Intradermal administration of immunoglobulin G preparations

Abstract

This application relates to the intradermal administration of immunoglobulin G (IgG) products. A method for administering an IgG product to a subject in need via the intradermal (ID) route includes: loading an ID delivery device comprising a needle with a volume of IgG product; applying the device to a skin delivery site; using the device to allow the needle to penetrate the skin; delivering the volume of IgG product at the skin delivery site; and removing the injection delivery device. The composition of the IgG product is used to treat a disease in a subject in need by the above method. This disease may be immunodeficiency.

Description

[0001] This application is a divisional application of the application filed on January 11, 2017, with application number 201710018106.8 and invention title "Intradermal Application of Immunoglobulin G Products". Technical Field

[0002] This disclosure relates to methods for administering IgG products to patients in need via the intradermal (ID) route, and to compositions for administering IgG products to patients via the ID route. Background Technology

[0003] Immunoglobulin G (IgG) is the most abundant immunoglobulin isotype in human serum, constituting approximately 80% of all immunoglobulins. IgG products are required for the treatment of a variety of diseases (are indicated for), among others, such as primary immunodeficiency, particularly congenital agammaglobulinemia and hypogammaglobulinemia, idiopathic thrombocytopenic purpura, as adjuvant therapy in the treatment of Kawasaki disease and bone marrow transplantation, and hypogammaglobulinemia associated with chronic lymphocytic leukemia as part of the treatment of HIV infection in pediatric patients. Summary of the Invention

[0004] In some embodiments, a method is provided for administering an IgG product to a patient in need via an intradermal (ID) route, the method comprising: loading an ID delivery device including a needle with a volume of IgG product; applying the device to a skin delivery site; using the device to allow the needle to penetrate the skin; delivering the volume of IgG product at the skin delivery site; and removing the delivery device.

[0005] In some embodiments of the method, the IgG product has an IgG concentration of about 15% (w / v) to about 30% (w / v). In some embodiments of the method, the IgG product has an IgG concentration of about 30% (w / v) or higher.

[0006] In some embodiments of the method, the pH of the IgG product is from about 4.5 to about 8.0. In some embodiments of the method, the pH of the IgG product is about 6.5.

[0007] In some embodiments of the method, the volume of the IgG product is up to about 10 mL / skin delivery site. In some embodiments of the method, the volume of the IgG product is between about 2 mL / skin delivery site and about 8 mL / skin delivery site. In some embodiments of the method, the volume of the IgG product is between about 4 mL / skin delivery site and about 6 mL / skin delivery site.

[0008] In some embodiments of the method, the IgG product contains one or more additional plasma proteins.

[0009] In some embodiments of the method, the subjects are pediatric patients. In some embodiments of the method, the subjects are non-pediatric patients.

[0010] In some embodiments, compositions comprising IgG products are provided for treating diseases in subjects with corresponding needs.

[0011] In some embodiments of the composition, the concentration of IgG in the IgG product is from about 15% (w / v) to about 30% (w / v). In some embodiments of the composition, the concentration of IgG in the IgG product is about 30% (w / v) or higher.

[0012] 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.

[0013] 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.

[0014] In some embodiments of the composition, the disease is immunodeficiency. In some embodiments of the composition, the immunodeficiency is one of primary immunodeficiency, secondary immunodeficiency, or acquired immunodeficiency.

[0015] In some embodiments of the composition, the IgG product comprises complete IgG molecules, therapeutically effective fragments of IgG, or a combination thereof.

[0016] In some embodiments of the composition, the IgG product contains one or more additional plasma proteins. Attached Figure Description

[0017] The contents of this disclosure are described below with reference to the following figures.

[0018] Figure 1 Linear graphs of plasma human IgG pharmacokinetics at 0–24 hours in farm piglets administered IgG products (20 mg / kg) via IV (n=4), SC (n=4), and ID (n=3) routes are shown.

