Antagonistic anti-OX40L antibodies and methods of their use

Patent metadata

Field	Value
Publication number	US-10167339-B2
Application number	US-201515501526-A
Country	US
Kind code	B2
Filing date	Aug 3, 2015
Priority date	Aug 4, 2014
Publication date	Jan 1, 2019
Grant date	Jan 1, 2019

Abstract

Described herein are methods and compositions for treating autoimmunity and inflammatory conditions without non-specific suppression of the host immune system. In particular, the anti-OX40L antibodies described herein are unique in that they not only inhibit the differentiation of inflammatory T cells but also promote the generation and function of regulatory T cells by inducing IL-10 and inhibiting TNF-α and by reducing aberrant Th2 cell responses. Furthermore, the methods and compositions described herein eliminate or reduce aberrant T follicular helper cell—(Tfh) responses that may contribute to the pathogenicity of autoimmune disease.

First claim

What is claimed is:

1. A method for treating an autoimmune disease, inflammation, and/or inflammation associated with an autoimmune disease, wherein the disease or inflammation is due, at least in part, to pathogenic Tfh cell responses, in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an OX40L inhibitor wherein the OX40L inhibitor comprises an OX40L antibody or OX40L antigen-binding fragment comprising one of:
a) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14;
b) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 26, SEQ ID NO: 27, and SEQ ID NO: 28; or
c) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42.

2. The method of claim 1 , wherein the disease or inflammation is allergic disease asthma, atopic dermatitis, experimental autoimmune encephalomyelitis, inflammatory bowel disease, contact hypersensitivity, asthmatic airway hyperreaction, autoimmune diabetes, atherosclerosis, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, ulcerative colitis, graft versus host disease, graft rejection, or polymyositis.

3. The method of claim 1 , wherein the subject is a human.

4. The method of claim 1 , wherein the anti-OX40L antibody is neutralizing.

5. The method of claim 1 , wherein the antibody is a human antibody, humanized antibody, recombinant antibody, chimeric antibody, an antibody derivative, a veneered antibody, a diabody, a monoclonal antibody, or a polyclonal antibody.

6. The method of claim 5 , wherein the antibody is a humanized antibody.

7. The method of claim 1 , wherein the antibody or antigen binding fragment thereof comprises a modification.

8. The method of claim 1 , wherein the OX40L inhibitor comprises an antibody selected from the group consisting of 5C6, 19A3, and 44F3, or a humanized or chimeric form thereof.

9. A method for treating systemic lupus erythematosus comprising administering to the subject a therapeutically effective amount of an OX40L inhibitor wherein the OX40L inhibitor comprises an OX40L antibody or OX40L antigen-binding fragment comprising one of:
a) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14;
b) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 26, SEQ ID NO: 27, and SEQ ID NO: 28; or
c) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42.

10. The method of claim 9 , wherein the subject is a human.

11. The method of claim 9 , wherein the OX40L inhibitor comprises an antibody selected from the group consisting of 5C6, 19A3, and 44F3, or a humanized or chimeric form thereof.

12. A method for preventing, treating, or reducing the symptoms of graft versus host disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an OX40L inhibitor wherein the OX40L inhibitor comprises an OX40L antibody or OX40L antigen-binding fragment comprising one of:
a) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14;
b) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 26, SEQ ID NO: 27, and SEQ ID NO: 28; or
c) a heavy chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 33, SEQ ID NO: 34, and SEQ ID NO: 35 and a light chain variable domain comprising the complementarity determining region (CDR) amino acid sequences of SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42.

13. The method of claim 12 , wherein the subject is one that will receive or has received transplanted tissues.

14. The method of claim 12 , wherein the OX40L inhibitor comprises an antibody selected from the group consisting of 5C6, 19A3, and 44F3, or a humanized or chimeric form thereof.

15. The method of claim 12 , wherein the subject is a human.

16. The method of claim 12 , wherein the method is for treating or reducing the symptoms of graft versus host disease.

Assignees

• Baylor Res Institute

Inventors

• Liu Yong-Jun
• Zurawski Sandra
• Oh Sangkon
• Hanabuchi Shino
• Fujita Haruyuki
• Ueno Hideki
• Blanco Patrick
• Joo Hyemee

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/02

  Immunomodulators · CPC title