Immunological reagents

1. A binding agent that binds human PD-1 and comprises a combination of a heavy chain variable region (VH) and a light chain variable region (VL) selected from the group consisting of:

(a) a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 as set forth in SEQ ID NOS: 17, 40, and 63, respectively; and a VL comprising CDRs 1, 2 and 3 as set forth in SEQ ID NOS: 86, 109, and 132, respectively;

(b) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 8, 31, and 54, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 77, 100, and 123, respectively;

(c) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 1, 24, and 47, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 70, 93, and 116, respectively;

(d) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 2, 25, and 48, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 71, 94, and 117, respectively;

(e) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 3, 26, and 49, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 72, 95, and 118, respectively;

(f) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 4, 27, and 50, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 73, 96, and 119, respectively;

(g) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 5, 28, and 51, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 74, 97, and 120, respectively;

(h) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 6, 29, and 52, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 75, 98, and 121, respectively;

(i) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 7, 30, and 53, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 76, 99 and 122, respectively;

(j) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 9, 32, and 55, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 78, 101, and 124, respectively;

(k) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 10, 33, and 56, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 79, 102, and 125, respectively;

(l) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 11, 34, and 57, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 80, 103, and 126, respectively;

(m) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 12, 35, and 58, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 81, 104, and 127, respectively;

(n) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 13, 36, and 59, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 82, 105, and 128, respectively;

(o) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 14, 37, and 60, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 83, 106, 129, respectively;

(p) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 15, 38, and 61, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 84, 107, and 130, respectively;

(q) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 16, 39, and 62, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 85, 108, and 131, respectively;

(r) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 18, 41, and 64, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 87, 110, and 133, respectively;

(s) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 19, 42, and 65, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 88, 111, and 134, respectively;

(t) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 20, 43, and 66, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 89, 112, and 135, respectively;

(u) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 21, 44, and 67, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 90, 113, and 136, respectively;

(v) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 22, 45, and 68, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 91, 114, and 137, respectively; and,

(w) a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 23, 46, and 69, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 92, 115, and 138, respectively.

2. The binding agent of claim 1 comprising a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS:17, 40, and 63, respectively; and a VL comprising CDRs 1, 2 and 3 as set forth in SEQ ID NOS: 86, 109, and 132, respectively.

3. The binding agent of claim 1 comprising a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 8, 31, and 54, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 77, 100, and 123, respectively.

4. The binding agent of claim 1 that is a chimeric antibody.

5. A composition comprising the binding agent of claim 1 and a pharmaceutically acceptable carrier.

6. A composition comprising the binding agent of claim 2 and a pharmaceutically acceptable carrier.

7. A composition comprising the binding agent of claim 3 and a pharmaceutically acceptable carrier.

8. A composition comprising the binding agent of claim 4 and a pharmaceutically acceptable carrier.

9. A composition comprising the binding agent of claim 2 and a binding agent comprising: a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 8, 31, and 54, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 77, 100, and 123, respectively.

10. A method for binding PD-1 on a cell comprising contacting the cell with a binding agent of claim 1 , or a composition comprising the same.

11. A method for binding PD-1 on a cell comprising contacting the cell with a binding agent of claim 2 , or a composition comprising the same.

12. A method for binding PD-1 on a cell comprising contacting the cell with a binding agent of claim 3 , or a composition comprising the same.

13. A method for binding PD-1 on a cell comprising contacting the cell with a binding agent of claim 4 , or a composition comprising the same.

14. A method for binding PD-1 on a cell comprising contacting the cell with the binding agent of claim 2 and a binding agent comprising: a VH comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 8, 31, and 54, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 77, 100, and 123, respectively; or a composition comprising the same.

15. The method of claim 10 that is a method for treating disease in a human.

16. The method of claim 15 wherein the disease is selected from the group consisting of cancer, autoimmunity, and infectious disease.

17. The method of claim 16 wherein the cancer is selected from the group consisting of breast, blood, colon, stomach, rectum, skeletal tissue, skin, brain, lung, bladder, kidney, ovary and liver cancer.

18. The method of claim 16 wherein the infectious disease is by human immunodeficiency virus (HIV).

19. The method of claim 11 that is a method for treating disease in a human.

20. The method of claim 19 wherein the disease is selected from the group consisting of cancer, autoimmunity, and infectious disease.

21. The method of claim 20 wherein the cancer is selected from the group consisting of breast, blood, colon, stomach, rectum, skeletal tissue, skin, brain, lung, bladder, kidney, ovary and liver cancer.

22. The method of claim 20 wherein the infectious disease is by human immunodeficiency virus (HIV).

23. The method of claim 12 that is a method for treating disease in a human.

24. The method of claim 23 wherein the disease is selected from the group consisting of cancer, autoimmunity, and infectious disease.

25. The method of claim 24 wherein the cancer is selected from the group consisting of breast, blood, colon, stomach, rectum, skeletal tissue, skin, brain, lung, bladder, kidney, ovary and liver cancer.

26. The method of claim 24 wherein the infectious disease is by human immunodeficiency virus (HIV).

27. The method of claim 13 that is a method for treating disease in a human.

28. The method of claim 27 wherein the disease is selected from the group consisting of cancer, autoimmunity, and infectious disease.

29. The method of claim 28 wherein the cancer is selected from the group consisting of breast, blood, colon, stomach, rectum, skeletal tissue, skin, brain, lung, bladder, kidney, ovary and liver cancer.

30. The method of claim 28 wherein the infectious disease is by human immunodeficiency virus (HIV).

31. The method of claim 14 that is a method for treating disease in a human.

32. The method of claim 31 wherein the disease is selected from the group consisting of cancer, autoimmunity, and infection.

33. The method of claim 32 wherein the cancer is selected from the group consisting of breast, blood, colon, stomach, rectum, skeletal tissue, skin, brain, lung, bladder, kidney, ovary and liver cancer.

34. The method of claim 32 wherein the infection is by human immunodeficiency virus (HIV).

35. An isolated polynucleotide encoding a binding agent of claim 1 .

36. An expression vector comprising a polynucleotide encoding a binding agent of claim 1 .

37. A host cell comprising an expression vector comprising a polynucleotide encoding a binding agent of claim 1 .