Anti-vista antibodies and fragments

Patent metadata

Field	Value
Publication number	US-10273301-B2
Application number	US-201415107784-A
Country	US
Kind code	B2
Filing date	Dec 22, 2014
Priority date	Dec 24, 2013
Publication date	Apr 30, 2019
Grant date	Apr 30, 2019

Abstract

The present invention relates to novel antibodies and fragments that bind to a V-domain Ig Suppressor of T cell Activation (VISTA), and methods of making and using same. Methods of use include methods of treatment of cancer, including leukemias, lymphomas, solid tumors and melanomas.

First claim

What is claimed:

1. An isolated antibody or antibody fragment thereof comprising an antigen binding region that binds to a V-domain Ig Suppressor of T cell Activation (VISTA), wherein binding of the antibody or antibody fragment to VISTA modulates or enhances an immune response and which antibody:
(i) comprises a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 19, a VH CDR2 having the amino acid sequence of SEQ ID NO:20 and a VH CDR3 having the amino acid sequence of SEQ ID NO:21, and further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:22, a VL CDR2 having the amino acid sequence of SEQ ID NO: 23 and a VL CDR3 having the amino acid sequence of SEQ ID NO:24; or
(ii) comprises a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 25, a VH CDR2 having the amino acid sequence of SEQ ID NO:26 and a VH CDR3 having the amino acid sequence of SEQ ID NO:27, and which further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:28, a VL CDR2 having the amino acid sequence of SEQ ID NO: 29 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 30.

2. The isolated antibody of claim 1 , which comprises a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 19, a VH CDR2 having the amino acid sequence of SEQ ID NO:20 and a VH CDR3 having the amino acid sequence of SEQ ID NO:21, and further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:22, a VL CDR2 having the amino acid sequence of SEQ ID NO: 23 and a VL CDR3 having the amino acid sequence of SEQ ID NO:24.

3. The isolated antibody of claim 1 , which a VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 25, a VH CDR2 having the amino acid sequence of SEQ ID NO:26 and a VH CDR3 having the amino acid sequence of SEQ ID NO:27, and which further comprises a VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:28, a VL CDR2 having the amino acid sequence of SEQ ID NO: 29 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 30.

4. The isolated antibody of claim 2 , which comprises a variable heavy chain polypeptide having a sequence at least 90% identical to SEQ ID NO:40.

5. The isolated antibody of claim 2 , which comprises a variable heavy chain polypeptide having a sequence identical to SEQ ID NO:40.

6. The isolated antibody of claim 2 , which comprises a variable light chain polypeptide having a sequence at least 90% identical to SEQ ID NO:43.

7. The isolated antibody of claim 2 , which comprises a variable light chain polypeptide having a sequence identical to SEQ ID NO:43.

8. The isolated antibody of claim 2 , which comprises a variable light chain polypeptide having the sequence of SEQ ID NO:43 and a variable heavy chain polypeptide having the sequence of SEQ ID NO:40.

9. The isolated antibody of claim 3 , which comprises a variable heavy chain polypeptide having a sequence at least 90% identical to SEQ ID NO:37.

10. The isolated antibody of claim 3 , which comprises a variable heavy chain polypeptide having the sequence of SEQ ID NO:37.

11. The isolated antibody of claim 3 , which comprises a variable light chain polypeptide at least 90% identical to SEQ ID NO:44.

12. The isolated antibody of claim 3 , which comprises a variable light chain polypeptide identical to SEQ ID NO:44.

13. The isolated antibody of claim 3 , which comprises a variable light chain polypeptide having the sequence of SEQ ID NO:44 and a variable heavy chain polypeptide having the sequence of SEQ ID NO:37.

14. The isolated antibody of claim 1 , which comprises a human constant domain.

15. The isolated antibody of claim 1 , which comprises a human IgG1 constant domain.

16. The isolated antibody of claim 1 which comprises a human constant domain which comprises a mutation which impairs FcR binding or protease cleavage.

17. The isolated antibody of claim 1 , which comprises a human IgG1 constant domain which comprises a mutation which impairs FcR binding or protease cleavage.

18. The isolated antibody of claim 1 , which comprises a human IgG1 heavy constant domain having the sequence of SEQ ID NO:60 or SEQ ID NO:61.

19. The isolated antibody of claim 1 which comprises a human IgG1 light constant domain having the sequence of SEQ ID NO:56.

20. The isolated antibody of claim 1 , which comprises a human IgG1 heavy constant domain which comprises SEQ ID NO:60 or SEQ ID NO:61 and further comprises a human IgG1 light constant domain which comprises SEQ ID NO:56.

21. The isolated antibody of claim 2 , which comprises a heavy chain polypeptide having a sequence at least 90% identical to SEQ ID NO: 53 and a light chain polypeptide at least 90% identical to SEQ ID NO: 54.

22. The isolated antibody of claim 2 , which comprises a heavy chain polypeptide having a sequence identical to SEQ ID NO: 53 and a light chain polypeptide having a sequence at least 90% identical to SEQ ID NO: 54.

23. The isolated antibody of claim 3 , which comprises a heavy chain polypeptide having a sequence at least 90% identical to SEQ ID NO: 55 and a light chain polypeptide having a sequence at least 90% identical to SEQ ID NO: 56.

24. The isolated antibody of claim 3 , which comprises a heavy chain polypeptide having a sequence identical to SEQ ID NO: 55 and a light chain polypeptide having a sequence identical to SEQ ID NO: 56.

25. The antibody or antibody fragment of claim 1 , wherein the antibody fragment is a Fab, F(ab′)2, or scFv antibody fragment.

26. The antibody or antibody fragment of claim 1 , wherein the antibody is a monoclonal antibody.

27. The antibody or antibody fragment of claim 1 which is a human or humanized antibody.

28. The antibody or antibody fragment claim 1 , wherein the antibody or fragment binds to human VISTA with an affinity of at least 1×10 −9 liter/mole.

29. The antibody or antibody fragment of claim 1 , wherein the antibody binds to human VISTA with an affinity of at least 1×10 −8 liter/mole.

30. The antibody or antibody fragment of claim 1 , wherein the antibody binds to human VISTA with an affinity of at least 1×10 −7 liter/mole.

31. A composition comprising the antibody or antibody fragment of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.

32. A composition comprising the antibody or antibody fragment of claim 4 and a pharmaceutically acceptable carrier, diluent, or excipient.

33. A composition comprising the antibody or antibody fragment of claim 5 and a pharmaceutically acceptable carrier, diluent, or excipient.

34. A composition comprising the antibody or antibody fragment of claim 6 and a pharmaceutically acceptable carrier, diluent, or excipient.

35. A composition comprising the antibody or antibody fragment of claim 7 and a pharmaceutically acceptable carrier, diluent, or excipient.

36. A composition comprising the antibody or antibody fragment of claim 8 and a pharmaceutically acceptable carrier, diluent, or excipient.

37. A composition comprising the antibody or antibody fragment of claim 9 and a pharmaceutically acceptable carrier, diluent, or excipient.

38. A composition

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Snyder Linda
• Powers Gordon

Classifications

• A61P43/00

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

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title