Anti-H7CR antibodies

Patent metadata

Field	Value
Publication number	US-9790277-B2
Application number	US-201314654109-A
Country	US
Kind code	B2
Filing date	Dec 23, 2013
Priority date	Dec 21, 2012
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

Antibodies and humanized variants thereof and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to the B7-H7 counter-receptor, H7CR, and their uses in enhancing immune responses and the treatment and diagnosis of cancer and other diseases are provided.

First claim

We claim:

1. A humanized antibody or an antigen-binding fragment thereof that specifically binds to human H7CR, comprising:
(A) (1) a light chain variable region having the amino acid sequence of any of SEQ ID NOS: 17-22; and
(2) a heavy chain variable region having the amino acid sequence of any of SEQ ID NOS: 23-28; or

(B) (1) a light chain variable region having the amino acid sequence of any of SEQ ID NOS: 33-38; and
(2) a heavy chain variable region having the amino acid sequence of any of SEQ ID NOS: 39-44.

2. The antibody or an antigen binding fragment thereof of claim 1 , wherein the H7CR which is specifically bound is:
(A) arrayed on the surface of a live cell; or
(B) expressed at an endogenous concentration.

3. The antibody or an antigen binding fragment thereof of claim 2 , wherein said live cell is a T cell, an NK cell, or a plasmacytoid dendritic cell.

4. The antibody or an antigen binding fragment thereof of claim 1 , wherein the binding of the antibody or the antigen binding fragment thereof to H7CR does not block a binding interaction of B7-H7 and H7CR.

5. The antibody or an antigen binding fragment thereof of claim 1 , wherein the antibody or an antigen binding fragment thereof modulates or agonizes H7CR activity.

6. The antibody or an antigen binding fragment thereof of claim 1 , wherein said antibody is a bispecific or multispecific antibody.

7. The antibody or an antigen binding fragment thereof of claim 1 , wherein said antibody or an antigen binding fragment thereof is detectably labeled or comprises a conjugated toxin, drug, receptor, enzyme, receptor ligand.

8. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or an antigen binding fragment thereof of claim 1 , and a physiologically acceptable carrier or excipient.

9. A method for enhancing an immune response in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 8 .

10. The method of claim 9 , wherein said subject has cancer.

11. The method of claim 9 , wherein said subject has an infectious disease.

12. The method of claim 11 , wherein said infectious disease is a chronic viral disease.

13. The method of claim 9 , wherein said pharmaceutical composition agonizes an H7CR function.

14. The antigen-binding fragment of the anti-H7CR antibody of claim 1 , wherein the antigen-binding fragment specifically binds to human H7CR as antigen.

15. The antigen-binding antibody fragment of claim 14 , wherein the antigen-binding fragment specifically binds to human H7CR which is:
(A) arrayed on the surface of a live cell; or
(B) expressed at an endogenous concentration.

16. The antigen-binding antibody fragment of claim 15 , wherein said live cell is a T cell, an NK cell, or a plasmacytoid dendritic cell.

17. The antigen-binding antibody fragment of claim 14 , wherein the binding of the antigen-binding fragment to H7CR does not block a binding interaction of B7-H7 and H7CR.

18. The antigen-binding antibody fragment of claim 14 , which is an antigen-binding fragment of a bispecific or a multispecific antibody.

19. An antigen-binding antibody fragment of a humanized anti-H7CR antibody that specifically binds to human H7CR as antigen, wherein the antigen-binding fragment comprises six CDRs, which comprise:
(A) three light chain CDRs having SEQ ID NOS: 29, 32, 45 and three heavy chain CDRs having SEQ ID NOS: 49, 52, and 56;
(B) three light chain CDRs having SEQ ID NOS: 30, 32, 46 and three heavy chain CDRs having SEQ ID NOS: 50, 53, and 57; or
(C) three light chain CDRs having SEQ ID NOS: 29, 32, 47 and three heavy chain CDRs having SEQ ID NOS: 50, 54, and 58.

20. The antigen-binding antibody fragment of claim 19 , which is an antigen-binding fragment of a bispecific or multispecific antibody.

21. The antigen-binding antibody fragment of claim 19 , which is detectably labeled or comprises a conjugated toxin, drug, receptor, enzyme, or receptor ligand.

22. A pharmaceutical composition comprising a therapeutically effective amount of the antigen-binding fragment of an anti-H7CR antibody of claim 14 , and a physiologically acceptable carrier or excipient.

23. A method for enhancing an immune response in a subject in need thereof, the method comprising: administering to said subject a therapeutically effective amount of the pharmaceutical composition of claim 22 .

24. The method of claim 23 , wherein said subject has cancer.

25. The method of claim 23 , wherein said subject has an infectious disease.

26. The method of claim 25 , wherein said infectious disease is a chronic viral disease.

27. The method of claim 23 , wherein said pharmaceutical composition agonizes an H7CR function.

28. An antigen-binding fragment of an anti-H7CR antibody that specifically binds to human H7CR, wherein said antigen-binding fragment comprises:
(A) (1) a light chain variable region having the amino acid sequence of SEQ ID NO: 5; and
(2) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 6;
(B) (1) a light chain variable region having the amino acid sequence of SEQ ID NO: 7; and
(2) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8; or

(C) (1) a light chain variable region having the amino acid sequence of SEQ ID NO: 9; and
(2) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 10.

29. A humanized antibody or an antigen-binding fragment thereof that specifically binds to human H7CR, comprising:
(1) a light chain variable region comprising amino acid sequence SEQ ID NO: 17 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 23;
(2) a light chain variable region comprising amino acid sequence SEQ ID NO: 17 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 24;
(3) a light chain variable region comprising amino acid sequence SEQ ID NO: 17 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 25;
(4) a light chain variable region comprising amino acid sequence SEQ ID NO: 17 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 26;
(5) a light chain variable region comprising amino acid sequence SEQ ID NO: 17 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 27;
(6) a light chain variable region comprising amino acid sequence SEQ ID NO: 17 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 28;
(7) a light chain variable region comprising amino acid sequence SEQ ID NO: 18 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 24;
(8) a light chain variable region comprising amino acid sequence SEQ ID NO: 18 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 25;
(9) a light chain variable region comprising amino acid sequence SEQ ID NO: 18 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 27;
(10) a light chain variable region comprising amino acid sequence SEQ ID NO: 18 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 28;
(11) a light chain variable region comprising amino acid sequence SEQ ID NO: 19 and a heavy chain variable region comprising amino acid sequence SEQ ID NO: 24;
(12) a light chain variable region com

Assignees

• Amplimmune Inc
• Univ Johns Hopkins
• Medimmune Llc

Inventors

• Langermann Solomon
• Liu Linda
• Yao Sheng
• Chen Lieping

Classifications

• A61P37/02

  Immunomodulators · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title