U.S. patent application number 14/969937 was filed with the patent office on 2016-08-25 for reactor systems.
This patent application is currently assigned to ABEC, Inc.. The applicant listed for this patent is ABEC, Inc.. Invention is credited to Brady Cole, Cindy L. Donovan, Todd Jones, Cameron Knight, Paul Kubera.
Application Number | 20160244707 14/969937 |
Document ID | / |
Family ID | 46831321 |
Filed Date | 2016-08-25 |
United States Patent
Application |
20160244707 |
Kind Code |
A1 |
Knight; Cameron ; et
al. |
August 25, 2016 |
Reactor Systems
Abstract
This disclosure relates to equipment utilized to manufacture
chemical agents, particularly biopharmaceuticals. In some
embodiments, reactor systems comprising a mobile carriage assembly;
a disposable reaction container removably attached to the carriage
assembly; and, a carriage holder into which the mobile carriage
assembly may be removably inserted are provided.
Inventors: |
Knight; Cameron;
(Springfield, MO) ; Jones; Todd; (New Tripoli,
PA) ; Cole; Brady; (Center Valley, PA) ;
Kubera; Paul; (Schnecksville, PA) ; Donovan; Cindy
L.; (Allentown, PA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ABEC, Inc. |
Bethlehem |
PA |
US |
|
|
Assignee: |
ABEC, Inc.
Bethlehem
PA
|
Family ID: |
46831321 |
Appl. No.: |
14/969937 |
Filed: |
December 15, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13420338 |
Mar 14, 2012 |
9228165 |
|
|
14969937 |
|
|
|
|
61453099 |
Mar 15, 2011 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01J 2219/24 20130101;
B01F 7/00133 20130101; C12M 27/02 20130101; B01J 19/1812 20130101;
C12M 23/28 20130101; B01F 7/00141 20130101; B01F 7/186 20130101;
B01F 15/00785 20130101; B01F 13/0032 20130101; B01F 15/00006
20130101; B01J 2219/1943 20130101; B01F 15/065 20130101; B01F
15/0085 20130101; B01F 15/00896 20130101; B01J 19/18 20130101; B01J
19/24 20130101; C12M 23/46 20130101; B01J 2219/00768 20130101; C12M
23/52 20130101; B01F 7/1605 20130101; B01J 2219/00094 20130101;
C12M 23/48 20130101; B01J 19/0066 20130101 |
International
Class: |
C12M 1/00 20060101
C12M001/00; C12M 1/06 20060101 C12M001/06; B01J 19/18 20060101
B01J019/18 |
Claims
1-19. (canceled)
20. A method for carrying out a reaction, the method comprising
combining the components of a reaction in a reaction vessel
comprising: a) a mobile carriage assembly holder comprising an
interior into which a mobile carriage assembly may be removably
inserted, the holder comprising: i) a receiving implement
comprising at least one wheel or track for receiving the mobile
carriage assembly; and, ii) a door for securing the mobile carriage
assembly within the interior of the holder following insertion of
the mobile carriage assembly into the holder; b) a mobile carriage
assembly comprising: i) at least one primary mobility implement
comprising at least one wheel or track for moving the mobile
carriage assembly prior to insertion of the mobile carriage
assembly into the holder; ii) secondary mobility implements, each
secondary mobility element comprising at least one wheel or track,
wherein: 1) the secondary mobility implements are not in contact
with the ground prior to or following insertion of the mobile
carriage assembly into the holder; 2) at least one secondary
mobility implement is proximal to the receiving implement and at
least one secondary mobility implement is distal from the receiving
implement prior to insertion of the mobile carriage assembly into
the holder; 3) the secondary mobility implements provide for
insertion of the mobile carriage assembly into the holder, and
removal of the mobile carriage assembly from the holder, using the
receiving implement of the holder; and, iii) a shaft and impellar
assembly; and,) c) a disposable reaction container removably
attached to the mobile carriage assembly that, when removably
attached to the mobile carriage assembly: 1) comprises an interior
chamber in which reaction components may be reacted with one
another; 2) encloses the shaft and impellar assembly; and, 3)
separates the reaction components from the external environment.
Description
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Ser. No. 61/453,099
filed Mar. 15, 2011.
FIELD OF DISCLOSURE
[0002] This disclosure relates to equipment utilized to manufacture
chemical agents, particularly biopharmaceuticals.