[0019] Figure 2 Linear graphs of plasma human IgG pharmacokinetics from 0 to 240 hours are shown in farm piglets administered IgG products (20 mg / kg) via IV (n=4), SC (n=4), and ID (n=3) routes. Detailed Implementation

[0020] Currently, there is a high demand for immunoglobulin G (IgG) that is multivalent for broad-spectrum human antibodies and has all functions (neutralizing ability, opsonization, constant half-life), complete molecules (integrity of crystallizable Fc fragments), and a normal distribution of IgG subclasses that are identical or equivalent to those in natural plasma.

[0021] Common routes of therapeutic administration for IgG products include intravenous (IV), subcutaneous (SC), and intramuscular (IM). Additionally, IgG can be administered via other routes such as oral, nasal (inhalation), or topical administration. In many countries, including the United States, IV administration has become the standard method for IgG supplementation.

[0022] However, while intravenous administration provides the most useful therapeutic indications for treating, for example, primary immunodeficiency or common variant immunodeficiency (deficiency of IgG and IgA subclasses), secondary or acquired immunodeficiency (e.g., infection by viruses such as cytomegalovirus, herpes zoster virus, and human immunodeficiency virus), and autoimmune diseases (e.g., thrombocytopenic purpura, Kawasaki syndrome), delivering plasma-derived protein therapies such as IgG (immunoglobulin G) to patients via intravenous administration may be associated with infusion-related adverse reactions such as flushing, fever, chills, and diarrhea. Intravenous infusion also requires trained and qualified personnel to administer it.

[0023] For IgG, the current primary alternative route of IV administration to patients is subcutaneous (SC). However, the SC route is associated with reaching peak plasma concentrations (Tc). max The slow progression of the disease, low plasma area under the curve (AUC), and pain and discomfort are associated with it.

[0024] The intradermal (ID) route, also known as transdermal delivery or percutaneous infiltration, is a non-invasive delivery route that is advantageous for the administration of many drugs and / or biologics. ID delivery also overcomes many challenges associated with subcutaneous injection by significantly reducing patient discomfort, needle anxiety, the risk of accidental needlestick injuries to the person administering the injection, and issues related to the handling of sharps. Furthermore, ID systems allow for self-administration, provide sustained release of drugs and / or biologics for up to a week, and improve patient compliance. Additionally, ID delivery systems are generally inexpensive.

[0025] Despite these numerous advantages, ID (invisible delivery) of drugs is limited to molecular types compatible with absorption through the skin. Delivering therapeutic proteins using conventional ID delivery methods is generally not feasible because the skin provides an effective protective barrier against these molecules, even in the presence of excipients that enhance absorption. For example, delivering large molecules via the ID pathway remains challenging.

[0026] Furthermore, despite significant progress in the development of systems for ID delivery, most commercially available devices for ID delivery of liquid formulations remain limited to relatively small volumes, typically less than 200 μL. This makes intradermal systems not considered a viable alternative to IgG therapies in which several grams of protein need to be administered daily.

[0027] However, Burton et al. (Burton SA et al., Pharmaceutical Research, Vol. 28, No. 1, pp. 31-40, (2011)) disclosed the intradermal delivery of up to 1.5 mL of various formulations containing a concentration of 57 mg / mL of polyclonal antibody to pigs over a period of 5-20 minutes using a microneedle delivery device. The amount of polyclonal antibody delivered using this system (approximately 85 mg) is still too low to be considered an option for IgG therapy, in which, for example, patients with myositis are typically prescribed a dose of 0.4 gm / kg to 40 gm / kg over 5 days, which can be repeated every 4-6 weeks.

[0028] This disclosure provides methods for administering common plasma proteins, and particularly IgG, to ID. The methods of this disclosure overcome the problems and limitations mentioned above.

[0029] method The ID pathway can provide novel methods for allowing self-administration of IgG. Therefore, in some embodiments, this disclosure provides methods for administering IgG products via the ID pathway. In some embodiments, the method provides self-administration of IgG products via the ID pathway. In some embodiments, the method provides better IgG plasma pharmacokinetic characteristics compared to the SC pathway. In some embodiments, the method achieves a faster T0 compared to the SC pathway. max It provides better IgG plasma pharmacokinetic characteristics.

