U.S. patent application number 15/407139 was filed with the patent office on 2017-08-10 for intradermal administration of immunoglobulin g preparation.
The applicant listed for this patent is GRIFOLS WORLDWIDE OPERATIONS LIMITED. Invention is credited to VIKRAM ARORA, KRISTINE BERGSTRAND, RALPH CHRISTIAN CRUMRINE, HONGBIN LI, TODD W. WILLIS.
Application Number | 20170226191 15/407139 |
Document ID | / |
Family ID | 57944251 |
Filed Date | 2017-08-10 |
United States Patent
Application |
20170226191 |
Kind Code |
A1 |
ARORA; VIKRAM ; et
al. |
August 10, 2017 |
INTRADERMAL ADMINISTRATION OF IMMUNOGLOBULIN G PREPARATION
Abstract
A method for administration of an IgG preparation by an
intradermal (ID) route to a subject includes loading with a volume
of the IgG preparation an ID delivery device including needles,
applying the device to a skin delivery site, using the device to
allow dermal penetration of the needles, delivering the volume of
the IgG preparation at the skin delivery site, and removing the
injection delivery device. The method can be used in the treatment
of a disease, such as an immunodeficiency.
Inventors: |
ARORA; VIKRAM; (RALEIGH,
NC) ; CRUMRINE; RALPH CHRISTIAN; (DURHAM, NC)
; BERGSTRAND; KRISTINE; (CHAPEL HILL, NC) ; LI;
HONGBIN; (MORRISVILLE, NC) ; WILLIS; TODD W.;
(CARY, NC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
GRIFOLS WORLDWIDE OPERATIONS LIMITED |
Dublin |
|
IE |
|
|
Family ID: |
57944251 |
Appl. No.: |
15/407139 |
Filed: |
January 16, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62292075 |
Feb 5, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 7/04 20180101; A61P
31/18 20180101; A61P 37/04 20180101; C07K 16/00 20130101; A61K
39/00 20130101; A61K 9/0021 20130101; A61K 2039/54 20130101; A61P
37/02 20180101; A61P 35/02 20180101; A61P 37/00 20180101; A61K
2039/505 20130101; A61M 37/00 20130101 |
International
Class: |
C07K 16/00 20060101
C07K016/00; A61M 37/00 20060101 A61M037/00 |
Claims
1. A method for administration of an IgG preparation by an
intradermal (ID) route to a subject in need thereof, the method
comprising: a) loading with a volume of the IgG preparation an ID
delivery device comprising needles; b) applying the device to a
skin delivery site; c) using the device to allow dermal penetration
of the needles; d) delivering the volume of the IgG preparation at
the skin delivery site; and e) removing the delivery device.
2. The method according to claim 1, wherein the IgG preparation has
an IgG concentration of about 15% to about 30% (w/v).
3. The method according to claim 1, wherein the IgG preparation has
an IgG concentration of about 30% (w/v) or higher.
4. The method according to claim 1, wherein a pH of the IgG
preparation is about 4.5 to about 8.0.
5. The method according to claim 4, wherein the pH of the IgG
preparation is about 6.5.
6. The method according to claim 1, wherein the volume of the IgG
preparation is up to about 10 mL per skin delivery site.
7. The method according to claim 6, wherein the volume of the IgG
preparation is between about 2 mL and about 8 mL per skin delivery
site.
8. The method according to claim 6, wherein the volume of the IgG
preparation is between about 4 mL and about 6 mL per skin delivery
site.
9. The method according to claim 1, wherein the IgG preparation
comprises one or more additional plasma proteins.
10. The method according to claim 1, wherein the subject is a
pediatric patient.
11. The method according to claim 1, wherein the subject is a
non-pediatric patient.
12. The method according to claim 1, wherein the subject is in need
of treatment for a disease.
13. The method according to claim 12, wherein the disease is an
immunodeficiency.
14. The method according to claim 13, wherein the immunodeficiency
is one of a primary immunodeficiency, a secondary immunodeficiency
or an acquired immunodeficiency.
15. The method according to claim 1, wherein the IgG preparation
comprises an entire IgG molecule, a therapeutically effective
fragment of IgG or a combination thereof.
