Antagonistic anti-OX40L antibodies and methods of their use

Patent metadata

Field	Value
Publication number	US-10570208-B2
Application number	US-201816210188-A
Country	US
Kind code	B2
Filing date	Dec 5, 2018
Priority date	Aug 4, 2014
Publication date	Feb 25, 2020
Grant date	Feb 25, 2020

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 pharmaceutical composition comprising a humanized antibody, a chimeric antibody, or an antibody fragment comprising:
i) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region of SEQ ID NO:4 and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region of SEQ ID NO:11;
ii) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region of SEQ ID NO:18 and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region of SEQ ID NO:25; or
iii) a heavy chain variable region comprising CDR1, CDR2, and CDR3 of the heavy chain variable region of SEQ ID NO:32 and a light chain variable region comprising CDR1, CDR2, and CDR3 of the light chain variable region of SEQ ID NO:39.

2. The pharmaceutical composition of claim 1 , wherein the antibody or fragment comprises 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.

3. The pharmaceutical composition of claim 1 , wherein the antibody or fragment comprises 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.

4. The pharmaceutical composition of claim 1 , wherein the antibody or fragment comprises 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.

5. The pharmaceutical composition of claim 1 , wherein the composition comprises a humanized antibody.

6. The pharmaceutical composition of claim 1 , further comprising a carrier.

7. The pharmaceutical composition of claim 1 , wherein the antibody or fragment thereof comprises a modification.

8. The pharmaceutical composition of claim 7 , wherein the modification is of conservative amino acid mutations in the Fc hinge region.

9. The pharmaceutical composition of claim 7 , wherein the modification is pegylation.

10. The pharmaceutical composition of claim 7 , wherein the modification is conjugation to a serum protein.

11. The pharmaceutical composition of claim 7 , wherein the modification is conjugation to human serum albumin.

12. The pharmaceutical composition of claim 7 , wherein the modification is conjugation to a detectable label or a diagnostic agent.

13. The pharmaceutical composition of claim 7 , wherein the modification is conjugation to an enzyme.

14. The pharmaceutical composition of claim 7 , wherein the modification is conjugation to a fluorescent, luminescent, or bioluminescent material.

15. The pharmaceutical composition of claim 7 , wherein the modification is conjugation to a radioactive material.

16. The pharmaceutical composition of claim 7 , wherein the modification is conjugation to a therapeutic agent.

17. An isolated polynucleotide comprising a nucleic acid sequence encoding a polypeptide comprising CDR1, CDR2, and CDR3 from a heavy or light chain variable region of an anti-OX40L antibody or antigen-binding fragment thereof wherein the heavy or light variable region is selected from SEQ ID NO:4, 11, 18, 25, 32, and 39.

18. An expression vector comprising the polynucleotide of claim 17 .

19. A host cell comprising the polynucleotide of claim 17 operably linked to a regulatory sequence.

20. A method for making an antibody, the method comprising expressing the polynucleotide of claim 17 in a host cell and isolating the polypeptide from the host cell.

Assignees

• Baylor Res Institute

Inventors

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

Classifications

• 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

• A61P37/06

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

• A61P37/02

  Immunomodulators · 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