Human CTLA-4 antibodies and their uses

1. An isolated human antibody or antigen binding portion thereof that: (a) is IgG1 isotype; (b) binds human CTLA-4 with a binding affinity of about 10 8 M −1 or greater; and (c) inhibits binding of human CTLA-4 to B7-1 and B7-2.

2. The antibody of claim 1 , wherein the antibody comprises at least one amino acid sequence selected from the group consisting of SEQ ID NOS:17, 19 and 23.

3. The antibody of claim 1 , wherein the antibody comprises at least one light chain variable region amino acid sequence selected from the group consisting of SEQ ID NOS: 7, 9 and 13.

4. An isolated human monoclonal antibody, or antigen-binding portion thereof that is IgG1 isotype and specifically binds to human CTLA-4, wherein the antibody or antigen-binding portion thereof has a binding affinity that is about 10 8 M −1 or greater affinity.

5. The antibody of claim 4 , wherein the antibody comprises at least one amino acid sequence selected from the group consisting of SEQ ID NOS:17, 19 and 23.

6. The antibody of claim 4 , wherein the antibody comprises at least one amino acid sequence selected from the group consisting of SEQ ID NOS: 7, 9 and 13.

7. An isolated monoclonal antibody, or an antigen binding portion thereof, which is IgG1 isotype and competes for binding to a human CTLA-4 polypeptide with an antibody comprising the amino acid sequence set forth in SEQ ID NO:17, and the amino acid sequence set forth in SEQ ID NO:7, wherein the monoclonal antibody or antigen-binding portion thereof has a binding affinity that is about 10 8 M −1 or greater affinity.

8. The antibody of claim 1 , wherein the antibody comprises: (a) a heavy chain variable region derived from a human V H 3-30.3 gene; and (b) a light chain variable region derived from a human V K A-27 gene.

9. The antibody of claim 4 , wherein the antibody comprises: (a) a heavy chain variable region derived from a human V H 3-33 gene; and (b) a light chain variable region derived from a human V K L-15 gene.

10. The antibody of claim 4 , wherein the antibody comprises: (a) a heavy chain variable region derived from a human V H 3-30.3 gene; and (b) a light chain variable region derived from a human V K A-27 gene.

11. The antibody of claim 1 , wherein the antibody comprises: (a) a heavy chain variable region derived from a human V H 3-33 gene; and (b) a light chain variable region derived from a human V K L-15 gene.

12. The antibody of claim 1 , wherein the antibody comprises a the amino acid sequence set forth in SEQ ID NO: 17 and the amino acid sequence set forth in SEQ ID NO: 7.

13. The antibody of claim 1 , wherein the antibody comprises the amino acid sequence set forth in SEQ ID NO: 19 and the amino acid sequence set forth in SEQ ID NO: 9.

14. The antibody of claim 1 , wherein the antibody comprises the amino acid sequence set forth in SEQ ID NO: 23 and the amino acid sequence set forth in SEQ ID NO: 13.

15. The antibody of claim 4 , wherein the antibody comprises the amino acid sequence set forth in SEQ ID NO: 17 and the amino acid sequence set forth in SEQ ID NO: 7.

16. The antibody of claim 4 , wherein the antibody comprises the amino acid sequence set forth in SEQ ID NO: 19 and the amino acid sequence set forth in SEQ ID NO: 9.

17. The antibody of claim 4 , wherein the antibody comprises the amino acid sequence set forth in SEQ ID NO: 23 and the amino acid sequence set forth in SEQ ID NO: 13.

18. The antibody of claim 1 , comprising: (a) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:27, 32 and 37, respectively; and (b) a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:24, 29 and 35, respectively.

19. The antibody of claim 1 , comprising: (a) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:27, 33 and 37, respectively; and (b) a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:25, 30 and 35, respectively.

20. The antibody of claim 1 , comprising: (a) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:28, 34 and 38, respectively; and (b) a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:26, 31 and 36, respectively.

21. The antibody of claim 4 , comprising: (a) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:27, 32 and 37, respectively; and (b) a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:24, 29 and 35, respectively.

22. The antibody of claim 4 , comprising: (a) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:27, 33 and 37, respectively; and (b) a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:25, 30 and 35, respectively.

23. The antibody of claim 4 , comprising: (a) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:28, 34 and 38, respectively; and (b) a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS:26, 31 and 36, respectively.

24. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.

25. The antibody of claim 4 , wherein the antibody is a monoclonal antibody.

26. The antibody of claim 7 , wherein the antibody is a monoclonal antibody.

27. The antibody of claim 1 , wherein the antibody is a human antibody.

28. The antibody of claim 4 , wherein the antibody is a human antibody.

29. The antibody of claim 7 , wherein the antibody is a human antibody.

30. A pharmaceutical composition comprising the antibody of claim 1 , and a pharmaceutically acceptable carrier.

31. A pharmaceutical composition comprising the antibody of claim 4 , and a pharmaceutically acceptable carrier.

32. A pharmaceutical composition comprising the antibody of claim 7 , and a pharmaceutically acceptable carrier.