Description
BACKGROUND
[0001] Field
[0002] The present disclosure is related to a method for
administration of IgG preparations by the intradermal (ID) route to
a patient in need thereof and a composition for administration of
IgG preparations by the ID route to a patient.
[0003] Description of the Related Art
[0004] Immunoglobulin G (IgG) is the most abundant immunoglobulin
isotype in human serum, comprising approximately 80% of all
immunoglobulins. IgG preparations are indicated for the treatment
of various diseases such as primary immunodeficiency, in particular
congenital agammaglobulinaemia and hypogammaglobulinaemia,
idiopathic thrombocytopenic purpura, as an adjuvant in the
treatment of Kawasaki's Disease and in transplant of bone marrow,
hypogammaglobulinaemia associated with chronic lymphocyte leukaemia
as part of HIV infection treatment in pediatric patients, among
others.
SUMMARY
[0005] In some embodiments, a method for administration of an IgG
preparation by an intradermal (ID) route to a subject in need
thereof is provided, the method comprising loading with a volume of
the IgG preparation an ID delivery device comprising needles,
applying the device to a skin delivery site, using the device to
allow dermal penetration of the needles, delivering the volume of
the IgG preparation at the skin delivery site, and removing the
delivery device.
[0006] In some embodiments of the method, the IgG preparation has
an IgG concentration of about 15% to about 30% (w/v). In some
embodiments of the method, the IgG preparation has an IgG
concentration of about 30% (w/v) or higher.
[0007] In some embodiments of the method, a pH of the IgG
preparation is about 4.5 to about 8.0. In some embodiments of the
method, the pH of the IgG preparation is about 6.5.
[0008] In some embodiments of the method, the volume of the IgG
preparation is up to about 10 mL per skin delivery site. In some
embodiments of the method, the volume of the IgG preparation is
between about 2 mL and about 8 mL per skin delivery site. In some
embodiments of the method, the volume of the IgG preparation is
between about 4 mL and about 6 mL per skin delivery site.
[0009] In some embodiments of the method, the IgG preparation
comprises one or more additional plasma proteins.
[0010] In some embodiments of the method, the subject is a
pediatric patient. In some embodiments of the method, the subject
is a non-pediatric patient.
[0011] In some embodiments, a composition comprising an IgG
preparation for treatment of a disease in a subject in need thereof
is provided.
[0012] In some embodiments of the composition, a concentration of
IgG in the IgG preparation is about 15% to about 30% (w/v). In some
embodiments of the composition, the concentration of IgG in the IgG
preparation is about 30% (w/v) or higher.
[0013] In some embodiments, the composition has a pH of about 4.5
and about 8.0. In some embodiments of the composition, the pH is
about 6.5.
[0014] In some embodiments of the composition, the subject is a
pediatric patient. In some embodiments of the composition, the
subject is a non-pediatric patient.
[0015] In some embodiments of the composition, the disease is an
immunodeficiency. In some embodiments of the composition, the
immunodeficiency is one of a primary immunodeficiency, a secondary
immunodeficiency or an acquired immunodeficiency.
[0016] In some embodiments of the composition, the IgG preparation
comprises an entire IgG molecule, a therapeutically effective
fragment of IgG or a combination thereof.
[0017] In some embodiments of the composition, the IgG preparation
comprises one or more additional plasma proteins.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The present disclosure is described below in reference to
the following figures.
[0019] FIG. 1 shows a line graph of plasma human IgG
pharmacokinetics at 0-24 h in young farm pigs that were
administered an IgG preparation (20 mg/kg) by the IV (n=4), SC
(n=4) and ID (n=3) routes.
[0020] FIG. 2 shows a line graph of plasma human IgG
pharmacokinetics at 0-240 h in young farm pigs that were
administered an IgG preparation (20 mg/kg) by the IV (n=4), SC
(n=4) and ID (n=3) routes
DETAILED DESCRIPTION
[0021] At present there is high demand for immunoglobulin G (IgG)
which is polyvalent with a wide spectrum of human antibodies and
has total functionality (neutralizing capacity, opsonization,
half-life conserved), with intact molecules (integrity of the
crystallizable Fc fragment) and a normal distribution of IgG
subclasses identical or equivalent to natural plasma.
