAATGAATACTATGCAGACTCCGTGAAGGGC
CGATTCACCATCTCCAGAGACACTTCCAAGAACACGCTGTATTTGCAAATGAACAGCCTGAGAGCT
GAGGACACGGCTGTATATTACTGTGCGAGAGAACGATATTTTGACTGGTCTTTTGACTACTGGGGC
CAGGGAACCCTGGTCAGCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC
TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA
CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA
CAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAG
ACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAA
ATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG
GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGT
GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCC
TCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC
CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA
CACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAG
GCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAG
AGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC
ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 645
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 646 4F3
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
GCAGCGTCTGGATTCTCCTTCAGTAGCTATGACATGGACTGGGTCCGCCAGACTCCAGGCAAGGGG
CTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAAATACTATGCAGACTCCGTGAGGGGC
CGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTTTCTGCAAATGAACAGCCTGAGAGTC
GAGGACACGGCTGTGTATTACTGTGCGAGAGAAACTGGGGAGGGCTGGTACTTCGATCTCTGGGGC
CGTGGCACCCTGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCT
CCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAAC
CGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTAC
AGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGA
CCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAA
TCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTC
TTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG
GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGT
GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCC
TCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC
CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA
CACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAG
GCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAG
ACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAG
AGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC
ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 647
QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 648 4F7
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
ACTGTCTCTGGTGGCTCCATCAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA
CTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA
GTCACCATATCATTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCG
GACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCTTCCACTTTGACTACTGGGGCCAGGGAACC
CTGGTCACCGTCTCTAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGA
GCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG
TGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAG
GACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCT
GCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGAC
AAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGAC
GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGC
CAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC
TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCC
CCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC
CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCC
CAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTC
CCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGC
AGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGA
GCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 649
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT
KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 650 16A4
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGCGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
ACTGTCTCTGGTGACTCCATCACTAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA
CTGGAGTGGATTGGGTATATCTATTACAGCGGGAGCACCAATTACAACCCCTCCCTCAAGAGTCGA
GTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGCTGCG
GACACGGCCGTGTATTACTGTGCGAGAGATCAAAGGCGGATAGCAGCAGCTGGTACCCACTTCTAC
GGTATGGACGTCTGGGGCCAAGGGACCACGGTCACTGTCTCCTCAGCTTCCACCAAGGGCCCATCC
GTCTTCCCCCTGGCGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC
AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCA
CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCC
AGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
CAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACT
CCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC
CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTA
CGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGT
ACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCA
AGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCT
GACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGC
CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCA
AGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG
GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO:
651
QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTTVTVSSASTKGPSVFPLAPS
SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP
EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 652 16C1
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACTTGT
ACTGTCTCTGGTGGCTCCATCAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA
CTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA
GTCACCATGTCAATAGACACGTCCAAGAACCAGTTCTCCCTGACGCTGAGCTCTTTGACCGCTGCG
GACACGGCCGTGTATTTCTGTGCGAGAGATGGGAGCAGTGGCTGGTACCGGTGGTTCGACCCCTGG
GGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGCG
CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC
GAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC
CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC
CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCC
CAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTC
AGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGA
GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG
TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA
GCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAA
AGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACA
AGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACT
ACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 653
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 654 17H8
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACGTGC
ACTGTCTCTGGTGGCTCCATCAATAGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA
CTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGC
GTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCG
GACACGGCCCTGTATTACTGTGCGAGAGATTCCCGGTATAGAAGTGGCTGGTACGATGCTTTTGAT
ATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCC
CTGGCGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTAC
TTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCG
GCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGG
GCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTT
GAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGA
CCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCA
CATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGC
GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGT
CAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAA
CAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCAC
AGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTG
GTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAA
CTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTG
GACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAA
CCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 655
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 656 19B5
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGC
AAGGTTTCTGGATACACCTTCACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAAGGG
CTTGAATGGATGGGAATTATCAACCCTATTAGTGTTAGCACAAGCTACGCACAGAAGTTCCAGGGC
AGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTGAGATC
TGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGATACAGCTATGGTTACATTTGGACTACTG
GGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGC
GCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC
CGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT
CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGC
CCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG
CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGG
AGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGC
GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA
AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCA
AAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC
TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 657
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 658 20D3
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGC
AAGGTTTCTGGATACACCTTCACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAAGGG
CTTGAGTGGATGGGAATAATCAACCCTATTAGTGTTAGCACAAGCTACGCACAGAAGTTCCAGGGC
AGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTGAGATC
TGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGATACAGCTATGGTTACATTTTGACTACTG
GGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGC
GCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC
CGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT
CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGC
CCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG
CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGG
AGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGC
GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA
AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCA
AAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC
TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 659
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 660 22D1
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAGGGTTTCCTGC
AAGGTTTCTGGATACACCTTCACCAGCTACTTTATTCACTGGGTACGCCAGGCCCCTGGACAAGGG
CTTGAGTGGATGGGAATAATCAACCCTATTAGTGTTAGCACAAGCTACGCACAGAAGTTCCAGGGC
AGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTGAGATC
TGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGATACAGCTATGGTTACATTTGGACTACTG
GGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGC
GCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC
CGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT
CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGC
CCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG
CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGG
AGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGC
GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA
AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCA
AAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC
TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 661
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 662 22G10
GAGGTGCAACTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGT
GCAGCCTCTGGATTCACCTTTAGCAGTTATGCCATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGG
CTGGAGTGGGTCTCAACTATTAGTGGTGGTGGTGCTAACACATACTACGCAGACTCCGTGAAGGGC
CGGTTCACCATCTCCAGTGACAATTCCAAGAGCACGCTGTATCTGCAAATGAACAGCCTGAGAGCC
GCGGACACGGCCGTATATCACTGTGCGAAAGGGGGAATGGGGGGATACTACTACGGTATGGACGT
CTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCT
GGCGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTT
CCCCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGC
TGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGC
ACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGA
GCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACC
GTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACA
TGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCA
GCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACA
AAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAG
GTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTC
AAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTA
CAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC
TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 663
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP
SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 664 23A10
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGT
GCAGCGTCTGGATTCACCTTCAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAGGGG
CTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAAATACTATGCAGACTCCGTGAAGGGC
CGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCTAATGAACAGCCTGAGAGCC
GAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCGGTATACCTGGAACTACGGGCTACTACTAT
GGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCC
GTCTTCCCCCTGGCGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTC
AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCA
CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCC
AGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGA
CAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACT
CCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC
CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTA
CGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGT
ACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCA
AGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCC
CGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCT
GACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGC
CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCA
AGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG
GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO:
665
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGR
FTISRDNSKNTLYLLMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 666 25F8
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGC
AAGGCATCTGGATACACCTTCACCAGCTACTATATTCACTGGGTGCGCCAGGCCCCTGGACAAGGA
CTTGAGTGGATGGGAATAATCAACCCCAGTGGTGGTAGCACAAGGTACGCACAGAAGTTCCAGGG
CAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTGAGAT
CTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGAATACAGCTATGGTTACATTTTGACTACT
GGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGG
CGCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCC
CCGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG
TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCA
CCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAG
CCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCG
TCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACAT
GCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG
GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAG
CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA
AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCA
AAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC
TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 667
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 668
25G10
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGC
ACTGTCTCTGGTGGCTCCATCAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGA
CTGGAGTGGATTGGGTATATCTATTACATTGGGAGCACCAACTACAACCCCTCCCTCAAGAGTCGA
GTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCTGCG
GACACGGCCGTGTATTACTGTGCGAGAGATGGGAGCAGTGGCTGGTACCGGTGGTTCGACCCCTGG
GGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGCG
CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC
GAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC
CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC
CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCC
CAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTC
AGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGA
GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG
TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA
GCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGT
GTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAA
AGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACA
AGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACA
AGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACT
ACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 669
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
VDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG SEQ ID NO: 670 26D1
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGT
AAGGCATCTAGATACACCTTCACCAGCTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAAGGG
CTTGAGTGGATGGGAATAATCCACCCTAGTGGTGGTGACACAACCTACGCACAGAAGTTCCAGGGC
AGAGTCACCATGACCGGGGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATC
TGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGATAAAACTATGGTTACATTTTGACTATTG
GGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGC
GCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC
CGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT
CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGC
CCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG
CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGG
AGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGC
GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA
AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCA
AAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC
TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 671
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 672 26F12
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGC
AAGGCATCTAGATACACCTTCACCAACTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAAGGG
CTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTGACTCAACCTACGCACAGAAGTTCCAGGGC
AGACTCACCATGACCGGGGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATC
TGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGATACAACTATGGTTACATTTTGACTACTG
GGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTTCCACCAAGGGCCCATCCGTCTTCCCCCTGGC
GCCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCC
CGAACCGGTGACGGTGTCGTGGAACTCAGGGGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT
CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCAC
CCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGC
CCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGT
CAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG
CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGG
AGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGC
GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA
AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGG
TGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCA
AAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC
AAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGAC
AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC
TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA SEQ ID NO: 673
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 674
TABLE-US-00014 TABLE IIIb Light Chain Variable and Contant Region
Polynucleotide and Amino acid Sequences 2G6
TCCTATGAACTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCTGC
TCTGGAGATAGGTTGGGGGAAAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCTTTG
CTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCT
GGTAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAG
GCGTGGGACAGCAGCACTGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTCAGCCCAA
GGCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTCCAAGCCAACAAGGCCACACT
AGTGTGTCTGATCAGTGACTTCTACCCGGGAGCTGTGACAGTGGCCTGGAAGGCAGATGGCAGCCC
CGTCAAGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAGTACGCGGCCAGCA
GCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTCACGCAT
GAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ ID NO: 675
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA
PTECS SEQ ID NO: 676 4A2
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
GCAGGGCCAGTCGGAATATTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT
CCCAGGCTCCTCATCTATGGTCCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT
GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTACAGTGTATTAC
TGTCAGCAGTATGGTAGCTCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAACGTACGGTG
GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTG
TGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC
AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC
AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCA
TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA SEQ ID NO: 677
EIVLTQSPGTLSLSPGERATLSCRASRNISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC SEQ ID NO: 678 4A9
CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAGGACAGAGGGTCACCATCTCCTGC
ACTGGGAGCAGCTCCAACATCGGGACAGGTTATGCTGTACACTGGTACCAGCAGTTTCCAGGAACA
GCCCCCAAACTCCTCATCTATGGTAACAACAATCGGCCCTCAGGGGTTCCTGACCGATTCTCTGGCT
CCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCTGATTATT
ACTGCCAGTCCTATGACAGCAGACTGAGTGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCC
TAGGTCAGCCCAAGGCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTCCAAGCCA
ACAAGGCCACACTAGTGTGTCTGATCAGTGACTTCTACCCGGGAGCTGTGACAGTGGCCTGGAAGG
CAGATGGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAG
TACGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCACAGAAGCTACAGCTG
CCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ
ID NO: 679
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQFPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 680 4B10
GAAATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
GCAGGGCCAGTCAGAGTGTTAGCAACACCTACTTAGCCTGGTACCATCAGAGACCTGGCCAGGCTC
CCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGATTCAGTGGCAGTG
GGTCTGGGACAGACTTCGCTCTCACCATCAGCAGTCTGGAGCCTGAAGATTTTGCAGTGTATTACT
GTCAGCAGTACAGTAACTCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTG
GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTG
TGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC
AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC
AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCA
TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA SEQ ID NO: 681
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FALTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 682 4F3
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
GCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT
CCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT
GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAACCTGAGGATTTTGCAGTGTATTAC
TGTCAGCAGTATGGTAGCTCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGTACGGT
GGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTT
GTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC
CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAG
CAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCC
ATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA SEQ ID NO:
683
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 684 4F7
CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAGGGCAGAGGGTCACCATCTCCTGC
ACTGGGAGCAGCTCCAATATCGGGACAGGTTATGATGTACACTGGTATCAGCAGCTTCCAGGAACA
GCCCCCAAACTCCTCATCCATGGTAACAGCAATCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGC
TCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCTGATTAT
TACTGCCAGTCCTATGACAGCAGTCTGAGTGGTTGGGTGTTCGGCGGAGGGACCAGGTTGACCGTC
CTAGGTCAGCCCAAGGCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTCCAAGCC
AACAAGGCCACACTAGTGTGTCTGATCAGTGACTTCTACCCGGGAGCTGTGACAGTGGCCTGGAAG
GCAGATGGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAA
GTACGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCACAGAAGCTACAGCT
GCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ
ID NO: 685
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTRLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 686 16A4
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
GCAGGGCCAGTCAGAGTGTTAGCAGCAGTTATTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTC
CCAGGCTCCTCATCTATGGTACATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTG
GGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTATT
GTCAGCAGTACGGTAGCTCACCTTTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTG
TGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCTGT
TGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCT
CCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCA
GCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC
CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA SEQ ID NO:
687
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSPFTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 688 16C1
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
GCAGGGCCAGCCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT
CCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT
GGGTCTGGGACAGACTTCACTCTCACCATCAGCGGACTGGAGCCTGAAGATTTTGCAGTGTATCAC
TGTCAGCAGTATGGTAACTCACCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACT
GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCTG
TTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCC
TCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCAC
CCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA SEQ ID NO:
689
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 690 17H8
GACATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
GCAGGGCCAGTCAGAGTGTTGCCGGCAGCTACCTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT
CCCAGGCTCCTCATCTCTGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT
GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTAC
TGTCAGCAGTATGGTAAATCACCGATCACCTTCGGCCAAGGGACACGACTGGAGATGAAAGGAAC
TGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCT
GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCC
CTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCT
CAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCA
CCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA SEQ ID NO:
691
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC SEQ ID NO: 692 19B5
CAGTCTGCGCTGACTCAGCCACCCTCAACGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGT
TCTGGAAGCAGGTCCAACATCGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACGGC
CCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCC
AAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGATTATTACT
GCGCAACATGGGATGACAGTATGAATGGTTGGGTGTTCGGCGGAGGGACCAAACTGACCGTCCTA
GGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAAC
AAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCA
GATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTA
CGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCC
AGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ ID
NO: 693
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 694 20D3
CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGT
TCTGGAAGCAGCTCCAACATCGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACGGCC
CCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCA
AGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGATTATTACTG
TGCAACATGGGATGACAGCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAG
GTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACA
AGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAG
ATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC
GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCA
GGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ ID
NO: 695
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 696 22D1
CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGT
TCTGGAAGCAGCTCCAACATCGGAAGCAATTTTGTAAACTGGTACAAGCAGCTCCCAGGAACGGCC
CCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCA
AGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGATTATTACTG
TGCAACATGGGATGACAGTATGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAG
GTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACA
AGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAG
ATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC
GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCA
GGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ ID
NO: 697
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 698 22G10
GAAATAGTGATGACGCAGTCTCCAGTCACCCTGTCTCTGTCTCTAGGGGAAAGAGCCACCCTCTCC
TGCAGGGCCAGTCAGAGTATTAGCAGCAACTTAGCCTGGTTCCAGCAGAAACCTGGCCAGGCTCCC
AGACTCCTCATCTATGGTGCATTTACCAGGGCCACTGGTATCCCAGCCAGGGTCAGTGGCAGTGGG
TCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGATTTTGCAGTTTATTACTGTC
AGCAGTATAATTACTGGCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAGCGAACTGTG
GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCTGTTG
TGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC
AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC
AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCA
TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA SEQ ID NO: 699
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 700 23A10
TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCTGC
TCTGGAGATAGATTGGGGGAGAAATATGTTTGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCTATA
CTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTG
GGAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGG
CGTGGGACAGCAGCACTGTGGTATTCGGCGGGGGGACCAAGCTGACCGTCCTAGGTCAGCCCAAG
GCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCCACACTG
GTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCC
GTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCCAGCAG
CTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTCACGCATGA
AGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ ID NO: 701
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVCWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDF
YPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS SEQ ID NO: 702 25F8
CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGT
TCTGGAAGCAGCTCCAACATCGGAAGGAATTTTGTAAACTGGTATAAGCAGCTCCCAGGAACGGCC
CCCAAAGTCCTCATTTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCA
AGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGTCTGATTATTACTG
TGCAGCATGGGATGACAGCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAG
GTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACA
AGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAG
ATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTAC
GCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCA
GGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ ID
NO: 703
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 704 25G10
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCT
GCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCT
CCCAGGCTCCTCATCTTTGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGT
GGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATCAC
TGTCAGCAGTATGGTAACTCACCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACT
GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGTACCGCCTCTG
TTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCC
TCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCAC
CCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTGA SEQ ID NO:
705
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 706 26D1
CACTCTGTGCTGACTCAGTCACCCTCAGCGTCTGGGACCCCCGGACAGAGGGTCACCATCTCTTGTT
CTGGAAGCCGCTCCAACATCGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACGGCCC
CCAAACTCCTCATCTATACTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAA
GTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTACTGT
GCAGTATGGGATGACAGCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGG
TCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACAA
GGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGA
TAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACG
CGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAG
GTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ ID
NO: 707
HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 708 26F12
CAGTCTGTGCTGACTCAGTCACCCTCAGCGTCTGGGACCCCCGGGCAGAAGGTCACCATCTCTTGTT
CTGGAAGCCGCTCCAACATCGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACGGCCC
CCAAACTCCTCATCTATACTAATTATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAA
GTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTACTGT
GCAGTATGGGATGACAGCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGG
TCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCACCCTCCTCTGAGGAGCTTCAAGCCAACAA
GGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGA
TAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACG
CGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAG
GTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCATGA SEQ ID
NO: 709
QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 710
TABLE-US-00015 TABLE IIIc Heavy Chain Variable and Contant Region
Polynucleotide and Amino acid Sequences 13586_HC [hu
anti-<huCDH19> 4F3 VH]::huIgG1z
QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 711 13589_HC [hu
anti-<huCDH19> 4A9 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT
AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 712 13590_HC [hu
anti-<huCDH19> 4B10 VH]::huIgG1z
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 713 13874_HC [hu
anti-<huCDH19> 17H8.2 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 714 13875_HC [hu
anti-<huCDH19> 16C1.1 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 715 13876_HC [hu
anti-<huCDH19> 16A4.1 VH]::huIgG1z
QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTTVTVSSASTKGPSVFPLAPS
SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP
EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 716 13877_HC
[hu anti-<huCDH19> 22G10.1 VH]::huIgG1z
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP
SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 717 13878_HC
[hu anti-<huCDH19> 20D3.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 718 13879_HC [hu
anti-<huCDH19> 22D1.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 719 13880_HC [hu
anti-<huCDH19> 25F8.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 720 13881_HC [hu
anti-<huCDH19> 26F12.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 721 13882_HC [hu
anti-<huCDH19> 26D1.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 722 13883_HC [hu
anti-<huCDH19> 25G10.1 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
VDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 723 13885_HC [hu
anti-<huCDH19> 19B5.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 724 14022_HC [hu
anti-<huCDH19> 4A2 VH]::huIgG1z
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV
TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 725 14024_HC [hu
anti-<huCDH19> 4A2 (1-472)(Q17E, H47P) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT
ISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 726 14025_HC [hu
anti-<huCDH19> 4A2 VH]::huIgG1z
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV
TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 727 14026_HC [hu
anti-<huCDH19> 4A2 (1-472)(Q17E, H47P) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT
ISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 728 14027_HC [hu
anti-<huCDH19> 4A2 (1-472)(Q17E, H47P, D111E) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT
ISVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 729 14028_HC [hu
anti-<huCDH19> 4A2 (1-472)(Q17E, H47P, D111E, W134Y)
VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPPGKGLEWIGYIYYTGSAYYNPSLKSRVT
ISVDTSKNQFSLKLSSVTAADTAVYYCAREGSSGYYFQYWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 730 14029_HC [hu
anti-<huCDH19> 4A2 VH]::huIgG1z
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSSGYYWSWIRQHPGKGLEWIGYIYYTGSAYYNPSLKSRV
TISVDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 731 14030_HC [hu
anti-<huCDH19> 4F3 (1-471)(R17G) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQTPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 732 14031_HC [hu
anti-<huCDH19> 4F3 (1-471)(R17G, T47A) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 733 14032_HC [hu
anti-<huCDH19> 4F3 (1-471)(R17G, T47A, R141Q) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYDGSNKYYADSVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 734 14033_HC [hu
anti-<huCDH19> 4F3 (1-471)(R17G, T47A, D61E, D72E,
R141Q) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYEGSNKYYAESVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGWYFDLWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 735 14034_HC [hu
anti-<huCDH19> 4F3 (1-471)(R17G, T47A, D61E, D72E, W134Y,
R141Q) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYDMDWVRQAPGKGLEWVAVIWYEGSNKYYAESVRG
RFTISRDNSKNTLFLQMNSLRVEDTAVYYCARETGEGYYFDLWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 736 14039_HC [hu
anti-<huCDH19> 2G6 (1-477)(R17G, D61E, D72E, K94N)
VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYEGSNKYYAESVKD
RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 737
14040_HC [hu anti-<huCDH19> 16C1.1 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLTLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 738 14041_HC [hu
anti-<huCDH19> 16C1.1 (1-469)(T92K) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 739 14042_HC [hu
anti-<huCDH19> 16C1.1 (1-469)(T92K, D109E) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLKLSSLTAADTAVYFCAREGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 740 14043_HC [hu
anti-<huCDH19> 16C1.1 (1-469)(T92K, W132Y, W135Y)
VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGYYRYFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSG
GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP
SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 741 14044_HC [hu
anti-<huCDH19> 16C1.1 (1-469)(T92K) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
IDTSKNQFSLKLSSLTAADTAVYFCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 742 14045_HC [hu
anti-<huCDH19> 17H8.2 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 743 14046_HC [hu
anti-<huCDH19> 17H8.2 (1-471)(D109E) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARESRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 744 14047_HC [hu
anti-<huCDH19> 17H8.2 (1-471)(D109E, W132Y) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARESRYRSGYYDAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 745 14048_HC [hu
anti-<huCDH19> 17H8.2 (1-471)(D109E) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTALYYCARESRYRSGWYDAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 746 14049_HC [hu
anti-<huCDH19> 4F7 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT
KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 747 14050_HC [hu
anti-<huCDH19> 4F7 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT
KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 748 14051_HC [hu
anti-<huCDH19> 4F7 (1-468)(W113Y) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNYAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT
KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 749 14052_HC [hu
anti-<huCDH19> 4B10 (1-471)(R17G, D61E, D72E, W134Y)
VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYEGTNEYYAESVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDYSFDYWGQGTLVSVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 750 14053_HC [hu
anti-<huCDH19> 4B10 VH]::huIgG1z
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 751 14054_HC [hu
anti-<huCDH19> 4B10 (1-471)(R17G) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYDGTNEYYADSVKG
RFTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 752 14055_HC [hu
anti-<huCDH19> 4B10 (1-471)(R17G, D61E, D72E) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVAVISYEGTNEYYAESVKGR
FTISRDTSKNTLYLQMNSLRAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 753 14056_HC [hu
anti-<huCDH19> 4A9 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWFAYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT
AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 754 14057_HC [hu
anti-<huCDH19> 4A9 (1-468)(F55I, A56G) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT
AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 755 14058_HC [hu
anti-<huCDH19> 4A9 (1-468)(F55I, A56G) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT
AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN
TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 756 14059_HC [hu
anti-<huCDH19> 4A9 (1-468)(F55I, A56G, W113Y) VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYFSYSGSTNYNPSLKSRVTLS
VDTSKNQFSLKLSSVTAADTAVYYCARNYAFHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT
KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 757 14060_HC [hu
anti-<huCDH19> 20D3.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 758 14061_HC [hu
anti-<huCDH19> 20D3.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 759 14062_HC [hu
anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 760 14063_HC [hu
anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 761 14064_HC [hu
anti-<huCDH19> 20D3.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 762 14065_HC [hu
anti-<huCDH19> 22G10.1 (1-470)(S82R, A99E) VH]::huIgG1z
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISRDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP
SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 763 14066_HC
[hu anti-<huCDH19> 22G10.1 (1-470)(A99E, H105Y) VH]::huIgG1z
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAEDTAVYYCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP
SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 764 14067_HC
[hu anti-<huCDH19> 22G10.1 (1-470)(A99E) VH]::huIgG1z
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP
SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 765 14068_HC
[hu anti-<huCDH19> 22G10.1 (1-470)(A99E) VH]::huIgG1z
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP
SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 766 14069_HC
[hu anti-<huCDH19> 22G10.1 (1-470)(D72E,A99E) VH]::huIgG1z
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYAESVKGRF
TISSDNSKSTLYLQMNSLRAEDTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPS
SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP
EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 767 14070_HC
[hu anti-<huCDH19> 22G10.1 (1-470)(H105Y) VH]::huIgG1z
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSTISGGGANTYYADSVKGR
FTISSDNSKSTLYLQMNSLRAADTAVYYCAKGGMGGYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP
SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 768 14071_HC
[hu anti-<huCDH19> 16A4.1 (1-474)(T144L) VH]::huIgG1z
QVQLQESGPGLAKPSETLSLTCTVSGDSITSYYWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISV
DTSKNQFSLKLSSVTAADTAVYYCARDQRRIAAAGTHFYGMDVWGQGTLVTVSSASTKGPSVFPLAPS
SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP
EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 769 14072_HC
[hu anti-<huCDH19> 19B5.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 770 14073_HC [hu
anti-<huCDH19> 19B5.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 771 14074_HC [hu
anti-<huCDH19> 19B5.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 772 14075_HC [hu
anti-<huCDH19> 19B5.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 773 14076_HC [hu
anti-<huCDH19> 19B5.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 774 14077_HC [hu
anti-<huCDH19> 23A10.3 (1-474)(L920) VH]::huIgG1z
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGR
FTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 775
14078_HC [hu anti-<huCDH19> 23A10.3 (1-474)(R17G, L920)
VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG
RFTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPSVF
PLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 776
14079_HC [hu anti-<huCDH19> 23A10.3 (1-474)(R17G, D61E, D72E,
L920) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYEGSNKYYAESVKGR
FTISRDNSKNTLYLQMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 777
14080_HC [hu anti-<huCDH19> 23A10.3 VH]::huIgG1z
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGR
FTISRDNSKNTLYLLMNSLRAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 778
14081_HC [hu anti-<huCDH19> 25G10.1 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
VDTSKNQFSLKLSSVTAADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKST
SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 779 14082_HC [hu
anti-<huCDH19> 25G10.1 (1-469)(D109E, W132Y, W135Y)
VH]:huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGKGLEWIGYIYYIGSTNYNPSLKSRVTMS
VDTSKNQFSLKLSSVTAADTAVYYCAREGSSGYYRYFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTS
GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK
PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 780 14083_HC [hu
anti-<huCDH19> 26D1.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 781 14084_HC [hu
anti-<huCDH19> 26D1.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 782 14085_HC [hu
anti-<huCDH19> 26D1.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 783 14086_HC [hu
anti-<huCDH19> 26D1.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 784 14087_HC [hu
anti-<huCDH19> 26D1.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIKLYLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 785 14088_HC [hu
anti-<huCDH19> 26D1.1 (1-469)(R27G, G82R) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMSWVRQAPGQGLEWMGIIHPSGGDTTYAQKFQGR
VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 786 14089_HC [hu
anti-<huCDH19> 26F12.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 787 14090_HC [hu
anti-<huCDH19> 26F12.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 788 14091_HC [hu
anti-<huCDH19>26F12.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 789 14092_HC [hu
anti-<huCDH19> 26F12.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQGLEWMGIINPSGGDSTYAQKFQG
RLTMTGDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 790 14093_HC [hu
anti-<huCDH19> 25F8.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 791 14094_HC [hu
anti-<huCDH19> 25F8.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 792 14095_HC [hu
anti-<huCDH19> 25F8.1 (1-469)(F90Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 793 14096_HC [hu
anti-<huCDH19>25F8.1 (1-469)(F90Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSASTKGPSVFPLAPSS
KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 794 14097_HC [hu
anti-<huCDH19> 25F8.1 (1-469)(F90Y, W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGIINPSGGSTRYAQKFQGR
VTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLYLHFDYWGQGTLVTVSSASTKGPSVFPLAPSSK
STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 795 14098_HC [hu
anti-<huCDH19> 22D1.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 796 14099_HC [hu
anti-<huCDH19> 22D1.1 VH]::huIgG1z
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 797 14100_HC [hu
anti-<huCDH19> 22D1.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 798 14101_HC [hu
anti-<huCDH19> 22D1.1 (1-469)(W133Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVFMELSSLRSEDTAVYYCARGGIQLYLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 799 14102_HC [hu
anti-<huCDH19> 22D1.1 (1-469)(F90Y) VH]::huIgG1z
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQGLEWMGIINPISVSTSYAQKFQGRV
TMTRDTSTSTVYMELSSLRSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSASTKGPSVFPLAPSSKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 800 13591_HC [hu
anti-<huCDH19> 4F7 VH]::huIgG1z
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTISL
DTSKNQFSLKLSSVTAADTAVYYCARNWAFHFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT
KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 801 14301_HC [hu
anti-<huCDH19> 2G6 VH]::huIgG1z
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD
RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 802
14302_HC [hu anti-<huCDH19> 2G6 (1-477)(R17G, K94N)
VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD
RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 803
14303_HC [hu anti-<huCDH19> 2G6 (1-477)(D61E, D72E)
VH]::huIgG1z
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYEGSNKYYAESVKD
RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 804
14304_HC [hu anti-<huCDH19> 2G6 (1-477)(R17G) VH]::huIgG1z
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFIWYDGSNKYYADSVKD
RFTISRDNSKNTLYLQMKSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSASTKGPSVFP
LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 805
TABLE-US-00016 TABLE IIId Light Chain Variable and Contant Region
Polynucleotide and Amino acid Sequences 13586_LC [hu
anti-<huCDH19> 4F3 VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 806 13589_LC [hu anti-<huCDH19> 4A9
VL]::huLLC-C1
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQFPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 807 13590_LC [hu anti-<huCDH19> 4B10
VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FALTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 808 13874_LC [hu anti-<huCDH19> 17H8.2
VL]::huKLC
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC SEQ ID NO: 809 13875_LC [hu anti-<huCDH19> 16C1.1
VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 810 13876_LC [hu anti-<huCDH19> 16A4.1
VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSPFTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 811 13877_LC [hu anti-<huCDH19> 22G10.1
VL]::huKLC
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 812 13878_LC [hu anti-<huCDH19> 20D3.1
VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 813 13879_LC [hu anti-<huCDH19> 22D1.1
VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 814 13880_LC [hu anti-<huCDH19> 25F8.1
VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 815 13881_LC [hu anti-<huCDH19> 26F12.1
VL]::huLLC-C2
QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 816 13882_LC [hu anti-<huCDH19> 26D1.1
VL]::huLLC-C2
HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 817 13883_LC [hu anti-<huCDH19> 25G10.1
VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYHCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 818 13885_LC [hu anti-<huCDH19> 19B5.1
VL]::huLLC-C2
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 819 14022_LC [hu anti-<huCDH19> 4A2
(1-236)(N30Q) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC SEQ ID NO: 820 14024_LC [hu anti-<huCDH19> 4A2
(1-236)(N30Q, T102A, P141Q) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC SEQ ID NO: 821 14025_LC [hu anti-<huCDH19> 4A2
(1-236)(N30Q, T102A) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC SEQ ID NO: 822 14026_LC [hu anti-<huCDH19> 4A2
(1-236)(N30Q, T102A) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC SEQ ID NO: 823 14027_LC [hu anti-<huCDH19> 4A2
(1-236)(N30Q, T102A, P141Q) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC SEQ ID NO: 824 14028_LC [hu anti-<huCDH19> 4A2
(1-236)(N30Q, T102A, P141Q) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFAVYYCQQYGSSFTFGQGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC SEQ ID NO: 825 14029_LC [hu anti-<huCDH19> 4A2
(1-236)(R29Q, N30S) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSISSSYLAWYQQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDF
TLTISRLEPEDFTVYYCQQYGSSFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
GEC SEQ ID NO: 826 14030_LC [hu anti-<huCDH19> 4F3 VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 827 14031_LC [hu anti-<huCDH19> 4F3
VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 828 14032_LC [hu anti-<huCDH19> 4F3
VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 829 14033_LC [hu anti-<huCDH19> 4F3
VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 830 14034_LC [hu anti-<huCDH19> 4F3
VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 831 14039_LC [hu anti-<huCDH19> 2G6
(1-234)(C42S, D110E) VL]::huLLC-C1
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA
PTECS SEQ ID NO: 832 14040_LC [hu anti-<huCDH19> 16C1.1
(1-235)(H105Y) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 833 14041_LC [hu anti-<huCDH19> 16C1.1
(1-235)(H105Y) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 834 14042_LC [hu anti-<huCDH19> 16C1.1
(1-235)(H105Y) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 835 14043_LC [hu anti-<huCDH19> 16C1.1
(1-235)(H105Y) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISGLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 836 14044_LC [hu anti-<huCDH19> 16C1.1
(1-235)(G95R, H105Y, G141Q) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGNSPLTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 837 14045_LC [hu anti-<huCDH19> 17H8.2
(1-235)(G149R) VL]::huKLC
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC SEQ ID NO: 838 14046_LC [hu anti-<huCDH19> 17H8.2
(1-235)(G149R) VL]::huKLC
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC SEQ ID NO: 839 14047_LC [hu anti-<huCDH19> 17H8.2
(1-235)(G149R) VL]::huKLC
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC SEQ ID NO: 840 14048_LC [hu anti-<huCDH19> 17H8.2
(1-235)(S57Y, G149R) VL]::huKLC
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT
DFTLTISRLEPEDFAVYYCQQYGKSPITFGQGTRLEMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC SEQ ID NO: 841 14049_LC [hu anti-<huCDH19> 4F7
(1-239)(H57Y) VL]::huLLC-C2
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTRLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 842 14050_LC [hu anti-<huCDH19> 4F7
(1-239)(H57Y, D110E) VL]::huLLC-C2
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYESSLSGWVFGGGTRLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 843 14051_LC [hu anti-<huCDH19> 4F7
(1-239)(D110E) VL]::huLLC-C2
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYESSLSGWVFGGGTRLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 844 14052_LC [hu anti-<huCDH19> 4B10
(1-236)(H45Q, A90T) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
RGEC SEQ ID NO: 845 14053_LC [hu anti-<huCDH19> 4B10
(1-236)(H45Q, A90T) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
RGEC SEQ ID NO: 846 14054_LC [hu anti-<huCDH19> 4B10
(1-236)(H45Q, A90T) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
RGEC SEQ ID NO: 847 14055_LC [hu anti-<huCDH19> 4B10
(1-236)(H45Q, A90T) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTD
FTLTISSLEPEDFAVYYCQQYSNSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN
RGEC SEQ ID NO: 848 14056_LC [hu anti-<huCDH19> 4A9
(1-239)(F47L) VL]::huLLC-C1
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 849 14057_LC [hu anti-<huCDH19> 4A9
(1-239)(F47L) VL]::huLLC-C1
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSRLSGWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 850 14058_LC [hu anti-<huCDH19> 4A9
(1-239)(F47L, D110E) VL]::huLLC-C1
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYESRLSGWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 851 14059_LC [hu anti-<huCDH19> 4A9
(1-239)(F47L, D110E) VL]::huLLC-C1
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYESRLSGWVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 852 14060_LC [hu anti-<huCDH19> 20D3.1
(1-235)(S102A) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 853 14061_LC [hu anti-<huCDH19> 20D3.1
(1-235)(K45Q, S102A) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 854 14062_LC [hu anti-<huCDH19> 20D3.1
(1-235)(K45Q, S102A) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 855 14063_LC [hu anti-<huCDH19> 20D3.1
(1-235)(K45Q, S102A, D111E, N135Q) VL]:: huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDESLQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 856 14064_LC [hu anti-<huCDH19> 20D3.1
(1-235)(W109Y) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDESDYYCATYDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 857 14065_LC [hu anti-<huCDH19> 22G10.1
VL]::huKLC
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 858 14066_LC [hu anti-<huCDH19> 22G10.1
VL]::huKLC
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 859 14067_LC [hu anti-<huCDH19> 22G10.1
(1-234)(Q97E, S98P) VL]::huKLC
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 860 14068_LC [hu anti-<huCDH19> 22G10.1
(1-234)(V78F, Q97E, S98P) VL]::huKLC
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARFSGSGSGTEF
TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 861 14069_LC [hu anti-<huCDH19> 22G10.1
(1-234)(V78F, Q97E, S98P) VL]::huKLC
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARFSGSGSGTEF
TLTISSLEPEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 862 14070_LC [hu anti-<huCDH19> 22G10.1
VL]::huKLC
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEF
TLTISSLQSEDFAVYYCQQYNYWPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 863 14071_LC [hu anti-<huCDH19> 16A4.1
(1-235)(G141Q) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGSSPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 864 14072_LC [hu anti-<huCDH19> 19B5.1
(1-235)(K45Q, S102A) VL]::huLLC-C2
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCL
ISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVE
KTVAPTECS SEQ ID NO: 865 14073_LC [hu anti-<huCDH19> 19B5.1
(1-235)(K45Q, S102A) VL]::huLLC-C2
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCL
ISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVE
KTVAPTECS SEQ ID NO: 866 14074_LC [hu anti-<huCDH19> 19B5.1
(1-235)(T11V, K45Q, S102A) VL]::huLLC-C2
QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 867 14075_LC [hu anti-<huCDH19> 19B5.1
(1-235)(T11V, K45Q, S102A, D111E, N135Q) VL]::huLLC-C2
QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCATWDESMQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 868 14076_LC [hu anti-<huCDH19> 19B5.1
(1-235)(T11V, K45Q, S102A, W109Y, D111E, N135Q) VL]::huLLC-C2
QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCATYDESMQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 869 14077_LC [hu anti-<huCDH19> 23A10.3
(1-231)(C42S) VL]::huLLC-C2
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDF
YPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS SEQ ID NO: 870 14078_LC [hu anti-<huCDH19> 23A10.3
(1-231)(C42S) VL]::huLLC-C2
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDF
YPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS SEQ ID NO: 871 14079_LC [hu anti-<huCDH19> 23A10.3
(1-231)(C42S, D110E) VL]::huLLC-C2
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDF
YPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS SEQ ID NO: 872 14080_LC [hu anti-<huCDH19> 23A10.3
(1-231)(C42Y) VL]::huLLC-C2
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVYWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDF
YPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS SEQ ID NO: 873 14081_LC [hu anti-<huCDH19> 25G10.1
(1-235)(H105Y) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 874 14082_LC [hu anti-<huCDH19> 25G10.1
(1-235)(H105Y) VL]::huKLC
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTD
FTLTISRLEPEDFAVYYCQQYGNSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF
NRGEC SEQ ID NO: 875 14083_LC [hu anti-<huCDH19> 26D1.1
(1-235)(S7P) VL]::huLLC-C2
HSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 876 14084_LC [hu anti-<huCDH19> 26D1.1
(1-235)(H1Q, S7P) VL]::huLLC-C2
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 877 14085_LC [hu anti-<huCDH19> 26D1.1
(1-235)(H1Q, S7P, W109Y) VL]::huLLC-C2
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVYDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 878 14086_LC [hu anti-<huCDH19> 26D1.1
(1-235)(H1Q, S7P, W109Y, D111E, N135Q) VL]::huLLC-C2
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 879 14087_LC [hu anti-<huCDH19> 26D1.1
(1-235)(H1Q, S7P, W109Y, D111E, N135Q) VL]::huLLC-C2
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 880 14088_LC [hu anti-<huCDH19> 26D1.1
(1-235)(H1Q, S7P) VL]::huLLC-C2
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 881 14089_LC [hu anti-<huCDH19> 26F12.1
(1-235)(S7P) VL]::huLLC-C2
QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 882 14090_LC [hu anti-<huCDH19> 26F12.1
(1-235)(S7P, D111E) VL]::huLLC-C2
QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDESLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 883 14091_LC [hu anti-<huCDH19> 26F12.1
(1-235)(S7P, D111E) VL]::huLLC-C2
QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVWDESLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 884 14092_LC [hu anti-<huCDH19> 26F12.1
(1-235)(S7P, W109Y, D111E, N135Q) VL]:: huLLC-C2
QSVLTQPPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCAVYDESLQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 885 14093_LC [hu anti-<huCDH19> 25F8.1
(1-235)(K45Q) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDESDYYCAAWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 886 14094_LC [hu anti-<huCDH19> 25F8.1
(1-235)(K45Q, S102A) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 887 14095_LC [hu anti-<huCDH19> 25F8.1
(1-235)(K45Q, S102A) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 888 14096_LC [hu anti-<huCDH19> 25F8.1
(1-235)(K45Q, S102A, D111E) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCAAWDESLNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 889 14097_LC [hu anti-<huCDH19> 25F8.1
(1-235)(K45Q, S102A, D111E, N135Q) VL]:: huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGT
SASLAISGLQSEDEADYYCAAWDESLQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 890 14098_LC [hu anti-<huCDH19> 22D1.1
(1-235)(K45Q, S102A) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCL
ISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVE
KTVAPTECS SEQ ID NO: 891 14099_LC [hu anti-<huCDH19> 22D1.1
(1-235)(K45Q, S102A, D111E, N135Q) VL]:: huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDESMQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCL
ISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVE
KTVAPTECS SEQ ID NO: 892 14100_LC [hu anti-<huCDH19> 22D1.1
(1-235)(K45Q, S102A, W109Y, D111E, N135Q) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATYDESMQGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 893 14101_LC [hu anti-<huCDH19> 22D1.1
(1-235)(K45Q, S102A, W109Y) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATYDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLI
SDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK
TVAPTECS SEQ ID NO: 894 14102_LC [hu anti-<huCDH19> 22D1.1
(1-235)(K45Q, S102A) VL]::huLLC-C2
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYQQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTS
ASLAISGLQSEDEADYYCATWDDSMNGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCL
ISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVE
KTVAPTECS SEQ ID NO: 895 13591_LC [hu anti-<huCDH19> 4F7
VL]::huLLC-C1
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPGTAPKLLIHGNSNRPSGVPDRFSGSKSG
TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGGTRLTVLGQPKANPTVTLFPPSSEELQANKATLVC
LISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV
EKTVAPTECS SEQ ID NO: 896 14301_LC [hu anti-<huCDH19> 2G6
(1-234)(D110E) VL]::huLLC-C1
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA
PTECS SEQ ID NO: 897 14302_LC [hu anti-<huCDH19> 2G6
(1-234)(C42S, D110E) VL]::huLLC-C1
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA
PTECS SEQ ID NO: 898 14303_LC [hu anti-<huCDH19> 2G6
(1-234)(C42S, D110E) VL]::huLLC-C1
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTAT
LTISGTQAMDEADYYCQAWESSTVVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFY
PGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA
PTECS SEQ ID NO: 899 14304_LC [hu anti-<huCDH19> 23A10.3
(1-231)(C42S) VL]::huLLC-C2
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTA
TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDF
YPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTV
APTECS SEQ ID NO: 900
TABLE-US-00017 TABLE IVa HEAVY CHAIN CDRs Ab Type CDR 1 CDR 2 CDR 3
14039 AA SYGMH FIWYEGSNKYYAESVKD RAGIIGTIGYYYGMDV 14303 SEQ ID NO:
28 SEQ ID NO: 901 SEQ ID NO: 30 14027 AA SSGYYWS YIYYTGSAYYNPSLKS
EGSSGWYFQY SEQ ID NO: 46 SEQ ID NO: 47 SEQ ID NO: 902 14028 AA
SSGYYWS YIYYTGSAYYNPSLKS EGSSGYYFQY SEQ ID NO: 46 SEQ ID NO: 47 SEQ
ID NO: 903 14059 AA GYYWS YFSYSGSTNYNPSLKS NYAFHFDF SEQ ID NO: 52
SEQ ID NO: 53 SEQ ID NO: 904 14052 AA SYDMH VISYEGTNEYYAESVKG
ERYFDYSFDY SEQ ID NO: 58 SEQ ID NO: 905 SEQ ID NO: 906 14055 AA
SYDMH VISYEGTNEYYAESVKG ERYFDWSFDY SEQ ID NO: 58 SEQ ID NO: 905 SEQ
ID NO: 60 14033 AA SYDMD VIWYEGSNKYYAESVRG ETGEGWYFDL SEQ ID NO: 70
SEQ ID NO: 907 SEQ ID NO: 72 14034 AA SYDMD VIWYEGSNKYYAESVRG
ETGEGYYFDL SEQ ID NO: 70 SEQ ID NO: 907 SEQ ID NO: 908 14051 AA
SYSWS YIYYSGSTNYNPSLKS NYAFHFDY SEQ ID NO: 82 SEQ ID NO: 83 SEQ ID
NO: 909 14046 AA SYYWS YIYYIGSTNYNPSLKS ESRYRSGWYDAFDI 14048 SEQ ID
NO: 94 SEQ ID NO: 95 SEQ ID NO: 910 14047 AA SYYWS YIYYIGSTNYNPSLKS
ESRYRSGYYDAFDI SEQ ID NO: 94 SEQ ID NO: 95 SEQ ID NO: 911 14042 AA
GYYWS YIYYIGSTNYNPSLKS EGSSGWYRWFDP SEQ ID NO: 100 SEQ ID NO: 101
SEQ ID NO: 912 14043 AA GYYWS YIYYIGSTNYNPSLKS DGSSGYYRYFDP SEQ ID
NO: 100 SEQ ID NO: 101 SEQ ID NO: 913 14069 AA SYAMN
TISGGGANTYYAESVKG GGMGGYYYGMDV SEQ ID NO: 118 SEQ ID NO: 914 SEQ ID
NO: 120 14062 AA SYFIH IINPISVSTSYAQKFQG GGIQLYLHFDY 14063 SEQ ID
NO: 124 SEQ ID NO: 125 SEQ ID NO: 915 14064 14100 AA SYFIH
IINPISVSTSYAQKFQG GGIQLYLHLDY 14101 SEQ ID NO: 130 SEQ ID NO: 131
SEQ ID NO: 916 14097 AA SYYIH IINPSGGSTRYAQKFQG GGIQLYLHFDY SEQ ID
NO: 136 SEQ ID NO: 137 SEQ ID NO: 917 14091 AA NYYMS
IINPSGGDSTYAQKFQG GGIQLYLHFDY 14092 SEQ ID NO: 142 SEQ ID NO: 143
SEQ ID NO: 918 14087 AA SYYMS IIHPSGGDTTYAQKFQG GGIKLYLHFDY SEQ ID
NO: 148 SEQ ID NO: 149 SEQ ID NO: 919 14082 AA GYYWS
YIYYIGSTNYNPSLKS EGSSGYYRYFDP SEQ ID NO: 154 SEQ ID NO: 155 SEQ ID
NO: 920 14079 AA RYGIH VIWYEGSNKYYAESVKG RAGIPGTTGYYYGMDV SEQ ID
NO: 160 SEQ ID NO: 921 SEQ ID NO: 162 14073 AA SYFIH
IINPISVSTSYAQKFQG GGIQLYLHLDY SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO:
3 14076 AA SYGMH VIWYDGSNKYYADSVKG RAGIIGTTGYYYGMDV SEQ ID NO: 4
SEQ ID NO: 5 SEQ ID NO: 6
TABLE-US-00018 TABLE IVb LIGHT CHAIN CDRs Ab Type CDR 1 CDR 2 CDR 3
14039 AA SGDRLGEKYTS QDTKRPS QAWESSTVV 14302 SEQ ID NO: 922 SEQ ID
NO: 197 SEQ ID NO: 923 14303 14301 AA SGDRLGEKYTC QDTKRPS QAWESSTVV
SEQ ID NO: 196 SEQ ID NO: 197 SEQ ID NO: 923 14022 AA RASRQISSSYLA
GPSSRAT QQYGSSFT 14024 SEQ ID NO: 924 SEQ ID NO: 215 SEQ ID NO: 216
14025 14026 14027 14028 14029 AA RASQSISSSYLA GPSSRAT QQYGSSFT SEQ
ID NO: 925 SEQ ID NO: 215 SEQ ID NO: 216 14058 AA TGSSSNIGTGYAVH
GNNNRPS QSYESRLSGWV 14059 SEQ ID NO: 220 SEQ ID NO: 221 SEQ ID NO:
926 14050 AA TGSSSNIGTGYDVH GNSNRPS QSYESSLSGWV 14051 SEQ ID NO:
250 SEQ ID NO: 251 SEQ ID NO: 927 14063 AA SGSSSNIGSNFVN TNNQRPS
ATWDESLQGWV SEQ ID NO: 292 SEQ ID NO: 293 SEQ ID NO: 928 14064 AA
SGSSSNIGSNFVN TNNQRPS ATYDDSLNGWV SEQ ID NO: 292 SEQ ID NO: 293 SEQ
ID NO: 929 14099 AA SGSSSNIGSNFVN TNNQRPS ATWDESMQGWV SEQ ID NO:
298 SEQ ID NO: 299 SEQ ID NO: 930 14100 AA SGSSSNIGSNFVN TNNQRPS
ATYDESMQGWV SEQ ID NO: 298 SEQ ID NO: 299 SEQ ID NO: 931 14101 AA
SGSSSNIGSNFVN TNNQRPS ATYDDSMNGWV SEQ ID NO: 298 SEQ ID NO: 299 SEQ
ID NO: 932 14096 AA SGSSSNIGRNEVN TNNQRPS AAWDESLNGWV SEQ ID NO:
304 SEQ ID NO: 305 SEQ ID NO: 933 14097 AA SGSSSNIGRNEVN TNNQRPS
AAWDESLQGWV SEQ ID NO: 304 SEQ ID NO: 305 SEQ ID NO: 934 14090 AA
SGSRSNIGSNEVN TNYQRPS AVWDESLNGWV 14091 SEQ ID NO: 310 SEQ ID NO:
311 SEQ ID NO: 935 14092 AA SGSRSNIGSNEVN TNYQRPS AVYDESLQGWV SEQ
ID NO: 310 SEQ ID NO: 311 SEQ ID NO: 936 14085 AA SGSRSNIGSNEVN
TNNQRPS AVYDDSLNGWV SEQ ID NO: 316 SEQ ID NO: 317 SEQ ID NO: 937
14086 AA SGSRSNIGSNEVN TNNQRPS AVYDESLQGWV 14087 SEQ ID NO: 316 SEQ
ID NO: 317 SEQ ID NO: 938 14077 AA SGDRLGEKYVS QDNKWPS QAWDSSTVV
14078 SEQ ID NO: 939 SEQ ID NO: 329 SEQ ID NO: 330 14304 14079 AA
SGDRLGEKYVS QDNKWPS QAWESSTVV SEQ ID NO: 939 SEQ ID NO: 329 SEQ ID
NO: 940 14080 AA SGDRLGEKYVY QDNKWPS QAWDSSTVV SEQ ID NO: 941 SEQ
ID NO: 329 SEQ ID NO: 330 14075 AA SGSRSNIGSNEVN TNNQRPS
ATWDESMQGWV SEQ ID NO: 334 SEQ ID NO: 335 SEQ ID NO: 942 14076 AA
SGSRSNIGSNEVN TNNQRPS ATYDESMQGWV SEQ ID NO: 334 SEQ ID NO: 335 SEQ
ID NO: 943
[0494] Human and Cynomologous Monkey Cadherin-19 Sequences
TABLE-US-00019 TABLE V SEQ ID NO. DESIGNATION SOURCE TYPE SEQUENCE
944 Human Human aa MNCYLLLRFMLGIPLLWPCLGATENSQTKKVKQPVRSHLRVKR
Cadherin-19 GWVWNQFFVPEEMNTTSHHIGQLRSDLDNGNNSFQYKLLGAGA
GSTFIIDERTGDIYAIQKLDREERSLYILRAQVIDIATGRAVE
PESEEVIKVSDINDNEPKELDEPYEAIVPEMSPEGTLVIQVTA
SDADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIRISSKMDRE
LQDEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVNDNKPIFKE
SLYRLTVSESAPTGTSIGTIMAYDNDIGENAEMDYSIEEDDSQ
TEDIITNHETQEGIVILKKKVDFEHQNHYGIRAKVKNHHVPEQ
LMKYHTEASTTFIKIQVEDVDEPPLFLLPYYVFEVFEETPQGS
FVGVVSATDPDNRKSPIRYSITRSKVFNINDNGTITTSNSLDR
EISAWYNLSITATEKYNIEQISSIPLYVQVLNINDHAPEFSQY
YETYVCENAGSGQVIQTISAVDRDESIEEHHEYFNLSVEDTNN
SSETIIDNQDNTAVILTNRTGENLQEEPVFYISILIADNGIPS
LTSTNTLTIHVCDCGDSGSTQTCQYQELVLSMGFKTEVIIAIL
ICIMIIFGFIFLTLGLKQRRKQILFPEKSEDFRENIFQYDDEG
GGEEDTEAFDIAELRSSTIMRERKTRKTTSAEIRSLYRQSLQV
GPDSAIFRKFILEKLEEANTDPCAPPFDSLQTYAFEGTGSLAG
SLSSLESAVSDQDESYDYLNELGPRFKRLACMFGSAVQSNN 945 Human Human nt
atgaactgttatttactgctgcgttttatgttgggaattcctc Cadherin-19
tcctatggccttgtcttggagcaacagaaaactctcaaacaaa
gaaagtcaagcagccagtgcgatctcatttgagagtgaagcgt
ggctgggtgtggaaccaattttttgtaccagaggaaatgaata
cgactagtcatcacatcggccagctaagatctgatttagacaa
tggaaacaattctttccagtacaagcttttgggagctggagct
ggaagtacttttatcattgatgaaagaacaggtgacatatatg
ccatacagaagcttgatagagaggagcgatccctctacatctt
aagagcccaggtaatagacatcgctactggaagggctgtggaa
cctgagtctgagtttgtcatcaaagtttcggatatcaatgaca
atgaaccaaaattcctagatgaaccttatgaggccattgtacc
agagatgtctccagaaggaacattagttatccaggtgacagca
agtgatgctgacgatccctcaagtggtaataatgctcgtctcc
tctacagcttacttcaaggccagccatatttttctgttgaacc
aacaacaggagtcataagaatatcttctaaaatggatagagaa
ctgcaagatgagtattgggtaatcattcaagccaaggacatga
ttggtcagccaggagcgttgtctggaacaacaagtgtattaat
taaactttcagatgttaatgacaataagcctatatttaaagaa
agtttataccgcttgactgtctctgaatctgcacccactggga
cttctataggaacaatcatggcatatgataatgacataggaga
gaatgcagaaatggattacagcattgaagaggatgattcgcaa
acatttgacattattactaatcatgaaactcaagaaggaatag
ttatattaaaaaagaaagtggattttgagcaccagaaccacta
cggtattagagcaaaagttaaaaaccatcatgttcctgagcag
ctcatgaagtaccacactgaggcttccaccactttcattaaga
tccaggtggaagatgttgatgagcctcctcttttcctccttcc
atattatgtatttgaagtttttgaagaaaccccacagggatca
tttgtaggcgtggtgtctgccacagacccagacaataggaaat
ctcctatcaggtattctattactaggagcaaagtgttcaatat
caatgataatggtacaatcactacaagtaactcactggatcgt
gaaatcagtgcttggtacaacctaagtattacagccacagaaa
aatacaatatagaacagatctcttcgatcccactgtatgtgca
agttcttaacatcaatgatcatgctcctgagttctctcaatac
tatgagacttatgtttgtgaaaatgcaggctctggtcaggtaa
ttcagactatcagtgcagtggatagagatgaatccatagaaga
gcaccatttttactttaatctatctgtagaagacactaacaat
tcaagttttacaatcatagataatcaagataacacagctgtca
ttttgactaatagaactggttttaaccttcaagaagaacctgt
cttctacatctccatcttaattgccgacaatggaatcccgtca
cttacaagtacaaacacccttaccatccatgtctgtgactgtg
gtgacagtgggagcacacagacctgccagtaccaggagcttgt
gctttccatgggattcaagacagaagtcatcattgctattctc
atttgcattatgatcatatttgggtttatttttttgactttgg
gtttaaaacaacggagaaaacagattctatttcctgagaaaag
tgaagatttcagagagaatatattccaatatgatgatgaaggg
ggtggagaagaagatacagaggcctttgatatagcagagctga
ggagtagtaccataatgcgggaacgcaagactcggaaaaccac
aagcgctgagatcaggagcctatacaggcagtctttgcaagtt
ggccccgacagtgccatattcaggaaattcattctggaaaagc
tcgaagaagctaatactgatccgtgtgcccctccttttgattc
cctccagacctacgcttttgagggaacagggtcattagctgga
tccctgagctccttagaatcagcagtctctgatcaggatgaaa
gctatgattaccttaatgagttgggacctcgctttaaaagatt
agcatgcatgtttggttctgcagtgcagtcaaataattag 946 Cyno Macaca aa
MNCYLLLPFMLGIPLLWPCLGATENSQTKKVQQPVGSHLRVKR Cadherin-19
fascicularis GWVWNQFFVPEEMNTTSHHVGRLRSDLDNGNNSFQYKLLGAGA
GSTFIIDERTGDIYAIEKLDREERSLYILRAQVIDITTGRAVE
PESEEVIKVSDINDNEPKELDEPYEAIVPEMSPEGTLVIQVTA
SDADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIRISSKMDRE
LQDEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVNDNKPIFKE
SLYRLTVSESAPTGTSIGTIMAYDNDIGENAEMDYSIEEDDSQ
TEDIITNHETQEGIVILKKKVNFEHQNHYGIRAKVKNHHVDEQ
LMKYHTEASTTFIKIQVEDVDEPPLELLPYYIFEIFEETPQGS
FVGVVSATDPDNRKSPIRYSITRSKVFNIDDNGTITTTNSLDR
EISAWYNLSITATEKYNIEQISSIPVYVQVLNINDHAPEFSQY
YESYVCENAGSGQVIQTISAVDRDESIEEHHEYFNLSVEDTNS
SSETIIDNQDNTAVILTNRTGFNLQEEPIFYISILIADNGIPS
LTSTNTLTIHVCDCDDSGSTQTCQYQELMLSMGFKTEVITAIL
ICIMVIEGFIFLTLGLKQRRKQILFPEKSEDFRENIFRYDDEG
GGEEDTEAFDVAALRSSTIMRERKTRKTTSAEIRSLYRQSLQV
GPDSAIFRKFILEKLEEADTDPCAPPFDSLQTYAFEGTGSLAG
SLSSLESAVSDQDESYDYLNELGPRFKRLACMFGSAVQSNN 947 Cyno Macaca nt
ATGAATTGTTATTTACTGCTGCCTTTTATGTTGGGAATTCCTC Cadherin-19
fascicularis TCCTATGGCCTTGTCTTGGAGCAACAGAAAACTCTCAAACAAA
GAAAGTCCAGCAGCCAGTAGGATCTCATCTGAGAGTGAAGCGT
GGCTGGGTGTGGAACCAATTTTTTGTACCAGAGGAAATGAATA
CGACTAGTCATCACGTTGGCCGGCTAAGATCTGATTTAGACAA
TGGAAACAATTCTTTCCAGTACAAGCTTTTGGGAGCTGGAGCT
GGAAGTACTTTTATCATTGATGAAAGAACAGGTGACATATATG
CCATAGAGAAGCTTGATAGAGAGGAGCGATCCCTCTACATCTT
AAGAGCCCAGGTAATAGACATCACTACTGGAAGGGCTGTGGAA
CCTGAGTCTGAGTTTGTCATCAAAGTTTCGGATATCAATGACA
ATGAACCAAAATTCCTAGATGAACCTTATGAGGCCATTGTACC
AGAGATGTCTCCAGAAGGAACATTAGTCATCCAGGTGACAGCA
AGTGATGCTGATGACCCTTCAAGTGGTAATAATGCTCGTCTCC
TCTACAGCTTATTACAAGGCCAGCCATATTTTTCTGTTGAACC
AACAACAGGAGTCATAAGAATATCTTCTAAAATGGATAGAGAA
CTGCAAGATGAGTATTGGGTAATCATTCAAGCCAAGGACATGA
TTGGTCAGCCAGGAGCGTTGTCTGGAACAACGAGTGTATTAAT
TAAACTTTCAGATGTTAATGACAATAAGCCTATATTTAAAGAA
AGTTTATACCGCCTGACGGTCTCTGAATCTGCACCCACTGGGA
CTTCTATAGGAACAATCATGGCATATGATAATGACATAGGAGA
GAATGCAGAAATGGATTACAGCATTGAAGAGGATGATTCACAG
ACATTTGACATTATTACTAATCATGAAACTCAAGAAGGAATAG
TTATATTAAAAAAGAAAGTGAATTTTGAGCACCAGAACCACTA
TGGTATTAGAGCAAAAGTTAAAAACCATCATGTTGATGAGCAG
CTCATGAAATACCACACTGAAGCTTCCACCACTTTCATTAAGA
TCCAGGTGGAAGATGTTGATGAGCCTCCTCTTTTCCTCCTTCC
GTATTACATATTTGAAATTTTTGAAGAAACCCCACAAGGATCA
TTTGTAGGCGTGGTGTCTGCCACAGACCCAGACAATAGGAAAT
CTCCTATCAGGTATTCTATTACTAGGAGCAAAGTGTTCAATAT
CGATGATAATGGTACAATCACTACAACTAACTCACTGGATCGG
GAAATCAGTGCTTGGTACAACCTAAGTATTACAGCCACAGAAA
AATACAATATAGAGCAGATCTCTTCGATCCCAGTGTATGTGCA
AGTTCTTAATATCAATGATCATGCTCCTGAGTTCTCTCAATAC
TATGAGAGTTATGTTTGTGAAAATGCAGGCTCTGGTCAGGTAA
TTCAGACTATCAGTGCAGTGGATAGAGATGAATCCATAGAAGA
GCACCATTTTTACTTTAATCTATCTGTAGAAGACACTAACTCT
TCAAGTTTTACAATCATAGACAATCAAGATAACACAGCTGTCA
TTTTGACTAATAGAACTGGTTTTAACCTTCAAGAAGAGCCCAT
CTTCTACATCTCCATCTTAATTGCCGACAATGGAATCCCGTCA
CTTACAAGTACAAACACCCTTACCATCCATGTCTGTGACTGTG
ATGACAGTGGGAGCACACAGACCTGCCAGTACCAGGAGCTTAT
GCTTTCCATGGGATTCAAGACAGAAGTCATCATTGCTATTCTC
ATTTGCATTATGGTAATATTTGGGTTTATTTTTTTGACTTTGG
GTTTAAAACAACGGAGAAAACAGATTCTATTTCCTGAGAAAAG
TGAAGATTTCAGAGAGAATATATTCCGATATGATGACGAAGGG
GGTGGAGAAGAAGATACAGAGGCCTTTGACGTAGCAGCGCTGA
GGAGTAGCACCATAATGCGGGAACGCAAGACTCGGAAAACCAC
CAGCGCTGAGATCAGGAGCCTATACAGGCAGTCTTTGCAAGTT
GGCCCCGACAGTGCCATATTCAGGAAGTTCATCCTGGAAAAGC
TCGAAGAAGCTGATACTGATCCGTGTGCCCCTCCTTTTGATTC
CCTCCAGACCTACGCTTTTGAGGGAACAGGGTCATTAGCTGGA
TCCCTGAGCTCCTTAGAATCAGCTGTCTCTGATCAGGATGAAA
GCTATGATTACCTTAACGAGTTGGGACCTCGCTTTAAAAGATT
AGCATGCATGTTTGGTTCTGCAGTGCAGTCAAATAATTAG 948 secreted Human aa
MNCYLLLRFMLGIPLLWPCLGATENSQTKKVKQPVRSHLRVKR Cadherin-19
GWVWNQFFVPEEMNTTSHHIGQLRSDLDNGNNSFQYKLLGAGA eto-domain
GSTFIIDERTGDIYAIQKLDREERSLYILRAQVIDIATGRAVE (amino acids
PESEFVIKVSDINDNEPKFLDEPYEAIVPEHSPEGTLVIQVTA 1-596)
SDADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIRISSKMDRE
LQDEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVNDNKPIFKE
SLYRLTVSESAPTGTSIGTIMAYDNDIGENAEMDYSIEEDDSQ
TFDIITNHETQEGIVILKKKVDFEHQNHYGIRAKVKNHHVPEQ
LMKYHTEASTTFIKIQVEDVDEPPLFLLPYYVFEVFEETPQGS
FVGVVSATDPDNRKSPIRYSITRSKVFNINDNGTITTSNSLDR
EISAWYNLSITATEKYNIEQISSIPLYVQVLNINDHAPEFSQY
YETYVCENAGSGQVIQTISAVDRDESIEEHHFYFNLSVEDTNN
SSFTIIDNQDNTAVILTNRTGFNLQEEPVFYISILIADNGIPS
LTSTNTLTIHVCDCGDSGSTQTCQYQEIVLSMGFKTE 949 secreted Human nt
atgaactgttatttactgctgcgttttatgttgggaattcctc Cadherin-19
tcctatggccttgtcttggagcaacagaaaactctcaaacaaa ecto-domain
gaaagtcaagcagccagtgcgatctcatttgagagtgaagcgt amino acids
ggctgggtgtggaaccaattttttgtaccagaggaaatgaata 1-596)
cgactagtcatcacatcggccagctaagatctgatttagacaa
tggaaacaattctttccagtacaagcttttgggagctggagct
ggaagtacttttatcattgatgaaagaacaggtgacatatatg
ccatacagaagcttgatagagaggagcgatccctctacatctt
aagagcccaggtaatagacatcgctactggaagggctgtggaa
cctgagtctgagtttgtcatcaaagtttcggatatcaatgaca
atgaaccaaaattcctagatgaaccttatgaggccattgtacc
agagatgtctccagaaggaacattagttatccaggtgacagca
agtgatgctgacgatccctcaagtggtaataatgctcgtctcc
tctacagcttacttcaaggccagccatatttttctgttgaacc
aacaacaggagtcataagaatatcttctaaaatggatagagaa
ctgcaagatgagtattgggtaatcattcaagccaaggacatga
ttggtcagccaggagcgttgtctggaacaacaagtgtattaat
taaactttcagatgttaatgacaataagcctatatttaaagaa
agtttataccgcttgactgtctctgaatctgcacccactggga
cttctataggaacaatcatggcatatgataatgacataggaga
gaatgcagaaatggattacagcattgaagaggatgattcgcaa
acatttgacattattactaatcatgaaactcaagaaggaatag
ttatattaaaaaagaaagtggattttgagcaccagaaccacta
cggtattagagcaaaagttaaaaaccatcatgttcctgagcag
ctcatgaagtaccacactgaggcttccaccactttcattaaga
tccaggtggaagatgttgatgagcctcctcttttcctccttcc
atattatgtatttgaagtttttgaagaaaccccacagggatca
tttgtaggcgtggtgtctgccacagacccagacaataggaaat
ctcctatcaggtattctattactaggagcaaagtgttcaatat
caatgataatggtacaatcactacaagtaactcactggatcgt
gaaatcagtgcttggtacaacctaagtattacagccacagaaa
aatacaatatagaacagatctcttcgatcccactgtatgtgca
agttcttaacatcaaLgatcatgctcctgagttctctcaatac
tatgagacttatgtttgtgaaaaLgcaggctctggtcaggtaa
ttcagactatcagtgcagtggatagagatgaatccatagaaga
gcaccatttttactttaatctatctgtagaagacactaacaat
tcaagttttacaatcatagataatcaagataacacagctgtca
ttttgactaatagaactggttttaaccttcaagaagaacctgt
cttctacatctccatcttaattgccgacaatggaatcccgtca
cttacaagtacaaacacccttaccatccatgtctgtgactgtg
gtgacagtgggagcacacagacctgccagtaccaggagcttgt
gctttccatgggattcaagacagaa 950 truncated Human aa
MNCYLLLRFMLGIPLLWPCLGATENSQTKKVKQPVRSHLRVKR membrane
GWVWNQFFVPEEMNTTSHHIGQLRSDLDNGNNSFQYKLLGAGA bound form of
GSTFIIDERTGDIYAIQKLDREERSLYILRAQVIDIATGRAVE human
PESEEVIKVSDINDNEPKELDEPYEAIVPEMSPEGTLVIQVTA cadherin-19
SDADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIRISSKMDRE amino acids
LQDEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVNDNKPIFKE 1-624)
SLYRLTVSESAPTGTSIGTIMAYDNDIGENAEMDYSIEEDDSQ
TEDIITNHETQEGIVILKKKVDFEHQNHYGIRAKVKNHHVPEQ
LMKYHTEASTTFIKIQVEDVDEPPLFLLPYYVFEVFEETPQGS
FVGVVSATDPDNRKSPIRYSITRSKVFNINDNGTITTSNSLDR
EISAWYNLSITATEKYNIEQISSIPLYVQVLNINDHAPEFSQY
YETYVCENAGSGQVIQTISAVDRDESIEEHHEYFNLSVEDTNN
SSETIIDNQDNTAVILTNRTGENLQEEPVFYISILIADNGIPS
LTSTNTLTIHVCDCGDSGSTQTCQYQELVLSMGFKTEVIIAIL ICIMIIFGFIFLTLGLKQRRKQ
951 truncated Humanl nt atgaactgttatttactgctgcgttttatgttgggaattcctc
membrane tcctatggccttgtcttggagcaacagaaaactctcaaacaaa bound form of
gaaagtcaagcagccagtgcgatctcatttgagagtgaagcgt human
ggctgggtgtggaaccaattttttgtaccagaggaaatgaata cadherin-19
cgactagtcatcacatcggccagctaagatctgatttagacaa (amino acids
tggaaacaattctttccagtacaagcttttgggagctggagct 1-624)
ggaagtacttttatcattgatgaaagaacaggtgacatatatg
ccatacagaagcttgatagagaggagcgatccctctacatctt
aagagcccaggtaatagacatcgctactggaagggctgtggaa
cctgagtctgagtttgtcatcaaagtttcggatatcaatgaca
atgaaccaaaattcctagatgaaccttatgaggccattgtacc
agagatgtctccagaaggaacattagttatccaggtgacagca
agtgatgctgacgatccctcaagtggtaataatgctcgtctcc
tctacagcttacttcaaggccagccatatttttctgttgaacc
aacaacaggagtcataagaatatcttctaaaatggatagagaa
ctgcaagatgagtattgggtaatcattcaagccaaggacatga
ttggtcagccaggagcgttgtctggaacaacaagtgtattaat
taaactttcagatgttaatgacaataagcctatatttaaagaa
agtttataccgcttgactgtctctgaatctgcacccactggga
cttctataggaacaatcatggcatatgataatgacataggaga
gaatgcagaaatggattacagcattgaagaggatgattcgcaa
acatttgacattattactaatcatgaaactcaagaaggaatag
ttatattaaaaaagaaagtggattttgagcaccagaaccacta
cggtattagagcaaaagttaaaaaccatcatgttcctgagcag
ctcatgaagtaccacactgaggcttccaccactttcattaaga
tccaggtggaagatgttgatgagcctcctcttttcctccttcc
atattatgtatttgaagtttttgaagaaaccccacagggatca
tttgtaggcgtggtgtctgccacagacccagacaataggaaat
ctcctatcaggtattctattactaggagcaaagtgttcaatat
caatgataatggtacaatcactacaagtaactcactggatcgt
gaaatcagtgcttggtacaacctaagtattacagccacagaaa
aatacaatatagaacagatctcttcgatcccactgtatgtgca
agttcttaacatcaatgatcatgctcctgagttctctcaatac
tatgagacttatgtttgtgaaaatgcaggctctggtcaggtaa
ttcagactatcagtgcagtggatagagatgaatccatagaaga
gcaccatttttactttaatctatctgtagaagacactaacaat
tcaagttttacaatcatagataatcaagataacacagctgtca
ttttgactaatagaactggttttaaccttcaagaagaacctgt
cttctacatctccatcttaattgccgacaatggaatcccgtca
cttacaagtacaaacacccttaccatccatgtctgtgactgtg
gtgacagtgggagcacacagacctgccagtaccaggagcttgt
gctttccatgggattcaagacagaagtcatcattgctattctc
atttgcattatgatcatatttgggtttatttttttgactttgg gtttaaaacaacggagaaaacag
952 C137897 artificial aa
GWVWNQFFVPEEMNTTSHHIGQLRSDLDNGNNSFQYKLLGAGA huCDH19
GSTFIIDERTGDIYAIQKLDREERSLYILRAQVIDIATGRAVE (44-141)
PESEEVIKVSDINDNEPRELDEPYEAIVPEMSPEGTEVIKVTA muCDH19
NDADDPSTGYHARILYNLERGQPYFSVEPTTGVIRISSKMDRE (140-770)
LQDTYCVIIQAKDMLGQPGALSGTTTVSIKLSDINDNKPIFKE
SFYRFTISESAPIGTSIGKIMAYDDDIGENAEMEYSIEDDDSK
IFDIIIDNDTQEGIVILKKKVDFEQQSYYGIRAKVKNCHVDEE
LAPAHVNASTTYIKVQVEDEDEPPVFLLPYYILEIPEGKPYGT
IVGTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIITTNMLDR
EVSAWYNLTVTATETYNVQQISSAHVYVQVFNINDNAPEFSQF
YETYVCENAESGEIVQIISAIDRDESIEDHHEYENHSLEDTNN
SSFMLTDNQDNTAVILSNRTGENLKEEPVEYMIILIADNGIPS
LTSTNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTEAIIAIM
ICVMVIFGEFFLILALKQRRKETLFPEKTEDFRENIFCYDDEG
GGEEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLYRQSLQV
GPDSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEGTGSSAG
SLSSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAVQPNN 953 C137897 artificial nt
ggctgggtgtggaaccaattttttgtaccagaggaaatgaata huCDH19
cgactagtcatcacatcggccagctaagatctgatttagacaa (44-141)
tggaaacaattctttccagtacaagcttttgggagctggagct muCDH19
ggaagtacttttatcattgatgaaagaacaggtgacatatatg (140-770)
ccatacagaagcttgatagagaggagcgatccctctacatctt
aagagcccaggtaatagacatcgctactggaagggctgtggaa
cctgagtctgagtttgtcatcaaagtttcggatatcaatgaca
atgaacccagattcctagatgaaccatatgaggccattgtacc
tgagatgtctccagaaggaacatttgtcatcaaggtgacagcc
aatgacgcagatgatccttcaactggctatcatgctcgcatcc
tatacaacttagaacgaggtcaaccatacttttctgttgagcc
aacaacaggagtcataaggatatcttctaagatggatagagag
ttgcaagatacatactgtgtaattattcaagccaaggacatgc
tcggtcagcctggagccttgtctggaacaacaaccgtatcaat
taagctgtcagatattaatgacaacaagccaatattcaaagaa
agtttctaccgcttcactatatctgaatctgcacccattggaa
catcaatagggaaaattatggcatatgatgatgacatagggga
gaatgcagagatggagtacagcattgaagatgatgattcaaaa
atatttgacataatcattgacaatgacacccaagaagggatag
ttatacttaaaaagaaagttgattttgagcagcagagctatta
tggcattagagctaaggttaaaaactgccatgtggatgaagag
cttgcacctgcccatgttaacgcttccacaacctacattaaag
ttcaagtagaagatgaagatgaacctcctgttttcctcttacc
atattacatacttgaaattcctgaaggaaaaccatatggaaca
attgtggggacggtttctgccacagacccagatcgaagacaat
ctcctatgagatattatctcactggaagcaaaatgtttgatat
caatgacaatggaacaataatcaccactaacatgcttgacaga
gaggtcagtgcttggtacaacttgactgtcacagctactgaaa
catacaatgtacaacagatctcttcagcccatgtttatgtaca
agtctttaacattaacgacaatgctccagagttctctcaattc
tatgagacttatgtttgtgaaaatgctgaatctggtgagatag
ttcagatcatcagtgcaattgatagagatgagtccatagaaga
tcaccatttttactttaatcactctctggaagacacaaacaac
tcaagttttatgctaacagacaatcaagataacacagctgtaa
ttctgagtaatagaactggtttcaatcttaaagaagagcctgt
cttctacatgatcatcttgattgctgataacgggatcccatct
ctcacaagcacaaacactctcactatccaagtctgtgactgtg
gagacagtagaaacacagaaacttgtgctaacaagggacttct
ctttatcatgggattcagaacagaggcaataattgccatcatg
atatgtgttatggtaatatttgggtttttctttttgattcttg
ctctgaaacagcgaagaaaggagactctatttccagagaagac
tgaagactttagggagaatatattttgctatgatgatgaaggc
ggcggggaagaagactcggaagcctttgacatcgtagagctga
gacaaagtacagtaatgagagaaagaaagcctcagagaagcaa
gagtgcggagatcaggagcttgtacaggcagtccctgcaggtg
ggcccagacagtgccatatttcgaaaatttatcctagagaagc
ttgaagaagccaacacagacccatgtgctcccccctttgattc
actacagacgtttgcctatgagggaacagggtcatcagctggc
tctctgagctccttggcatccagagacactgatcaggaggatg
acttcgactaccttaatgacctgggacctcgttttaaaagatt
agcaagcatgtttggctctgcagtacaacccaacaattag 954 C137896 artificial aa
GWVWNQFFVPEEMNTTSHHIGQLRSDLDNGNNSFQYKLLGAGA huCDH19
GSTFIIDERTGDIYAIQKLDREERSLYILRAQVIDIATGRAVE (44-249)
PESEEVIKVSDINDNEPKELDEPYEAIVPEMSPEGTLVIQVTA muCDH19
SDADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIRISSKMDRE (248-770)
LQDEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVNDNKPIFKE
SFYRFTISESAPIGTSIGKIMAYDDDIGENAEMEYSIEDDDSK
IFDIIIDNDTQEGIVILKKKVDFEQQSYYGIRAKVKNCHVDEE
LAPAHVNASTTYIKVQVEDEDEPPVFLLPYYILEIPEGKPYGT
IVGTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIITTNMLDR
EVSAWYNLTVTATETYNVQQISSAHVYVQVFNINDNAPEFSQF
YETYVCENAESGEIVQIISAIDRDESIEDHHEYENHSLEDTNN
SSFMLTDNQDNTAVILSNRTGENLKEEPVEYMIILIADNGIPS
LTSTNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTEAIIAIM
ICVMVIFGEFFLILALKQRRKETLFPEKTEDFRENIFCYDDEG
GGEEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLYRQSLQV
GPDSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEGTGSSAG
SLSSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAVQPNN 955 C137896 artificial nt
ggctgggtgtggaaccaattttttgtaccagaggaaatgaata huCDH19
cgactagtcatcacatcggccagctaagatctgatttagacaa (44-249)
tggaaacaattctttccagtacaagcttttgggagctggagct muCDH19
ggaagtacttttatcattgatgaaagaacaggtgacatatatg (248-770)