[0030] In some embodiments, this method provides improved steady-state IgG plasma levels due to more frequent dosing regimens such as convenient daily IgG injections. In some embodiments, this method minimizes infusion-related adverse events such as infusion-related pain and discomfort. In some embodiments, this method improves patient administration comfort and compliance.

[0031] In some implementations, methods for administering IgG products via the intradermal route include: a) Loading an ID delivery device, including a needle, with a defined volume of IgG product; b) Apply the device to the skin delivery site; c) Use a device to allow the needle to penetrate the skin; d) Delivery of this volume of IgG product at the skin delivery site; and e) Remove the delivery device.

[0032] In some embodiments, an ID delivery device including a needle is provided for the application method applicable to this disclosure.

[0033] In some embodiments, the skin delivery site is located close to the area requiring treatment. In some embodiments, the skin delivery site is located away from the area requiring treatment. In some embodiments, the skin delivery site is a site convenient for drug administration. In some embodiments, the skin delivery site is a site convenient for drug administration and located close to the area requiring treatment. In some embodiments, the skin delivery site is a site convenient for drug administration and located away from the area requiring treatment. In some embodiments, the skin delivery site is convenient for self-administration. In some embodiments, the skin delivery site is convenient for a person administering the drug.

[0034] In some embodiments, the method allows for the administration of volumes up to about 10 mL per site. In some embodiments, the volume is between about 2 mL per site and about 8 mL per site. In some embodiments, the volume is between about 4 mL per site and about 6 mL per site. In some embodiments, the volume is about 0.25 mL, 0.5 mL, 0.75 mL, 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL per site.

[0035] In some embodiments, the volume depends on the characteristics of the injection solution. In some embodiments, the volume depends on the viscosity of the IgG product. In some embodiments, the volume depends on the IgG concentration in the IgG product. In some embodiments, the volume depends on the limitations of the selected ID injection device.

[0036] The duration of treatment using this method can vary depending on, but is not limited to, the nature of the disease, the age of the subject, the frequency of administration, the dosage of the IgG product, patient compliance, and the quality and potency of the IgG product.

[0037] In some embodiments, the duration and frequency of administration depend on, but are not limited to, the amount of IgG administered, how rapidly the IgG product is administered, and the pharmacokinetics and pharmacodynamics of the IgG product. 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 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 about 1 week to about 52 weeks. In some embodiments, the duration of treatment can be 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 implementations, the duration of treatment is indefinite, for example, the patient's lifetime. In some implementations, the frequency of administration is daily. In some implementations, the frequency of administration is once daily, twice daily, three times daily, or four times daily. In some implementations, the frequency of administration is daily, and the duration of treatment is indefinite. In some implementations, the frequency of administration is once daily, twice daily, three times daily, or four times daily, and the duration of treatment is indefinite.

[0038] In some implementations of this method, daily administration resulted in more stable IgG plasma concentrations compared to IV infusions or SC administration every 3-4 weeks.

[0039] In some embodiments, the method includes treating the disease with IgG products. In some embodiments, the disease includes primary immunodeficiency. In some embodiments, primary immunodeficiency includes congenital agammaglobulinemia and hypogammaglobulinemia, as well as idiopathic thrombocytopenic purpura. In some embodiments, the primary immunodeficiency is pediatric primary immunodeficiency. In some embodiments, pediatric primary immunodeficiency is hypogammaglobulinemia associated with chronic lymphocytic leukemia. In some embodiments, pediatric primary immunodeficiency is hypogammaglobulinemia associated with chronic lymphocytic leukemia as part of treatment for HIV infection in pediatric patients.

[0040] In some embodiments, the immunodeficiency is a common variant immunodeficiency. In some embodiments, the common variant immunodeficiency is a deficiency of an IgG subclass. In some embodiments, the immunodeficiency is a secondary or acquired immunodeficiency. In some embodiments, the secondary or acquired immunodeficiency is caused by infection with viruses such as cytomegalovirus, herpes zoster virus, or human immunodeficiency virus. In some embodiments, the secondary or acquired immunodeficiency is caused by an autoimmune disease, such as thrombocytopenic purpura or Kawasaki syndrome. In some embodiments, IgG products can be used as adjuvants in the treatment of Kawasaki disease and bone marrow transplantation.