BACKGROUND INFORMATION
[0003] This disclosure relates to equipment having reaction vessels
used to manufacture chemical and/or biological products such as
biopharmaceuticals. For instance, fermenters commonly provide a
reaction vessel for cultivation of microbial organisms or
mammalian, insect, or plant cells to produce such products.
Currently available systems do not provide for simple removal of
the components of a reaction from a reaction container and cleaning
of equipment after a reaction is completed. The systems described
herein solve these problems by providing a custom geometry, and
optionally a sterile container used for reactions (e.g.,
biological, chemical), that does not require cleaning and
re-sterilization after use is solved by the system described
herein. The system also provides for ease of use in loading and
unloading the disposable reaction container from a holder (e.g., an
external jacket system).
SUMMARY OF THE DISCLOSURE
[0004] The systems described herein provide a mobile single-use
disposable reaction container that may be housed within a holding
system (e.g., external jacket system). In some embodiments, reactor
systems comprising a mobile carriage assembly; a disposable
reaction container removably attached to the carriage assembly;
and, a carriage holder into which the mobile carriage assembly may
be removably inserted are provided. In certain embodiments, the
carriage holder comprises a heat transfer jacket. The mobile
carriage may optionally comprise at least one implement selected
from the group consisting of at least one wheel or track, an
implement providing for fixably attaching the disposable reaction
container to the carriage, an implement providing for fixably
attaching the carriage to the holder, and an implement for mixing
the components of the reaction. The implement for mixing the
components of the reaction may be, for example, an agitator that
optionally comprises a shaft and impeller that is incorporated in
the reaction container and that connects to a drive mechanism
fixably attached to the carriage. The disposable reaction container
may comprise a sterile, sealable interior chamber in which reaction
components may be reacted with one another; may be reversibly
fixably attached to the mobile carriage assembly; may be removed
from the mobile carriage assembly after the reaction is complete;
may separate the contents of the reaction from the external
environment after removal from the mobile carriage assembly;
and/or, incorporate a sparge or other accessory. In certain
embodiments, the holder may comprise a receiving implement with
which the carriage may be inserted into and optionally affixed to
the holder; maintain the desired geometry of the disposable
reaction container, optionally including reaction container
anti-swirl baffles; provide for heating and/or cooling of the
reaction components within the reaction container; comprise a door
for maintaining the reaction container separated from the exterior
of the holder; and/or, comprise one or more anti-swirl and/or heat
exchange baffles. In some embodiments, the receiving implement
comprises one or more wheels or tracks. Other features of these
reactor systems will be apparent from the description provided
herein including, for example, FIGS. 1-4. Thus, in some
embodiments, the reactor systems may comprise:
[0005] 1) a mobile carriage assembly;
[0006] 2) a disposable reaction container removably attached to the
carriage assembly; and,
[0007] 3) a holder with a heat transfer jacket (e.g., external
jacket system) comprising an opening into which the carriage (e.g.,
and reaction container) may be removably inserted;
wherein:
[0008] a) the mobile carriage assembly optionally comprises [at
least one of]: [0009] i. at least one implement providing mobility
to the carriage, such as one or more wheels or tracks; [0010] ii.
at least one implement providing for fixably attaching the
disposable reaction container to the carriage; and, [0011] iii. at
least one implement providing for fixably attaching the carriage to
the holder; [0012] iv. one or more implements such as an agitator
that optionally comprises a shaft and impellar fixably attached to
the carriage and providing for mixing of the contents of the
reaction within the reaction container;
[0013] b) the disposable reaction container: [0014] i. provides a
sterile, sealable interior chamber in which reaction components may
be reacted with one another; [0015] ii. may be reversibly fixably
attached to the carriage such that one or more of the implements of
the carriage may be coupled to the reaction container (e.g.,
agitator (e.g., the shaft and impellar being affixed to a motor on
the carriage and providing for mixing of the contents of the
reaction within the reaction container)) while others may be
positioned outside the reaction container (e.g., the baffle(s))
and/or other components of the system); [0016] iii. may be removed
from the carriage after the reaction is complete, optionally
keeping the contents of the reaction separated from the external
environment (e.g., under sterile conditions); and, [0017] iv.
optionally comprises a sparge (e.g., gas introduction device);
and,
[0018] c) the holder [may]: [0019] i. comprises an receiving
implement (e.g., one or more tracks) with which the carriage may be
inserted into and optionally affixed to the holder; [0020] ii.
maintains the desired geometry (e.g., shape) of the disposable
reaction container, optionally including reaction container
anti-swirl baffles; [0021] iii. provides for heating and/or cooling
of the reaction components within the reaction container; [0022]
iv. comprises a door for maintaining the carriage and reaction
container separated from the exterior of the holder (e.g., locking
the carriage/reaction container within the holder); and, [0023] v.
optionally comprises one or more anti-swirl and/or heat exchange
baffle(s).
