CN-122028914-A - Combination therapy for autoimmune disorders

Abstract

Methods of treating rheumatoid arthritis are provided, comprising administering to a subject in need of such treatment a therapeutically effective amount of a degradation agent of immunoglobulin G and an anti-arthritic agent. Also provided are pharmaceutical compositions comprising the degradation agents of immunoglobulin G and an anti-arthritic agent.

Inventors

• V. Colizzi

Assignees

• 拜奥海芬治疗学有限公司

Dates

Publication Date

20260512

Application Date

20241015

Priority Date

20231013

Claims (20)

1. 1. A composition comprising a degradation agent for immunoglobulin G and an anti-arthritic agent, wherein the degradation agent for immunoglobulin G has the structure: Wherein [ CPBM ] is an IgG binding moiety that binds to IgG; [ CRBM ] is a cellular receptor binding moiety that is a binding moiety that binds to hepatocytes or other cells through asialoglycoprotein receptors or other receptors on the surface of hepatocytes and other degradation cells; Each [ CON ] is an optional LINKER chemical moiety, which when present is directly linked to [ CPBM ] or to [ CRBM ] or links [ LINKER ] to [ CPBM ] or to [ CRBM ], and [ LINKER ] is a chemical moiety covalently attached to one or more [ CRBM ] and/or [ CPBM ] groups, or Pharmaceutically acceptable salts, stereoisomers, solvates or polymorphs thereof.
2. 2. The composition of claim 1, wherein the degradation agent for immunoglobulin G has the structure: wherein [ CPBM ] is an IgG binding moiety that binds to the FcIII region of IgG; [ CRBM ] is a cellular receptor binding moiety that is a binding moiety that binds to hepatocytes or other cells through asialoglycoprotein receptors or other receptors on the surface of hepatocytes and other degradation cells; Each [ CON ] is an optional LINKER chemical moiety, which when present is directly linked to [ CPBM ] or to [ CRBM ] or links [ LINKER ] to [ CPBM ] or to [ CRBM ], and [ LINKER ] is a chemical moiety covalently attached to one or more [ CRBM ] and/or [ CPBM ] groups.
3. 3. The composition of claim 1, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
4. 4. The composition of claim 1, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
5. 5. The composition of claim 1, wherein the degradation agent for immunoglobulin G has the structure: , Or a pharmaceutically acceptable salt thereof.
6. 6. The composition of claim 1, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
7. 7. The composition of claim 1, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
8. 8. The composition of claim 1, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
9. 9. The composition of claim 1, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
10. 10. A method of reducing the level of IgG in a subject by administering to the subject a degradation agent for immunoglobulin G and an anti-arthritic agent, comprising wherein the degradation agent for immunoglobulin G has the structure: Wherein [ CPBM ] is an IgG binding moiety that binds to IgG; [ CRBM ] is a cellular receptor binding moiety that is a binding moiety that binds to hepatocytes or other cells through asialoglycoprotein receptors or other receptors on the surface of hepatocytes and other degradation cells; Each [ CON ] is an optional LINKER chemical moiety, which when present is directly linked to [ CPBM ] or to [ CRBM ] or links [ LINKER ] to [ CPBM ] or to [ CRBM ], and [ LINKER ] is a chemical moiety covalently attached to one or more [ CRBM ] and/or [ CPBM ] groups, or Pharmaceutically acceptable salts, stereoisomers, solvates or polymorphs thereof.
11. 11. The method of claim 10, wherein the degradation agent for immunoglobulin G has the structure: wherein [ CPBM ] is an IgG binding moiety that binds to the FcIII region of IgG; [ CRBM ] is a cellular receptor binding moiety that is a binding moiety that binds to hepatocytes or other cells through asialoglycoprotein receptors or other receptors on the surface of hepatocytes and other degradation cells; Each [ CON ] is an optional LINKER chemical moiety, which when present is directly linked to [ CPBM ] or to [ CRBM ] or links [ LINKER ] to [ CPBM ] or to [ CRBM ], and [ LINKER ] is a chemical moiety covalently attached to one or more [ CRBM ] and/or [ CPBM ] groups.
12. 12. The method of claim 10, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
13. 13. The method of claim 10, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
14. 14. The method of claim 10, wherein the degradation agent for immunoglobulin G has the structure: , Or a pharmaceutically acceptable salt thereof.
15. 15. The method of claim 10, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
16. 16. The method of claim 10, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
17. 17. The method of claim 10, wherein the degradation agent for immunoglobulin G has the structure: Or a pharmaceutically acceptable salt thereof.
18. 18. The method of claim 10, wherein the degradation agent of immunoglobulin G is injected subcutaneously.
19. 19. The method of claim 10, wherein the anti-arthritic agent is subcutaneously injected or orally administered.
20. 20. A method of treating rheumatoid arthritis comprising administering to a subject in need of such treatment a therapeutically effective amount of a degradation agent of immunoglobulin G and an anti-arthritic agent, wherein the degradation agent of immunoglobulin G has the structure: Wherein [ CPBM ] is an IgG binding moiety that binds to IgG; [ CRBM ] is a cellular receptor binding moiety that is a binding moiety that binds to hepatocytes or other cells through asialoglycoprotein receptors or other receptors on the surface of hepatocytes and other degradation cells; Each [ CON ] is an optional LINKER chemical moiety, which when present is directly linked to [ CPBM ] or to [ CRBM ] or links [ LINKER ] to [ CPBM ] or to [ CRBM ], and [ LINKER ] is a chemical moiety covalently attached to one or more [ CRBM ] and/or [ CPBM ] groups, or Pharmaceutically acceptable salts, stereoisomers, solvates or polymorphs thereof.