[0022] The usual routes for the therapeutic administration of IgG
preparations include intravenous (IV), subcutaneous (SC) and
intramuscular (IM). In addition, IgG may be administered by other
routes such as the oral, nasal (inhaled) or topical routes. IV
administration has become the standard approach for IgG
supplementation in many countries, including the United States.
[0023] However, although IV administration offers the most useful
therapeutic indications, for example, for the treatment of primary
immunodeficiencies or for variable common immunodeficiency (deficit
of IgG and IgA subclasses), secondary or acquired
immunodeficiencies (for example infection by viruses such as
cytomegalovirus, herpes zoster, human immunodeficiency) and
diseases of an autoimmune origin (thrombocytopenic purpura,
Kawasaki's Syndrome, for example), delivery of plasma-derived
protein therapies such as IgG (Immune globulin G) to patients by IV
administration route can be associated with infusion-related
adverse effects such as flushing, fever, chills and diarrhea. IV
infusions also require trained and qualified personnel to
administer.
[0024] The current primary alternative to IV administration route
for patients for IgG is the subcutaneous (SC) route. However, the
SC route has been associated with slow progression to peak plasma
concentration (T.sub.max), low plasma area-under-curve (AUC), as
well as pain and discomfort.
[0025] The intradermal (ID) route, also known as transdermal
delivery or percutaneous permeation, is a non-invasive delivery
route which is advantageous for the administration of many drugs
and/or biologics. ID delivery also overcomes many of the challenges
associated with subcutaneous injection by greatly reducing patient
discomfort, needle anxiety, risk of accidental needle stick injury
to the personnel administering the injection and issues surrounding
sharps disposal. In addition, ID systems allow for
self-administration, provide sustained release of drugs and/or
biologics for periods of time up to one week, and improve patient
compliance. Furthermore, ID delivery systems are generally
inexpensive.
[0026] Despite these many advantages, the ID delivery of drugs is
confined to classes of molecules compatible with absorption through
the skin. Delivery of therapeutic proteins is not typically viable
with traditional ID delivery, as the skin provides an effective
protective barrier to these molecules even in the presence of
absorption-enhancing excipients. For example, it has been difficult
to exploit the ID route to deliver macromolecules.
[0027] In addition, although much progress has been made in the
development of systems for ID delivery, most commercially available
devices that provide ID delivery of liquid formulations remain
confined to relatively small volumes, typically less than 200
.mu.L. This makes the intradermal systems not to be considered as a
viable alternative for IgG therapy in which grams of proteins have
to be administered daily.
[0028] However, Burton et al. (Burton S. A. et al., Pharmaceutical
Research, Vol. 28, Issue 1, pp. 31-40, (2011)) disclosed
intradermal delivery into swine of up to 1.5 mL of a variety of
formulations including a polyclonal antibody at a concentration of
57 mg/mL during 5-20 minutes using a microneedle delivery device.
The amount of polyclonal antibody delivered with this system
(approximately 85 mg) is still very low to be considered as an
option for IgG therapy in which, for example, a patient with
myositis is typically prescribed with 0.4 to 40 gm/kg over five
days, which can be repeated every 4-6 weeks.
[0029] The present disclosure provides a method for ID
administration of plasma proteins in general and IgG in particular.
The method of the present disclosure overcomes the above-mentioned
problems and limitations.
Method
[0030] The ID route can provide a novel method for allowing
self-administration of IgG. Thus, in some embodiments, the present
disclosure provides a method for administration of IgG preparations
by the ID route. In some embodiments, the method provides for
self-administration of IgG preparations by the ID route. In some
embodiments, the method provides a superior plasma pharmacokinetic
profile of IgG as compared to the SC route. In some embodiments,
the method provides a superior plasma pharmacokinetic profile of
IgG with a faster T.sub.max as compared to the SC route.
[0031] In some embodiments, the method provides improved steady
state IgG plasma levels due to more frequent dosing regimen, such
as a convenient daily injection of IgG. In some embodiments, the
method minimizes infusion-related adverse events, such as pain and
discomfort related to infusion. In some embodiments, the method
improves patient ease of administration and compliance.