[0041] In some embodiments, the method includes treating the patient's immunodeficiency. 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 from about 15% (w / v) to about 30% (w / v). In some embodiments of the method for treating primary immunodeficiency, the concentration of IgG is about 15% (w / v), 16% (w / v), 17% (w / v), 18% (w / v), 19% (w / v), 20% (w / v), 21% (w / v), 22% (w / v), 23% (w / v), 24% (w / v), 25% (w / v), 26% (w / v), 27% (w / v), 28% (w / v), 29% (w / v), 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 product has a pH of about 4.5 to about 8.0. In some embodiments of the method, the IgG product has a pH of about 6.5. In some embodiments of the method, the IgG product 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.

[0042] In some embodiments, the age of the subjects 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 subjects is less than about 10 years. In some embodiments, the age of the subjects is greater than about 70 years. In some embodiments, the method enables the treatment of pediatric patients. In some embodiments, the age range of pediatric patients can be from about 1 day to about 18 years. In some embodiments, the sex of the subjects is male. In some embodiments, the sex of the subjects is female.

[0043] In some implementations, the method can be administered in hospitals, nursing homes, retirement homes, or pediatric care facilities. In some implementations, the method can be administered at home. In some implementations, the method includes self-administration, administration by a healthcare worker, or administration by a family member.

[0044] In some embodiments, this disclosure provides methods for delivering therapeutic plasma proteins to patients with appropriate needs. In some embodiments, the therapeutic plasma protein is whole IgG. In some embodiments, the therapeutic plasma protein is a therapeutic fragment of IgG. In some embodiments, this disclosure provides methods for self-administering therapeutic plasma proteins. For example, in some embodiments, patients with primary immunodeficiency can self-administer therapeutic plasma proteins such as IgG at home instead of going to a clinic for IV administration. This method provides a more convenient and less painful administration route compared to other routes, and therefore enables greater patient compliance.

[0045] Composition 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% (w / v) 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% (w / v), 6% (w / v), 7% (w / v), 8% (w / v), 9% (w / v), 10% (w / v), 11% (w / v), 12% (w / v), 13% (w / v), 14% (w / v), 15% (w / v), 16% (w / v), 17% (w / v), 18% (w / v), 19% (w / v), 20% (w / v), 21% (w / v), 22% (w / v), 23% (w / v), 24% (w / v), 25% (w / v), 26% (w / v), 27% (w / v), 28% (w / v), 29% (w / v), or 30% (w / v). In some embodiments, the concentration is about 30% or higher.

[0046] In some embodiments, the composition comprises an intact IgG molecule. In some embodiments, the composition comprises a therapeutically effective IgG fragment. In some embodiments, the composition may comprise additional antibody types such as IgM, IgA, or combinations thereof.

[0047] In some embodiments, the composition comprises IgG for treating immunodeficiency in patients with corresponding needs. In some embodiments, the composition for treating immunodeficiency has an IgG concentration of about 15% (w / v) 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 pediatric patients.

[0048] 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 product does not cause crusting at the application site and is well tolerated.

[0049] In some embodiments, the composition is delivered at a skin delivery site close to the area requiring treatment. In some embodiments, the composition is delivered at a skin delivery site distant from the area requiring treatment. In some embodiments, the skin delivery site is an easy-to-apply site. In some embodiments, the skin delivery site is an easy-to-apply site and close to the area requiring treatment. In some embodiments, the skin delivery site is an easy-to-apply site and distant from the area requiring treatment. In some embodiments, the skin delivery site is easy for self-application. In some embodiments, the skin delivery site is easy for a person administering the medication.

[0050] In some embodiments, the composition is applied at a volume of up to about 10 mL per part. In some embodiments, the volume is between about 2 mL per part and about 8 mL per part. In some embodiments, the volume is between about 4 mL per part and about 6 mL per part. In some embodiments, the volume is about 0.25 mL, 0.5 mL, 0.75 mL, 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, or 15 mL per part.