ccatacagaagcttgatagagaggagcgatccctctacatctt
aagagcccaggtaatagacatcgctactggaagggctgtggaa
cctgagtctgagtttgtcatcaaagtttcggatatcaatgaca
atgaaccaaaattcctagatgaaccttatgaggccattgtacc
agagatgtctccagaaggaacattagttatccaggtgacagca
agtgatgctgacgatccctcaagtggtaataatgctcgtctcc
tctacagcttacttcaaggccagccatatttttctgttgaacc
aacaacaggagtcataagaatatcttctaaaatggatagagaa
ctgcaagatgagtattgggtaatcattcaagccaaggacatga
ttggtcagccaggagcgttgtctggaacaacaagtgtattaat
taaactttcagatgttaatgacaacaagccaatattcaaagaa
agtttctaccgcttcactatatctgaatctgcacccattggaa
catcaatagggaaaattatggcatatgatgatgacatagggga
gaatgcagagatggagtacagcattgaagatgatgattcaaaa
atatttgacataatcattgacaatgacacccaagaagggatag
ttatacttaaaaagaaagttgattttgagcagcagagctatta
tggcattagagctaaggttaaaaactgccatgtggatgaagag
cttgcacctgcccatgttaacgcttccacaacctacattaaag
ttcaagtagaagatgaagatgaacctcctgttttcctcttacc
atattacatacttgaaattcctgaaggaaaaccatatggaaca
attgtggggacggtttctgccacagacccagatcgaagacaat
ctcctatgagatattatctcactggaagcaaaatgtttgatat
caatgacaatggaacaataatcaccactaacatgcttgacaga
gaggtcagtgcttggtacaacttgactgtcacagctactgaaa
catacaatgtacaacagatctcttcagcccatgtttatgtaca
agtctttaacattaacgacaatgctccagagttctctcaattc
tatgagacttatgtttgtgaaaatgctgaatctggtgagatag
ttcagatcatcagtgcaattgatagagatgagtccatagaaga
tcaccatttttactttaatcactctctggaagacacaaacaac
tcaagttttatgctaacagacaatcaagataacacagctgtaa
ttctgagtaatagaactggtttcaatcttaaagaagagcctgt
cttctacatgatcatcttgattgctgataacgggatcccatct
ctcacaagcacaaacactctcactatccaagtctgtgactgtg
gagacagtagaaacacagaaacttgtgctaacaagggacttct
ctttatcatgggattcagaacagaggcaataattgccatcatg
atatgtgttatggtaatatttgggtttttctttttgattcttg
ctctgaaacagcgaagaaaggagactctatttccagagaagac
tgaagactttagggagaatatattttgctatgatgatgaaggc
ggcggggaagaagactcggaagcctttgacatcgtagagctga
gacaaagtacagtaatgagagaaagaaagcctcagagaagcaa
gagtgcggagatcaggagcttgtacaggcagtccctgcaggtg
ggcccagacagtgccatatttcgaaaatttatcctagagaagc
ttgaagaagccaacacagacccatgtgctcccccctttgattc
actacagacgtttgcctatgagggaacagggtcatcagctggc
tctctgagctccttggcatccagagacactgatcaggaggatg
acttcgactaccttaatgacctgggacctcgttttaaaagatt
agcaagcatgtttggctctgcagtacaacccaacaattag 956 C137913 artificial aa
AWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQYKLLGIGAG muCDH19
SFSINERTGEICAIQKLDREEKSLYILRAQVIDTTIGKAVETE (44-139)
SEEVIRVLDINDNEPKELDEPYEAIVPEMSPEGTLVIQVTASD huCDH19
ADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIRISSKMDRELQ (142-249)
DEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVNDNKPIFKESF muCDH19
YRFTISESAPIGTSIGKIMAYDDDIGENAEMEYSIEDDDSKIF (248-770)
DIIIDNDTQEGIVILKKKVDFEQQSYYGIRAKVKNCHVDEELA
PAHVNASTTYIKVQVEDEDEPPVFLLPYYILEIPEGKPYGTIV
GTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIITTNMLDREV
SAWYNLTVTATETYNVQQISSAHVYVQVFNINDNAPEFSQFYE
TYVCENAESGEIVQIISAIDRDESIEDHHEYENHSLEDTNNSS
FMLTDNQDNTAVILSNRTGENLKEEPVEYMIILIADNGIPSLT
STNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTEAIIAIMIC
VMVIFGEFFLILALKQRRKETLFPEKTEDFRENIFCYDDEGGG
EEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLYRQSLQVGP
DSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEGTGSSAGSL
SSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAVQPNN 957 C137913 artificial nt
gcctgggtgtggagaccatttgttgttctagaagaaatggatg muCDH19
atatacaatgtgttggaaagctaagatctgacttagacaatgg (44-139)
aaacaactctttccagtacaagctactggggattggcgctgga huCDH19
agctttagcattaatgaaagaacaggtgaaatatgtgccatac (142-249)
agaagcttgatagagaggaaaaatccctctacattctgagagc muCDH19
ccaggtaatagacaccactattgggaaggctgtggaaactgaa (248-770)
tccgagtttgtcatcagagttttggatatcaatgacaatgaac
caaaattcctagatgaaccttatgaggccattgtaccagagat
gtctccagaaggaacattagttatccaggtgacagcaagtgat
gctgacgatccctcaagtggtaataatgctcgtctcctctaca
gcttacttcaaggccagccatatttttctgttgaaccaacaac
aggagtcataagaatatcttctaaaatggatagagaactgcaa
gatgagtattgggtaatcattcaagccaaggacatgattggtc
agccaggagcgttgtctggaacaacaagtgtattaattaaact
ttcagatgttaatgacaacaagccaatattcaaagaaagtttc
taccgcttcactatatctgaatctgcacccattggaacatcaa
tagggaaaattatggcatatgatgatgacataggggagaatgc
agagatggagtacagcattgaagatgatgattcaaaaatattt
gacataatcattgacaatgacacccaagaagggatagttatac
ttaaaaagaaagttgattttgagcagcagagctattatggcat
tagagctaaggttaaaaactgccatgtggatgaagagcttgca
cctgcccatgttaacgcttccacaacctacattaaagttcaag
tagaagatgaagatgaacctcctgttttcctcttaccatatta
catacttgaaattcctgaaggaaaaccatatggaacaattgtg
gggacggtttctgccacagacccagatcgaagacaatctccta
tgagatattatctcactggaagcaaaatgtttgatatcaatga
caatggaacaataatcaccactaacatgcttgacagagaggtc
agtgcttggtacaacttgactgtcacagctactgaaacataca
atgtacaacagatctcttcagcccatgtttatgtacaagtctt
taacattaacgacaatgctccagagttctctcaattctatgag
acttatgtttgtgaaaatgctgaatctggtgagatagttcaga
tcatcagtgcaattgatagagatgagtccatagaagatcacca
tttttactttaatcactctctggaagacacaaacaactcaagt
tttatgctaacagacaatcaagataacacagctgtaattctga
gtaatagaactggtttcaatcttaaagaagagcctgtcttcta
catgatcatcttgattgctgataacgggatcccatctctcaca
agcacaaacactctcactatccaagtctgtgactgtggagaca
gtagaaacacagaaacttgtgctaacaagggacttctctttat
catgggattcagaacagaggcaataattgccatcatgatatgt
gttatggtaatatttgggtttttctttttgattcttgctctga
aacagcgaagaaaggagactctatttccagagaagactgaaga
ctttagggagaatatattttgctatgatgatgaaggcggcggg
gaagaagactcggaagcctttgacatcgtagagctgagacaaa
gtacagtaatgagagaaagaaagcctcagagaagcaagagtgc
ggagatcaggagcttgtacaggcagtccctgcaggtgggccca
gacagtgccatatttcgaaaatttatcctagagaagcttgaag
aagccaacacagacccatgtgctcccccctttgattcactaca
gacgtttgcctatgagggaacagggtcatcagctggctctctg
agctccttggcatccagagacactgatcaggaggatgacttcg
actaccttaatgacctgggacctcgttttaaaagattagcaag
catgtttggctctgcagtacaacccaacaattag 958 C137847 artificial aa
AWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQYKLLGIGAG muCDH19
SFSINERTGEICAIQKLDREEKSLYILRAQVIDTTIGKAVETE (44-139)
SEEVIRVLDINDNEPKELDEPYEAIVPEMSPEGTLVIQVTASD huCDH19
ADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIRISSKMDRELQ (142-364)
DEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVNDNKPIFKESL muCDH19
YRLTVSESAPTGTSIGTIMAYDNDIGENAEMDYSIEEDDSQTF (363-770)
DIITNHETQEGIVILKKKVDFEHQNHYGIRAKVKNHHVPEQLM
KYHTEASTTFIKIQVEDVDEPPVFLLPYYILEIPEGKPYGTIV
GTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIITTNMLDREV
SAWYNLTVTATETYNVQQISSAHVYVQVFNINDNAPEFSQFYE
TYVCENAESGEIVQIISAIDRDESIEDHHEYENHSLEDTNNSS
FMLTDNQDNTAVILSNRTGENLKEEPVEYMIILIADNGIPSLT
STNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTEAIIAIMIC
VMVIFGEFFLILALKQRRKETLFPEKTEDFRENIFCYDDEGGG
EEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLYRQSLQVGP
DSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEGTGSSAGSL
SSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAVQPNN
959 C137847 artificial nt
gcctgggtgtggagaccatttgttgttctagaagaaatggatg muCDH19
atatacaatgtgttggaaagctaagatctgacttagacaatgg (44-139)
aaacaactctttccagtacaagctactggggattggcgctgga huCDH19
agctttagcattaatgaaagaacaggtgaaatatgtgccatac (142-364)
agaagcttgatagagaggaaaaatccctctacattctgagagc muCDH19
ccaggtaatagacaccactattgggaaggctgtggaaactgaa (363-770)
tccgagtttgtcatcagagttttggatatcaatgacaatgaac
caaaattcctagatgaaccttatgaggccattgtaccagagat
gtctccagaaggaacattagttatccaggtgacagcaagtgat
gctgacgatccctcaagtggtaataatgctcgtctcctctaca
gcttacttcaaggccagccatatttttctgttgaaccaacaac
aggagtcataagaatatcttctaaaatggatagagaactgcaa
gatgagtattgggtaatcattcaagccaaggacatgattggtc
agccaggagcgttgtctggaacaacaagtgtattaattaaact
ttcagatgttaatgacaataagcctatatttaaagaaagttta
taccgcttgactgtctctgaatctgcacccactgggacttcta
taggaacaatcatggcatatgataatgacataggagagaatgc
agaaatggattacagcattgaagaggatgattcgcaaacattt
gacattattactaatcatgaaactcaagaaggaatagttatat
taaaaaagaaagtggattttgagcaccagaaccactacggtat
tagagcaaaagttaaaaaccatcatgttcctgagcagctcatg
aagtaccacactgaggcttccaccactttcattaagatccagg
tggaagatgttgatgaacctcctgttttcctcttaccatatta
catacttgaaattcctgaaggaaaaccatatggaacaattgtg
gggacggtttctgccacagacccagatcgaagacaatctccta
tgagatattatctcactggaagcaaaatgtttgatatcaatga
caatggaacaataatcaccactaacatgcttgacagagaggtc
agtgcttggtacaacttgactgtcacagctactgaaacataca
atgtacaacagatctcttcagcccatgtttatgtacaagtctt
taacattaacgacaatgctccagagttctctcaattctatgag
acttatgtttgtgaaaatgctgaatctggtgagatagttcaga
tcatcagtgcaattgatagagatgagtccatagaagatcacca
tttttactttaatcactctctggaagacacaaacaactcaagt
tttatgctaacagacaatcaagataacacagctgtaattctga
gtaatagaactggtttcaatcttaaagaagagcctgtcttcta
catgatcatcttgattgctgataacgggatcccatctctcaca
agcacaaacactctcactatccaagtctgtgactgtggagaca
gtagaaacacagaaacttgtgctaacaagggacttctctttat
catgggattcagaacagaggcaataattgccatcatgatatgt
gttatggtaatatttgggtttttctttttgattcttgctctga
aacagcgaagaaaggagactctatttccagagaagactgaaga
ctttagggagaatatattttgctatgatgatgaaggcggcggg
gaagaagactcggaagcctttgacatcgtagagctgagacaaa
gtacagtaatgagagaaagaaagcctcagagaagcaagagtgc
ggagatcaggagcttgtacaggcagtccctgcaggtgggccca
gacagtgccatatttcgaaaatttatcctagagaagcttgaag
aagccaacacagacccatgtgctcccccctttgattcactaca
gacgtttgcctatgagggaacagggtcatcagctggctctctg
agctccttggcatccagagacactgatcaggaggatgacttcg
actaccttaatgacctgggacctcgttttaaaagattagcaag
catgtttggctctgcagtacaacccaacaattag 960 C137911 artificial aa
AWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQYKLLGIGAG muCDH19
SFSINERTGEICAIQKLDREEKSLYILRAQVIDTTIGKAVETE (44-247)
SEEVIRVLDINDNEPRELDEPYEAIVPEMSPEGTEVIKVTAND huCDH19
ADDPSTGYHARILYNLERGQPYFSVEPTTGVIRISSKMDRELQ (250-364)
DTYCVIIQAKDMLGQPGALSGTTTVSIKLSDINDNKPIFKESL muCDH19
YRLTVSESAPTGTSIGTIMAYDNDIGENAEMDYSIEEDDSQTF (363-770)
DIITNHETQEGIVILKKKVDFEHQNHYGIRAKVKNHHVPEQLM
KYHTEASTTFIKIQVEDVDEPPVFLLPYYILEIPEGKPYGTIV
GTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIITTNMLDREV
SAWYNLTVTATETYNVQQISSAHVYVQVFNINDNAPEFSQFYE
TYVCENAESGEIVQIISAIDRDESIEDHHEYENHSLEDTNNSS
FMLTDNQDNTAVILSNRTGENLKEEPVEYMIILIADNGIPSLT
STNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTEAIIAIMIC
VMVIFGEFFLILALKQRRKETLFPEKTEDFRENIFCYDDEGGG
EEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLYRQSLQVGP
DSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEGTGSSAGSL
SSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAVQPNN 961 C137911 artificial nt
gcctgggtgtggagaccatttgttgttctagaagaaatggatg muCDH19
atatacaatgtgttggaaagctaagatctgacttagacaatgg (44-247)
aaacaactctttccagtacaagctactggggattggcgctgga huCDH19
agctttagcattaatgaaagaacaggtgaaatatgtgccatac (250-364)
agaagcttgatagagaggaaaaatccctctacattctgagagc muCDH19
ccaggtaatagacaccactattgggaaggctgtggaaactgaa (363-770)
tccgagtttgtcatcagagttttggatatcaatgacaatgaac
ccagattcctagatgaaccatatgaggccattgtacctgagat
gtctccagaaggaacatttgtcatcaaggtgacagccaatgac
gcagatgatccttcaactggctatcatgctcgcatcctataca
acttagaacgaggtcaaccatacttttctgttgagccaacaac
aggagtcataaggatatcttctaagatggatagagagttgcaa
gatacatactgtgtaattattcaagccaaggacatgctcggtc
agcctggagccttgtctggaacaacaaccgtatcaattaagct
gtcagatattaatgacaataagcctatatttaaagaaagttta
taccgcttgactgtctctgaatctgcacccactgggacttcta
taggaacaatcatggcatatgataatgacataggagagaatgc
agaaatggattacagcattgaagaggatgattcgcaaacattt
gacattattactaatcatgaaactcaagaaggaatagttatat
taaaaaagaaagtggattttgagcaccagaaccactacggtat
tagagcaaaagttaaaaaccatcatgttcctgagcagctcatg
aagtaccacactgaggcttccaccactttcattaagatccagg
tggaagatgttgatgaacctcctgttttcctcttaccatatta
catacttgaaattcctgaaggaaaaccatatggaacaattgtg
gggacggtttctgccacagacccagatcgaagacaatctccta
tgagatattatctcactggaagcaaaatgtttgatatcaatga
caatggaacaataatcaccactaacatgcttgacagagaggtc
agtgcttggtacaacttgactgtcacagctactgaaacataca
atgtacaacagatctcttcagcccatgtttatgtacaagtctt
taacattaacgacaatgctccagagttctctcaattctatgag
acttatgtttgtgaaaatgctgaatctggtgagatagttcaga
tcatcagtgcaattgatagagatgagtccatagaagatcacca
tttttactttaatcactctctggaagacacaaacaactcaagt
tttatgctaacagacaatcaagataacacagctgtaattctga
gtaatagaactggtttcaatcttaaagaagagcctgtcttcta
catgatcatcttgattgctgataacgggatcccatctctcaca
agcacaaacactctcactatccaagtctgtgactgtggagaca
gtagaaacacagaaacttgtgctaacaagggacttctctttat
catgggattcagaacagaggcaataattgccatcatgatatgt
gttatggtaatatttgggtttttctttttgattcttgctctga
aacagcgaagaaaggagactctatttccagagaagactgaaga
ctttagggagaatatattttgctatgatgatgaaggcggcggg
gaagaagactcggaagcctttgacatcgtagagctgagacaaa
gtacagtaatgagagaaagaaagcctcagagaagcaagagtgc
ggagatcaggagcttgtacaggcagtccctgcaggtgggccca
gacagtgccatatttcgaaaatttatcctagagaagcttgaag
aagccaacacagacccatgtgctcccccctttgattcactaca
gacgtttgcctatgagggaacagggtcatcagctggctctctg
agctccttggcatccagagacactgatcaggaggatgacttcg
actaccttaatgacctgggacctcgttttaaaagattagcaag
catgtttggctctgcagtacaacccaacaattag 962 C137917 artificial aa
AWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQYKLLGIGAG muCDH19
SFSINERTGEICAIQKLDREEKSLYILRAQVIDTTIGKAVETE (44-362)
SEEVIRVLDINDNEPRELDEPYEAIVPEMSPEGTEVIKVTAND huCDH19
ADDPSTGYHARILYNLERGQPYFSVEPTTGVIRISSKMDRELQ (365-772)
DTYCVIIQAKDMLGQPGALSGTTTVSIKLSDINDNKPIFKESF
YRFTISESAPIGTSIGKIMAYDDDIGENAEMEYSIEDDDSKIF
DIIIDNDTQEGIVILKKKVDFEQQSYYGIRAKVKNCHVDEELA
PAHVNASTTYIKVQVEDEDEPPLELLPYYVFEVFEETPQGSFV
GVVSATDPDNRKSPIRYSITRSKVFNINDNGTITTSNSLDREI
SAWYNLSITATEKYNIEQISSIPLYVQVLNINDHAPEFSQYYE
TYVCENAGSGQVIQTISAVDRDESIEEHHEYFNLSVEDTNNSS
FTIIDNQDNTAVILTNRTGENLQEEPVFYISILIADNGIPSLT
STNTLTIHVCDCGDSGSTQTCQYQELVLSMGFKTEVIIAILIC
IMIIFGFIFLTLGLKQRRKQILFPEKSEDFRENIFQYDDEGGG
EEDTEAFDIAELRSSTIMRERKTRKTTSAEIRSLYRQSLQVGP
DSAIFRKFILEKLEEANTDPCAPPFDSLQTYAFEGTGSLAGSL
SSLESAVSDQDESYDYLNELGPRFKRLACMFGSAVQSNN 963 C137917 artificial nt
gcctgggtgtggagaccatttgttgttctagaagaaatggatg muCDH19
atatacaatgtgttggaaagctaagatctgacttagacaatgg (44-362)
aaacaactctttccagtacaagctactggggattggcgctgga huCDH19
agctttagcattaatgaaagaacaggtgaaatatgtgccatac (365-772)
agaagcttgatagagaggaaaaatccctctacattctgagagc
ccaggtaatagacaccactattgggaaggctgtggaaactgaa
tccgagtttgtcatcagagttttggatatcaatgacaatgaac
ccagattcctagatgaaccatatgaggccattgtacctgagat
gtctccagaaggaacatttgtcatcaaggtgacagccaatgac
gcagatgatccttcaactggctatcatgctcgcatcctataca
acttagaacgaggtcaaccatacttttctgttgagccaacaac
aggagtcataaggatatcttctaagatggatagagagttgcaa
gatacatactgtgtaattattcaagccaaggacatgctcggtc
agcctggagccttgtctggaacaacaaccgtatcaattaagct
gtcagatattaatgacaacaagccaatattcaaagaaagtttc
taccgcttcactatatctgaatctgcacccattggaacatcaa
tagggaaaattatggcatatgatgatgacataggggagaatgc
agagatggagtacagcattgaagatgatgattcaaaaatattt
gacataatcattgacaatgacacccaagaagggatagttatac
ttaaaaagaaagttgattttgagcagcagagctattatggcat
tagagctaaggttaaaaactgccatgtggatgaagagcttgca
cctgcccatgttaacgcttccacaacctacattaaagttcaag
tagaagatgaagatgagcctcctcttttcctccttccatatta
tgtatttgaagtttttgaagaaaccccacagggatcatttgta
ggcgtggtgtctgccacagacccagacaataggaaatctccta
tcaggtattctattactaggagcaaagtgttcaatatcaatga
taatggtacaatcactacaagtaactcactggatcgtgaaatc
agtgcttggtacaacctaagtattacagccacagaaaaataca
atatagaacagatctcttcgatcccactgtatgtgcaagttct
taacatcaatgatcatgctcctgagttctctcaatactatgag
acttatgtttgtgaaaatgcaggctctggtcaggtaattcaga
ctatcagtgcagtggatagagatgaatccatagaagagcacca
tttttactttaatctatctgtagaagacactaacaattcaagt
tttacaatcatagataatcaagataacacagctgtcattttga
ctaatagaactggttttaaccttcaagaagaacctgtcttcta
catctccatcttaattgccgacaatggaatcccgtcacttaca
agtacaaacacccttaccatccatgtctgtgactgtggtgaca
gtgggagcacacagacctgccagtaccaggagcttgtgctttc
catgggattcaagacagaagtcatcattgctattctcatttgc
attatgatcatatttgggtttatttttttgactttgggtttaa
aacaacggagaaaacagattctatttcctgagaaaagtgaaga
tttcagagagaatatattccaatatgatgatgaagggggtgga
gaagaagatacagaggcctttgatatagcagagctgaggagta
gtaccataatgcgggaacgcaagactcggaaaaccacaagcgc
tgagatcaggagcctatacaggcagtctttgcaagttggcccc
gacagtgccatattcaggaaattcattctggaaaagctcgaag
aagctaatactgatccgtgtgcccctccttttgattccctcca
gacctacgcttttgagggaacagggtcattagctggatccctg
agctccttagaatcagcagtctctgatcaggatgaaagctatg
attaccttaatgagttgggacctcgctttaaaagattagcatg
catgtttggttctgcagtgcagtcaaataattag 964 C137915 artificial aa
AWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQYKLLGIGAG muCDH19
SFSINERTGEICAIQKLDREEKSLYILRAQVIDTTIGKAVETE (44-461)
SEEVIRVLDINDNEPRELDEPYEAIVPEMSPEGTEVIKVTAND huCDH19
ADDPSTGYHARILYNLERGQPYFSVEPTTGVIRISSKMDRELQ (464-772)
DTYCVIIQAKDMLGQPGALSGTTTVSIKLSDINDNKPIFKESF
YRFTISESAPIGTSIGKIMAYDDDIGENAEMEYSIEDDDSKIF
DIIIDNDTQEGIVILKKKVDFEQQSYYGIRAKVKNCHVDEELA
PAHVNASTTYIKVQVEDEDEPPVFLLPYYILEIPEGKPYGTIV
GTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIITTNMLDREV
SAWYNLTVTATETYNVQQISSAHVYVQVFNINDHAPEFSQYYE
TYVCENAGSGQVIQTISAVDRDESIEEHHFYFNLSVEDTNNSS
FTIIDNQDNTAVILTNRTGFNLQEEPVFYISILIADNGIPSLT
STNTLTIHVCDCGDSGSTQTCQYQELVLSMGFKTEVIIAILIC
IMIIFGFIFLTLGLKQRRKQILFPEKSEDFRENIFQYDDEGGG
EEDTEAFDIAELRSSTIMRERKTRKTTSAEIRSLYRQSLQVGP
DSAIFRKFILEKLEEANTDPCAPPFDSLQTYAFEGTGSLAGSL
SSLESAVSDQDESYDYLNELGPRFKRLACMFGSAVQSNN 965 C137915 artificial nt
gcctgggtgtggagaccatttgttgttctagaagaaatggatg muCDH19
atatacaatgtgttggaaagctaagatctgacttagacaatgg (44-461)
aaacaactctttccagtacaagctactggggattggcgctgga huCDH19
agctttagcattaatgaaagaacaggtgaaatatgtgccatac (464-772)
agaagcttgatagagaggaaaaatccctctacattctgagagc
ccaggtaatagacaccactattgggaaggctgtggaaactgaa
tccgagtttgtcatcagagttttggatatcaatgacaatgaac
ccagattcctagatgaaccatatgaggccattgtacctgagat
gtctccagaaggaacatttgtcatcaaggtgacagccaatgac
gcagatgatccttcaactggctatcatgctcgcatcctataca
acttagaacgaggtcaaccatacttttctgttgagccaacaac
aggagtcataaggatatcttctaagatggatagagagttgcaa
gatacatactgtgtaattattcaagccaaggacatgctcggtc
agcctggagccttgtctggaacaacaaccgtatcaattaagct
gtcagatattaatgacaacaagccaatattcaaagaaagtttc
taccgcttcactatatctgaatctgcacccattggaacatcaa
tagggaaaattatggcatatgatgatgacataggggagaatgc
agagatggagtacagcattgaagatgatgattcaaaaatattt
gacataatcattgacaatgacacccaagaagggatagttatac
ttaaaaagaaagttgattttgagcagcagagctattatggcat
tagagctaaggttaaaaactgccatgtggatgaagagcttgca
cctgcccatgttaacgcttccacaacctacattaaagttcaag
tagaagatgaagatgaacctcctgttttcctcttaccatatta
catacttgaaattcctgaaggaaaaccatatggaacaattgtg
gggacggtttctgccacagacccagatcgaagacaatctccta
tgagatattatctcactggaagcaaaatgtttgatatcaatga
caatggaacaataatcaccactaacatgcttgacagagaggtc
agtgcttggtacaacttgactgtcacagctactgaaacataca
atgtacaacagatctcttcagcccatgtttatgtacaagtctt
taacattaatgatcatgctcctgagttctctcaatactatgag
acttatgtttgtgaaaatgcaggctctggtcaggtaattcaga
ctatcagtgcagtggatagagatgaatccatagaagagcacca
tttttactttaatctatctgtagaagacactaacaattcaagt
tttacaatcatagataatcaagataacacagctgtcattttga
ctaatagaactggttttaaccttcaagaagaacctgtcttcta
catctccatcttaattgccgacaatggaatcccgtcacttaca
agtacaaacacccttaccatccatgtctgtgactgtggtgaca
gtgggagcacacagacctgccagtaccaggagcttgtgctttc
catgggattcaagacagaagtcatcattgctattctcatttgc
attatgatcatatttgggtttatttttttgactttgggtttaa
aacaacggagaaaacagattctatttcctgagaaaagtgaaga
tttcagagagaatatattccaatatgatgatgaagggggtgga
gaagaagatacagaggcctttgatatagcagagctgaggagta
gtaccataatgcgggaacgcaagactcggaaaaccacaagcgc
tgagatcaggagcctatacaggcagtctttgcaagttggcccc
gacagtgccatattcaggaaattcattctggaaaagctcgaag
aagctaatactgatccgtgtgcccctccttttgattccctcca
gacctacgcttttgagggaacagggtcattagctggatccctg
agctccttagaatcagcagtctctgatcaggatgaaagctatg
attaccttaatgagttgggacctcgctttaaaagattagcatg
catgtttggttctgcagtgcagtcaaataattag 966 C71144 artificial aa
AWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQYKLLGIGAG muCDH19
SFSINERTGEICAIQKLDREEKSLYILRAQVIDTTIGKAVETE (44-770)
SEEVIRVLDINDNEPRELDEPYEAIVPEMSPEGTEVIKVTAND
ADDPSTGYHARILYNLERGQPYFSVEPTTGVIRISSKMDRELQ
DTYCVIIQAKDMLGQPGALSGTTTVSIKLSDINDNKPIFKESF
YRFTISESAPIGTSIGKIMAYDDDIGENAEMEYSIEDDDSKIF
DIIIDNDTQEGIVILKKKVDFEQQSYYGIRAKVKNCHVDEELA
PAHVNASTTYIKVQVEDEDEPPVFLLPYYILEIPEGKPYGTIV
GTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIITTNMLDREV
SAWYNLTVTATETYNVQQISSAHVYVQVFNINDNAPEFSQFYE
TYVCENAESGEIVQIISAIDRDESIEDHHEYENHSLEDTNNSS
FMLTDNQDNTAVILSNRTGENLKEEPVEYMIILIADNGIPSLT
STNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTEAIIAIMIC
VMVIFGEFFLILALKQRRKETLFPEKTEDFRENIFCYDDEGGG
EEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLYRQSLQVGP
DSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEGTGSSAGSL
SSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAVQPNN 967 C71144 artificial nt
gcctgggtgtggagaccatttgttgttctagaagaaatggatg muCDH19
atatacaatgtgttggaaagctaagatctgacttagacaatgg (44-770)
aaacaactctttccagtacaagctactggggattggcgctgga
agctttagcattaatgaaagaacaggtgaaatatgtgccatac
agaagcttgatagagaggaaaaatccctctacattctgagagc
ccaggtaatagacaccactattgggaaggctgtggaaactgaa
tccgagtttgtcatcagagttttggatatcaatgacaatgaac
ccagattcctagatgaaccatatgaggccattgtacctgagat
gtctccagaaggaacatttgtcatcaaggtgacagccaatgac
gcagatgatccttcaactggctatcatgctcgcatcctataca
acttagaacgaggtcaaccatacttttctgttgagccaacaac
aggagtcataaggatatcttctaagatggatagagagttgcaa
gatacatactgtgtaattattcaagccaaggacatgctcggtc
agcctggagccttgtctggaacaacaaccgtatcaattaagct
gtcagatattaatgacaacaagccaatattcaaagaaagtttc
taccgcttcactatatctgaatctgcacccattggaacatcaa
tagggaaaattatggcatatgatgatgacataggggagaatgc
agagatggagtacagcattgaagatgatgattcaaaaatattt
gacataatcattgacaatgacacccaagaagggatagttatac
ttaaaaagaaagttgattttgagcagcagagctattatggcat
tagagctaaggttaaaaactgccatgtggatgaagagcttgca
cctgcccatgttaacgcttccacaacctacattaaagttcaag
tagaagatgaagatgaacctcctgttttcctcttaccatatta
catacttgaaattcctgaaggaaaaccatatggaacaattgtg
gggacggtttctgccacagacccagatcgaagacaatctccta
tgagatattatctcactggaagcaaaatgtttgatatcaatga
caatggaacaataatcaccactaacatgcttgacagagaggtc
agtgcttggtacaacttgactgtcacagctactgaaacataca
atgtacaacagatctcttcagcccatgtttatgtacaagtctt
taacattaacgacaatgctccagagttctctcaattctatgag
acttatgtttgtgaaaatgctgaatctggtgagatagttcaga
tcatcagtgcaattgatagagatgagtccatagaagatcacca
tttttactttaatcactctctggaagacacaaacaactcaagt
tttatgctaacagacaatcaagataacacagctgtaattctga
gtaatagaactggtttcaatcttaaagaagagcctgtcttcta
catgatcatcttgattgctgataacgggatcccatctctcaca
agcacaaacactctcactatccaagtctgtgactgtggagaca
gtagaaacacagaaacttgtgctaacaagggacttctctttat
catgggattcagaacagaggcaataattgccatcatgatatgt
gttatggtaatatttgggtttttctttttgattcttgctctga
aacagcgaagaaaggagactctatttccagagaagactgaaga
ctttagggagaatatattttgctatgatgatgaaggcggcggg
gaagaagactcggaagcctttgacatcgtagagctgagacaaa
gtacagtaatgagagaaagaaagcctcagagaagcaagagtgc
ggagatcaggagcttgtacaggcagtccctgcaggtgggccca
gacagtgccatatttcgaaaatttatcctagagaagcttgaag
aagccaacacagacccatgtgctcccccctttgattcactaca
gacgtttgcctatgagggaacagggtcatcagctggctctctg
agctccttggcatccagagacactgatcaggaggatgacttcg
actaccttaatgacctgggacctcgttttaaaagattagcaag
catgtttggctctgcagtacaacccaacaattag 968 Flag Tag artificial aa
DYKDDDDK 969 Flag Tag artificial nt gactacaaagacgatgacgacaag
[0495] Bispecific Binding Molecules
TABLE-US-00020 TABLE VI SEQ ID NO. DESIGNATION SOURCE TYPE SEQUENCE
970 CDR-H1 of artificial AA SYGMH CDH19 2G6 971 CDR-H2 of
artificial AA FIWYDGSNKYYADSVKD CDH19 2G6 972 CDR-H3 of artificial
AA RAGIIGTIGYYYGMDV CDH19 2G6 973 CDR-L1 of artificial AA
SGDRLGEKYTC CDH19 2G6 974 CDR-L2 of artificial AA QDTKRPS CDH19 2G6
975 CDR-L3 of artificial AA QAWDSSTVV CDH19 2G6 976 VH of CDH19
artificial NT CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG 2G6
GCCGGTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCACCTT
CTCCAGCTACGGCATGCACTGGGTCCGACAGGCCCCTGGCAAG
GGCCTGGAATGGGTGGCCTTCATTTGGTACGACGGCTCCAACA
AGTACTACGCCGACTCCGTGAAGGACCGGTTCACCATCTCCCG
GGACAACTCCAAGAACACCCTGTACCTGCAGATGAAGTCCCTG
CGGGCCGAGGACACCGCCGTGTACTACTGTGCCAGAAGGGCCG
GCATCATCGGCACCATCGGCTACTACTACGGCATGGACGTGTG
GGGCCAGGGCACCACCGTGACCGTGTCTAGC 977 VH of CDH19 artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK 2G6
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS 978 VL of CDH19 artificial
NT TACGAGCTGACCCAGCCCCCCTCCGTGTCCGTGTCTCCTGGCC 2G6
AGACCGCCTCCATCACCTGTTCTGGCGACCGGCTGGGCGAGAA
GTACACCTGTTGGTATCAGCAGCGGCCTGGCCAGTCCCCCCTG
CTGGTCATCTACCAGGACACCAAGCGGCCCTCCGGCATCCCTG
AGCGGTTCTCCGGCTCCAACTCCGGCAACACCGCCACCCTGAC
CATCTCCGGCACCCAGGCCATGGACGAGGCCGACTACTACTGC
CAGGCCTGGGACTCCTCCACCGTGGTGTTCGGCGGAGGCACCA AGCTGACCGTGCTG 979 VL
of CDH19 artificial AA SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSP
2G6 LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY
CQAWDSSTVVFGGGTKLTVL 980 VH-VL of artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG CDH19 2G6
GCCGGTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCACCTT
CTCCAGCTACGGCATGCACTGGGTCCGACAGGCCCCTGGCAAG
GGCCTGGAATGGGTGGCCTTCATTTGGTACGACGGCTCCAACA
AGTACTACGCCGACTCCGTGAAGGACCGGTTCACCATCTCCCG
GGACAACTCCAAGAACACCCTGTACCTGCAGATGAAGTCCCTG
CGGGCCGAGGACACCGCCGTGTACTACTGTGCCAGAAGGGCCG
GCATCATCGGCACCATCGGCTACTACTACGGCATGGACGTGTG
GGGCCAGGGCACCACCGTGACCGTGTCTAGCGGAGGCGGAGGA
TCTGGTGGCGGTGGTTCTGGCGGCGGAGGCTCCTCTTACGAGC
TGACCCAGCCCCCCTCCGTGTCCGTGTCTCCTGGCCAGACCGC
CTCCATCACCTGTTCTGGCGACCGGCTGGGCGAGAAGTACACC
TGTTGGTATCAGCAGCGGCCTGGCCAGTCCCCCCTGCTGGTCA
TCTACCAGGACACCAAGCGGCCCTCCGGCATCCCTGAGCGGTT
CTCCGGCTCCAACTCCGGCAACACCGCCACCCTGACCATCTCC
GGCACCCAGGCCATGGACGAGGCCGACTACTACTGCCAGGCCT
GGGACTCCTCCACCGTGGTGTTCGGCGGAGGCACCAAGCTGAC CGTGCTG 981 VH-VL of
artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK CDH19 2G6
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
CWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVL 982 CDH19 2G6 x artificial
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK I2C
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
CWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 983 CDR-H1 of artificial AA
SYGMH CDH19 16E2.1 984 CDR-H2 of artificial AA VIWYDGSNKYYADSVKG
CDH19 16E2.1 985 CDR-H3 of artificial AA DGWELSFDY CDH19 16E2.1 986
CDR-L1 of artificial AA RASQGISNYLA CDH19 16E2.1 987 CDR-L2 of
artificial AA AASSLQS CDH19 16E2.1 988 CDR-L3 of artificial AA
QHYFTYPRT CDH19 16E2.1 989 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG 16E2.1
GCCGGTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCATCTT
CTCCAGCTACGGCATGCACTGGGTCCGACAGACCCCCGGCAAG
GGCCTGGAATGGGTGGCCGTGATTTGGTACGACGGCTCCAACA
AGTACTACGCCGACTCCGTGAAGGGCCGGTTCACCATCTCCCG
GGACATCTCCAAGAACACCCTGTACCTGCAGATGAACTCCCTG
CGGGTGGAAGATACCGCCGTGTACTACTGCGCCAGGGACGGCT
GGGAGCTGTCCTTCGATTACTGGGGCCAGGGCACCCTGGTCAC CGTGTCTAGC 990 VH of
CDH19 artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYGMHWVRQTPGK
16E2.1 GLEWVAVIWYDGSNKYYADSVKGRFTISRDISKNTLYLQMNSL
RVEDTAVYYCARDGWELSFDYWGQGTLVTVSS 991 VL of CDH19 artificial NT
GACATCCAGATGACCCAGTCCCCCTCCAGCCTGTCCGCCTCCG 16E2.1
TGGGCGACAGAGTGACCATCACCTGTCGGGCCTCCCAGGGCAT
CAGCAACTACCTGGCCTGGCTGCAGCAGAAGCCCGGCAAGGCC
CCCAAGTCCCTGATCTACGCCGCCAGCTCCCTGCAGTCCGGCG
TGCCCTCCAAGTTCTCCGGCTCTGGCTCCGGCACCGACTTCAC
CCTGACCATCTCCAGCCTGCAGCCCGAGGACTTCGCCACCTAC
TACTGCCAGCACTACTTCACCTACCCCCGGACCTTCGGACAGG GCACCAAGGTGGAAATCAAG
992 VL of CDH19 artificial AA
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWLQQKPGKA 16E2.1
PKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATY YCQHYFTYPRTFGQGTKVEIK
993 VH-VL of artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG CDH19 16E2.1
GCCGGTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCATCTT
CTCCAGCTACGGCATGCACTGGGTCCGACAGACCCCCGGCAAG
GGCCTGGAATGGGTGGCCGTGATTTGGTACGACGGCTCCAACA
AGTACTACGCCGACTCCGTGAAGGGCCGGTTCACCATCTCCCG
GGACATCTCCAAGAACACCCTGTACCTGCAGATGAACTCCCTG
CGGGTGGAAGATACCGCCGTGTACTACTGCGCCAGGGACGGCT
GGGAGCTGTCCTTCGATTACTGGGGCCAGGGCACCCTGGTCAC
CGTGTCTAGCGGAGGCGGAGGATCTGGTGGCGGTGGTTCTGGC
GGCGGAGGCTCCGACATCCAGATGACCCAGTCCCCCTCCAGCC
TGTCCGCCTCCGTGGGCGACAGAGTGACCATCACCTGTCGGGC
CTCCCAGGGCATCAGCAACTACCTGGCCTGGCTGCAGCAGAAG
CCCGGCAAGGCCCCCAAGTCCCTGATCTACGCCGCCAGCTCCC
TGCAGTCCGGCGTGCCCTCCAAGTTCTCCGGCTCTGGCTCCGG
CACCGACTTCACCCTGACCATCTCCAGCCTGCAGCCCGAGGAC
TTCGCCACCTACTACTGCCAGCACTACTTCACCTACCCCCGGA
CCTTCGGACAGGGCACCAAGGTGGAAATCAAG 994 VH-VL of artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYGMHWVRQTPGK CDH19 16E2.1
GLEWVAVIWYDGSNKYYADSVKGRFTISRDISKNTLYLQMNSL
RVEDTAVYYCARDGWELSFDYWGQGTLVTVSSGGGGSGGGGSG
GGGSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWLQQK
PGKAPKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPED
FATYYCQHYFTYPRTFGQGTKVEIK 995 CDH19 16E2.1 artificial
QVQLVESGGGVVQPGRSLRLSCAASGFIFSSYGMHWVRQTPGK x I2C
GLEWVAVIWYDGSNKYYADSVKGRFTISRDISKNTLYLQMNSL
RVEDTAVYYCARDGWELSFDYWGQGTLVTVSSGGGGSGGGGSG
GGGSDIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWLQQK
PGKAPKSLIYAASSLQSGVPSKFSGSGSGTDFTLTISSLQPED
FATYYCQHYFTYPRTFGQGTKVEIKSGGGGSEVQLVESGGGLV
QPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKY
NNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYC
VRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQ
TVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQ
APRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAE
YYCVLWYSNRWVFGGGTKLTVLHHHHHH 996 CDR-H1 of artificial AA SYYWS
CDH19 17H8.2 997 CDR-H2 of artificial AA YIYYIGSTNYNPSLKS CDH19
17H8.2 998 CDR-H3 of artificial AA DSRYRSGWYDAFDI CDH19 17H8.2 999
CDR-L1 of artificial AA RASQSVAGSYLA CDH19 17H8.2 1000 CDR-L2 of
artificial AA GASSRAT CDH19 17H8.2 1001 CDR-L3 of artificial AA
QQYGKSPIT CDH19 17H8.2 1002 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAATCCGGCCCTGGCCTGGTCAAGCCCT 17H8.2