[0032] In some embodiments, the method for administration of an IgG
preparation by intradermal route comprises: [0033] a) loading with
a volume of the IgG preparation an ID delivery device comprising
needles; [0034] b) applying the device to a skin delivery site;
[0035] c) using the device to allow dermal penetration of the
needles; [0036] d) delivering the volume of the IgG preparation at
the skin delivery site; and [0037] e) removing the delivery
device.
[0038] In some embodiments, an ID delivery device comprising
needles suitable for the method of administration of the present
disclosure is provided.
[0039] In some embodiments, the skin delivery site is proximal to
where treatment is desired. In some embodiments, the skin delivery
site is distal to where treatment is desired. In some embodiments,
the skin delivery site is where it is convenient to administer a
drug. In some embodiments, the skin delivery site is where it is
convenient to administer a drug and proximal to where treatment is
desired. In some embodiments, the skin delivery site is where it is
convenient to administer a drug and distal to where treatment is
desired. In some embodiments, the skin delivery site is convenient
for self-administration. In some embodiments, the skin delivery
site is convenient for drug administration for the person
administering a drug.
[0040] In some embodiments, the method allows for the
administration of a volume of up to about 10 mL per site. In some
embodiments, the volume is between about 2 mL and about 8 mL per
site. In some embodiments, the volume is between about 4 mL and
about 6 mL per site. In some embodiments, the volume is about 0.25,
0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 mL
per site.
[0041] In some embodiments, the volume is dependent on the
injection solution characteristics. In some embodiments, the volume
is dependent on the viscosity of the IgG preparation. In some
embodiments, the volume is dependent on the IgG concentration in
the IgG preparation. In some embodiments, the volume is dependent
on the limitation of the selected ID injection device.
[0042] The duration of therapy by the method can vary, without
limitation, on the nature of a disease, age of a subject, frequency
of administration, dose of IgG preparation, patient compliance,
quality and effectiveness of the IgG preparation.
[0043] In some embodiments, the duration and frequency of
administration depend on, without limitation, the amount of IgG
administered, how rapidly the IgG preparation is administered and
the pharmacokinetics and pharmacodynamics of the IgG preparation.
For example, in some embodiments, the duration of treatment can
range from about 1 day to about 28 days. In some embodiments, the
duration of treatment can be for about 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,
27 or 28 days. In some embodiments, the duration of treatment can
be for about 1 week to about 52 weeks. In some embodiments, the
duration of treatment can be for about 5, 6, 7, 8, 9, 10, 11, 12,
13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29
or 30 weeks. In some embodiments, the duration of treatment is
indefinite, for example, the lifetime of a patient. In some
embodiments, the frequency of administration is daily. In some
embodiments, the frequency of administration is once, twice, thrice
or four times daily. In some embodiments, the frequency of
administration is daily and the duration of treatment is
indefinite. In some embodiments, the frequency of administration is
once, twice, thrice or four times daily and the duration of
treatment is indefinite.
[0044] In some embodiments of the present method, a daily
administration regimen would result in more stable plasma
concentrations of IgG as compared to IV infusion or SC
administration every 3-4 weeks.
[0045] In some embodiments, the method comprises using the IgG
preparation for the treatment of a disease. In some embodiments,
the disease comprises primary immunodeficiency. In some
embodiments, the primary immunodeficiency comprises congenital
agammaglobulinaemia and hypogammaglobulinaemia and idiopathic
thrombocytopenic purpura. In some embodiments, the primary
immunodeficiency is a pediatric primary immunodeficiency. In some
embodiments, the pediatric primary immunodeficiency is
hypogammaglobulinaemia associated with chronic lymphocyte
leukaemia. In some embodiments, the pediatric primary
immunodeficiency is hypogammaglobulinaemia associated with chronic
lymphocyte leukaemia as part of HIV infection treatment in
pediatric patients.