[0051] In some embodiments, the volume depends on the characteristics of the injection solution. In some embodiments, the volume depends on the viscosity of the IgG product. In some embodiments, the volume depends on the IgG concentration in the IgG product. In some embodiments, the volume depends on the limitations of the selected ID injection device.

[0052] In some embodiments, the duration and frequency of administration of the composition depend on, but are not limited to, the amount of IgG administered, how rapidly the IgG product is administered, and the pharmacokinetics and pharmacodynamics of the IgG product. 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 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 about 1 week to about 52 weeks. In some embodiments, the duration of treatment can be 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 implementations, the duration of treatment is indefinite, for example, the patient's lifetime. In some implementations, the frequency of administration is daily. In some implementations, the frequency of administration is once daily, twice daily, three times daily, or four times daily. In some implementations, the frequency of administration is daily, and the duration of treatment is indefinite. In some implementations, the frequency of administration is once daily, twice daily, three times daily, or four times daily, and the duration of treatment is indefinite.

[0053] In some embodiments, the composition comprises an IgG product, said composition being used to treat a disease. In some embodiments, the disease includes primary immunodeficiency. In some embodiments, primary immunodeficiency includes congenital agammaglobulinemia and hypogammaglobulinemia, as well as idiopathic thrombocytopenic purpura. In some embodiments, the primary immunodeficiency is pediatric primary immunodeficiency. In some embodiments, pediatric primary immunodeficiency is hypogammaglobulinemia associated with chronic lymphocytic leukemia. In some embodiments, pediatric primary immunodeficiency is hypogammaglobulinemia associated with chronic lymphocytic leukemia as part of treatment for HIV infection in pediatric patients.

[0054] In some embodiments, the immunodeficiency is a common variant immunodeficiency. In some embodiments, the common variant immunodeficiency is a deficiency of an IgG subclass. In some embodiments, the immunodeficiency is a secondary or acquired immunodeficiency. In some embodiments, the secondary or acquired immunodeficiency is caused by infection with viruses such as cytomegalovirus, herpes zoster virus, or human immunodeficiency virus. In some embodiments, the secondary or acquired immunodeficiency is caused by an autoimmune disease, such as thrombocytopenic purpura or Kawasaki syndrome. In some embodiments, IgG products can be used as adjuvants in the treatment of Kawasaki disease and bone marrow transplantation.

[0055] In some embodiments, the composition includes treatment for an 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 used to treat primary immunodeficiency, and the concentration of IgG is from about 15% (w / v) to about 22% (w / v). In some embodiments, the composition is used to treat primary immunodeficiency, and the concentration of IgG is about 15% (w / v), 16% (w / v), 17% (w / v), 18% (w / v), 19% (w / v), 20% (w / v), 21% (w / v), 22% (w / v), 23% (w / v), 24% (w / v), 25% (w / v), 26% (w / v), 27% (w / v), 28% (w / v), 29% (w / v), 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 product has a pH of about 4.5 to about 8.0. In some embodiments of the composition, the IgG product has a pH of about 6.5. In some embodiments of the composition, the IgG product 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.

[0056] In some embodiments, the subject's age ranges from about 18 years to about 70 years. The subject's age can be 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 years. In some embodiments, the subject's age is less than about 18 years. In some embodiments, the subject's age is greater than about 70 years. In some embodiments, the composition enables the treatment of pediatric patients. In some embodiments, the pediatric patient's age range can be from about 1 day to about 18 years. In some embodiments, the subject's sex is male. In some embodiments, the subject's sex is female.

[0057] In some embodiments, the composition may be administered in hospitals, nursing homes, retirement homes, or pediatric care facilities. In some embodiments, the composition may be administered at home. In some embodiments, the composition may be self-administered, administered by a healthcare worker, or administered by a family member.

