Pd-1 agonist antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2019270818-A1
Application number	US-201916282609-A
Country	US
Kind code	A1
Filing date	Feb 22, 2019
Priority date	Mar 2, 2018
Publication date	Sep 5, 2019
Grant date	—

Abstract

The present invention relates to anti-human PD-1 agonist antibodies, and uses thereof for treating autoimmune disorders such as rheumatoid arthritis or for decreasing rejection of transplanted cells and/or tissues.

First claim

We claim:

1 . An antibody that binds human PD-1, comprising: 1) a heavy chain variable region (HCVR); and 2) a light chain variable region (LCVR), wherein the HCVR comprises a HCDR1, HCDR2, and HCDR3, and the LCVR comprises a LCDR1, LCDR2, and LCDR3, wherein the amino acid sequence of the HCDR1 is SEQ ID NO:5, the amino acid sequence of the HCDR2 is SEQ ID NO:6, and the amino acid sequence of the HCDR3 is SEQ ID NO:7, the amino acid sequence of the LCDR1 is SEQ ID NO:8, the amino acid sequence of the LCDR2 is SEQ ID NO:9, and the amino acid sequence of the LCDR3 is SEQ ID NO:10, and wherein the antibody is an IgG1.

2 . The antibody of claim 1 , wherein the amino acid sequence of the HCVR is SEQ ID NO:3 and the amino acid sequence of the LCVR is SEQ ID NO:4.

3 . The antibody of claim 2 comprising: 1) a HC; and 2) a LC, wherein the amino acid sequence of the HC is SEQ ID NO:1, and the amino acid sequence of the LC is SEQ ID NO:2.

4 . The antibody of claim 3 comprising two HCs and two LCs, wherein the amino acid sequence of each of the HCs is SEQ ID NO:1, and the amino acid sequence of each of the LCs is SEQ ID NO:2.

5 . The antibody of claim 1 , wherein the antibody is an agonist of human PD-1 as determined in an in vivo model of an autoimmune disorder or transplant rejection.

6 . The antibody of claim 5 wherein the in vivo model is a model for GVHD, solid organ transplantation rejection, vasculitis, SLE, T1DM, MS, GCA, PsO, PsA, RA, IBD, UC, AS, SjS, autoimmune hepatitis, or scleroderma.

7 . The antibody of claim 5 wherein the in vivo model is a mouse model for GVHD and/or lupus nephritis.

8 . A pharmaceutical composition comprising the antibody of claim 1 , and one or more pharmaceutically acceptable carriers, diluents, or excipients.

9 . A method of treating an autoimmune disease comprising administering to a patient in need thereof, an effective amount of the antibody of claim 1 .

10 . The method of claim 9 , wherein the autoimmune disease is GVHD, solid organ transplantation rejection, vasculitis, SLE, T1DM, MS, GCA, PsO, PsA, RA, IBD, UC, AS, Sj S, autoimmune hepatitis, scleroderma, celiac disease, Addison's disease, Hashimoto's disease, Graves' disease, atrophic gastritis/pernicious anemia, acquired hypogonadism/infertility, hypoparathyroidism, Coombs positive-hemolytic anemia, chronic allergic diseases (such as asthma, hay fever, or allergic rhinitis), Crohn's disease, male or female infertility, Behcet's, Wegener's granulomatosis, myocarditis, myositis, PMR, spontaneous abortion, vitiligo, atherosclerosis, autoimmune pancreatitis, bullous pemphigoid, chronic viral infections, or myasthenia gravis.

11 . The method of claim 10 , wherein the autoimmune disease is GVHD, solid organ transplantation rejection, vasculitis, SLE, T1DM, MS, GCA, PsO, PsA, RA, IBD, UC, AS, Sj S, autoimmune hepatitis, or scleroderma.

12 . The method of claim 10 , wherein the antibody is administered in combination with another therapeutic agent effective for the treatment of an autoimmune disease.

Assignees

• Lilly Co Eli

Inventors

• Yachi Pia Pauliina
• Chai Qing
• Feng Yiqing
• Newburn Kristin Paige
• Truhlar Stephanie Marie
• Verdino Petra

Classifications

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C07K16/2818 Primary

  against CD28 or CD152 · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/75

  Agonist effect on antigen · CPC title

• A61P37/06

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