[0046] In some embodiments, the immunodeficiency is a variable
common immunodeficiency. In some embodiments, the variable common
immunodeficiency is deficiency of the IgG subclass. In some
embodiments, the immunodeficiency is a secondary or acquired
immunodeficiency. In some embodiments, the secondary or acquired
immunodeficiency is due to infection, for example, by viruses such
as cytomegalovirus, herpes zoster virus, human immunodeficiency
virus. In some embodiments, the secondary or acquired
immunodeficiency is due to a disease of autoimmune origin, for
example, thrombocytopenic purpura, Kawasaki's Syndrome. In some
embodiments, the IgG preparation can be used as an adjuvant in the
treatment of Kawasaki's disease and in bone marrow transplant.
[0047] In some embodiments, the method comprises treatment of
immunodeficiency in a patient. In some embodiments, the
immunodeficiency is primary immunodeficiency. In some embodiments,
the immunodeficiency is primary immunodeficiency in a pediatric
patient. In some embodiments of the method for treating primary
immunodeficiency, the concentration of IgG is about 15% to about
30% (w/v). In some embodiments of the method for treating primary
immunodeficiency, the concentration of IgG is about 15, 16, 17, 18,
19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30% (w/v). In some
embodiments of the method for treating primary immunodeficiency,
the concentration of IgG is about 30% (w/v) or higher. In some
embodiments of the method, the IgG preparation has a pH of about
4.5 to about 8.0. In some embodiments of the method, the IgG
preparation has a pH of about 6.5. In some embodiments of the
method, the IgG preparation has a pH of about 4.5, 4.75, 5.0, 5.25,
5.5, 5.75, 6.0, 6.25, 6.5, 6.75, 7.0, 7.25, 7.5, 7.75 or 8.0.
[0048] In some embodiments, the age of the subject is from about
10, 15 or 18 years to about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65
or 70 years. In some embodiments, the age of the subject is lower
than about 10 years. In some embodiments, the age of the subject is
higher than about 70 years. In some embodiments, the method enables
treatment of pediatric patients. In some embodiments, the age of
the pediatric patient can range from about 1 day to about 18 years.
In some embodiments, the sex of the subject is a male. In some
embodiments, the sex of the subject is a female.
[0049] In some embodiments, the method can be practiced in a
hospital, a nursing home, an old age home or a pediatric care
facility. In some embodiments, the method can be practiced at home.
In some embodiments, the method comprises self-administration,
administration by a health care worker or administration by a
family member.
[0050] In some embodiments, the present disclosure provides a
method for the delivery of a therapeutic plasma protein to a
patient in need thereof. In some embodiments, the therapeutic
plasma protein is an entire IgG. In some embodiments, the
therapeutic plasma protein is a therapeutic fragment of an IgG. In
some embodiments, the present disclosure provides a method for
self-administration of a therapeutic plasma protein. For example,
in some embodiments, a patient with a primary immunodeficiency
could self-administer a therapeutic plasma protein such as IgG at
home rather than going to a clinic for IV administration of the
therapeutic plasma protein. The present method provides an
administration route that is convenient and less painful as
compared to other routes of administration and therefore could lead
to greater patient compliance.
Composition
[0051] In some embodiments, the composition is an IgG preparation.
In some embodiments, the composition is an IgG solution. In some
embodiments, the concentration of IgG can be between about 15% and
about 30% (w/v). In some embodiments, the concentration is about 7%
to about 14%. In some embodiments, the concentration is about 23%
to about 30%. In some embodiments, the concentration is about 5, 6,
7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29 or 30% (w/v). In some embodiments, the
concentration is about 30% or higher.
[0052] In some embodiments, the composition comprises the entire
IgG molecule. In some embodiments, the composition comprises IgG
fragments that are therapeutically effective. In some embodiments,
the composition can comprise additional antibody types such as IgM,
IgA or a combination thereof.
[0053] In some embodiments, the composition comprises IgG for the
treatment of immunodeficiency in a patient in need thereof. In some
embodiments, the composition for treating immunodeficiency has an
IgG concentration of about 15% to about 30% (w/v). In some
embodiments, the composition for treating immunodeficiency has an
IgG concentration of about 30% (w/v) or higher. In some
embodiments, the composition for treating immunodeficiency has a pH
of about 4.5 to about 8.0. In some embodiments, the composition for
treating immunodeficiency has a pH of about 6.5. In some
embodiments, the immunodeficiency is primary immunodeficiency. In
some embodiments, the immunodeficiency is primary immunodeficiency
in a pediatric patient.