[0058] Example Example 1. Administration of IgG products to pigs via IV, SC, and ID. IgG (20 mg / kg) was administered to farm piglets (20–25 kg) via IV (n=4), SC (n=4), and ID (n=3) routes. Venous blood samples were obtained daily at 2, 30, and 60 minutes, 3 and 6 hours, and then for 10 days following IgG administration for the measurement of human-specific IgG by immunoassay.

[0059] like Figure 1 As shown, the ID pathway delivers IgG into plasma compartments more rapidly than the SC pathway. Following administration via the ID pathway, plasma IgG concentrations reach C0.05 within 1 hour. max For the SC route, if C is not reached within 24 hours... max . Figure 1 and Figure 2 The time course of plasma IgG is shown after administration via IV, ID, and SC routes. Within 0-24 hours ( Figure 1 ) and within 10 days on the compressed X-axis ( Figure 2 The same plasma pharmacokinetic data are shown. Clearly, in this experimental model, plasma IgG levels are similar from 24 hours onwards, regardless of the route of administration. Therefore, the clearance half-life (T½) is very similar for all three routes.

[0060] Example 2. Effect of pH on the delivery site of IgG products To evaluate the effect of pH on the delivery site of IgG products, farm piglets were administered 2 mL of Gamunex® and IGSC 20% IgG formulation (Grifols Therapeuctics Inc., USA) at pH 4.0 and IGIM-S / D (Grifols Therapeuctics Inc., USA) at pH 6.5.

[0061] Three days after administration of 2 mL of IgG, low pH application caused skin crusting at the application site, while neutral pH IgG showed good tolerability.

[0062] Example 3. Pediatric Treatment The method according to this disclosure can be used to treat pediatric patients with primary immunodeficiency. The patient's weight is approximately 25 kg. The general dose range for these patients is approximately 300 mg / kg body weight to approximately 800 mg / kg body weight over approximately 4 weeks. This dose can be achieved using this method by administering approximately 2 mL or approximately 4 mL of concentrated IgG product as a single ID. The concentrated IgG product has an IgG concentration of approximately 16.5% (w / v) or approximately 20% (w / v).

Claims

1. Use of a composition comprising an IgG product in the preparation of a medicament for treating immunodeficiency in a subject with a corresponding need, wherein when the medicament is administered to the subject, the IgG product is administered to the subject with a corresponding need via an ID route using a removable intradermal (ID) delivery device comprising a needle, and the device is applied to a skin delivery site, wherein the IgG product has an IgG concentration of 16.5% (w / v) to 30% (w / v) and wherein the pH of the IgG product is 5.0 to 7.

0.

2. The use according to claim 1, wherein the pH of the IgG product is 6.

5.

3. The use according to claim 1, wherein the volume of the IgG product is up to 10 mL per skin delivery site.

4. The use according to claim 3, wherein the volume of the IgG product is between 2 mL / skin delivery site and 8 mL / skin delivery site.

5. The use according to claim 3, wherein the volume of the IgG product is between 4 mL / skin delivery site and 6 mL / skin delivery site.

6. The use according to claim 1, wherein the IgG product comprises one or more additional plasma proteins.

7. The use according to claim 1, wherein the subject is a pediatric patient.

8. The use according to claim 1, wherein the subject is a non-pediatric patient.

9. A composition comprising an IgG preparation for treating a disease in a subject with a corresponding need via an intradermal route, wherein the concentration of IgG in the IgG preparation is from 16.5% (w / v) to 30% (w / v), and wherein the composition has a pH of 5.0 to 7.

0.

10. The composition according to claim 9, wherein the pH is 6.

5.

11. The composition of claim 9, wherein the subject is a pediatric patient.

12. The composition of claim 9, wherein the subject is a non-pediatric patient.

13. The composition of claim 9, wherein the disease is immunodeficiency.

14. The composition of claim 13, wherein the immunodeficiency is one of primary immunodeficiency, secondary immunodeficiency, or acquired immunodeficiency.

15. The composition of claim 9, wherein the IgG product comprises an intact IgG molecule, a therapeutically effective fragment of IgG, or a combination thereof.

16. The composition of claim 9, wherein the IgG product comprises one or more additional plasma proteins.

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