[0024] In some embodiments, a mobile carriage assembly to which a
disposable reaction container may be removably attached, the mobile
carriage assembly comprising at least one wheel and/or track Sand
an implement for mixing the components of the reaction in the
reaction chamber, is provided. Exemplary of such embodiments may be
those shown in FIGS. 1 and 2. Such a mobile carriage assembly may
be placed into a holder as, for example, described herein to carry
out a reaction within the disposable reaction container (FIG.
3).
[0025] The reactor systems described herein may be used to carry
out any of a variety of reactions, such as a chemical process, a
pharmaceutical process, and/or a biological process (or
combinations thereof). Exemplary biological processes may include,
for example, microbiological culture, mammalian cell culture, and
plant cell culture. In some embodiments, the reaction may be may be
use in at least one step of a process for the production of a
composition comprising a peptide, protein, nucleic acid, complex
thereof, combination thereof, or the like for use in, for example,
for the prevention and/or treatment of a disease (e.g., as a
vaccine). Also provided are methods for carrying out such reactions
using the reactor systems described herein. The products of such
reactions are also provided by this disclosure. Additional
embodiments and advantages of these systems are described
below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] FIG. 1. Exemplary carriage assembly.
[0027] FIG. 2. Exemplary carriage assembly with reversibly attached
reaction container (4).
[0028] FIG. 3. Exemplary carriage assembly and holder (e.g.,
external jacket system) and exemplary tracks (8) for reversibly
inserting carriage assembly (optionally also comprising reaction
container) into holder.
[0029] FIG. 4. Exemplary reactor system in which carriage assembly
is contained within holder and separated from exterior by door
(7).
DETAILED DESCRIPTION
[0030] The systems described herein provide a mobile single-use
disposable reaction container that may be housed within a holding
system (e.g., external jacket system). These systems are fully
customizable in terms of the types and size of reactions that may
be performed therein. The reaction systems may be designed to
accommodate nearly any size reaction by coordinating the size of
the various components relative to one another such that the
required attachments may be made and various reaction conditions
supported. The types of reactions may also vary as the components
may be made of any suitable material required to withstand the
reaction conditions (e.g., types of reactants, heat, pressure,
etc.) In some embodiments, the system comprises a mobile carriage
assembly, a disposable reaction container removably attached to the
mobile carriage assembly; and, a holder with a heat transfer jacket
(e.g., external jacket system) comprising an opening into which the
mobile carriage assembly (e.g., and reaction container) may be
removably inserted. In some embodiments, the holder may not
comprise a heat transfer jacket. The mobile carriage assembly
optionally comprises at least one implement providing mobility to
the carriage, such as one or more wheels and/or tracks; at least
one implement providing for fixably attaching the disposable
reaction container to the mobile carriage assembly; and, at least
one implement providing for fixably attaching the mobile carriage
assembly to the holder; and/or one or more implements such as an
agitator that optionally comprises a shaft and impellar fixably
attached to the mobile carriage assembly and providing for mixing
of the contents of the reaction within the reaction container. The
disposable reaction container may comprise a sterile, sealable,
interior chamber in which reaction components may be reacted with
one another; may be reversibly fixably attached to the mobile
carriage assembly such that one or more of the implements of the
mobile carriage assembly may be coupled to the reaction container
(e.g., agitator (e.g., the shaft and impellar being affixed to a
motor on the mobile carriage assembly and providing for mixing of
the contents of the reaction within the reaction container)) while
others may be positioned outside the reaction container (e.g., the
baffle(s)) and/or other components of the system); may be removed
from the mobile carriage assembly after the reaction is complete,
optionally keeping the contents of the reaction separated from the
external environment (e.g., under sterile conditions); and/or
optionally comprises a sparge (e.g., gas introduction device). The
holder may comprise a receiving implement (e.g., one or more