[0054] In some embodiments, the pH of the IgG solution can be
between about 4.5 and about 8.0. In some embodiments, the pH is
about 4.5, 4.75, 5.0, 5.25, 5.5, 5.75, 6.0, 6.25, 6.5, 6.75, 7.0,
7.25 7.5, 7.75 or 8.0. In some embodiments, the pH is about 6.5.
The pH of the IgG preparation does not cause scabbing of the skin
at administration site and is well tolerated.
[0055] In some embodiments, the composition is delivered at a skin
delivery site that is proximal to where treatment is desired. In
some embodiments, the composition is delivered at a skin delivery
site that is distal to where treatment is desired. In some
embodiments, the skin delivery site is where it is convenient to
administer a drug. In some embodiments, the skin delivery site is
where it is convenient to administer a drug and proximal to where
treatment is desired. In some embodiments, the skin delivery site
is where it is convenient to administer a drug and distal to where
treatment is desired. In some embodiments, the skin delivery site
is convenient for self-administration. In some embodiments, the
skin delivery site is convenient for drug administration for the
person administering a drug.
[0056] In some embodiments, the composition is administered at a
volume of up to about 10 mL per site. In some embodiments, the
volume is between about 2 mL and about 8 mL per site. In some
embodiments, the volume is between about 4 mL and about 6 mL per
site. In some embodiments, the volume is about 0.25, 0.5, 0.75, 1,
2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 mL per site.
[0057] In some embodiments, the volume is dependent on the
injection solution characteristics. In some embodiments, the volume
is dependent on the viscosity of the IgG preparation. In some
embodiments, the volume is dependent on the IgG concentration in
the IgG preparation. In some embodiments, the volume is dependent
on the limitation of the selected ID injection device.
[0058] In some embodiments, the duration and frequency of
administration of the composition depend on, without limitation,
the amount of IgG administered, how rapidly the IgG preparation is
administered and the pharmacokinetics and pharmacodynamics of the
IgG preparation. For example, in some embodiments, the duration of
treatment can range from about 1 day to about 28 days. In some
embodiments, the duration of treatment can be for about 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,
23, 24, 25, 26, 27 or 28 days. In some embodiments, the duration of
treatment can be for about 1 week to about 52 weeks. In some
embodiments, the duration of treatment can be for about 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,
26, 27, 28, 29 or 30 weeks. In some embodiments, the duration of
treatment is indefinite, for example, the lifetime of a patient. In
some embodiments, the frequency of administration is daily. In some
embodiments, the frequency of administration is once, twice, thrice
or four times daily. In some embodiments, the frequency of
administration is daily and the duration of treatment is
indefinite. In some embodiments, the frequency of administration is
once, twice, thrice or four times daily and the duration of
treatment is indefinite.
[0059] In some embodiments, the composition comprises an IgG
preparation for the treatment of a disease. In some embodiments,
the disease comprises primary immunodeficiency. In some
embodiments, the primary immunodeficiency comprises congenital
agammaglobulinaemia and hypogammaglobulinaemia and idiopathic
thrombocytopenic purpura. In some embodiments, the primary
immunodeficiency is a pediatric primary immunodeficiency. In some
embodiments, the pediatric primary immunodeficiency is
hypogammaglobulinaemia associated with chronic lymphocyte
leukaemia. In some embodiments, the pediatric primary
immunodeficiency is hypogammaglobulinaemia associated with chronic
lymphocyte leukaemia as part of HIV infection treatment in
pediatric patients.
[0060] In some embodiments, the immunodeficiency is a variable
common immunodeficiency. In some embodiments, the variable common
immunodeficiency is deficiency of the IgG subclass. In some
embodiments, the immunodeficiency is a secondary or acquired
immunodeficiency. In some embodiments, the secondary or acquired
immunodeficiency is due to infection, for example, by viruses such
as cytomegalovirus, herpes zoster virus, human immunodeficiency
virus. In some embodiments, the secondary or acquired
immunodeficiency is due to a disease of autoimmune origin, for
example, thrombocytopenic purpura, Kawasaki's Syndrome. In some
embodiments, the IgG preparation can be used as an adjuvant in the
treatment of Kawasaki's disease and in bone marrow transplant.