CCGAGACACTGTCCCTGACCTGCACCGTGTCCGGCGGCTCCAT
CAACTCCTACTACTGGTCCTGGATCCGGCAGCCCCCTGGCAAG
GGCCTGGAATGGATCGGCTACATCTACTACATCGGCTCCACCA
ACTACAACCCCAGCCTGAAGTCCAGAGTGACCATCTCCGTGGA
CACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCCGTGACC
GCCGCTGACACCGCCCTGTACTACTGCGCCAGAGACTCCCGGT
ACAGATCCGGGTGGTACGACGCCTTCGACATCTGGGGCCAGGG CACCATGGTCACCGTGTCCTCT
1003 VH of CDH19 artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGK 17H8.2
GLEWIGYIYYIGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVT
AADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSS 1004 VL of CDH19 artificial NT
GATATCGTGCTGACCCAGTCCCCCGGCACCCTGTCTCTGAGCC 17H8.2
CTGGCGAGAGAGCCACCCTGTCCTGCAGAGCCTCTCAGTCCGT
GGCCGGCTCCTACCTGGCTTGGTATCAGCAGAAGCCCGGCCAG
GCCCCTCGGCTGCTGATCTCCGGCGCCTCTTCTAGAGCCACCG
GCATCCCTGACCGGTTCTCCGGCTCTGGCTCCGGCACCGACTT
CACCCTGACCATCAGCCGGCTGGAACCCGAGGACTTCGCCGTG
TACTATTGCCAGCAGTACGGCAAGTCCCCCATCACCTTCGGCC AGGGAACCCGGCTGGAAATGAAG
1005 VL of CDH19 artificial AA
DIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLAWYQQKPGQ 17H8.2
APRLLISGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV YYCQQYGKSPITFGQGTRLEMK
1006 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAATCCGGCCCTGGCCTGGTCAAGCCCT CDH19 17H8.2
CCGAGACACTGTCCCTGACCTGCACCGTGTCCGGCGGCTCCAT
CAACTCCTACTACTGGTCCTGGATCCGGCAGCCCCCTGGCAAG
GGCCTGGAATGGATCGGCTACATCTACTACATCGGCTCCACCA
ACTACAACCCCAGCCTGAAGTCCAGAGTGACCATCTCCGTGGA
CACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCCGTGACC
GCCGCTGACACCGCCCTGTACTACTGCGCCAGAGACTCCCGGT
ACAGATCCGGGTGGTACGACGCCTTCGACATCTGGGGCCAGGG
CACCATGGTCACCGTGTCCTCTGGTGGCGGAGGCTCTGGCGGA
GGTGGAAGCGGAGGCGGCGGATCCGATATCGTGCTGACCCAGT
CCCCCGGCACCCTGTCTCTGAGCCCTGGCGAGAGAGCCACCCT
GTCCTGCAGAGCCTCTCAGTCCGTGGCCGGCTCCTACCTGGCT
TGGTATCAGCAGAAGCCCGGCCAGGCCCCTCGGCTGCTGATCT
CCGGCGCCTCTTCTAGAGCCACCGGCATCCCTGACCGGTTCTC
CGGCTCTGGCTCCGGCACCGACTTCACCCTGACCATCAGCCGG
CTGGAACCCGAGGACTTCGCCGTGTACTATTGCCAGCAGTACG
GCAAGTCCCCCATCACCTTCGGCCAGGGAACCCGGCTGGAAAT GAAG 1007 VH-VL of
artificial AA QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGK CDH19
17H8.2 GLEWIGYIYYIGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVT
AADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSSGGGGSGG
GGSGGGGSDIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLA
WYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISR
LEPEDFAVYYCQQYGKSPITFGQGTRLEMK 1008 CDH19 17H8.2 artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWSWIRQPPGK
x I2C GLEWIGYIYYIGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVT
AADTALYYCARDSRYRSGWYDAFDIWGQGTMVTVSSGGGGSGG
GGSGGGGSDIVLTQSPGTLSLSPGERATLSCRASQSVAGSYLA
WYQQKPGQAPRLLISGASSRATGIPDRFSGSGSGTDFTLTISR
LEPEDFAVYYCQQYGKSPITFGQGTRLEMKSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1009 CDR-H1 of artificial AA
SYFIH CDH19 19B5.1 1010 CDR-H2 of artificial AA IINPISVSTSYAQKFQG
CDH19 19B5.1 1011 CDR-H3 of artificial AA GGIQLWLHLDY CDH19 19B5.1
1012 CDR-L1 of artificial AA SGSRSNIGSNFVN CDH19 19B5.1 1013 CDR-L2
of artificial AA TNNQRPS CDH19 19B5.1 1014 CDR-L3 of artificial AA
ATWDDSMNGWV CDH19 19B5.1 1015 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG 19B5.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGTGTCCGGCTACACCTT
CACCAGCTACTTCATCCACTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCTATCTCCGTGTCCA
CCTCCTACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCCG
GGACACCTCCACCTCCACCGTGTTCATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACCTGGACTATTGGGGCCAGGGCACCCT GGTCACCGTGTCCTCT 1016
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ 19B5.1
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS 1017 VL of CDH19 artificial NT
CAGTCTGCCCTGACCCAGCCTCCCTCCACCACCGGCACACCTG 19B5.1
GCCAGCGCGTGACCATCTCCTGCTCCGGCTCCCGGTCCAACAT
CGGCTCCAACTTCGTGAACTGGTACAAGCAGCTGCCCGGCACC
GCCCCCAAGGTGCTGATCTACACCAACAACCAGCGGCCCTCCG
GCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGGCACCTCCGC
CTCCCTGGCCATCTCCGGCCTGCAGTCCGAGGACGAGTCCGAC
TACTACTGTGCCACCTGGGACGACTCCATGAACGGCTGGGTGT
TCGGCGGAGGCACCAAGCTGACCGTGCTG 1018 VL of CDH19 artificial AA
QSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWYKQLPGT 19B5.1
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
YYCATWDDSMNGWVFGGGTKLTVL 1019 VH-VL of artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG CDH19 19B5.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGTGTCCGGCTACACCTT
CACCAGCTACTTCATCCACTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCTATCTCCGTGTCCA
CCTCCTACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCCG
GGACACCTCCACCTCCACCGTGTTCATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACCTGGACTATTGGGGCCAGGGCACCCT
GGTCACCGTGTCCTCTGGTGGCGGAGGATCTGGCGGAGGTGGA
AGCGGAGGCGGCGGATCTCAGTCTGCCCTGACCCAGCCTCCCT
CCACCACCGGCACACCTGGCCAGCGCGTGACCATCTCCTGCTC
CGGCTCCCGGTCCAACATCGGCTCCAACTTCGTGAACTGGTAC
AAGCAGCTGCCCGGCACCGCCCCCAAGGTGCTGATCTACACCA
ACAACCAGCGGCCCTCCGGCGTGCCCGACCGGTTCTCTGGCTC
CAAGTCTGGCACCTCCGCCTCCCTGGCCATCTCCGGCCTGCAG
TCCGAGGACGAGTCCGACTACTACTGTGCCACCTGGGACGACT
CCATGAACGGCTGGGTGTTCGGCGGAGGCACCAAGCTGACCGT GCTG 1020 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ CDH19
19B5.1 GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWY
KQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDESDYYCATWDDSMNGWVFGGGTKLTVL 1021 CDH19 19B5.1 artificial
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ x I2C
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSTTGTPGQRVTISCSGSRSNIGSNFVNWY
KQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDESDYYCATWDDSMNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1022 CDR-H1 of artificial AA
SYFIH CDH19 20D3.1 1023 CDR-H2 of artificial AA IINPISVSTSYAQKFQG
CDH19 20D3.1 1024 CDR-H3 of artificial AA GGIQLWLHFDY CDH19 20D3.1
1025 CDR-L1 of artificial AA SGSSSNIGSNFVN CDH19 20D3.1 1026 CDR-L2
of artificial AA TNNQRPS CDH19 20D3.1 1027 CDR-L3 of artificial AA
ATWDDSLNGWV CDH19 20D3.1 1028 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG 20D3.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGTGTCCGGCTACACCTT
CACCAGCTACTTCATCCACTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCTATCTCCGTGTCCA
CCTCCTACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCCG
GGACACCTCCACCTCCACCGTGTTCATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACTTCGACTACTGGGGCCAGGGCACCCT GGTCACCGTGTCTAGC 1029
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ 20D3.1
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS 1030 VL of CDH19 artificial NT
CAGTCTGCCCTGACCCAGCCTCCTTCTGCCACCGGCACCCCTG 20D3.1
GCCAGCGCGTGACCATCTCCTGCTCCGGCTCCTCCTCCAACAT
CGGCTCCAACTTCGTGAACTGGTACAAGCAGCTGCCCGGCACC
GCCCCCAAGGTGCTGATCTACACCAACAACCAGCGGCCCTCCG
GCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGGCACCTCCGC
CTCCCTGGCCATCTCCGGCCTGCAGTCCGAGGACGAGTCCGAC
TACTACTGTGCCACCTGGGACGACTCCCTGAACGGCTGGGTGT
TCGGCGGAGGCACCAAGCTGACCGTGCTG 1031 VL of CDH19 artificial AA
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGT 20D3.1
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
YYCATWDDSLNGWVFGGGTKLTVL 1032 VH-VL of artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG CDH19 20D3.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGTGTCCGGCTACACCTT
CACCAGCTACTTCATCCACTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCTATCTCCGTGTCCA
CCTCCTACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCCG
GGACACCTCCACCTCCACCGTGTTCATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACTTCGACTACTGGGGCCAGGGCACCCT
GGTCACCGTGTCTAGCGGAGGCGGAGGATCTGGTGGCGGTGGT
TCTGGCGGCGGAGGCTCTCAGTCTGCCCTGACCCAGCCTCCTT
CTGCCACCGGCACCCCTGGCCAGCGCGTGACCATCTCCTGCTC
CGGCTCCTCCTCCAACATCGGCTCCAACTTCGTGAACTGGTAC
AAGCAGCTGCCCGGCACCGCCCCCAAGGTGCTGATCTACACCA
ACAACCAGCGGCCCTCCGGCGTGCCCGACCGGTTCTCTGGCTC
CAAGTCTGGCACCTCCGCCTCCCTGGCCATCTCCGGCCTGCAG
TCCGAGGACGAGTCCGACTACTACTGTGCCACCTGGGACGACT
CCCTGAACGGCTGGGTGTTCGGCGGAGGCACCAAGCTGACCGT GCTG 1033 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ CDH19
20D3.1 GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWY
KQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDESDYYCATWDDSLNGWVFGGGTKLTVL 1034 CDH19 20D3.1 artificial
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ x I2C
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWY
KQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDESDYYCATWDDSLNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1035 CDR-H1 of artificial AA
SYFIH CDH19 22D1.1 1036 CDR-H2 of artificial AA IINPISVSTSYAQKFQG
CDH19 22D1.1 1037 CDR-H3 of artificial AA GGIQLWLHLDY CDH19 22D1.1
1038 CDR-L1 of artificial AA SGSSSNIGSNFVN CDH19 22D1.1 1039 CDR-L2
of artificial AA TNNQRPS CDH19 22D1.1 1040 CDR-L3 of artificial AA
ATWDDSMNGWV CDH19 22D1.1 1041 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG 22D1.1
GCGCCTCCGTGCGGGTGTCCTGCAAGGTGTCCGGCTACACCTT
CACCAGCTACTTCATCCACTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCTATCTCCGTGTCCA
CCTCCTACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCCG
GGACACCTCCACCTCCACCGTGTTCATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACCTGGACTATTGGGGCCAGGGCACCCT GGTCACCGTGTCCTCT 1042
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQ 22D1.1
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS 1043 VL of CDH19 artificial NT
CAGTCTGCCCTGACCCAGCCTCCTTCCGCTACCGGCACCCCTG 22D1.1
GCCAGCGCGTGACCATCTCCTGCTCCGGCTCCTCCTCCAACAT
CGGCTCCAACTTCGTGAACTGGTACAAGCAGCTGCCCGGCACC
GCCCCCAAGGTGCTGATCTACACCAACAACCAGCGGCCCTCCG
GCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGGCACCTCCGC
CTCCCTGGCCATCTCCGGCCTGCAGTCCGAGGACGAGTCCGAC
TACTACTGTGCCACCTGGGACGACTCCATGAACGGCTGGGTGT
TCGGCGGAGGCACCAAGCTGACCGTGCTG 1044 VL of CDH19 artificial AA
QSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWYKQLPGT 22D1.1
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
YYCATWDDSMNGWVFGGGTKLTVL 1045 VH-VL of artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG CDH19 22D1.1
GCGCCTCCGTGCGGGTGTCCTGCAAGGTGTCCGGCTACACCTT
CACCAGCTACTTCATCCACTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCTATCTCCGTGTCCA
CCTCCTACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCCG
GGACACCTCCACCTCCACCGTGTTCATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACCTGGACTATTGGGGCCAGGGCACCCT
GGTCACCGTGTCCTCTGGTGGCGGAGGATCTGGCGGAGGTGGA
AGCGGAGGCGGCGGATCTCAGTCTGCCCTGACCCAGCCTCCTT
CCGCTACCGGCACCCCTGGCCAGCGCGTGACCATCTCCTGCTC
CGGCTCCTCCTCCAACATCGGCTCCAACTTCGTGAACTGGTAC
AAGCAGCTGCCCGGCACCGCCCCCAAGGTGCTGATCTACACCA
ACAACCAGCGGCCCTCCGGCGTGCCCGACCGGTTCTCTGGCTC
CAAGTCTGGCACCTCCGCCTCCCTGGCCATCTCCGGCCTGCAG
TCCGAGGACGAGTCCGACTACTACTGTGCCACCTGGGACGACT
CCATGAACGGCTGGGTGTTCGGCGGAGGCACCAAGCTGACCGT GCTG 1046 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQ CDH19
22D1.1 GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWY
KQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDESDYYCATWDDSMNGWVFGGGTKLTVL 1047 CDH19 22D1.1 artificial
QVQLVQSGAEVKKPGASVRVSCKVSGYTFTSYFIHWVRQAPGQ x I2C
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSATGTPGQRVTISCSGSSSNIGSNFVNWY
KQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDESDYYCATWDDSMNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1048 CDR-H1 of artificial AA
SYAMN CDH19 22G10.1 1049 CDR-H2 of artificial AA TISGGGANTYYADSVKG
CDH19 22G10.1 1050 CDR-H3 of artificial AA GGMGGYYYGMDV CDH19
22G10.1 1051 CDR-L1 of artificial AA RASQSISSNLA CDH19 22G10.1 1052
CDR-L2 of artificial AA GAFTRAT CDH19 22G10.1 1053 CDR-L3 of
artificial AA QQYNYWPLT CDH19 22G10.1 1054 VH of CDH19 artificial
NT GAGGTGCAGCTGCTGGAATCCGGCGGAGGACTGGTGCAGCCTG 22G10.1
GCGGCTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCACCTT
CTCCAGCTACGCCATGAACTGGGTCCGACAGGCCCCTGGCAAG
GGCCTGGAATGGGTGTCCACCATCAGCGGCGGAGGCGCCAACA
CCTACTACGCCGACTCCGTGAAGGGCCGGTTCACCATCTCCTC
CGACAACTCCAAGTCCACCCTGTACCTGCAGATGAACTCCCTG
AGAGCCGCCGACACCGCCGTGTACCACTGTGCTAAGGGCGGCA
TGGGCGGCTACTACTACGGCATGGATGTGTGGGGCCAGGGCAC CACCGTGACCGTGTCTAGC
1055 VH of CDH19 artificial AA
EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMNWVRQAPGK 22G10.1
GLEWVSTISGGGANTYYADSVKGRFTISSDNSKSTLYLQMNSL
RAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSS 1056 VL of CDH19 artificial NT
GAGATCGTGATGACCCAGTCCCCCGTGACCCTGTCCCTGAGCC 22G10.1
TGGGCGAGAGAGCCACCCTGTCTTGCCGGGCCTCCCAGTCCAT
CTCCAGCAACCTGGCCTGGTTCCAGCAGAAGCCCGGCCAGGCC
CCTCGGCTGCTGATCTACGGCGCCTTTACCCGGGCCACCGGCA
TCCCTGCCAGAGTGTCTGGCTCCGGCTCCGGCACCGAGTTCAC
CCTGACCATCAGCTCCCTGCAGTCCGAGGACTTTGCCGTGTAC
TACTGCCAGCAGTACAACTACTGGCCCCTGACCTTCGGAGGCG GCACCAAGGTGGAAATCAAG
1057 VL of CDH19 artificial AA
EIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWFQQKPGQA 22G10.1
PRLLIYGAFTRATGIPARVSGSGSGTEFTLTISSLQSEDFAVY YCQQYNYWPLTFGGGTKVEIK
1058 VH-VL of artificial NT
GAGGTGCAGCTGCTGGAATCCGGCGGAGGACTGGTGCAGCCTG CDH19
GCGGCTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCACCTT 22G10.1
CTCCAGCTACGCCATGAACTGGGTCCGACAGGCCCCTGGCAAG
GGCCTGGAATGGGTGTCCACCATCAGCGGCGGAGGCGCCAACA
CCTACTACGCCGACTCCGTGAAGGGCCGGTTCACCATCTCCTC
CGACAACTCCAAGTCCACCCTGTACCTGCAGATGAACTCCCTG
AGAGCCGCCGACACCGCCGTGTACCACTGTGCTAAGGGCGGCA
TGGGCGGCTACTACTACGGCATGGATGTGTGGGGCCAGGGCAC
CACCGTGACCGTGTCTAGCGGAGGCGGAGGATCTGGCGGTGGT
GGTTCTGGCGGAGGCGGCTCCGAGATCGTGATGACCCAGTCCC
CCGTGACCCTGTCCCTGAGCCTGGGCGAGAGAGCCACCCTGTC
TTGCCGGGCCTCCCAGTCCATCTCCAGCAACCTGGCCTGGTTC
CAGCAGAAGCCCGGCCAGGCCCCTCGGCTGCTGATCTACGGCG
CCTTTACCCGGGCCACCGGCATCCCTGCCAGAGTGTCTGGCTC
CGGCTCCGGCACCGAGTTCACCCTGACCATCAGCTCCCTGCAG
TCCGAGGACTTTGCCGTGTACTACTGCCAGCAGTACAACTACT
GGCCCCTGACCTTCGGAGGCGGCACCAAGGTGGAAATCAAG 1059 VH-VL of artificial
AA EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGK CDH19
GLEWVSTISGGGANTYYADSVKGRFTISSDNSKSTLYLQMNSL 22G10.1
RAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSGGGGSGGG
GSGGGGSEIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWF
QQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEFTLTISSLQ
SEDFAVYYCQQYNYWPLTFGGGTKVEIK 1060 CDH19 artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGK 22G10.1 x I2C
GLEWVSTISGGGANTYYADSVKGRFTISSDNSKSTLYLQMNSL
RAADTAVYHCAKGGMGGYYYGMDVWGQGTTVTVSSGGGGSGGG
GSGGGGSEIVMTQSPVTLSLSLGERATLSCRASQSISSNLAWF
QQKPGQAPRLLIYGAFTRATGIPARVSGSGSGTEFTLTISSLQ
SEDFAVYYCQQYNYWPLTFGGGTKVEIKSGGGGSEVQLVESGG
GLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIR
SKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAV
YYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGG
GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQK
PGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPED
EAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1061 CDR-H1 of artificial AA RYGIH
CDH19 23A10.3 1062 CDR-H2 of artificial AA VIWYDGSNKYYADSVKG CDH19
23A10.3 1063 CDR-H3 of artificial AA RAGIPGTTGYYYGMDV CDH19 23A10.3
1064 CDR-L1 of artificial AA SGDRLGEKYVC CDH19 23A10.3 1065 CDR-L2
of artificial AA QDNKWPS CDH19 23A10.3 1066 CDR-L3 of artificial AA
QAWDSSTVV CDH19 23A10.3 1067 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG 23A10.3
GCCGGTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCACCTT
CTCCAGATACGGCATCCACTGGGTCCGACAGGCCCCTGGCAAG
GGCCTGGAATGGGTGGCCGTGATTTGGTACGACGGCTCCAACA
AGTACTACGCCGACTCCGTGAAGGGCCGGTTCACCATCTCCCG
GGACAACTCCAAGAACACCCTGTACCTGCTGATGAACTCCCTG
CGGGCCGAGGACTCCGCCGTGTACTACTGTGCCAGAAGGGCCG
GCATCCCCGGCACCACCGGCTACTACTACGGCATGGATGTGTG
GGGCCAGGGCACCACCGTGACCGTGTCTAGC 1068 VH of CDH19 artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK 23A10.3
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLLMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS 1069 VL of CDH19 artificial
NT TACGAGCTGACCCAGCCCCCCTCCGTGTCCGTGTCTCCTGGCC 23A10.3
AGACCGCCTCCATCACCTGTTCTGGCGACCGGCTGGGCGAGAA
ATACGTGTGCTGGTATCAGCAGAAGCCCGGCCAGTCCCCCATC
CTGGTCATCTACCAGGACAACAAGTGGCCCTCCGGCATCCCTG
AGCGGTTCTCCGGCTCCAACTCCGGCAACACCGCCACCCTGAC
CATCTCCGGCACCCAGGCCATGGACGAGGCCGACTACTACTGC
CAGGCCTGGGACTCCTCCACCGTGGTGTTCGGCGGAGGCACCA AGCTGACCGTGCTG 1070 VL
of CDH19 artificial AA SYELTQPPSVSVSPGQTASITCSGDRLGEKYVCWYQQKPGQSP
23A10.3 ILVIYQDNKWPSGIPERFSGSNSGNTATLTISGTQAMDEADYY
CQAWDSSTVVFGGGTKLTVL 1071 VH-VL of artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG CDH19
GCCGGTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCACCTT 23A10.3
CTCCAGATACGGCATCCACTGGGTCCGACAGGCCCCTGGCAAG
GGCCTGGAATGGGTGGCCGTGATTTGGTACGACGGCTCCAACA
AGTACTACGCCGACTCCGTGAAGGGCCGGTTCACCATCTCCCG
GGACAACTCCAAGAACACCCTGTACCTGCTGATGAACTCCCTG
CGGGCCGAGGACTCCGCCGTGTACTACTGTGCCAGAAGGGCCG
GCATCCCCGGCACCACCGGCTACTACTACGGCATGGATGTGTG
GGGCCAGGGCACCACCGTGACCGTGTCTAGCGGAGGCGGAGGA
TCTGGTGGCGGTGGTTCTGGCGGCGGAGGCTCCTCTTACGAGC
TGACCCAGCCCCCCTCCGTGTCCGTGTCTCCTGGCCAGACCGC
CTCCATCACCTGTTCTGGCGACCGGCTGGGCGAGAAATACGTG
TGCTGGTATCAGCAGAAGCCCGGCCAGTCCCCCATCCTGGTCA
TCTACCAGGACAACAAGTGGCCCTCCGGCATCCCTGAGCGGTT
CTCCGGCTCCAACTCCGGCAACACCGCCACCCTGACCATCTCC
GGCACCCAGGCCATGGACGAGGCCGACTACTACTGCCAGGCCT
GGGACTCCTCCACCGTGGTGTTCGGCGGAGGCACCAAGCTGAC CGTGCTG 1072 VH-VL of
artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK CDH19
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLLMNSL 23A10.3
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
CWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVL 1073 CDH19 artificial
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK 23A10.3 x I2C
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLLMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
CWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1074 CDR-H1 of artificial AA
SYYIH CDH19 25F8.1 1075 CDR-H2 of artificial AA IINPSGGSTRYAQKFQG
CDH19 25F8.1 1076 CDR-H3 of artificial AA GGIQLWLHFDY CDH19 25F8.1
1077 CDR-L1 of artificial AA SGSSSNIGRNFVN CDH19 25F8.1 1078 CDR-L2
of artificial AA TNNQRPS CDH19 25F8.1 1079 CDR-L3 of artificial AA
AAWDDSLNGWV CDH19 25F8.1 1080 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG 25F8.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGCCTCCGGCTACACCTT
CACCAGCTACTACATCCACTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCCTCCGGCGGCTCCA
CCAGATACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCCG
GGACACCTCCACCTCCACCGTGTTCATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACTTCGACTACTGGGGCCAGGGCACCCT GGTCACCGTGTCTAGC 1081
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ 25F8.1
GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS 1082 VL of CDH19 artificial NT
CAGTCTGCCCTGACCCAGCCTCCTTCTGCCACCGGCACCCCTG 25F8.1
GCCAGCGCGTGACCATCTCCTGCTCCGGCTCCTCCTCCAACAT
CGGCCGGAACTTCGTGAACTGGTACAAGCAGCTGCCCGGCACC
GCCCCCAAGGTGCTGATCTACACCAACAACCAGCGGCCCTCCG
GCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGGCACCTCCGC
CTCCCTGGCCATCTCCGGCCTGCAGTCCGAGGACGAGTCCGAC
TACTACTGTGCCGCCTGGGACGACTCCCTGAACGGCTGGGTGT
TCGGCGGAGGCACCAAGCTGACCGTGCTG 1083 VL of CDH19 artificial AA
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYKQLPGT 25F8.1
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDESD
YYCAAWDDSLNGWVFGGGTKLTVL 1084 VH-VL of artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG CDH19 25F8.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGCCTCCGGCTACACCTT
CACCAGCTACTACATCCACTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCCTCCGGCGGCTCCA
CCAGATACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCCG
GGACACCTCCACCTCCACCGTGTTCATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACTTCGACTACTGGGGCCAGGGCACCCT
GGTCACCGTGTCTAGCGGAGGCGGAGGATCTGGTGGCGGTGGT
TCTGGCGGCGGAGGCTCTCAGTCTGCCCTGACCCAGCCTCCTT
CTGCCACCGGCACCCCTGGCCAGCGCGTGACCATCTCCTGCTC
CGGCTCCTCCTCCAACATCGGCCGGAACTTCGTGAACTGGTAC
AAGCAGCTGCCCGGCACCGCCCCCAAGGTGCTGATCTACACCA
ACAACCAGCGGCCCTCCGGCGTGCCCGACCGGTTCTCTGGCTC
CAAGTCTGGCACCTCCGCCTCCCTGGCCATCTCCGGCCTGCAG
TCCGAGGACGAGTCCGACTACTACTGTGCCGCCTGGGACGACT
CCCTGAACGGCTGGGTGTTCGGCGGAGGCACCAAGCTGACCGT GCTG 1085 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ CDH19
25F8.1 GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWY
KQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDESDYYCAAWDDSLNGWVFGGGTKLTVL 1086 CDH19 25F8.1 artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ x I2C
GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWY
KQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDESDYYCAAWDDSLNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1087 CDR-H1 of artificial AA
GYYWS CDH19 25G10.1 1088 CDR-H2 of artificial AA YIYYIGSTNYNPSLKS
CDH19 25G10.1 1089 CDR-H3 of artificial AA DGSSGWYRWFDP CDH19
25G10.1 1090 CDR-L1 of artificial AA RASQSVSSSYLA CDH19 25G10.1
1091 CDR-L2 of artificial AA GASSRAT CDH19 25G10.1 1092 CDR-L3 of
artificial AA QQYGNSPLT CDH19 25G10.1 1093 VH of CDH19 artificial
NT CAGGTGCAGCTGCAGGAATCCGGCCCTGGCCTGGTCAAGCCCT 25G10.1
CCGAGACACTGTCCCTGACCTGCACCGTGTCCGGCGGCTCCAT
CTCCGGCTACTACTGGTCCTGGATCCGGCAGCCCCCTGGCAAG
GGCCTGGAATGGATCGGCTACATCTACTACATCGGCTCCACCA
ACTACAACCCCAGCCTGAAGTCCAGAGTGACCATGTCCGTGGA
CACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCCGTGACC
GCCGCTGACACCGCCGTGTACTACTGCGCCAGAGATGGCTCCT
CCGGCTGGTATCGTTGGTTCGACCCTTGGGGCCAGGGCACCCT GGTCACCGTGTCTAGC 1094
VH of CDH19 artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK 25G10.1
GLEWIGYIYYIGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVT
AADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSS 1095 VL of CDH19 artificial NT
GAGATCGTGCTGACCCAGTCCCCTGGCACCCTGTCCCTGAGCC 25G10.1
CTGGCGAGAGAGCCACCCTGTCCTGCAGAGCCTCCCAGTCCGT
GTCCTCCTCCTACCTGGCTTGGTATCAGCAGAAGCCCGGCCAG
GCCCCTCGGCTGCTGATCTTCGGCGCCTCTTCCAGAGCCACCG
GCATCCCTGACCGGTTCTCCGGCTCTGGCTCCGGCACCGACTT
CACCCTGACCATCTCCCGGCTGGAACCCGAGGACTTCGCTGTG
TACCACTGCCAGCAGTACGGCAACAGCCCCCTGACCTTCGGCG GAGGCACCAAGGTGGAAATCAAG
1096 VL of CDH19 artificial AA
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ 25G10.1
APRLLIFGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV YHCQQYGNSPLTFGGGTKVEIK
1097 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAATCCGGCCCTGGCCTGGTCAAGCCCT CDH19
CCGAGACACTGTCCCTGACCTGCACCGTGTCCGGCGGCTCCAT 25G10.1
CTCCGGCTACTACTGGTCCTGGATCCGGCAGCCCCCTGGCAAG
GGCCTGGAATGGATCGGCTACATCTACTACATCGGCTCCACCA
ACTACAACCCCAGCCTGAAGTCCAGAGTGACCATGTCCGTGGA
CACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCCGTGACC
GCCGCTGACACCGCCGTGTACTACTGCGCCAGAGATGGCTCCT
CCGGCTGGTATCGTTGGTTCGACCCTTGGGGCCAGGGCACCCT
GGTCACCGTGTCTAGCGGAGGCGGAGGATCTGGTGGCGGTGGT
TCTGGCGGCGGAGGCTCCGAGATCGTGCTGACCCAGTCCCCTG
GCACCCTGTCCCTGAGCCCTGGCGAGAGAGCCACCCTGTCCTG
CAGAGCCTCCCAGTCCGTGTCCTCCTCCTACCTGGCTTGGTAT
CAGCAGAAGCCCGGCCAGGCCCCTCGGCTGCTGATCTTCGGCG
CCTCTTCCAGAGCCACCGGCATCCCTGACCGGTTCTCCGGCTC
TGGCTCCGGCACCGACTTCACCCTGACCATCTCCCGGCTGGAA
CCCGAGGACTTCGCTGTGTACCACTGCCAGCAGTACGGCAACA
GCCCCCTGACCTTCGGCGGAGGCACCAAGGTGGAAATCAAG 1098 VH-VL of artificial
AA QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK CDH19
GLEWIGYIYYIGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVT 25G10.1
AADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSSGGGGSGGGG
SGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWY
QQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTDFTLTISRLE
PEDFAVYHCQQYGNSPLTFGGGTKVEIK 1099 CDH19 artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK 25G10.1 x I2C
GLEWIGYIYYIGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVT
AADTAVYYCARDGSSGWYRWFDPWGQGTLVTVSSGGGGSGGGG
SGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWY
QQKPGQAPRLLIFGASSRATGIPDRFSGSGSGTDFTLTISRLE
PEDFAVYHCQQYGNSPLTFGGGTKVEIKSGGGGSEVQLVESGG
GLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIR
SKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAV
YYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGG
GSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQK
PGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPED
EAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1100 CDR-H1 of artificial AA SYYMS
CDH19 26D1.1 1101 CDR-H2 of artificial AA IIHPSGGDTTYAQKFQG CDH19
26D1.1 1102 CDR-H3 of artificial AA GGIKLWLHFDY CDH19 26D1.1 1103
CDR-L1 of artificial AA SGSRSNIGSNFVN CDH19 26D1.1 1104 CDR-L2 of
artificial AA TNNQRPS CDH19 26D1.1 1105 CDR-L3 of artificial AA
AVWDDSLNGWV CDH19 26D1.1 1106 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG 26D1.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGCCTCCCGGTACACCTT
CACCAGCTACTACATGTCCTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCCACCCCTCTGGCGGCGACA
CCACCTACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCGG
CGACACCTCCACCTCCACCGTGTATATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCAAGCTGTGGCTGCACTTCGACTACTGGGGCCAGGGCACCCT GGTCACCGTGTCTAGC 1107
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQ 26D1.1
GLEWMGIIHPSGGDTTYAQKFQGRVTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS 1108 VL of CDH19 artificial NT
CATTCCGTGCTGACCCAGTCTCCTTCCGCCTCCGGCACCCCTG 26D1.1
GCCAGCGCGTGACCATCTCCTGCTCCGGCTCCCGGTCCAACAT
CGGCTCCAACTTCGTGAACTGGTATCAGCAGCTGCCCGGCACC
GCCCCCAAGCTGCTGATCTACACCAACAACCAGCGGCCCTCCG
GCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGGCACCTCCGC
CTCCCTGGCCATCTCCGGCCTGCAGTCTGAGGACGAGGCCGAC
TACTACTGTGCCGTGTGGGACGACTCCCTGAACGGCTGGGTGT
TCGGCGGAGGCACCAAGCTGACCGTGCTG 1109 VL of CDH19 artificial AA
HSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGT 26D1.1
APKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCAVWDDSLNGWVFGGGTKLTVL 1110 VH-VL of artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG CDH19 26D1.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGCCTCCCGGTACACCTT
CACCAGCTACTACATGTCCTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCCACCCCTCTGGCGGCGACA
CCACCTACGCCCAGAAATTCCAGGGCAGAGTGACCATGACCGG
CGACACCTCCACCTCCACCGTGTATATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCAAGCTGTGGCTGCACTTCGACTACTGGGGCCAGGGCACCCT
GGTCACCGTGTCTAGCGGAGGCGGAGGATCTGGTGGCGGTGGT
TCTGGCGGCGGAGGCTCCCATTCCGTGCTGACCCAGTCTCCTT
CCGCCTCCGGCACCCCTGGCCAGCGCGTGACCATCTCCTGCTC
CGGCTCCCGGTCCAACATCGGCTCCAACTTCGTGAACTGGTAT
CAGCAGCTGCCCGGCACCGCCCCCAAGCTGCTGATCTACACCA
ACAACCAGCGGCCCTCCGGCGTGCCCGACCGGTTCTCTGGCTC
CAAGTCTGGCACCTCCGCCTCCCTGGCCATCTCCGGCCTGCAG
TCTGAGGACGAGGCCGACTACTACTGTGCCGTGTGGGACGACT
CCCTGAACGGCTGGGTGTTCGGCGGAGGCACCAAGCTGACCGT GCTG 1111 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQ CDH19
26D1.1 GLEWMGIIHPSGGDTTYAQKFQGRVTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSHSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAVWDDSLNGWVFGGGTKLTVL 1112 CDH19 26D1.1 artificial
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQ x I2C
GLEWMGIIHPSGGDTTYAQKFQGRVTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSHSVLTQSPSASGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAVWDDSLNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1113 CDR-H1 of artificial AA
NYYMS CDH19 26F12.1 1114 CDR-H2 of artificial AA IINPSGGDSTYAQKFQG
CDH19 26F12.1 1115 CDR-H3 of artificial AA GGIQLWLHFDY CDH19
26F12.1 1116 CDR-L1 of artificial AA SGSRSNIGSNFVN CDH19 26F12.1
1117 CDR-L2 of artificial AA TNYQRPS CDH19 26F12.1 1118 CDR-L3 of
artificial AA AVWDDSLNGWV
CDH19 26F12.1 1119 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG 26F12.1
GCGCCTCCGTGAAGGTGTCCTGCAAGGCCTCCCGGTACACCTT
CACCAACTACTACATGTCCTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCCTCTGGCGGCGACT
CCACCTACGCCCAGAAGTTCCAGGGCCGGCTGACCATGACCGG
CGACACCTCCACCTCCACCGTGTATATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACTTCGACTACTGGGGCCAGGGCACCCT GGTCACCGTGTCTAGC 1120
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQ 26F12.1
GLEWMGIINPSGGDSTYAQKFQGRLTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS 1121 VL of CDH19 artificial NT
CAGTCTGTGCTGACCCAGTCCCCTTCCGCCTCTGGCACCCCTG 26F12.1
GCCAGAAAGTGACCATCTCCTGCTCCGGCTCCCGGTCCAACAT
CGGCTCCAACTTCGTGAACTGGTATCAGCAGCTGCCCGGCACC
GCCCCCAAGCTGCTGATCTACACCAACTACCAGCGGCCCTCCG
GCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGGCACCTCCGC
CTCCCTGGCCATCTCCGGCCTGCAGTCTGAGGACGAGGCCGAC
TACTACTGTGCCGTGTGGGACGACTCCCTGAACGGCTGGGTGT
TCGGCGGAGGCACCAAGCTGACCGTGCTG 1122 VL of CDH19 artificial AA
QSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWYQQLPGT 26F12.1
APKLLIYTNYQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCAVWDDSLNGWVFGGGTKLTVL 1123 VH-VL of artificial NT
CAGGTGCAGCTGGTGCAGTCTGGCGCCGAAGTGAAGAAACCTG CDH19
GCGCCTCCGTGAAGGTGTCCTGCAAGGCCTCCCGGTACACCTT 26F12.1
CACCAACTACTACATGTCCTGGGTCCGACAGGCCCCAGGCCAG
GGCCTGGAATGGATGGGCATCATCAACCCCTCTGGCGGCGACT
CCACCTACGCCCAGAAGTTCCAGGGCCGGCTGACCATGACCGG
CGACACCTCCACCTCCACCGTGTATATGGAACTGTCCTCCCTG
CGGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAGGCGGCA
TCCAGCTGTGGCTGCACTTCGACTACTGGGGCCAGGGCACCCT
GGTCACCGTGTCTAGCGGAGGCGGAGGATCTGGTGGCGGTGGT
TCTGGCGGCGGAGGCTCCCAGTCTGTGCTGACCCAGTCCCCTT
CCGCCTCTGGCACCCCTGGCCAGAAAGTGACCATCTCCTGCTC
CGGCTCCCGGTCCAACATCGGCTCCAACTTCGTGAACTGGTAT
CAGCAGCTGCCCGGCACCGCCCCCAAGCTGCTGATCTACACCA
ACTACCAGCGGCCCTCCGGCGTGCCCGACCGGTTCTCTGGCTC
CAAGTCTGGCACCTCCGCCTCCCTGGCCATCTCCGGCCTGCAG
TCTGAGGACGAGGCCGACTACTACTGTGCCGTGTGGGACGACT
CCCTGAACGGCTGGGTGTTCGGCGGAGGCACCAAGCTGACCGT GCTG 1124 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQ CDH19
GLEWMGIINPSGGDSTYAQKFQGRLTMTGDTSTSTVYMELSSL 26F12.1
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWY
QQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAVWDDSLNGWVFGGGTKLTVL 1125 CDH19 artificial
QVQLVQSGAEVKKPGASVKVSCKASRYTFTNYYMSWVRQAPGQ 26F12.1 x I2C
GLEWMGIINPSGGDSTYAQKFQGRLTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSVLTQSPSASGTPGQKVTISCSGSRSNIGSNFVNWY
QQLPGTAPKLLIYTNYQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAVWDDSLNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1126 CDR-H1 of artificial AA
GYYWS CDH19 4A9 1127 CDR-H2 of artificial AA YFSYSGSTNYNPSLKS CDH19
4A9 1128 CDR-H3 of artificial AA NWAFHFDF CDH19 4A9 1129 CDR-L1 of
artificial AA TGSSSNIGTGYAVH CDH19 4A9 1130 CDR-L2 of artificial AA
GNNNRPS CDH19 4A9 1131 CDR-L3 of artificial AA QSYDSRLSGWV CDH19
4A9 1132 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAATCCGGCCCTGGCCTGGTCAAGCCCT 4A9
CCGAGACACTGTCCCTGACCTGCACCGTGTCCGGCGGCTCCAT
CTCCGGCTACTACTGGTCCTGGATCCGGCAGCCCCCTGGCAAG
GGCCTGGAATGGTTCGCCTACTTCTCCTACTCCGGCTCCACCA
ACTACAACCCCAGCCTGAAGTCCAGAGTGACCCTGTCCGTGGA
CACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCCGTGACC
GCCGCTGACACCGCCGTGTACTACTGCGCCCGGAACTGGGCCT
TCCACTTCGATTTCTGGGGCCAGGGCACCCTGGTCACCGTGTC TAGC 1133 VH of CDH19
artificial AA QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK 4A9
GLEWFAYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSS 1134 VL of CDH19 artificial NT
CAGTCTGTGCTGACCCAGCCTCCCTCTGTGTCTGGCGCCCCTG 4A9
GCCAGAGAGTGACCATCTCCTGCACCGGCTCCTCCAGCAACAT
CGGCACCGGCTACGCCGTGCACTGGTATCAGCAGTTCCCCGGC
ACCGCCCCCAAGCTGCTGATCTACGGCAACAACAACCGGCCCT
CCGGCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGGCACCTC
CGCCTCCCTGGCTATCACCGGCCTGCAGGCTGAGGACGAGGCC
GACTACTACTGCCAGTCCTACGACTCCCGGCTGTCCGGCTGGG
TGTTCGGCGGAGGCACCAAGCTGACCGTGCTG 1135 VL of CDH19 artificial AA
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQFPG 4A9
TAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSRLSGWVFGGGTKLTVL 1136 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAATCCGGCCCTGGCCTGGTCAAGCCCT CDH19 4A9
CCGAGACACTGTCCCTGACCTGCACCGTGTCCGGCGGCTCCAT
CTCCGGCTACTACTGGTCCTGGATCCGGCAGCCCCCTGGCAAG
GGCCTGGAATGGTTCGCCTACTTCTCCTACTCCGGCTCCACCA
ACTACAACCCCAGCCTGAAGTCCAGAGTGACCCTGTCCGTGGA
CACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCCGTGACC
GCCGCTGACACCGCCGTGTACTACTGCGCCCGGAACTGGGCCT
TCCACTTCGATTTCTGGGGCCAGGGCACCCTGGTCACCGTGTC
TAGCGGAGGCGGAGGATCTGGTGGCGGTGGTTCTGGCGGCGGA
GGCTCCCAGTCTGTGCTGACCCAGCCTCCCTCTGTGTCTGGCG
CCCCTGGCCAGAGAGTGACCATCTCCTGCACCGGCTCCTCCAG
CAACATCGGCACCGGCTACGCCGTGCACTGGTATCAGCAGTTC
CCCGGCACCGCCCCCAAGCTGCTGATCTACGGCAACAACAACC
GGCCCTCCGGCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGG
CACCTCCGCCTCCCTGGCTATCACCGGCCTGCAGGCTGAGGAC
GAGGCCGACTACTACTGCCAGTCCTACGACTCCCGGCTGTCCG
GCTGGGTGTTCGGCGGAGGCACCAAGCTGACCGTGCTG 1137 VH-VL of artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK CDH19 4A9
GLEWFAYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQF
PGTAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSRLSGWVFGGGTKLTVL 1138 CDH19 4A9 x artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK I2C
GLEWFAYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQF
PGTAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSRLSGWVFGGGTKLTVLSGGGGSEVQLVESGGG
LVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRS
KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY
YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG
SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKP
GQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE
AEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1139 CDR-H1 of artificial AA SYDMH
CDH19 4B10 1140 CDR-H2 of artificial AA VISYDGTNEYYADSVKG CDH19
4B10 1141 CDR-H3 of artificial AA ERYFDWSFDY CDH19 4B10 1142 CDR-L1
of artificial AA RASQSVSNTYLA CDH19 4B10 1143 CDR-L2 of artificial
AA GASSRAT CDH19 4B10 1144 CDR-L3 of artificial AA QQYSNSWT CDH19
4B10 1145 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG 4B10
GCCGGTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCACCTT
CTCCAGCTACGACATGCACTGGGTCCGACAGGCCCCTGGCAAG
GGCCTGGAATGGGTGGCCGTGATCTCCTACGACGGCACCAACG
AGTACTACGCCGACTCCGTGAAGGGCCGGTTCACCATCTCCCG
GGACACCTCCAAGAACACCCTGTACCTGCAGATGAACTCCCTG
CGGGCCGAGGACACCGCCGTGTACTACTGCGCCAGAGAGCGGT
ACTTCGACTGGTCCTTCGACTACTGGGGCCAGGGCACCCTGGT GTCCGTGTCTAGC 1146 VH
of CDH19 artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK
4B10 GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS 1147 VL of CDH19 artificial NT
GAGATCGTGCTGACCCAGTCCCCTGGCACCCTGTCCCTGAGCC 4B10
CTGGCGAGAGAGCCACCCTGTCTTGCCGGGCCTCCCAGTCCGT
GTCCAACACCTACCTGGCCTGGTATCACCAGCGCCCTGGCCAG
GCCCCTCGGCTGCTGATCTACGGCGCCTCTTCCAGAGCCACCG
GCATCCCTGACCGGTTCTCCGGCTCTGGCTCTGGCACCGACTT
CGCCCTGACCATCTCCAGCCTGGAACCCGAGGATTTCGCTGTG
TACTATTGCCAGCAGTACTCCAACTCCTGGACCTTCGGACAGG GCACCAAGGTGGAAATCAAG
1148 VL of CDH19 artificial AA
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYHQRPGQ 4B10
APRLLIYGASSRATGIPDRFSGSGSGTDFALTISSLEPEDFAV YYCQQYSNSWTFGQGTKVEIK
1149 VH-VL of artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG CDH19 4B10
GCCGGTCCCTGAGACTGTCTTGCGCCGCCTCCGGCTTCACCTT
CTCCAGCTACGACATGCACTGGGTCCGACAGGCCCCTGGCAAG
GGCCTGGAATGGGTGGCCGTGATCTCCTACGACGGCACCAACG
AGTACTACGCCGACTCCGTGAAGGGCCGGTTCACCATCTCCCG
GGACACCTCCAAGAACACCCTGTACCTGCAGATGAACTCCCTG
CGGGCCGAGGACACCGCCGTGTACTACTGCGCCAGAGAGCGGT
ACTTCGACTGGTCCTTCGACTACTGGGGCCAGGGCACCCTGGT
GTCCGTGTCTAGCGGAGGCGGAGGATCTGGTGGCGGTGGTTCT
GGCGGCGGAGGCTCCGAGATCGTGCTGACCCAGTCCCCTGGCA
CCCTGTCCCTGAGCCCTGGCGAGAGAGCCACCCTGTCTTGCCG
GGCCTCCCAGTCCGTGTCCAACACCTACCTGGCCTGGTATCAC
CAGCGCCCTGGCCAGGCCCCTCGGCTGCTGATCTACGGCGCCT
CTTCCAGAGCCACCGGCATCCCTGACCGGTTCTCCGGCTCTGG
CTCTGGCACCGACTTCGCCCTGACCATCTCCAGCCTGGAACCC
GAGGATTTCGCTGTGTACTATTGCCAGCAGTACTCCAACTCCT
GGACCTTCGGACAGGGCACCAAGGTGGAAATCAAG 1150 VH-VL of artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK CDH19 4B10
GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSGGGGSGGGGS
GGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYH
QRPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFALTISSLEP
EDFAVYYCQQYSNSWTFGQGTKVEIK 1151 CDH19 4B10 x artificial
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGK I2C
GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSGGGGSGGGGS
GGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYH
QRPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFALTISSLEP
EDFAVYYCQQYSNSWTFGQGTKVEIKSGGGGSEVQLVESGGGL
VQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK
YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYY
CVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPG
QAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA
EYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1152 CDR-H1 of artificial AA SYDMD
CDH19 4F3 1153 CDR-H2 of artificial AA VIWYDGSNKYYADSVRG
CDH19 4F3 1154 CDR-H3 of artificial AA ETGEGWYFDL CDH19 4F3 1155
CDR-L1 of artificial AA RASQSVSSSYLA CDH19 4F3 1156 CDR-L2 of
artificial AA GASSRAT CDH19 4F3 1157 CDR-L3 of artificial AA
QQYGSSWT CDH19 4F3 1158 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG 4F3
GCCGGTCCCTGAGACTGTCTTGTGCCGCCTCCGGCTTCAGCTT
CTCCTCCTACGACATGGACTGGGTCCGACAGACCCCCGGCAAG
GGCCTGGAATGGGTGGCCGTGATTTGGTACGACGGCTCCAACA
AGTACTACGCCGACTCCGTGCGGGGCAGATTCACCATCTCCCG
GGACAACTCCAAGAACACCCTGTTTCTGCAGATGAACTCCCTG
CGGGTGGAAGATACCGCCGTGTACTACTGCGCCAGAGAGACAG
GCGAGGGCTGGTACTTCGACCTGTGGGGCAGAGGCACCCTGGT CACCGTGTCTAGC 1159 VH
of CDH19 artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGK
4F3 GLEWVAVIWYDGSNKYYADSVRGRFTISRDNSKNTLFLQMNSL
RVEDTAVYYCARETGEGWYFDLWGRGTLVTVSS 1160 VL of CDH19 artificial NT
GAGATCGTGCTGACCCAGTCCCCTGGCACCCTGTCCCTGAGCC 4F3
CTGGCGAGAGAGCCACCCTGTCCTGCAGAGCCTCCCAGTCCGT
GTCCTCCTCCTACCTGGCCTGGTATCAGCAGAAGCCCGGCCAG
GCCCCTCGGCTGCTGATCTACGGCGCCTCTTCCAGAGCCACCG
GCATCCCTGACCGGTTCTCCGGCTCTGGCTCCGGCACCGACTT
CACCCTGACCATCAGCCGGCTGGAACCCGAGGACTTCGCTGTG
TACTATTGCCAGCAGTACGGCTCCTCCTGGACCTTCGGCCAGG GCACCAAGGTGGAAATCAAG
1161 VL of CDH19 artificial AA
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQ 4F3
APRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV YYCQQYGSSWTFGQGTKVEIK
1162 VH-VL of artificial NT
CAGGTGCAGCTGGTGGAATCCGGCGGAGGCGTGGTGCAGCCTG CDH19 4F3
GCCGGTCCCTGAGACTGTCTTGTGCCGCCTCCGGCTTCAGCTT
CTCCTCCTACGACATGGACTGGGTCCGACAGACCCCCGGCAAG
GGCCTGGAATGGGTGGCCGTGATTTGGTACGACGGCTCCAACA
AGTACTACGCCGACTCCGTGCGGGGCAGATTCACCATCTCCCG
GGACAACTCCAAGAACACCCTGTTTCTGCAGATGAACTCCCTG
CGGGTGGAAGATACCGCCGTGTACTACTGCGCCAGAGAGACAG
GCGAGGGCTGGTACTTCGACCTGTGGGGCAGAGGCACCCTGGT
CACCGTGTCTAGCGGAGGCGGAGGATCTGGTGGCGGTGGTTCT
GGCGGCGGAGGCTCCGAGATCGTGCTGACCCAGTCCCCTGGCA
CCCTGTCCCTGAGCCCTGGCGAGAGAGCCACCCTGTCCTGCAG
AGCCTCCCAGTCCGTGTCCTCCTCCTACCTGGCCTGGTATCAG
CAGAAGCCCGGCCAGGCCCCTCGGCTGCTGATCTACGGCGCCT
CTTCCAGAGCCACCGGCATCCCTGACCGGTTCTCCGGCTCTGG
CTCCGGCACCGACTTCACCCTGACCATCAGCCGGCTGGAACCC
GAGGACTTCGCTGTGTACTATTGCCAGCAGTACGGCTCCTCCT
GGACCTTCGGCCAGGGCACCAAGGTGGAAATCAAG 1163 VH-VL of artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGK CDH19 4F3
GLEWVAVIWYDGSNKYYADSVRGRFTISRDNSKNTLFLQMNSL
RVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSGGGGSGGGGS
GGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ
QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEP
EDFAVYYCQQYGSSWTFGQGTKVEIK 1164 CDH19 4F3 x artificial
QVQLVESGGGVVQPGRSLRLSCAASGFSFSSYDMDWVRQTPGK I2C
GLEWVAVIWYDGSNKYYADSVRGRFTISRDNSKNTLFLQMNSL
RVEDTAVYYCARETGEGWYFDLWGRGTLVTVSSGGGGSGGGGS
GGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ
QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEP
EDFAVYYCQQYGSSWTFGQGTKVEIKSGGGGSEVQLVESGGGL
VQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK
YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYY
CVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPG
QAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA
EYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1165 CDR-H1 of artificial AA SYSWS
CDH19 4F7 1166 CDR-H2 of artificial AA YIYYSGSTNYNPSLKS CDH19 4F7
1167 CDR-H3 of artificial AA NWAFHFDY CDH19 4F7 1168 CDR-L1 of
artificial AA TGSSSNIGTGYDVH CDH19 4F7 1169 CDR-L2 of artificial AA
GNSNRPS CDH19 4F7 1170 CDR-L3 of artificial AA QSYDSSLSGWV CDH19
4F7 1171 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAATCCGGCCCTGGCCTGGTCAAGCCCT 4F7
CCGAGACACTGTCCCTGACCTGCACCGTGTCCGGCGGCTCCAT
CTCCTCCTACTCTTGGTCCTGGATCCGGCAGCCCCCTGGCAAG
GGCCTGGAATGGATCGGCTACATCTACTACTCCGGCTCCACCA
ACTACAACCCCAGCCTGAAGTCCAGAGTGACCATCTCCCTGGA
CACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCCGTGACC
GCCGCTGACACCGCCGTGTACTACTGCGCCCGGAACTGGGCCT
TCCACTTCGACTACTGGGGCCAGGGCACCCTGGTCACCGTGTC TAGC 1172 VH of CDH19
artificial AA QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK 4F7
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSS 1173 VL of CDH19 artificial NT
CAGTCTGTGCTGACCCAGCCTCCCTCTGTGTCTGGCGCCCCTG 4F7
GCCAGCGCGTGACCATTTCCTGCACCGGCTCCTCCAGCAACAT
CGGCACCGGCTACGACGTGCACTGGTATCAGCAGCTGCCCGGC
ACCGCCCCCAAGCTGCTGATCCACGGCAACTCCAACCGGCCCT
CCGGCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGGCACCTC
CGCCTCCCTGGCTATCACCGGCCTGCAGGCTGAGGACGAGGCC
GACTACTACTGCCAGTCCTACGACTCCTCCCTGTCCGGCTGGG
TGTTCGGCGGAGGCACCAGACTGACCGTGCTG 1174 VL of CDH19 artificial AA
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPG 4F7
TAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSSLSGWVFGGGTRLTVL 1175 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAATCCGGCCCTGGCCTGGTCAAGCCCT CDH19 4F7
CCGAGACACTGTCCCTGACCTGCACCGTGTCCGGCGGCTCCAT
CTCCTCCTACTCTTGGTCCTGGATCCGGCAGCCCCCTGGCAAG
GGCCTGGAATGGATCGGCTACATCTACTACTCCGGCTCCACCA
ACTACAACCCCAGCCTGAAGTCCAGAGTGACCATCTCCCTGGA
CACCTCCAAGAACCAGTTCTCCCTGAAGCTGTCCTCCGTGACC
GCCGCTGACACCGCCGTGTACTACTGCGCCCGGAACTGGGCCT
TCCACTTCGACTACTGGGGCCAGGGCACCCTGGTCACCGTGTC
TAGCGGAGGCGGAGGATCTGGTGGCGGTGGTTCTGGCGGCGGA
GGCTCCCAGTCTGTGCTGACCCAGCCTCCCTCTGTGTCTGGCG
CCCCTGGCCAGCGCGTGACCATTTCCTGCACCGGCTCCTCCAG
CAACATCGGCACCGGCTACGACGTGCACTGGTATCAGCAGCTG
CCCGGCACCGCCCCCAAGCTGCTGATCCACGGCAACTCCAACC
GGCCCTCCGGCGTGCCCGACCGGTTCTCTGGCTCCAAGTCTGG
CACCTCCGCCTCCCTGGCTATCACCGGCCTGCAGGCTGAGGAC
GAGGCCGACTACTACTGCCAGTCCTACGACTCCTCCCTGTCCG
GCTGGGTGTTCGGCGGAGGCACCAGACTGACCGTGCTG 1176 VH-VL of artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK CDH19 4F7
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQL
PGTAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLSGWVFGGGTRLTVL 1177 CDH19 4F7 x artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK I2C
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQL
PGTAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLSGWVFGGGTRLTVLSGGGGSEVQLVESGGG
LVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRS
KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY
YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG
SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKP
GQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE
AEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1178 CDR-H1 of artificial AA SYGMH
CDH19 14039 1179 CDR-H2 of artificial AA FIWYEGSNKYYAESVKD CDH19
14039 1180 CDR-H3 of artificial AA RAGIIGTIGYYYGMDV CDH19 14039
1181 CDR-L1 of artificial AA SGDRLGEKYTS CDH19 14039 1182 CDR-L2 of
artificial AA QDTKRPS CDH19 14039 1183 CDR-L3 of artificial AA
QAWESSTVV CDH19 14039 1184 VH of CDH19 artificial NT
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14039
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGAGGGAAGTAATA
AATACTATGCAGAGTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGT 1185 VH of CDH19 artificial AA
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK 14039
GLEWVAFIWYEGSNKYYAESVKDRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS 1186 VL of CDH19 artificial
NT TCCTATGAACTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14039
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGGTTGGGGGA
AAAATATACTAGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGTAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGAGAGCAGCACTGTGGTATTCGGCGGAGGGA CCAAGCTGACCGTCCTA 1187
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSP 14039
LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWESSTVVFGGGTKLTVL
1188 VH-VL of artificial NT
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14039
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGAGGGAAGTAATA
AATACTATGCAGAGTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGTGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAAC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGGTTGGGGGAAAAATATACT
AGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCTTTGCTGGTCA
TCTATCAAGATACCAAGCGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGTAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGAGAGCAGCACTGTGGTATTCGGCGGAGGGACCAAGCTGAC CGTCCTA 1189 VH-VL of
artificial AA QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK CDH19
14039 GLEWVAFIWYEGSNKYYAESVKDRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
SWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVL 1190 CDH19 14039 artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK x I2C
GLEWVAFIWYEGSNKYYAESVKDRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
SWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1191 CDR-H1 of artificial AA
SYGMH CDH19 14304 1192 CDR-H2 of artificial AA FIWYDGSNKYYADSVKD
CDH19 14304 1193 CDR-H3 of artificial AA RAGIIGTIGYYYGMDV CDH19
14304 1194 CDR-L1 of artificial AA SGDRLGEKYVS CDH19 14304 1195
CDR-L2 of artificial AA QDNKWPS CDH19 14304 1196 CDR-L3 of
artificial AA QAWDSSTVV CDH19 14304 1197 VH of CDH19 artificial NT
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14304
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGT 1198 VH of CDH19 artificial AA
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK 14304
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS 1199 VL of CDH19 artificial
NT TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14304
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
GAAATATGTTAGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
ATACTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGGGGGA CCAAGCTGACCGTCCTA 1200
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSP 14304
ILVIYQDNKWPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWDSSTVVFGGGTKLTVL
1201 VH-VL of artificial NT
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14304
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGTGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAGC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGATTGGGGGAGAAATATGTT
AGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCTATACTGGTCA
TCTATCAAGATAATAAGTGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGACAGCAGCACTGTGGTATTCGGCGGGGGGACCAAGCTGAC CGTCCTA 1202 VH-VL of
artificial AA QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK CDH19
14304 GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
SWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVL 1203 CDH19 14304 artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK x I2C
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
SWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1204 CDR-H1 of artificial AA
SYGMH CDH19 14301 1205 CDR-H2 of artificial AA FIWYDGSNKYYADSVKD
CDH19 14301 1206 CDR-H3 of artificial AA RAGIIGTIGYYYGMDV CDH19
14301 1207 CDR-L1 of artificial AA SGDRLGEKYTC CDH19 14301 1208
CDR-L2 of artificial AA QDTKRPS CDH19 14301 1209 CDR-L3 of
artificial AA QAWESSTVV CDH19 14301 1210 VH of CDH19 artificial NT
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14301
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGT 1211 VH of CDH19 artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK 14301
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS 1212 VL of CDH19 artificial
NT TCCTATGAACTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14301
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGGTTGGGGGA
AAAATATACTTGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGTAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGAGAGCAGCACTGTGGTATTCGGCGGAGGGA CCAAGCTGACCGTCCTA 1213
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTCWYQQRPGQSP 14301
LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWESSTVVFGGGTKLTVL
1214 VH-VL of artificial NT
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14301
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGTGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAAC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGGTTGGGGGAAAAATATACT
TGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCTTTGCTGGTCA
TCTATCAAGATACCAAGCGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGTAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGAGAGCAGCACTGTGGTATTCGGCGGAGGGACCAAGCTGAC CGTCCTA 1215 VH-VL of
artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK CDH19
14301 GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
CWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVL 1216 CDH19 14301 artificial
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK x I2C
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
CWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1217 CDR-H1 of artificial AA
RYGIH CDH19 14079 1218 CDR-H2 of artificial AA VIWYEGSNKYYAESVKG
CDH19 14079 1219 CDR-H3 of artificial AA RAGIPGTTGYYYGMDV CDH19
14079 1220 CDR-L1 of artificial AA SGDRLGEKYVS CDH19 14079 1221
CDR-L2 of artificial AA QDNKWPS CDH19 14079 1222 CDR-L3 of
artificial AA QAWESSTVV CDH19 14079 1223 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14079
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGAGGGAAGTAATA
AATACTATGCAGAGTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 1224 VH of CDH19 artificial AA
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGK 14079
GLEWVAVIWYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS 1225 VL of CDH19 artificial
NT TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14079
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
GAAATATGTTAGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
ATACTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGAGAGCAGCACTGTGGTATTCGGCGGGGGGA CCAAGCTGACCGTCCTA 1226
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSP 14079
ILVIYQDNKWPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWESSTVVFGGGTKLTVL
1227 VH-VL of artificial NT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14079
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGAGGGAAGTAATA
AATACTATGCAGAGTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCAGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAGC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGATTGGGGGAGAAATATGTT
AGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCTATACTGGTCA
TCTATCAAGATAATAAGTGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGAGAGCAGCACTGTGGTATTCGGCGGGGGGACCAAGCTGAC CGTCCTA
1228 VH-VL of artificial AA
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGK CDH19 14079
GLEWVAVIWYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
SWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVL 1229 CDH19 14079 artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGK x I2C
GLEWVAVIWYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
SWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1230 CDR-H1 of artificial AA
RYGIH CDH19 14077 1231 CDR-H2 of artificial AA VIWYDGSNKYYADSVKG
CDH19 14077 1232 CDR-H3 of artificial AA RAGIPGTTGYYYGMDV CDH19
14077 1233 CDR-L1 of artificial AA SGDRLGEKYVS CDH19 14077 1234
CDR-L2 of artificial AA QDNKWPS CDH19 14077 1235 CDR-L3 of
artificial AA QAWDSSTVV CDH19 14077 1236 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14077
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 1237 VH of CDH19 artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK 14077
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS 1238 VL of CDH19 artificial
NT TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14077
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
GAAATATGTTAGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
ATACTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGGGGGA CCAAGCTGACCGTCCTA 1239
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSP 14077
ILVIYQDNKWPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWDSSTVVFGGGTKLTVL
1240 VH-VL of artificial NT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14077
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCAGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAGC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGATTGGGGGAGAAATATGTT
AGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCTATACTGGTCA
TCTATCAAGATAATAAGTGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGACAGCAGCACTGTGGTATTCGGCGGGGGGACCAAGCTGAC CGTCCTA 1241 VH-VL of
artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK CDH19
14077 GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
SWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVL 1242 CDH19 14077 artificial
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK x I2C
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
SWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1243 CDR-H1 of artificial AA
SYYIH CDH19 14096 1244 CDR-H2 of artificial AA IINPSGGSTRYAQKFQG
CDH19 14096 1245 CDR-H3 of artificial AA GGIQLWLHFDY CDH19 14096
1246 CDR-L1 of artificial AA SGSSSNIGRNFVN CDH19 14096 1247 CDR-L2
of artificial AA TNNQRPS CDH19 14096 1248 CDR-L3 of artificial AA
AAWDESLNGWV CDH19 14096 1249 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG 14096
GGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTT
CACCAGCTACTATATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGACTTGAGTGGATGGGAATAATCAACCCCAGTGGTGGTAGCA
CAAGGTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGAA
TACAGCTATGGTTACATTTTGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 1250
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ 14096
GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVYMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSS 1251 VL of CDH19 artificial NT
CAGTCTGCGCTGACTCAGCCACCCTCAGCGACTGGGACCCCCG 14096
GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACAT
CGGAAGGAATTTTGTAAACTGGTATCAGCAGCTCCCAGGAACG
GCCCCCAAAGTCCTCATTTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
TATTACTGTGCAGCATGGGATGAGAGCCTGAATGGTTGGGTGT
TCGGCGGAGGGACCAAGCTGACCGTCCTA 1252 VL of CDH19 artificial AA
QSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWYQQLPGT
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCAAWDESLNGWVFGGGTKLTVL 1253 VH-VL of artificial NT
CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG CDH19 14096
GGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTT
CACCAGCTACTATATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGACTTGAGTGGATGGGAATAATCAACCCCAGTGGTGGTAGCA
CAAGGTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGAA
TACAGCTATGGTTACATTTTGACTACTGGGGCCAGGGAACCCT
GGTCACCGTCTCCTCAGGTGGCGGAGGATCTGGCGGAGGTGGA
AGCGGAGGCGGCGGATCTCAGTCTGCGCTGACTCAGCCACCCT
CAGCGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGTTC
TGGAAGCAGCTCCAACATCGGAAGGAATTTTGTAAACTGGTAT
CAGCAGCTCCCAGGAACGGCCCCCAAAGTCCTCATTTATACTA
ATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTC
CAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAG
TCTGAGGATGAGGCTGATTATTACTGTGCAGCATGGGATGAGA
GCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGT CCTA 1254 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ CDH19
14096 GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVYMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWY
QQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAAWDESLNGWVFGGGTKLTVL 1255 CDH19 14096 artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ x I2C
GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVYMELSSL
RSEDTAVYYCARGGIQLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSATGTPGQRVTISCSGSSSNIGRNFVNWY
QQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAAWDESLNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1256 CDR-H1 of artificial AA
SYYMS CDH19 14088 1257 CDR-H2 of artificial AA IIHPSGGDTTYAQKFQG
CDH19 14088 1258 CDR-H3 of artificial AA GGIKLWLHFDY CDH19 14088
1259 CDR-L1 of artificial AA SGSRSNIGSNFVN CDH19 14088 1260 CDR-L2
of artificial AA TNNQRPS CDH19 14088 1261 CDR-L3 of artificial AA
AVWDDSLNGWV CDH19 14088 1262 VH of CDH19 artificial NT
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG 14088
GGGCCTCAGTGAAGGTTTCCTGTAAGGCATCTGGATACACCTT
CACCAGCTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGAATAATCCACCCTAGTGGTGGTGACA
CAACCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGA
TAAAACTATGGTTACATTTTGACTATTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 1263
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMSWVRQAPGQ 14088
GLEWMGIIHPSGGDTTYAQKFQGRVTMTRDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS 1264 VL of CDH19 artificial NT
CAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCG 14088
GACAGAGGGTCACCATCTCTTGTTCTGGAAGCCGCTCCAACAT
CGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACG
GCCCCCAAACTCCTCATCTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
TATTACTGTGCAGTATGGGATGACAGCCTGAATGGTTGGGTGT
TCGGCGGAGGGACCAAGCTGACCGTCCTA 1265 VL of CDH19 artificial AA
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGT 14088
APKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCAVWDDSLNGWVFGGGTKLTVL 1266 VH-VL of artificial NT
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG CDH19 14088
GGGCCTCAGTGAAGGTTTCCTGTAAGGCATCTGGATACACCTT
CACCAGCTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGAATAATCCACCCTAGTGGTGGTGACA
CAACCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGA
TAAAACTATGGTTACATTTTGACTATTGGGGCCAGGGAACCCT
GGTCACCGTCTCCTCAGGTGGCGGAGGATCTGGCGGAGGTGGA
AGCGGAGGCGGCGGATCTCAGTCTGTGCTGACTCAGCCACCCT
CAGCGTCTGGGACCCCCGGACAGAGGGTCACCATCTCTTGTTC
TGGAAGCCGCTCCAACATCGGAAGTAATTTTGTAAACTGGTAC
CAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATACTA
ATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTC
CAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAG
TCTGAGGATGAGGCTGATTATTACTGTGCAGTATGGGATGACA
GCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGT CCTA 1267 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMSWVRQAPGQ CDH19
14088 GLEWMGIIHPSGGDTTYAQKFQGRVTMTRDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAVWDDSLNGWVFGGGTKLTVL 1268 CDH19 14088 artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMSWVRQAPGQ x I2C
GLEWMGIIHPSGGDTTYAQKFQGRVTMTRDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAVWDDSLNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1269 CDR-H1 of artificial AA
SYYMS CDH19 14085 1270 CDR-H2 of artificial AA IIHPSGGDTTYAQKFQG
CDH19 14085 1271 CDR-H3 of artificial AA GGIKLWLHFDY CDH19 14085
1272 CDR-L1 of artificial AA SGSRSNIGSNFVN CDH19 14085 1273 CDR-L2
of artificial AA TNNQRPS CDH19 14085 1274 CDR-L3 of artificial AA
AVYDDSLNGWV CDH19 14085 1275 VH of CDH19 artificial NT
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG 14085
GGGCCTCAGTGAAGGTTTCCTGTAAGGCATCTAGATACACCTT
CACCAGCTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGAATAATCCACCCTAGTGGTGGTGACA
CAACCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCGG
GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGA
TAAAACTATGGTTACATTTTGACTATTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 1276
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQ 14085
GLEWMGIIHPSGGDTTYAQKFQGRVTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSS 1277 VL of CDH19 artificial NT
CAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCG 14085
GACAGAGGGTCACCATCTCTTGTTCTGGAAGCCGCTCCAACAT
CGGAAGTAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACG
GCCCCCAAACTCCTCATCTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
TATTACTGTGCAGTATACGATGACAGCCTGAATGGTTGGGTGT
TCGGCGGAGGGACCAAGCTGACCGTCCTA 1278 VL of CDH19 artificial AA
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGT 14085
APKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCAVYDDSLNGWVFGGGTKLTVL 1279 VH-VL of artificial NT
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG CDH19 14085
GGGCCTCAGTGAAGGTTTCCTGTAAGGCATCTAGATACACCTT
CACCAGCTACTATATGTCCTGGGTGCGACAGGCCCCTGGACAA
GGGCTTGAGTGGATGGGAATAATCCACCCTAGTGGTGGTGACA
CAACCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCGG
GGACACGTCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGGGA
TAAAACTATGGTTACATTTTGACTATTGGGGCCAGGGAACCCT
GGTCACCGTCTCCTCAGGTGGCGGAGGATCTGGCGGAGGTGGA
AGCGGAGGCGGCGGATCTCAGTCTGTGCTGACTCAGCCACCCT
CAGCGTCTGGGACCCCCGGACAGAGGGTCACCATCTCTTGTTC
TGGAAGCCGCTCCAACATCGGAAGTAATTTTGTAAACTGGTAC
CAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATACTA
ATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTC
CAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAG
TCTGAGGATGAGGCTGATTATTACTGTGCAGTATACGATGACA
GCCTGAATGGTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGT CCTA 1280 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQ CDH19
14085 GLEWMGIIHPSGGDTTYAQKFQGRVTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAVYDDSLNGWVFGGGTKLTVL 1281 CDH19 14085 artificial
QVQLVQSGAEVKKPGASVKVSCKASRYTFTSYYMSWVRQAPGQ x I2C
GLEWMGIIHPSGGDTTYAQKFQGRVTMTGDTSTSTVYMELSSL
RSEDTAVYYCARGGIKLWLHFDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSVLTQPPSASGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKLLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCAVYDDSLNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1282 CDR-H1 of artificial AA
SYFIH CDH19 14074 1283 CDR-H2 of artificial AA IINPISVSTSYAQKFQG
CDH19 14074 1284 CDR-H3 of artificial AA GGIQLWLHLDY CDH19 14074
1285 CDR-L1 of artificial AA SGSRSNIGSNFVN CDH19 14074 1286 CDR-L2
of artificial AA TNNQRPS CDH19 14074 1287 CDR-L3 of artificial AA
ATWDDSMNGWV CDH19 14074 1288 VH of CDH19 artificial NT
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG 14074
GGGCCTCAGTGAAGGTTTCCTGCAAGGTTTCTGGATACACCTT
CACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGGCTTGAATGGATGGGAATTATCAACCCTATTAGTGTTAGCA
CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
TACAGCTATGGTTACATTTGGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 1289
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ 14074
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS 1290 VL of CDH19 artificial NT
CAGTCTGCGCTGACTCAGCCACCCTCAGTGACTGGGACCCCCG 14074
GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGGTCCAACAT
CGGAAGCAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACG
GCCCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
TATTACTGCGCAACATGGGATGACAGTATGAATGGTTGGGTGT
TCGGCGGAGGGACCAAACTGACCGTCCTA 1291 VL of CDH19 artificial AA
QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGT 14074
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCATWDDSMNGWVFGGGTKLTVL 1292 VH-VL of artificial NT
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG CDH19 14074
GGGCCTCAGTGAAGGTTTCCTGCAAGGTTTCTGGATACACCTT
CACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGGCTTGAATGGATGGGAATTATCAACCCTATTAGTGTTAGCA
CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
TACAGCTATGGTTACATTTGGACTACTGGGGCCAGGGAACCCT
GGTCACCGTCTCCTCAGGTGGCGGAGGATCTGGCGGAGGTGGA
AGCGGAGGCGGCGGATCTCAGTCTGCGCTGACTCAGCCACCCT
CAGTGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGTTC
TGGAAGCAGGTCCAACATCGGAAGCAATTTTGTAAACTGGTAC
CAGCAGCTCCCAGGAACGGCCCCCAAAGTCCTCATCTATACTA
ATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTC
CAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAG
TCTGAGGATGAGGCTGATTATTACTGCGCAACATGGGATGACA
GTATGAATGGTTGGGTGTTCGGCGGAGGGACCAAACTGACCGT CCTA 1293 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ CDH19
14074 GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCATWDDSMNGWVFGGGTKLTVL 1294 CDH19 14074 artificial
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ x I2C
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCATWDDSMNGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1295 CDR-H1 of artificial AA
SYFIH CDH19 14075 1296 CDR-H2 of artificial AA IINPISVSTSYAQKFQG
CDH19 14075 1297 CDR-H3 of artificial AA GGIQLWLHLDY CDH19 14075
1298 CDR-L1 of artificial AA SGSRSNIGSNFVN CDH19 14075 1299 CDR-L2
of artificial AA TNNQRPS CDH19 14075 1300 CDR-L3 of artificial AA
ATWDESMQGWV CDH19 14075 1301 VH of CDH19 artificial NT
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG 14075
GGGCCTCAGTGAAGGTTTCCTGCAAGGTTTCTGGATACACCTT
CACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGGCTTGAATGGATGGGAATTATCAACCCTATTAGTGTTAGCA
CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
TACAGCTATGGTTACATTTGGACTACTGGGGCCAGGGAACCCT GGTCACCGTCTCCTCA 1302
VH of CDH19 artificial AA
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ 14075
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSS 1303 VL of CDH19 artificial NT
CAGTCTGCGCTGACTCAGCCACCCTCAGTGACTGGGACCCCCG 14075
GGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGGTCCAACAT
CGGAAGCAATTTTGTAAACTGGTACCAGCAGCTCCCAGGAACG
GCCCCCAAAGTCCTCATCTATACTAATAATCAGCGGCCCTCAG
GGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGC
CTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGAT
TATTACTGCGCAACATGGGATGAGAGTATGCAGGGTTGGGTGT
TCGGCGGAGGGACCAAACTGACCGTCCTA
1304 VL of CDH19 artificial AA
QSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWYQQLPGT 14075
APKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEAD
YYCATWDESMQGWVFGGGTKLTVL 1305 VH-VL of artificial NT
CAGGTGCAGTTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTG CDH19 14075
GGGCCTCAGTGAAGGTTTCCTGCAAGGTTTCTGGATACACCTT
CACCAGCTACTTTATTCACTGGGTGCGCCAGGCCCCTGGACAA
GGGCTTGAATGGATGGGAATTATCAACCCTATTAGTGTTAGCA
CAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAG
GGACACGTCCACGAGCACAGTCTTCATGGAGCTGAGCAGCCTG
AGATCTGAGGACACGGCCGTGTATTACTGTGCGCGAGGGGGGA
TACAGCTATGGTTACATTTGGACTACTGGGGCCAGGGAACCCT
GGTCACCGTCTCCTCAGGTGGCGGAGGATCTGGCGGAGGTGGA
AGCGGAGGCGGCGGATCTCAGTCTGCGCTGACTCAGCCACCCT
CAGTGACTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGTTC
TGGAAGCAGGTCCAACATCGGAAGCAATTTTGTAAACTGGTAC
CAGCAGCTCCCAGGAACGGCCCCCAAAGTCCTCATCTATACTA
ATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTC
CAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAG
TCTGAGGATGAGGCTGATTATTACTGCGCAACATGGGATGAGA
GTATGCAGGGTTGGGTGTTCGGCGGAGGGACCAAACTGACCGT CCTA 1306 VH-VL of
artificial AA QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ CDH19
14075 GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCATWDESMQGWVFGGGTKLTVL 1307 CDH19 14075 artificial
QVQLVQSGAEVKKPGASVKVSCKVSGYTFTSYFIHWVRQAPGQ x I2C
GLEWMGIINPISVSTSYAQKFQGRVTMTRDTSTSTVFMELSSL
RSEDTAVYYCARGGIQLWLHLDYWGQGTLVTVSSGGGGSGGGG
SGGGGSQSALTQPPSVTGTPGQRVTISCSGSRSNIGSNFVNWY
QQLPGTAPKVLIYTNNQRPSGVPDRFSGSKSGTSASLAISGLQ
SEDEADYYCATWDESMQGWVFGGGTKLTVLSGGGGSEVQLVES
GGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVAR
IRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT
AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSG
GGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQ
QKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQP
EDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1308 CDR-H1 of artificial AA
SSGYY CDH19 14024 1309 CDR-H2 of artificial AA YIYYTGSAYYNPSLKS
CDH19 14024 1310 CDR-H3 of artificial AA DGSSGWYFQY CDH19 14024
1311 CDR-L1 of artificial AA RASRQISSSYLA CDH19 14024 1312 CDR-L2
of artificial AA GPSSRAT CDH19 14024 1313 CDR-L3 of artificial AA
QQYGSSFT CDH19 14024 1314 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT 14024
CAGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGCAGTAGTGGTTACTACTGGAGCTGGATCCGCCAGCCCCCA
GGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACACTGGGA
GCGCCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATATC
AGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCT
GTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGATG
GAAGCAGTGGCTGGTACTTCCAGTATTGGGGCCAGGGCACCCT GGTCACCGTCTCTAGT 1315
VH of CDH19 artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPP 14024
GKGLEWIGYIYYTGSAYYNPSLKSRVTISVDTSKNQFSLKLSS
VTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSS 1316 VL of CDH19 artificial NT
GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC 14024
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCGGCAGAT
TAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTCCATCCAGCAGGGCCACTG
GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTG
TATTACTGTCAGCAGTATGGTAGCTCATTCACTTTCGGCCAGG GGACCAAAGTGGATATCAAA
1317 VL of CDH19 artificial AA
EIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWYQQKPGQ 14024
APRLLIYGPSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAV YYCQQYGSSFTFGQGTKVDIK
1318 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT CDH19
CAGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGCAGTAGTGGTTACTACTGGAGCTGGATCCGCCAGCCCCCA
GGGAAGGGCCTGGAGTGGATTGGGTACATCTATTACACTGGGA
GCGCCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATATC
AGTAGACACGTCTAAGAACCAGTTCTCCCTGAAGCTGAGCTCT
GTGACTGCCGCGGACACGGCCGTGTATTACTGTGCGAGAGATG
GAAGCAGTGGCTGGTACTTCCAGTATTGGGGCCAGGGCACCCT
GGTCACCGTCTCTAGTGGTGGCGGAGGATCTGGCGGAGGTGGA
AGCGGAGGCGGCGGATCTGAAATTGTGTTGACGCAGTCTCCAG
GCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTG
CAGGGCCAGTCGGCAGATTAGCAGCAGCTACTTAGCCTGGTAC
CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTC
CATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAG
TGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAG
CCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCT
CATTCACTTTCGGCCAGGGGACCAAAGTGGATATCAAA 1319 VH-VL of artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPP CDH19 14024
GKGLEWIGYIYYTGSAYYNPSLKSRVTISVDTSKNQFSLKLSS
VTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSGGGGSGGGG
SGGGGSEIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWY
QQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDFTLTISRLE
PEDFAVYYCQQYGSSFTFGQGTKVDIK 1320 CDH19 14024 artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSGYYWSWIRQPP x I2C
GKGLEWIGYIYYTGSAYYNPSLKSRVTISVDTSKNQFSLKLSS
VTAADTAVYYCARDGSSGWYFQYWGQGTLVTVSSGGGGSGGGG
SGGGGSEIVLTQSPGTLSLSPGERATLSCRASRQISSSYLAWY
QQKPGQAPRLLIYGPSSRATGIPDRFSGSGSGTDFTLTISRLE
PEDFAVYYCQQYGSSFTFGQGTKVDIKSGGGGSEVQLVESGGG
LVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRS
KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY
YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG
SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKP
GQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE
AEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1321 CDR-H1 of artificial AA SYDMH
CDH19 14054 1322 CDR-H2 of artificial AA VISYDGTNEYYADSVKG CDH19
14054 1323 CDR-H3 of artificial AA ERYFDWSFDY CDH19 14054 1324
CDR-L1 of artificial AA RASQSVSNTYLA CDH19 14054 1325 CDR-L2 of
artificial AA GASSRAT CDH19 14054 1326 CDR-L3 of artificial AA
QQYSNSWT CDH19 14054 1327 VH of CDH19 artificial NT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14054
GGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
CAGTAGCTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAATG
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACACTTCCAAGAACACGCTGTATTTGCAAATGAACAGCCTG
AGAGCTGAGGACACGGCTGTATATTACTGTGCGAGAGAACGAT
ATTTTGACTGGTCTTTTGACTACTGGGGCCAGGGAACCCTGGT CAGCGTCTCTAGT 1328 VH
of CDH19 artificial AA QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGK
14054 GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSS 1329 VL of CDH19 artificial NT
GAAATTGTATTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTC 14054
CAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGT
TAGCAACACCTACTTAGCCTGGTACCAGCAGAGACCTGGCCAG
GCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTG
GCATCCCAGACAGATTCAGTGGCAGTGGGTCTGGGACAGACTT
CACTCTCACCATCAGCAGTCTGGAGCCTGAAGATTTTGCAGTG
TATTACTGTCAGCAGTACAGTAACTCGTGGACGTTCGGCCAAG GGACCAAGGTGGAAATCAAA
1330 VL of CDH19 artificial AA
EIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQQRPGQ 14054
APRLLIYGASSRATGIPDRFSGSGSGTDFTLTISSLEPEDFAV YYCQQYSNSWTFGQGTKVEIK
1331 VH-VL of artificial NT
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14054
GGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTT
CAGTAGCTATGACATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAATG
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACACTTCCAAGAACACGCTGTATTTGCAAATGAACAGCCTG
AGAGCTGAGGACACGGCTGTATATTACTGTGCGAGAGAACGAT
ATTTTGACTGGTCTTTTGACTACTGGGGCCAGGGAACCCTGGT
CAGCGTCTCTAGTGGTGGCGGAGGATCTGGCGGAGGTGGAAGC
GGAGGCGGCGGATCTGAAATTGTATTGACGCAGTCTCCAGGCA
CCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAG
GGCCAGTCAGAGTGTTAGCAACACCTACTTAGCCTGGTACCAG
CAGAGACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCAT
CCAGCAGGGCCACTGGCATCCCAGACAGATTCAGTGGCAGTGG
GTCTGGGACAGACTTCACTCTCACCATCAGCAGTCTGGAGCCT
GAAGATTTTGCAGTGTATTACTGTCAGCAGTACAGTAACTCGT
GGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA 1332 VH-VL of artificial AA
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGK CDH19 14054
GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSGGGGSGGGGS
GGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQ
QRPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISSLEP
EDFAVYYCQQYSNSWTFGQGTKVEIK 1333 CDH19 14054 artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYDMHWVRQAPGK x I2C
GLEWVAVISYDGTNEYYADSVKGRFTISRDTSKNTLYLQMNSL
RAEDTAVYYCARERYFDWSFDYWGQGTLVSVSSGGGGSGGGGS
GGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSNTYLAWYQ
QRPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISSLEP
EDFAVYYCQQYSNSWTFGQGTKVEIKSGGGGSEVQLVESGGGL
VQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK
YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYY
CVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPG
QAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEA
EYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1334 CDR-H1 of artificial AA GYYWS
CDH19 14056 1335 CDR-H2 of artificial AA YFSYSGSTNYNPSLKS CDH19
14056 1336 CDR-H3 of artificial AA NWAFHFDF CDH19 14056 1337 CDR-L1
of artificial AA TGSSSNIGTGYAVH CDH19 14056 1338 CDR-L2 of
artificial AA GNNNRPS CDH19 14056 1339 CDR-L3 of artificial AA
QSYDSRLSGWV CDH19 14056 1340 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT 14056
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGAAAG
GGACTGGAGTGGTTTGCATATTTCTCTTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCTTATCAGTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTC TAGT 1341 VH of CDH19
artificial AA QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK 14056
GLEWFAYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSS 1342 VL of CDH19 artificial NT
CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG 14056
GACAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAACAT
CGGGACAGGTTATGCTGTACACTGGTACCAGCAGCTTCCAGGA
ACAGCCCCCAAACTCCTCATCTATGGTAACAACAATCGGCCCT
CAGGGGTTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
GATTATTACTGCCAGTCCTATGACAGCAGACTGAGTGGTTGGG
TGTTCGGCGGAGGGACCAAGCTGACCGTCCTA 1343 VL of CDH19 artificial AA
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPG 14056
TAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSRLSGWVFGGGTKLTVL 1344 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT CDH19 14056
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGAAAG
GGACTGGAGTGGTTTGCATATTTCTCTTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCTTATCAGTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTC
TAGTGGTGGCGGAGGATCTGGCGGAGGTGGAAGCGGAGGCGGC
GGATCTCAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGG
CCCCAGGACAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTC
CAACATCGGGACAGGTTATGCTGTACACTGGTACCAGCAGCTT
CCAGGAACAGCCCCCAAACTCCTCATCTATGGTAACAACAATC
GGCCCTCAGGGGTTCCTGACCGATTCTCTGGCTCCAAGTCTGG
CACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGAT
GAGGCTGATTATTACTGCCAGTCCTATGACAGCAGACTGAGTG
GTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTA 1345 VH-VL of artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK CDH19 14056
GLEWFAYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQL
PGTAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSRLSGWVFGGGTKLTVL 1346 CDH19 14056 artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK x I2C
GLEWFAYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQL
PGTAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSRLSGWVFGGGTKLTVLSGGGGSEVQLVESGGG
LVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGLEWVARIRS
KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY
YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG
SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKP
GQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE
AEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1347 CDR-H1 of artificial AA GYYWS
CDH19 14057 1348 CDR-H2 of artificial AA YFSYSGSTNYNPSLKS CDH19
14057 1349 CDR-H3 of artificial AA NWAFHFDF CDH19 14057 1350 CDR-L1
of artificial AA TGSSSNIGTGYAVH CDH19 14057 1351 CDR-L2 of
artificial AA GNNNRPS CDH19 14057 1352 CDR-L3 of artificial AA
QSYDSRLSGWV CDH19 14057 1353 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT 14057
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGAAAG
GGACTGGAGTGGATTGGATATTTCTCTTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCTTATCAGTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTC TAGT 1354 VH of CDH19
artificial AA QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK 14057
GLEWIGYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSS 1355 VL of CDH19 artificial NT
CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG 14057
GACAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAACAT
CGGGACAGGTTATGCTGTACACTGGTACCAGCAGCTTCCAGGA
ACAGCCCCCAAACTCCTCATCTATGGTAACAACAATCGGCCCT
CAGGGGTTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
GATTATTACTGCCAGTCCTATGACAGCAGACTGAGTGGTTGGG
TGTTCGGCGGAGGGACCAAGCTGACCGTCCTA 1356 VL of CDH19 artificial AA
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQLPG 14057
TAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSRLSGWVFGGGTKLTVL 1357 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT CDH19 14057
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTGGTTACTACTGGAGCTGGATCCGGCAGCCCCCAGGAAAG
GGACTGGAGTGGATTGGATATTTCTCTTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCTTATCAGTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTC
TAGTGGTGGCGGAGGATCTGGCGGAGGTGGAAGCGGAGGCGGC
GGATCTCAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGG
CCCCAGGACAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTC
CAACATCGGGACAGGTTATGCTGTACACTGGTACCAGCAGCTT
CCAGGAACAGCCCCCAAACTCCTCATCTATGGTAACAACAATC
GGCCCTCAGGGGTTCCTGACCGATTCTCTGGCTCCAAGTCTGG
CACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGAT
GAGGCTGATTATTACTGCCAGTCCTATGACAGCAGACTGAGTG
GTTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTA 1358 VH-VL of artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK CDH19 14057
GLEWIGYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQL
PGTAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSRLSGWVFGGGTKLTVL 1359 CDH19 14057 artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISGYYWSWIRQPPGK x I2C
GLEWIGYFSYSGSTNYNPSLKSRVTLSVDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDFWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYAVHWYQQL
PGTAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSRLSGWVFGGGTKLTVLSGGGGSEVQLVESGGG
LVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRS
KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY
YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG
SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKP
GQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE
AEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1360 CDR-H1 of artificial AA SYSWS
CDH19 14049 1361 CDR-H2 of artificial AA YIYYSGSTNYNPSLKS CDH19
14049 1362 CDR-H3 of artificial AA NWAFHFDY CDH19 14049 1363 CDR-L1
of artificial AA TGSSSNIGTGYDVH CDH19 14049 1364 CDR-L2 of
artificial AA GNSNRPS CDH19 14049 1365 CDR-L3 of artificial AA
QSYDSSLSGWV CDH19 14049 1366 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT 14049
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCATTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC TAGT 1367 VH of CDH19
artificial AA QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK 14049
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSS 1368 VL of CDH19 artificial NT
CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG 14049
GGCAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAATAT
CGGGACAGGTTATGATGTACACTGGTATCAGCAGCTTCCAGGA
ACAGCCCCCAAACTCCTCATCTATGGTAACAGCAATCGGCCCT
CAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
GATTATTACTGCCAGTCCTATGACAGCAGTCTGAGTGGTTGGG
TGTTCGGCGGAGGGACCAGGTTGACCGTCCTA 1369 VL of CDH19 artificial AA
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPG 14049
TAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSSLSGWVFGGGTRLTVL 1370 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT CDH19 14049
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCATTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC
TAGTGGTGGCGGAGGATCTGGCGGAGGTGGAAGCGGAGGCGGC
GGATCTCAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGG
CCCCAGGGCAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTC
CAATATCGGGACAGGTTATGATGTACACTGGTATCAGCAGCTT
CCAGGAACAGCCCCCAAACTCCTCATCTATGGTAACAGCAATC
GGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGG
CACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGAT
GAGGCTGATTATTACTGCCAGTCCTATGACAGCAGTCTGAGTG
GTTGGGTGTTCGGCGGAGGGACCAGGTTGACCGTCCTA 1371 VH-VL of artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK CDH19 14049
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQL
PGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLSGWVFGGGTRLTVL 1372 CDH19 14049 artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK x I2C
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQL
PGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLSGWVFGGGTRLTVLSGGGGSEVQLVESGGG
LVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRS
KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY
YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG
SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKP
GQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE
AEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1373 CDR-H1 of artificial AA SYGMH
CDH19 14302 1374 CDR-H2 of artificial AA FIWYDGSNKYYADSVKD CDH19
14302 1375 CDR-H3 of artificial AA RAGIIGTIGYYYGMDV CDH19 14302
1376 CDR-L1 of artificial AA SGDRLGEKYTS CDH19 14302 1377 CDR-L2 of
artificial AA QDTKRPS CDH19 14302 1378 CDR-L3 of artificial AA
QAWESSTVV CDH19 14302 1379 VH of CDH19 artificial NT
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG
14302 GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGT 1380 VH of CDH19 artificial AA
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK 14302
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS 1381 VL of CDH19 artificial
nt TCCTATGAACTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14302
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGGTTGGGGGA
AAAATATACTAGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGTAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGAGAGCAGCACTGTGGTATTCGGCGGAGGGA CCAAGCTGACCGTCCTA 1382
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSP 14302
LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWESSTVVFGGGTKLTVL
1383 VH-VL of artificial nt
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14302
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAATAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGTGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAAC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGGTTGGGGGAAAAATATACT
AGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCTTTGCTGGTCA
TCTATCAAGATACCAAGCGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGTAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGAGAGCAGCACTGTGGTATTCGGCGGAGGGACCAAGCTGAC CGTCCTA 1384 VH-VL of
artificial AA QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK CDH19
14302 GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
SWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVL 1385 CDH19 14302 artificial aa
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGK x I2C
GLEWVAFIWYDGSNKYYADSVKDRFTISRDNSKNTLYLQMNSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
SWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1386 CDR-H1 of artificial AA
SYGMH CDH19 14303 1387 CDR-H2 of artificial AA FIWYEGSNKYYAESVKD
CDH19 14303 1388 CDR-H3 of artificial AA RAGIIGTIGYYYGMDV CDH19
14303 1389 CDR-L1 of artificial AA SGDRLGEKYTS CDH19 14303 1390
CDR-L2 of artificial AA QDTKRPS CDH19 14303 1391 CDR-L3 of
artificial AA QAWESSTVV CDH19 14303 1392 VH of CDH19 artificial nt
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14303
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGAGGGAAGTAATA
AATACTATGCAGAGTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGT 1393 VH of CDH19 artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK 14303
GLEWVAFIWYEGSNKYYAESVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSS 1394 VL of CDH19 artificial
nt TCCTATGAACTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14303
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGGTTGGGGGA
AAAATATACTAGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCT
TTGCTGGTCATCTATCAAGATACCAAGCGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGTAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGAGAGCAGCACTGTGGTATTCGGCGGAGGGA CCAAGCTGACCGTCCTA 1395
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSP 14303
LLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWESSTVVFGGGTKLTVL
1396 VH-VL of artificial nt
CAGGTGCAGTTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14303