tracks) with which the mobile carriage assembly may be inserted
into and optionally affixed to the holder; may maintain the desired
geometry (e.g., shape) of the disposable reaction container,
optionally including reaction container anti-swirl baffles; may
provide for heating and/or cooling of the reaction components
within the reaction container; comprises a door for maintaining the
mobile carriage assembly and reaction container separated from the
exterior of the holder (e.g., locking the carriage/reaction
container within the holder); and/or comprises one or more
anti-swirl and/or heat exchange baffle(s). The reactor system may
be used to carry out reaction involving, for example, a chemical
process, a pharmaceutical process, and a biological process. For
instance, a biological process may be a microbiological culture,
mammalian cell culture, and plant cell culture. In some
embodiments, the reaction may be use in at least one step of a
process for the production of a composition comprising a peptide,
protein, nucleic acid, complex thereof, combination thereof, or the
like for use in, for example, for the prevention and/or treatment
of a disease (e.g., as a vaccine). Methods for carrying out these
reactions are also provided. It is noted that the terms "attached",
"fixably attached", "affixed", and / or "adjoined" mean that at
least two materials are linked or bonded to one another in a
temporary or permanent (or substantially permanent) manner. And
parts are "reversibly" attached where one part may be attached and
detached from another part. For example, one of ordinary skill in
the art would understand that the at least one implement providing
for fixably attaching the disposable reaction container to the
mobile carriage assembly may also provide for removal of the
disposable reaction container from the carriage. Similarly, the at
least one implement providing for fixably attaching the mobile
carriage assembly to the holder may also provide for removal of the
mobile carriage assembly from the holder. The mobile carriage
assembly and diposable reaction container may be of any suitable
size, as long as the components are compatible with one
another.
[0031] FIG. 1 illustrates an exemplary mobile carriage assembly
assembly. As briefly described above, the mobile carriage assembly
assembly may comprise a mobility implement, such as wheels (1) or
tracks. The mobile carriage assembly may also comprise a set of
primary and secondary mobility implements (1a, 1b). The primary
mobility implements (1a) may be used, for example, to move (e.g.,
roll) the mobile carriage assembly. The secondary mobility
implements (1b) may be used to insert/attach and/or remove the
mobile carriage assembly into or from, respectively, the holder
(e.g., 8 in FIG. 3). The mobile carriage assembly may also include
a platform (3) and one or more additional implements such as an
agitator (2). As mentioned above, the shaft/impellar assembly may
be affixed to a motor on the mobile carriage assembly. The motor
may also be found elsewhere (e.g., not affixed to the carriage) as
long as it is capable of powering the shaft/impellar assembly such
that the reaction components may be mixed.
[0032] As shown in FIG. 2, the reaction container (4) in which the
reaction is carried out may be attached to the platform (3). The
reaction container may be reversibly affixed to the platform so
that it may be attached before the reaction takes place and removed
after the reaction is complete. The reaction containers may be made
from a polymer film, typically as a monolayer "sandwich" of a
product contact layer (e.g., typically low-density polyethylene), a
gas barrier layer (e.g., ethyl vinyl acetate), and a strength
layer. Film sheets may be welded together to form the desired
reaction container shape; access ports for material
additions/withdrawals, instruments, agitator(s), etc., may be also
welded in place. Access ports are typically sealed as appropriate.
For sterile reactions, the completed reaction container assembly
may be sterilized before use by, for example, exposure to
gamma-irradiation. The reaction container assembly (e.g., mobile
carriage assembly with fixably, reversibly attached reaction
container) may be loaded into a holder before use (e.g., as shown
in FIG. 3 using wheel/track assembly 1b and track 8), and properly
positioned/secured. The agitator drive attachment and sterile
connections are typically then made via tube welding using the
appropriate connectors, etc. before charging the reaction container
with the reaction components (e.g., sterile media) and/or, for
biological reactions, inoculation.