Description

Combination therapy for autoimmune disorders Technical Field The present invention relates to a pharmaceutical formulation for treating rheumatoid arthritis by a combination of two or more drugs. In particular, the invention relates to the treatment of rheumatoid arthritis by a degradation agent of immunoglobulin G and another therapeutic agent. Background Rheumatoid Arthritis (RA) is a form of inflammatory polyarthritis that can lead to joint destruction, deformity, and loss of function. The disease is often characterized by swelling of the facet joints (especially the hands and feet). However, most joints within the body may ultimately be affected. In addition to joints, other manifestations of the disease can be seen, including subcutaneous nodules, ocular inflammation, decreased white blood cell count, and lung disease. Common symptoms include fatigue and joint stiffness, especially in the morning and after prolonged rest. Currently, there is no known therapy for rheumatoid arthritis. The discovery of drugs that alter the early established course of disease and the availability of new classes of drugs has greatly improved the expected disease outcome over the last few years. The goal of rheumatoid arthritis treatment is now to achieve the lowest possible level and remission (if possible) of arthritis disease activity, minimize joint damage, and enhance physical function and quality of life. While some classes of drugs are currently available in the art, there is a need for new drugs that can effectively treat or delay the progression of the disease. New therapeutic approaches that can reduce the impact of rheumatoid arthritis on more patients are urgently needed. Disclosure of Invention The present invention relates to the treatment of rheumatoid arthritis by the combination of two or more therapeutically effective agents. In one embodiment, the present invention provides a composition comprising a degradation agent for immunoglobulin G and an anti-arthritic agent, wherein the degradation agent for immunoglobulin G has the structure: Wherein [ CPBM ] is an IgG binding moiety that binds to IgG; [ CRBM ] is a cellular receptor binding moiety that is a binding moiety that binds to hepatocytes or other cells through asialoglycoprotein receptors or other receptors on the surface of hepatocytes and other degradation cells; Each [ CON ] is an optional LINKER chemical moiety, which when present is directly linked to [ CPBM ] or to [ CRBM ] or links [ LINKER ] to [ CPBM ] or to [ CRBM ], and [ LINKER ] is a chemical moiety covalently attached to one or more [ CRBM ] and/or [ CPBM ] groups, or Pharmaceutically acceptable salts, stereoisomers, solvates or polymorphs thereof. Preferably, the IgG binding moiety does not bind IgG in the FcRn region of IgG. In another embodiment, the present invention provides a composition comprising a degradation agent for immunoglobulin G and an anti-arthritic agent, wherein the degradation agent for immunoglobulin G has the structure: wherein [ CPBM ] is an IgG binding moiety that binds to the FcIII region of IgG; [ CRBM ] is a cellular receptor binding moiety that is a binding moiety that binds to hepatocytes or other cells through asialoglycoprotein receptors or other receptors on the surface of hepatocytes and other degradation cells; Each [ CON ] is an optional LINKER chemical moiety, which when present is directly linked to [ CPBM ] or to [ CRBM ] or links [ LINKER ] to [ CPBM ] or to [ CRBM ], and [ LINKER ] is a chemical moiety covalently attached to one or more [ CRBM ] and/or [ CPBM ] groups, or Pharmaceutically acceptable salts, stereoisomers, solvates or polymorphs thereof. In a particular embodiment, the invention provides a composition comprising a degradation agent for immunoglobulin G and an anti-arthritic agent, wherein the degradation agent for immunoglobulin G is FcIII-GN3. In one embodiment, the anti-arthritic agent may be a disease modifying antirheumatic drug (DMARD). In another embodiment, the anti-arthritic agent may be selected from the Markush group of disease-modifying antirheumatic drugs (DMARDs) consisting of tumor necrosis factor (TNF inhibitors), T cell costimulatory blockers, B cell depleting agents, IL-1 receptor antagonists, and immunomodulators and cytotoxic agents. In another embodiment, the invention provides a method of reducing the level of IgG in a subject by administering to the subject a degradation agent for immunoglobulin G and an anti-arthritic agent. Lowering IgG levels may be useful for conditions including IgG myeloma, liver disease, sarcoidosis, chronic infections, autoimmune disorders (including rheumatoid arthritis), malignant tumors, and parasitic diseases. In another embodiment, the degradation agent of immunoglobulin G is administered to the subject or patient t >12 hours prior to administration of the anti-arthritic agent. In several embodiments, FCIII-GN3 is administered intravenously at 50 mg, 125 mg, 250 mg, or 500 mg. FCIII