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCATTTATATGGTATGAGGGAAGTAATA
AATACTATGCAGAGTCCGTGAAGGACCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAAAAGCCTG
AGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATAATAGGAACTATAGGCTACTACTACGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCTAGTGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAAC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGGTTGGGGGAAAAATATACT
AGCTGGTATCAGCAGAGGCCAGGCCAGTCCCCTTTGCTGGTCA
TCTATCAAGATACCAAGCGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGTAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGAGAGCAGCACTGTGGTATTCGGCGGAGGGACCAAGCTGAC CGTCCTA 1397 VH-VL of
artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK CDH19
14303 GLEWVAFIWYEGSNKYYAESVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
SWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVL 1398 CDH19 14303 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGK x I2C
GLEWVAFIWYEGSNKYYAESVKDRFTISRDNSKNTLYLQMKSL
RAEDTAVYYCARRAGIIGTIGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYT
SWYQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWESSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1399 CDR-H1 of artificial AA
RYGIH CDH19 14078 1400 CDR-H2 of artificial AA VIWYDGSNKYYADSVKG
CDH19 14078 1401 CDR-H3 of artificial AA RAGIPGTTGYYYGMDV CDH19
14078 1402 CDR-L1 of artificial AA SGDRLGEKYVS CDH19 14078 1403
CDR-L2 of artificial AA QDNKWPS CDH19 14078 1404 CDR-L3 of
artificial AA QAWDSSTVV CDH19 14078 1405 VH of CDH19 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14078
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 1406 VH of CDH19 artificial AA
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGK 14078
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS 1407 VL of CDH19 artificial
nt TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14078
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
GAAATATGTTAGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
ATACTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGGGGGA CCAAGCTGACCGTCCTA 1408
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVSWYQQKPGQSP 14078
ILVIYQDNKWPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWDSSTVVFGGGTKLTVL
1409 VH-VL of artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14078
GGGGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCAGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAGC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGATTGGGGGAGAAATATGTT
AGCTGGTATCAGCAGAAGCCAGGCCAGTCCCCTATACTGGTCA
TCTATCAAGATAATAAGTGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGACAGCAGCACTGTGGTATTCGGCGGGGGGACCAAGCTGAC CGTCCTA 1410 VH-VL of
artificial AA QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGK CDH19
14078 GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
SWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVL 1411 CDH19 14078 artificial aa
QVQLVESGGGVVQPGGSLRLSCAASGFTFSRYGIHWVRQAPGK x I2C
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
SWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1412 CDR-H1 of artificial AA
RYGIH CDH19 14080 1413 CDR-H2 of artificial AA
VIWYDGSNKYYADSVKG
CDH19 14080 1414 CDR-H3 of artificial AA RAGIPGTTGYYYGMDV CDH19
14080 1415 CDR-L1 of artificial AA SGDRLGEKYVY CDH19 14080 1416
CDR-L2 of artificial AA QDNKWPS CDH19 14080 1417 CDR-L3 of
artificial AA QAWDSSTVV CDH19 14080 1418 VH of CDH19 artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG 14080
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCTAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCA 1419 VH of CDH19 artificial AA
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK 14080
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLLMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSS 1420 VL of CDH19 artificial
nt TCCTATGAGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAG 14080
GACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGGGGGA
GAAATATGTTTACTGGTATCAGCAGAAGCCAGGCCAGTCCCCT
ATACTGGTCATCTATCAAGATAATAAGTGGCCCTCAGGGATCC
CTGAGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCT
GACCATCAGCGGGACCCAGGCTATGGATGAGGCTGACTATTAC
TGTCAGGCGTGGGACAGCAGCACTGTGGTATTCGGCGGGGGGA CCAAGCTGACCGTCCTA 1421
VL of CDH19 artificial AA
SYELTQPPSVSVSPGQTASITCSGDRLGEKYVYWYQQKPGQSP 14080
ILVIYQDNKWPSGIPERFSGSNSGNTATLTISGTQAMDEADYY CQAWDSSTVVFGGGTKLTVL
1422 VH-VL of artificial nt
CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTG CDH19 14080
GGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTT
CAGTCGCTATGGCATACACTGGGTCCGCCAGGCTCCAGGCAAG
GGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATA
AATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAG
AGACAATTCCAAGAACACGCTGTATCTGCTAATGAACAGCCTG
AGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAGGGCCG
GTATACCTGGAACTACGGGCTACTACTATGGTATGGACGTCTG
GGGCCAAGGGACCACGGTCACCGTCTCCTCAGGTGGCGGAGGA
TCTGGCGGAGGTGGAAGCGGAGGCGGCGGATCTTCCTATGAGC
TGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGC
CAGCATCACCTGCTCTGGAGATAGATTGGGGGAGAAATATGTT
TACTGGTATCAGCAGAAGCCAGGCCAGTCCCCTATACTGGTCA
TCTATCAAGATAATAAGTGGCCCTCAGGGATCCCTGAGCGATT
CTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGC
GGGACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGT
GGGACAGCAGCACTGTGGTATTCGGCGGGGGGACCAAGCTGAC CGTCCTA 1423 VH-VL of
artificial AA QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK CDH19
14080 GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLLMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
YWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVL 1424 CDH19 14080 artificial aa
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGIHWVRQAPGK x I2C
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLLMNSL
RAEDSAVYYCARRAGIPGTTGYYYGMDVWGQGTTVTVSSGGGG
SGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYV
YWYQQKPGQSPILVIYQDNKWPSGIPERFSGSNSGNTATLTIS
GTQAMDEADYYCQAWDSSTVVFGGGTKLTVLSGGGGSEVQLVE
SGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVA
RIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED
TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGS
GGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWV
QQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQ
PEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1425 CDR-H1 of artificial AA
SYSWS CDH19 13591 1426 CDR-H2 of artificial AA YIYYSGSTNYNPSLKS
CDH19 13591 1427 CDR-H3 of artificial AA NWAFHFDY CDH19 13591 1428
CDR-L1 of artificial AA TGSSSNIGTGYDVH CDH19 13591 1429 CDR-L2 of
artificial AA GNSNRPS CDH19 13591 1430 CDR-L3 of artificial AA
QSYDSSLSGWV CDH19 13591 1431 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT 13591
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCATTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC TAGT 1432 VH of CDH19
artificial AA QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK 13591
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSS 1433 VL of CDH19 artificial NT
CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG 13591
GGCAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAATAT
CGGGACAGGTTATGATGTACACTGGTATCAGCAGCTTCCAGGA
ACAGCCCCCAAACTCCTCATCCATGGTAACAGCAATCGGCCCT
CAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
GATTATTACTGCCAGTCCTATGACAGCAGTCTGAGTGGTTGGG
TGTTCGGCGGAGGGACCAGGTTGACCGTCCTA 1434 VL of CDH19 artificial AA
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPG 13591
TAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSSLSGWVFGGGTRLTVL 1435 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT CDH19 1591
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCATTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC
TAGTGGTGGCGGAGGATCTGGCGGAGGTGGAAGCGGAGGCGGC
GGATCTCAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGG
CCCCAGGGCAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTC
CAATATCGGGACAGGTTATGATGTACACTGGTATCAGCAGCTT
CCAGGAACAGCCCCCAAACTCCTCATCCATGGTAACAGCAATC
GGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGG
CACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGAT
GAGGCTGATTATTACTGCCAGTCCTATGACAGCAGTCTGAGTG
GTTGGGTGTTCGGCGGAGGGACCAGGTTGACCGTCCTA 1436 VH-VL of artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK CDH19 13591
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQL
PGTAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLSGWVFGGGTRLTVL 1437 CDH19 13591 artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK x I2C
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQL
PGTAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLSGWVFGGGTRLTVLSGGGGSEVQLVESGGG
LVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRS
KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY
YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG
SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKP
GQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE
AEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1438 CDR-H1 of artificial AA SYSWS
CDH19 14299 1439 CDR-H2 of artificial AA YIYYSGSTNYNPSLKS CDH19
14299 1440 CDR-H3 of artificial AA NWAFHFDY CDH19 14299 1441 CDR-L1
of artificial AA TGSSSNIGTGYDVH CDH19 14299 1442 CDR-L2 of
artificial AA GNSNRPS CDH19 14299 1443 CDR-L3 of artificial AA
QSYDSSLSGWV CDH19 14299 1444 VH of CDH19 artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT 14299
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCATTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC TAGT 1445 VH of CDH19
artificial AA QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK 14299
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSS 1446 VL of CDH19 artificial NT
CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAG 14299
GGCAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTCCAATAT
CGGGACAGGTTATGATGTACACTGGTATCAGCAGCTTCCAGGA
ACAGCCCCCAAACTCCTCATCCATGGTAACAGCAATCGGCCCT
CAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTC
AGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCT
GATTATTACTGCCAGTCCTATGACAGCAGTCTGAGTGGTTGGG
TGTTCGGCGGAGGGACCAGGTTGACCGTCCTA 1447 VL of CDH19 artificial AA
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQLPG 14299
TAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEA
DYYCQSYDSSLSGWVFGGGTRLTVL 1448 VH-VL of artificial NT
CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTT CDH19 14299
CGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCAT
CAGTAGTTACTCCTGGAGCTGGATCCGGCAGCCCCCAGGGAAG
GGACTGGAGTGGATTGGGTATATCTATTACAGTGGGAGCACCA
ACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCATTAGA
CACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACC
GCTGCGGACACGGCCGTGTATTACTGTGCGAGGAACTGGGCCT
TCCACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC
TAGTGGTGGCGGAGGATCTGGCGGAGGTGGAAGCGGAGGCGGC
GGATCTCAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGG
CCCCAGGGCAGAGGGTCACCATCTCCTGCACTGGGAGCAGCTC
CAATATCGGGACAGGTTATGATGTACACTGGTATCAGCAGCTT
CCAGGAACAGCCCCCAAACTCCTCATCCATGGTAACAGCAATC
GGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGG
CACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGAT
GAGGCTGATTATTACTGCCAGTCCTATGACAGCAGTCTGAGTG
GTTGGGTGTTCGGCGGAGGGACCAGGTTGACCGTCCTA 1449 VH-VL of artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK CDH19 14299
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQL
PGTAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLSGWVFGGGTRLTVL 1450 CDH19 14299 artificial AA
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYSWSWIRQPPGK x I2C
GLEWIGYIYYSGSTNYNPSLKSRVTISLDTSKNQFSLKLSSVT
AADTAVYYCARNWAFHFDYWGQGTLVTVSSGGGGSGGGGSGGG
GSQSVLTQPPSVSGAPGQRVTISCTGSSSNIGTGYDVHWYQQL
PGTAPKLLIHGNSNRPSGVPDRFSGSKSGTSASLAITGLQAED
EADYYCQSYDSSLSGWVFGGGTRLTVLSGGGGSEVQLVESGGG
LVQPGGSLKLSCAASGETENKYAMNWVRQAPGKGLEWVARIRS
KYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY
YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG
SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKP
GQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE
AEYYCVLWYSNRWVFGGGTKLTVLHHHHHH 1451 ckCDH19(1-43) artificial aa
MNCSTFLSLVLALVQLQLCSPTTQIFSAQKTDQSYTTIRRVKR ::FLAG::
DYKDDDDKGWVWEPLFVTEEETSTMPMYVGQLKSDLDKEDGSL ckCDH19(44-776)
QYILTGEGADSIFFINEHGKIYVRQKLDREKKSFYILRAQVIN
RKTRHPIEPDSEFIIKVRDINDHEPQFLDGPYVATVPEMSPEG
TSVTQVTATDGDDPSYGNNARLLYSLIQGQPYFSVEPKTGVIR
MTSQMDRETKDQYLVVIQAKDMVGQAGAFSATATVTINLSDVN
DNPPKFQQRLYYLNVSEEAPVGTTVGRLLAEDSDIGENAAMNY
FIEEDSSDVFGIITDRETQEGIIILKKRVDYESKRKHSVRVKA
VNRYIDDRFLKEGPFEDITIVQISVVDADEPPVFTLESYVMEI
AEGVVSGSLVGTVSARDLDNDDSSVRYSIVQGLHLKRLFSINE
HNGTIITTEPLDREKASWHNITVTATETRNPEKISEANVYIQV
LDVNDHAPEFSKYYETFVCENAVPGQLIQNISAVDKDDSAENH
RFYFSLAQATNSSHFTVKDNQDNTAGIFTAGSGFSRKEQFYFF
LPILILDNGSPPLTSTNTLTVTVCDCDTEVNTLYCRYGAFLYS
IGLSTEALVAVLACLLILLVFFLAIIGIRQQRKKTLFSEKVEE
FRENIVRYDDEGGGEEDTEAFDISALRTRAVLRTHKPRKKITT
EIHSLYRQSLQVGPDSAIFRQFISEKLEEANTDPSVPPYDSLQ
TYAFEGTGSLAGSLSSLGSNTSDVDQNYEYLVGWGPPFKQLAG MYTSQRSTRD 1452
huCDH19(1-43) artificial aa
MNCYLLLRFMLGIPLLWPCLGATENSQTKKVKQPVRSHLRVKR ::FLAG::hu
DYKDDDDKGWVWNQFFVPEEMNTTSHHIGQLRSDLDNGNNSFQ (44-141)
YKLLGAGAGSTFIIDERTGDIYAIQKLDREERSLYILRAQVID ::ckCDH19
IATGRAVEPESEEVIKVSDINDHEPQFLDGPYVATVPEMSPEG (142-776)
TSVTQVTATDGDDPSYGNNARLLYSLIQGQPYFSVEPKTGVIR
MTSQMDRETKDQYLVVIQAKDMVGQAGAFSATATVTINLSDVN
DNPPKFQQRLYYLNVSEEAPVGTTVGRLLAEDSDIGENAAMNY
FIEEDSSDVEGIITDRETQEGIIILKKRVDYESKRKHSVRVKA
VNRYIDDRFLKEGPFEDITIVQISVVDADEPPVFTLESYVMEI
AEGVVSGSLVGTVSARDLDNDDSSVRYSIVQGLHLKRLFSINE
HNGTIITTEPLDREKASWHNITVTATETRNPEKISEANVYIQV
LDVNDHAPEFSKYYETFVCENAVPGQLIQNISAVDKDDSAENH
RFYFSLAQATNSSHFTVKDNQDNTAGIFTAGSGFSRKEQFYFF
LPILILDNGSPPLTSTNTLTVTVCDCDTEVNTLYCRYGAFLYS
IGLSTEALVAVLACLLILLVFFLAIIGIRQQRKKTLFSEKVEE
FRENIVRYDDEGGGEEDTEAFDISALRTRAVLRTHKPRKKITT
EIHSLYRQSLQVGPDSAIFRQFISEKLEEANTDPSVPPYDSLQ
TYAFEGTGSLAGSLSSLGSNTSDVDQNYEYLVGWGPPFKQLAG MYTSQRSTRD 1453
ckCDH19(1-43) artificial aa
MNCSTFLSLVLALVQLQLCSPTTQIFSAQKTDQSYTTIRRVKR ::FLAG::
DYKDDDDKGWVWEPLFVTEEETSTMPMYVGQLKSDLDKEDGSL ckCDH19(44-141)
QYILTGEGADSIFFINEHGKIYVRQKLDREKKSFYILRAQVIN ::huCDH19
RKTRHPIEPDSEFIIKVRDINDNEPKELDEPYEAIVPEMSPEG (142-249)
TLVIQVTASDADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIR ::ckCDH19
ISSKMDRELQDEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVN (250-776)
DNPPKFQQRLYYLNVSEEAPVGTTVGRLLAEDSDIGENAAMNY
FIEEDSSDVEGIITDRETQEGIIILKKRVDYESKRKHSVRVKA
VNRYIDDRFLKEGPFEDITIVQISVVDADEPPVFTLESYVMEI
AEGVVSGSLVGTVSARDLDNDDSSVRYSIVQGLHLKRLFSINE
HNGTIITTEPLDREKASWHNITVTATETRNPEKISEANVYIQV
LDVNDHAPEFSKYYETFVCENAVPGQLIQNISAVDKDDSAENH
RFYFSLAQATNSSHFTVKDNQDNTAGIFTAGSGFSRKEQFYFF
LPILILDNGSPPLTSTNTLTVTVCDCDTEVNTLYCRYGAFLYS
IGLSTEALVAVLACLLILLVFFLAIIGIRQQRKKTLFSEKVEE
FRENIVRYDDEGGGEEDTEAFDISALRTRAVLRTHKPRKKITT
EIHSLYRQSLQVGPDSAIFRQFISEKLEEANTDPSVPPYDSLQ
TYAFEGTGSLAGSLSSLGSNTSDVDQNYEYLVGWGPPFKQLAG MYTSQRSTRD 1454
ckCDH19(1-43) artificial aa
MNCSTFLSLVLALVQLQLCSPTTQIFSAQKTDQSYTTIRRVKR ::FLAG::
DYKDDDDKGWVWEPLFVTEEETSTMPMYVGQLKSDLDKEDGSL ckCDH19(44-249)
QYILTGEGADSIFFINEHGKIYVRQKLDREKKSFYILRAQVIN ::huCDH19
RKTRHPIEPDSEFIIKVRDINDHEPQFLDGPYVATVPEMSPEG (250-364)
TSVTQVTATDGDDPSYGNNARLLYSLIQGQPYFSVEPKTGVIR ::ckCDH19
MTSQMDRETKDQYLVVIQAKDMVGQAGAFSATATVTINLSDVN (365-776)
DNKPIFKESLYRLTVSESAPTGTSIGTIMAYDNDIGENAEMDY
SIEEDDSQTEDIITNHETQEGIVILKKKVDFEHQNHYGIRAKV
KNHHVPEQLMKYHTEASTTFIKIQVEDVDEPPVFTLESYVMEI
AEGVVSGSLVGTVSARDLDNDDSSVRYSIVQGLHLKRLFSINE
HNGTIITTEPLDREKASWHNITVTATETRNPEKISEANVYIQV
LDVNDHAPEFSKYYETFVCENAVPGQLIQNISAVDKDDSAENH
RFYFSLAQATNSSHFTVKDNQDNTAGIFTAGSGFSRKEQFYFF
LPILILDNGSPPLTSTNTLTVTVCDCDTEVNTLYCRYGAFLYS
IGLSTEALVAVLACLLILLVFFLAIIGIRQQRKKTLFSEKVEE
FRENIVRYDDEGGGEEDTEAFDISALRTRAVLRTHKPRKKITT
EIHSLYRQSLQVGPDSAIFRQFISEKLEEANTDPSVPPYDSLQ
TYAFEGTGSLAGSLSSLGSNTSDVDQNYEYLVGWGPPFKQLAG MYTSQRSTRD 1455
ckCDH19(1-43) artificial aa
MNCSTFLSLVLALVQLQLCSPTTQIFSAQKTDQSYTTIRRVKR ::FLAG::
DYKDDDDKGWVWEPLFVTEEETSTMPMYVGQLKSDLDKEDGSL ckCDH19(44-364)
QYILTGEGADSIFFINEHGKIYVRQKLDREKKSFYILRAQVIN ::huCDH19
RKTRHPIEPDSEFIIKVRDINDHEPQFLDGPYVATVPEMSPEG (365-463)
TSVTQVTATDGDDPSYGNNARLLYSLIQGQPYFSVEPKTGVIR ::ckCDH19
MTSQMDRETKDQYLVVIQAKDMVGQAGAFSATATVTINLSDVN (469-776)
DNPPKFQQRLYYLNVSEEAPVGTTVGRLLAEDSDIGENAAMNY
FIEEDSSDVEGIITDRETQEGIIILKKRVDYESKRKHSVRVKA
VNRYIDDRFLKEGPFEDITIVQISVVDADEPPLFLLPYYVFEV
FEETPQGSFVGVVSATDPDNRKSPIRYSITRSKVFNINDNGTI
TTSNSLDREISAWYNLSITATEKYNIEQISSIPLYVQVLNIND
HAPEFSKYYETFVCENAVPGQLIQNISAVDKDDSAENHRFYFS
LAQATNSSHFTVKDNQDNTAGIFTAGSGFSRKEQFYFFLPILI
LDNGSPPLTSTNTLTVTVCDCDTEVNTLYCRYGAFLYSIGLST
EALVAVLACLLILLVFFLAIIGIRQQRKKTLFSEKVEEFRENI
VRYDDEGGGEEDTEAFDISALRTRAVLRTHKPRKKITTEIHSL
YRQSLQVGPDSAIFRQFISEKLEEANTDPSVPPYDSLQTYAFE
GTGSLAGSLSSLGSNTSDVDQNYEYLVGWGPPFKQLAGMYTSQ RSTRD 1456 (1-43)
artificial aa MNCSTFLSLVLALVQLQLCSPTTQIFSAQKTDQSYTTIRRVKR ::FLAG::
DYKDDDDKGWVWEPLFVTEEETSTMPMYVGQLKSDLDKEDGSL ckCDH19(44-468)
QYILTGEGADSIFFINEHGKIYVRQKLDREKKSFYILRAQVIN ::huCDH19
RKTRHPIEPDSEFIIKVRDINDHEPQFLDGPYVATVPEMSPEG (464-772)
TSVTQVTATDGDDPSYGNNARLLYSLIQGQPYFSVEPKTGVIR
MTSQMDRETKDQYLVVIQAKDMVGQAGAFSATATVTINLSDVN
DNPPKFQQRLYYLNVSEEAPVGTTVGRLLAEDSDIGENAAMNY
FIEEDSSDVEGIITDRETQEGIIILKKRVDYESKRKHSVRVKA
VNRYIDDRFLKEGPFEDITIVQISVVDADEPPVFTLESYVMEI
AEGVVSGSLVGTVSARDLDNDDSSVRYSIVQGLHLKRLFSINE
HNGTIITTEPLDREKASWHNITVTATETRNPEKISEANVYIQV
LDVNDHAPEFSQYYETYVCENAGSGQVIQTISAVDRDESIEEH
HEYFNLSVEDTNNSSETIIDNQDNTAVILTNRTGENLQEEPVF
YISILIADNGIPSLTSTNTLTIHVCDCGDSGSTQTCQYQELVL
SMGFKTEVITATLICIMIIFGFIFLTLGLKQRRKQILFPEKSE
DFRENIFQYDDEGGGEEDTEAFDIAELRSSTIMRERKTRKTTS
AEIRSLYRQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSL
QTYAFEGTGSLAGSLSSLESAVSDQDESYDYLNELGPRFKRLA CMFGSAVQSNN 1457
rhCDH19(1-43) artificial aa
MNCYLLLPFMLGIPLLWPCLGATENSQTKKVQQPVGSHLRVKR ::FLAG::
DYKDDDDKGWVWNQFFVPEEMNTTSHHVGRLRSDLDNGNNSFQ rhCDH19(44-772)
YKLLGAGAGSTFIIDERTGDIYAIEKLDREERSLYILRAQVID
ITTGRAVEPESEFVIKVSDINDNEPKELDEPYEAIVPEMSPEG
TLVIQVTASDADDPSSGNNARLLYSLLQGQPYFSVEPTTGVIR
ISSKMDRELQDEYWVIIQAKDMIGQPGALSGTTSVLIKLSDVN
DNKPIFKESLYRLTVSESAPTGTSIGTIMAYDNDIGENAEMDY
SIEEDDSQTEDIITNHETQEGIVILKKKVNFEHQNHYGIRAKV
KNHHVDEQLMKYHTEASTTFIKIQVEDVDEPPLELLPYYIFEI
FEETPQGSFVGVVSATDPDNRKSPIRYSITRSKVFNIDDNGTI
TTTNSLDREISAWYNLSITATEKYNIEQISSIPVYVQVLNIND
HAPEFSQYYESYVCENAGSGQVIQTISAVDRDESIEEHHEYEN
LSVEDTNSSSETIIDNQDNTAVILTNRTGFNLQEEPIFYISIL
IADNGIPSLTSTNTLTIHVCDCDDSGSTQTCQYQELMLSMGFK
TEVIIAILICIMVIEGFIFLTLGLKQRRKQILFPEKSEDFREN
IFRYDDEGGGEEDTEAFDVAALRSSTIMRERKTRKTTSAEIRS
LYRQSLQVGPDSAIFRKFILEKLEEADTDPCAPPFDSLQTYAF
EGTGSLAGSLSSLESAVSDQDESYDYLNELGPRFKRLACMFGS AVQSNN 1458
caCDH19(1-42) artificial aa
QFFVPEEMNKTDYHIGQLRSDLDNGNNSFQYKLLGAGAGSIFV ::FLAG::
IDERTGDIYAIQKLDREERSLYTLRAQVIDSTTGRAVEPESEF caCDH19(43-770)
VIRVSDINDNEPKELDEPYEAIVPEMSPEGTLVIQVTATDADD
PASGNNARLLYSLLQGQPYFSIEPTTGVIRISSKMDRELQDEY
WVIIQAKDMIGLPGALSGTTSVLIKLSDVNDNKPIFKERLYRL
TVSESAPTGTSIGRIMAYDNDIGENAEMDYSIEDDSQTFDIIT
NNETQEGIVILKKKVDFEHQNHYLIRANVKNRHVAEHLMEYHV
EASTTEVRVQVEDEDEPPVELLPYYLFEILEESPHGSFVGMVS
ATDPDQRKSPIRYSITRSKVFSIDDNGTIITTNPLDREISAWY
NLSITATEKYNVQQISAVPVYVQVLNINDHAPEFSEYYDSYVC
ENAGSGQVIQTISAVDRDESVEDHHEYFNLSVEDTKNSSFIII
DNEDNTAVILTNRTGFSLQEEPVFYISVLIADNGIPSLTSTNT
LTIHICDCDDYGSTQTCRDKDLLLSMGFRTEVILAILISIMII
FGFIFLILGLKQRRKPTLFPEKGEDFRENIFRYDDEGGGEEDT
EAFDIVQLRSSTIMRERKTRKTAAAEIRSLYRQSLQVGPDSAI
FRKFILEKLEEANTDPCAPPFDSLQTYAFEGTGSLAGSLSSLG
SAVSDQDENYDYLNELGPRFKRLACMFGSAMQSNN 1459 rhCDH19(1-43) artificial
aa MNCYLLLPFMLGIPLLWPCLGATENSQTKKVQQPVGSHLRVKR :FLAG::
DYKDDDDKGWVWNQFFVPEEMNTTSHHVGRLRSDLDNGNNSFQ rhCDH19(44-141)
YKLLGAGAGSTFIIDERTGDIYAIEKLDREERSLYILRAQVID ::caCDH19
ITTGRAVEPESEFVIKVSDINDNEPKFLDEPYEAIVPEMSPEG (141-770)
TLVIQVTATDADDPASGNNARLLYSLLQGQPYFSIEPTTGVIR
ISSKMDRELQDEYWVIIQAKDMIGLPGALSGTTSVLIKLSDVN
DNKPIFKERLYRLTVSESAPTGTSIGRIMAYDNDIGENAEMDY
SIEDDSQTFDIITNNETQEGIVILKKKVDFEHQNHYLIRANVK
NRHVAEHLMEYHVEASTTEVRVQVEDEDEPPVELLPYYLFEIL
EESPHGSFVGMVSATDPDQRKSPIRYSITRSKVFSIDDNGTII
TTNPLDREISAWYNLSITATEKYNVQQISAVPVYVQVLNINDH
APEFSEYYDSYVCENAGSGQVIQTISAVDRDESVEDHHEYFNL
SVEDTKNSSFIIIDNEDNTAVILTNRTGFSLQEEPVFYISVLI
ADNGIPSLTSTNTLTIHICDCDDYGSTQTCRDKDLLLSMGERT
EVILAILISIMIIFGFIFLILGLKQRRKPTLFPEKGEDFRENI
FRYDDEGGGEEDTEAFDIVQLRSSTIMRERKTRKTAAAEIRSL
YRQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSLQTYAFE
GTGSLAGSLSSLGSAVSDQDENYDYLNELGPRFKRLACMFGSA MQSNN 1460
rhCDH19(1-43) artificial aa
MNCYLLLPFMLGIPLLWPCLGATENSQTKKVQQPVGSHLRVKR ::FLAG::
DYKDDDDKGWVWNQFFVPEEMNTTSHHVGRLRSDLDNGNNSFQ rhCDH19(44-65)
YKLLGAGAGSIFVIDERTGDIYAIQKLDREERSLYTLRAQVID ::caCDH19
STTGRAVEPESEEVIRVSDINDNEPKELDEPYEAIVPEMSPEG (65-770)
TLVIQVTATDADDPASGNNARLLYSLLQGQPYFSIEPTTGVIR
ISSKMDRELQDEYWVIIQAKDMIGLPGALSGTTSVLIKLSDVN
DNKPIFKERLYRLTVSESAPTGTSIGRIMAYDNDIGENAEMDY
SIEDDSQTFDIITNNETQEGIVILKKKVDFEHQNHYLIRANVK
NRHVAEHLMEYHVEASTTEVRVQVEDEDEPPVELLPYYLFEIL
EESPHGSFVGMVSATDPDQRKSPIRYSITRSKVFSIDDNGTII
TTNPLDREISAWYNLSITATEKYNVQQISAVPVYVQVLNINDH
APEFSEYYDSYVCENAGSGQVIQTISAVDRDESVEDHHEYFNL
SVEDTKNSSFIIIDNEDNTAVILTNRTGFSLQEEPVFYISVLI
ADNGIPSLTSTNTLTIHICDCDDYGSTQTCRDKDLLLSMGERT
EVILAILISIMIIFGFIFLILGLKQRRKPTLFPEKGEDFRENI
FRYDDEGGGEEDTEAFDIVQLRSSTIMRERKTRKTAAAEIRSL
YRQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSLQTYAFE
GTGSLAGSLSSLGSAVSDQDENYDYLNELGPRFKRLACMFGSA MQSNN 1461
caCDH19(1-43) artificial aa
MNYCFLLPLMLGIPLIWPCFTASESSKTEVKHQAGSHLRVKRD ::FLAG::
YKDDDDKGWMWNQFFVPEEMNKTDYHIGQLRSDLDNGNNSFQY DcaCH19(44-87)
KLLGAGAGSTFIIDERTGDIYAIEKLDREERSLYILRAQVIDS ::rhCDH19
TTGRAVEPESEEVIRVSDINDNEPKELDEPYEAIVPEMSPEGT (89-114)
LVIQVTATDADDPASGNNARLLYSLLQGQPYFSIEPTTGVIRI ::caCDH19
SSKMDRELQDEYWVIIQAKDMIGLPGALSGTTSVLIKLSDVND (115-770)
NKPIFKERLYRLTVSESAPTGTSIGRIMAYDNDIGENAEMDYS
IEDDSQTFDIITNNETQEGIVILKKKVDFEHQNHYLIRANVKN
RHVAEHLMEYHVEASTTEVRVQVEDEDEPPVELLPYYLFEILE
ESPHGSFVGMVSATDPDQRKSPIRYSITRSKVFSIDDNGTIIT
TNPLDREISAWYNLSITATEKYNVQQISAVPVYVQVLNINDHA
PEFSEYYDSYVCENAGSGQVIQTISAVDRDESVEDHHEYFNLS
VEDTKNSSFIIIDNEDNTAVILTNRTGFSLQEEPVFYISVLIA
DNGIPSLTSTNTLTIHICDCDDYGSTQTCRDKDLLLSMGERTE
VILAILISIMIIFGFIFLILGLKQRRKPTLFPEKGEDFRENIF
RYDDEGGGEEDTEAFDIVQLRSSTIMRERKTRKTAAAEIRSLY
RQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSLQTYAFEG
TGSLAGSLSSLGSAVSDQDENYDYLNELGPRFKRLACMFGSAM QSNN 1462 caCDH19(1-43)
artificial aa MNYCFLLPLMLGIPLIWPCFTASESSKTEVKHQAGSHLRVKRD ::FLAG::
YKDDDDKGWMWNQFFVPEEMNKTDYHIGQLRSDLDNGNNSFQY caCDH19(44-120)
KLLGAGAGSIFVIDERTGDIYAIQKLDREERSLYTLRAQVIDI ::rhCDH19
TTGRAVEPESEEVIKVSDINDNEPKELDEPYEAIVPEMSPEGT (122-137)
LVIQVTATDADDPASGNNARLLYSLLQGQPYFSIEPTTGVIRI ::caCDH19
SSKMDRELQDEYWVIIQAKDMIGLPGALSGTTSVLIKLSDVND (137-770)
NKPIFKERLYRLTVSESAPTGTSIGRIMAYDNDIGENAEMDYS
IEDDSQTFDIITNNETQEGIVILKKKVDFEHQNHYLIRANVKN
RHVAEHLMEYHVEASTTEVRVQVEDEDEPPVELLPYYLFEILE
ESPHGSFVGMVSATDPDQRKSPIRYSITRSKVFSIDDNGTIIT
TNPLDREISAWYNLSITATEKYNVQQISAVPVYVQVLNINDHA
PEFSEYYDSYVCENAGSGQVIQTISAVDRDESVEDHHEYFNLS
VEDTKNSSFIIIDNEDNTAVILTNRTGFSLQEEPVFYISVLIA
DNGIPSLTSTNTLTIHICDCDDYGSTQTCRDKDLLLSMGERTE
VILAILISIMIIFGFIFLILGLKQRRKPTLFPEKGEDFRENIF
RYDDEGGGEEDTEAFDIVQLRSSTIMRERKTRKTAAAEIRSLY
RQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSLQTYAFEG
TGSLAGSLSSLGSAVSDQDENYDYLNELGPRFKRLACMFGSAM QSNN 1463 rhCDH19(1-43)
artificial aa MNCYLLLPFMLGIPLLWPCLGATENSQTKKVQQPVGSHLRVKR ::FLAG::
DYKDDDDKGWVWNQFFVPEEMNTTSHHVGRLRSDLDNGNNSFQ rhCDH19(44-141)
YKLLGAGAGSTFIIDERTGDIYAIEKLDREERSLYILRAQVID ::raCDH19
ITTGRAVEPESEFVIKVSDINDNEPRFLDEPYEAIVPEMSPEG (140-247)
TFVIKVTANDADDPTSGYHARILYNLEQGQPYFSVEPTTGVIR ::rhCDH19
ISSKMDRELQDTYCVIIQAKDMLGQPGALSGTTTISIKLSDIN (250-772)
DNKPIFKESLYRLTVSESAPTGTSIGTIMAYDNDIGENAEMDY
SIEEDDSQTFDIITNHETQEGIVILKKKVNFEHQNHYGIRAKV
KNHHVDEQLMKYHTEASTTFIKIQVEDVDEPPLFLLPYYIFEI
FEETPQGSFVGVVSATDPDNRKSPIRYSITRSKVFNIDDNGTI
TTTNSLDREISAWYNLSITATEKYNIEQISSIPVYVQVLNIND
HAPEFSQYYESYVCENAGSGQVIQTISAVDRDESIEEHHEYEN
LSVEDTNSSSETIIDNQDNTAVILTNRTGFNLQEEPIFYISIL
IADNGIPSLTSTNTLTIHVCDCDDSGSTQTCQYQELMLSMGFK
TEVIIAILICIMVIEGFIFLTLGLKQRRKQILFPEKSEDFREN
IFRYDDEGGGEEDTEAFDVAALRSSTIMRERKTRKTTSAEIRS
LYRQSLQVGPDSAIFRKFILEKLEEADTDPCAPPFDSLQTYAF
EGTGSLAGSLSSLESAVSDQDESYDYLNELGPRFKRLACMFGS AVQSNN 1464
raCDH19(1-43) artificial aa
MNHYFLKYWILMVPLIWPCLKVAETLKIEKAQRAVPSLGRAKR ::FLAG::
DYKDDDDKGWVWKQFVVPEEMDTIQHVGRLRSDLDNGNNSFQY raCDH19(44-770)
KLLGTGDGSFSIDEKTGDIFAMQKLDREKQSLYILRAQVIDTT
IGKAVEPESEEVIRVSDVNDNEPRELDEPYEAIVPEMSPEGTF
VIKVTANDADDPTSGYHARILYNLEQGQPYFSVEPTTGVIRIS
SKMDRELQDTYCVIIQAKDMLGQPGALSGTTTISIKLSDINDN
KPIFKESFYRFTISESAPSGTTIGKIMAYDDDIGENAEMDYSI
EDDESQIFDIVIDNETQEGIVILKKKVDFEHQNHYGIRVKVKN
CHVDEELAPAHVNASTTYIKVQVEDEDEPPTFLLPYYIFEIPE
GKPYGTMVGTVSAVDPDRRQSPMRYSLIGSKMFDINGNGTIVT
TNLLDREVSAWYNLSVTATETYNVQQISSAHVYVQVLNINDHA
PEFSQLYETYVCENAESGEIIQTISAIDRDESIEDHHEYENHS
VEDTNNSSFILTDNQDNTAVILSNRAGESLKEETVEYMIILIA
DNGIPPLTSTNTLTIQVCDCGDSRSTETCTSKELLFIMGFKAE
AIIAIVICVMVIEGFIFLILALKQRRKETLFPEKTEDFRENIF
CYDDEGGGEEDSEAFDIIELRQSTVMRERKPRKSRSAEIRSLY
RQSLQVGPDSAIFRKFILEKLEEANTDSSAPPFDSLQTFAYEG
TGSSAGSLSSLGSSVTDQEDDFDYLNDLGPCFKRLANMFGSAV QPDN 1465 (1-43)
artificial aa MNYCFLKHWILMIPLLWPCLKVSETLKAEKARRTVPSTWRAKR ::FLAG::
DYKDDDDKAWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQY muCDH19(44-323)
KLLGIGAGSFSINERTGEICAIQKLDREEKSLYILRAQVIDTT ::raCDH19
IGKAVETESEFVIRVLDINDNEPRELDEPYEAIVPEMSPEGTF (324-327)
VIKVTANDADDPSTGYHARILYNLERGQPYFSVEPTTGVIRIS ::muCDH19
SKMDRELQDTYCVIIQAKDMLGQPGALSGTTTVSIKLSDINDN (328-770)
KPIFKESFYRFTISESAPIGTSIGKIMAYDDDIGENAEMEYSI
EDDDSKIFDIIIDNDTQEGIVILKKKVDFEHQNHYGIRAKVKN
CHVDEELAPAHVNASTTYIKVQVEDEDEPPVFLLPYYILEIPE
GKPYGTIVGTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIIT
TNMLDREVSAWYNLTVTATETYNVQQISSAHVYVQVFNINDNA
PEFSQFYETYVCENAESGEIVQIISAIDRDESIEDHHEYENHS
LEDTNNSSFMLTDNQDNTAVILSNRTGENLKEEPVEYMIILIA
DNGIPSLTSTNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTE
AIIAIMICVMVIFGEFFLILALKQRRKETLFPEKTEDFRENIF
CYDDEGGGEEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLY
RQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEG
TGSSAGSLSSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAV QPNN 1466 muCDH19(1-43)
artificial aa MNYCFLKHWILMIPLLWPCLKVSETLKAEKARRTVPSTWRAKR ::FLAG::
DYKDDDDKAWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQY muCDH19(44-770)
KLLGIGAGSFSINERTGEICAIQKLDREEKSLYILRAQVIDTT ::raCDH19
IGKAVETESEFVIRVLDINDNEPRELDEPYEAIVPEMSPEGTF (290, 299, 308)
VIKVTANDADDPSTGYHARILYNLERGQPYFSVEPTTGVIRIS
SKMDRELQDTYCVIIQAKDMLGQPGALSGTTTVSIKLSDINDN
KPIFKESFYRFTISESAPIGTSIGKIMAYDDDIGENAEMEYSI
EDDDSKIFDIIIDNDTQEGIVILKKKVDFEQQSYYGIRAKVKN
CHVDEELAPAHVNASTTYIKVQVEDEDEPPVFLLPYYILEIPE
GKPYGTIVGTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIIT
TNMLDREVSAWYNLTVTATETYNVQQISSAHVYVQVFNINDNA
PEFSQFYETYVCENAESGEIVQIISAIDRDESIEDHHEYENHS
LEDTNNSSFMLTDNQDNTAVILSNRTGENLKEEPVEYMIILIA
DNGIPSLTSTNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTE
AIIAIMICVMVIFGEFFLILALKQRRKETLFPEKTEDFRENIF
CYDDEGGGEEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLY
RQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEG
TGSSAGSLSSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAV QPNN 1467 muCDH19(1-43)
artificial aa MNYCFLKHWILMIPLLWPCLKVSETLKAEKARRTVPSTWRAKR ::FLAG::
DYKDDDDKAWVWRPFVVLEEMDDIQCVGKLRSDLDNGNNSFQY muCDH19(44-770)
KLLGIGAGSFSINERTGEICAIQKLDREEKSLYILRAQVIDTT ::huCDH19
IGKAVETESEFVIRVLDINDNEPRELDEPYEAIVPEMSPEGTF (271)
VIKVTANDADDPSTGYHARILYNLERGQPYFSVEPTTGVIRIS
SKMDRELQDTYCVIIQAKDMLGQPGALSGTTTVSIKLSDINDN
KPIFKESFYRFTISESAPTGTSIGKIMAYDDDIGENAEMEYSI
EDDDSKIFDIIIDNDTQEGIVILKKKVDFEQQSYYGIRAKVKN
CHVDEELAPAHVNASTTYIKVQVEDEDEPPVFLLPYYILEIPE
GKPYGTIVGTVSATDPDRRQSPMRYYLTGSKMFDINDNGTIIT
TNMLDREVSAWYNLTVTATETYNVQQISSAHVYVQVFNINDNA
PEFSQFYETYVCENAESGEIVQIISAIDRDESIEDHHFYFNHS
LEDTNNSSFMLTDNQDNTAVILSNRTGFNLKEEPVFYMIILIA
DNGIPSLTSTNTLTIQVCDCGDSRNTETCANKGLLFIMGFRTE
AIIAIMICVMVIFGFFFLILALKQRRKETLFPEKTEDFRENIF
CYDDEGGGEEDSEAFDIVELRQSTVMRERKPQRSKSAEIRSLY
RQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSLQTFAYEG
TGSSAGSLSSLASRDTDQEDDFDYLNDLGPRFKRLASMFGSAV QPNN
Sequence CWU 0 SQTB SEQUENCE LISTING The patent application
contains a lengthy "Sequence Listing" section. A copy of the
"Sequence Listing" is available in electronic form from the USPTO
web site
(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20200071405A1).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
0 SQTB SEQUENCE LISTING The patent application contains a lengthy
"Sequence Listing" section. A copy of the "Sequence Listing" is
available in electronic form from the USPTO web site
(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20200071405A1).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
* * * * *
References