[0033] FIG. 3 illustrates another view of an exemplary reactor
system in which the mobile carriage assembly (5) may be loaded onto
(or inserted into) the holder (6). As briefly mentioned above, the
mobile carriage assembly may be loaded onto (or inserted into)
holder (6) using wheel/track assembly made up of wheel 1b and track
8. The mobile carriage assembly may also be removed from the holder
using the wheel/track assembly. Wheels 1a may or may not remain in
contact with the ground once the mobile carriage assembly is loaded
onto (or inserted into) holder (6). The reaction container may be
fixably reversibly attached to the mobile carriage assembly (e.g.,
to platform (3)) prior to loading or inserting of assembly into the
holder. The reaction container may also be attached to the mobile
carriage assembly after the mobile carriage assembly has been
loaded onto (or inserted into) the holder (6). For example, the
reaction container may be loaded into the holder (6) from the open
top thereof and rested upon (e.g., reversibly fixably attached) the
mobile carriage assembly (5). Holder (6) may contain one or more
heat transfer (e.g., heat exchange) and/or anti-swirl baffles (9).
FIG. 4 illustrates a closed system in which the mobile carriage
assembly (e.g. (5) as shown in FIG. 3) is contained within holder
(6) using a door (7) or other suitable implement. These systems may
also include a cover device to restrain the top of the reaction
container (e.g., attached to the holder, such as a lid), thus
allowing operation at higher pressure to improve the driving force
for oxygen transfer, thus improving process performance.
[0034] The holder (e.g., 6 in FIG. 4) may be of any suitable
format. For instance, while a door (e.g., 7 in FIG. 4) may be used
to contain the mobile carriage assembly/reaction container, the
holder may also be configured to have a "clam shell"-type
structure. In such embodiments, the holder circumference would
typically comprise or open along a vertical seam and further
comprise one or more vertical hinges (e.g., opposite the seam). The
vertical seam may also include a locking mechanism. Thus, in one
embodiment, a reactor system may include a holder comprising one or
more vertical seams at which the holder may be opened and/or closed
and/or may further comprise one or more vertical hinges. In certain
embodiments, the one or more vertical hinges may be positioned
approximately opposite the one or more vertical seams. Such a
format may make loading and unloading of the mobile carriage
assembly simpler for the operator.
[0035] As mentioned above, the holder may comprise one or more heat
transfer (e.g., heat exchange) and/or anti-swirl baffles (e.g.,
(9)). Such baffles may serve as "speed bumps" on the holder wall
that the reaction container may wrap around without tearing yet
still provide sufficient resistance to flow. Other baffles may
include those described in, for example, U.S. Ser. No. 12/605,329,
published as US 2011-0059523 A1 (incorporated herein by reference
in its entirety). The holder (6) and/or baffle(s) may be formed of
any suitable material (e.g., carbon steel, stainless steel (e.g.,
304, 304L, 316, 316L, 317, 317L, AL6XN), aluminum, Inconel.RTM.
(e.g., Inconel 625, Chronin 625, Altemp 625, Haynes 625, Nickelvac
625 and Nicrofer 6020), Incoloy.RTM., Hastelloy (e.g., A, B, B2,
B3, B142T, Hybrid-BC1, C, C4, C22, C22HS, C2000, C263, C276, D, G,
G2, G3, G30, G50, H9M, N, R235, S, W, X), Monel.RTM., titanium,
Carpenter 20.RTM., plastic, rubber, and/or mixtures of such
materials. The baffle may be incorporated into, attached or affixed
to a reaction vessel (e.g., holder (6)) by any suitable method
provides provided that method provides a substantially seamless
attachment point (e.g., a seamless joint or boundary between
materials) to provide a surface that may be simply and efficiently
sanitized. A "substantially seamless attachment point", "seamless
joint", or "crevice-free joint" typically indicates that the
boundary between the baffle and the reaction vessel is
substantially undetectable by either visual and/or other means
(e.g., microscopy). It may also indicate that the boundary does not
retain any residue from prior reactions following a standard
cleaning procedure typically used by the skilled artisan to
"sanitize" such equipment. The system is therefore suitable for
sanitization using industry-accepted "clean-in-place" and
"sterilize-in-place" systems using any suitable cleaning agent
including but not limited to detergents, brushes, and/or steam.
Such a boundary affords itself to simple and efficient
sanitization, as defined below. Other types of baffles, materials,
and the like may also be suitable as would be understood by one of
ordinary skill in the art.
[0036] All documents cited or referred to herein are hereby
incorporated by reference in their entirety into this description.
While the description provided herein may be presented in terms of
the preferred embodiments, it is understood that variations and
modifications will occur to those skilled in the art. Therefore, it
is intended that the appended claims cover all such equivalent
variations that come within the scope of the claimed subject
matter.
* * * * *