[0061] In some embodiments, the composition comprises treatment of
immunodeficiency in a patient. In some embodiments, the
immunodeficiency is primary immunodeficiency. In some embodiments,
the immunodeficiency is primary immunodeficiency in a pediatric
patient. In some embodiments, the composition is for treating
primary immunodeficiency, the concentration of IgG is about 15% to
about 22% (w/v). In some embodiments, the composition is for
treating primary immunodeficiency, the concentration of IgG is
about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or
30% (w/v). In some embodiments of the composition for treating
primary immunodeficiency, the concentration of IgG is about 30%
(w/v) or higher. In some embodiments of the composition, the IgG
preparation has a pH of about 4.5 to about 8.0. In some embodiments
of the composition, the IgG preparation has a pH of about 6.5. In
some embodiments of the composition, the IgG preparation has a pH
of about 4.5, 4.75, 5.0, 5.25, 5.5, 5.75, 6.0, 6.25, 6.5, 6.75,
7.0, 7.25, 7.5, 7.75 or 8.0.
[0062] In some embodiments, the age of the subject is from about 18
years to about 70 years. The age of the subject may be 10, 15, 20,
25, 30, 35, 40, 45, 50, 55, 60, 65 or 70 years. In some
embodiments, the age of the subject is lower than about 18 years.
In some embodiments, the age of the subject is higher than about 70
years. In some embodiments, the composition enables treatment of
pediatric patients. In some embodiments, the age of the pediatric
patient can range from about 1 day to about 18 years. In some
embodiments, the sex of the subject is a male. In some embodiments,
the sex of the subject is a female.
[0063] In some embodiments, the composition can be administered in
a hospital, a nursing home, an old age home or a pediatric care
facility. In some embodiments, the composition can be administered
at home. In some embodiments, the composition can be
self-administered, administered by a health care worker or
administered by a family member.
EXAMPLES
Example 1
Administration of an IgG Preparation to Pigs Via IV, SC and ID
[0064] Young farm pigs (20-25 kg) were administered with IgG (20
mg/kg) by the IV (n=4), SC (n=4) and ID (n=3) routes. Venous blood
samples were obtained at 2, 30 and 60 min; 3 and 6 hours and then
daily for 10 days after IgG administration for measurement of
human-specific IgG by immunoassay.
[0065] As shown in FIG. 1, the ID route had faster uptake of IgG
into the plasma compartment as compared to the SC route. The plasma
concentration of IgG approached C.sub.max within 1 hour after
administration by the ID route, whereas C.sub.max for the SC route
was not achieved for 24 hours. FIG. 1 and FIG. 2 show the time
course of plasma IgG after administration by IV, ID and SC routes.
The same plasma pharmacokinetic data are shown 0-24 hours (FIG. 1)
as well as on a compressed X-axis over 10 days (FIG. 2). Clearly,
24 hours onwards in this experimental model, the plasma levels of
IgG are similar irrespective of the route of administration. Thus,
the elimination half-life (T.sup.1/2) for all three routes is very
similar.
Example 2
Influence of IgG Preparation pH on the Delivery Site
[0066] To evaluate the influence of the IgG preparation pH on the
delivery site, 2 mL of Gamunex.RTM. and IGSC 20% IgG formulations
(Grifols Therapeuctics Inc., USA) both at pH 4.0, and IGIM-S/D
(Grifols Therapeuctics Inc., USA) at pH 6.5, were administered to
young farm pigs.
[0067] Three days following 2 mL administration of IgG, the low pH
administration causes scabbing of the skin at administration site
whereas neutral pH IgG appears to have good tolerability.
Example 3
Pediatric Treatment
[0068] The method according to the present disclosure can be used
for treating a pediatric patient with a primary immunodeficiency.
The weight of the patient is about 25 kg. The typical dose range
for such a patient is about 300 to about 800 mg/kg body weight over
about 4 weeks. This does can be achieved using the present method
with one ID administration of about 2 mL or about 4 mL of a
concentrated IgG preparation. The concentrated IgG preparation has
a concentration of IgG of about 16.5% or about 20% (w/v).
* * * * *