IP Library › Granted Patent US 12,312,405
Granted Patent B2
US 12,312,405 · App. 17/328,050 · Granted May 27, 2025

Anti-PD-1 antibodies

Inventors: David A. Blair (Sandy Hook, CT); Nicole K. Garaffa (Trumbull, CT); Pankaj Gupta (Scarsdale, NY); Priyanka Gupta (Newtown, CT); Fei Han (Acton, MA); Aaron Timothy Karlak (Beacon Falls, CT); Dongmei Liu (Oxford, CT); Mouhamadou Lamine Mbow (Echichens, CH); Joseph A. Mozdzierz (Mahopac, NY); Kerry L. M. Ralph (Bethel, CT); Abdulsalam Shaaban (Ridgefield, CT); Helen Haixia Wu (Danbury, CT); Guangwei Yang (Cheshire, CT)
C07K16/2818C07K16/2803A61K2039/505C07K2317/24C07K2317/31C07K2317/75C07K2317/92
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Quick Facts
Patent No.
US 12,312,405
App. No.
17/328,050
Granted
May 27, 2025
Kind
B2
Abstract

The present invention relates to new anti-PD-1 (Programmed cell death 1) antibodies and antigen-binding fragments thereof for therapeutic and diagnostic methods and compositions using them.

Claims (221)

1. An anti-Programmed cell death 1 (PD-1) antibody or antigen-binding fragment thereof comprising:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 (H-CDR1); the amino acid sequence of SEQ ID NO: 44 (H-CDR2); and the amino acid sequence of SEQ ID NO: 45 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 1 (L-CDR1); the amino acid sequence of SEQ ID NO: 2 (L-CDR2); and the amino acid sequence of SEQ ID NO: 3 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 (H-CDR1); the amino acid sequence of SEQ ID NO: 46 (H-CDR2); and the amino acid sequence of SEQ ID NO: 45 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 1 (L-CDR1); the amino acid sequence of SEQ ID NO: 2 (L-CDR2); and the amino acid sequence of SEQ ID NO: 3 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 47 (H-CDR1); the amino acid sequence of SEQ ID NO: 48 (H-CDR2); and the amino acid sequence of SEQ ID NO: 49 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4 (L-CDR1); the amino acid sequence of SEQ ID NO: 5 (L-CDR2); and the amino acid sequence of SEQ ID NO: 6 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 50 (H-CDR1); the amino acid sequence of SEQ ID NO: 51 (H-CDR2); and the amino acid sequence of SEQ ID NO: 52 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 7 (L-CDR1); the amino acid sequence of SEQ ID NO: 8 (L-CDR2); and the amino acid sequence of SEQ ID NO: 9 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 53 (H-CDR1); the amino acid sequence of SEQ ID NO: 54 (H-CDR2); and the amino acid sequence of SEQ ID NO: 55 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 10 (L-CDR1); the amino acid sequence of SEQ ID NO: 11 (L-CDR2); and the amino acid sequence of SEQ ID NO: 12 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 56 (H-CDR1); the amino acid sequence of SEQ ID NO: 57 (H-CDR2); and the amino acid sequence of SEQ ID NO: 58 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 13 (L-CDR1); the amino acid sequence of SEQ ID NO: 14 (L-CDR2); and the amino acid sequence of SEQ ID NO: 15 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 59 (H-CDR1); the amino acid sequence of SEQ ID NO: 60 (H-CDR2); and the amino acid sequence of SEQ ID NO: 61 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 16 (L-CDR1); the amino acid sequence of SEQ ID NO: 17 (L-CDR2); and the amino acid sequence of SEQ ID NO: 18 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 62 (H-CDR1); the amino acid sequence of SEQ ID NO: 63 (H-CDR2); and the amino acid sequence of SEQ ID NO: 64 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 19 (L-CDR1); the amino acid sequence of SEQ ID NO: 20 (L-CDR2); and the amino acid sequence of SEQ ID NO: 21 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 65 (H-CDR1); the amino acid sequence of SEQ ID NO: 66 (H-CDR2); and the amino acid sequence of SEQ ID NO: 67 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 22 (L-CDR1); the amino acid sequence of SEQ ID NO: 23 (L-CDR2); and the amino acid sequence of SEQ ID NO: 24 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 68 (H-CDR1); the amino acid sequence of SEQ ID NO: 69 (H-CDR2); and the amino acid sequence of SEQ ID NO: 70 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 25 (L-CDR1); the amino acid sequence of SEQ ID NO: 26 (L-CDR2); and the amino acid sequence of SEQ ID NO: 27 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 71 (H-CDR1); the amino acid sequence of SEQ ID NO: 72 (H-CDR2); and the amino acid sequence of SEQ ID NO: 58 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28 (L-CDR1); the amino acid sequence of SEQ ID NO: 14 (L-CDR2); and the amino acid sequence of SEQ ID NO: 29 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 74 (H-CDR2); and the amino acid sequence of SEQ ID NO: 75 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 78 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 164 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 78 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 167 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 80 (H-CDR1); the amino acid sequence of SEQ ID NO: 81 (H-CDR2); and the amino acid sequence of SEQ ID NO: 82 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 33 (L-CDR1); the amino acid sequence of SEQ ID NO: 14 (L-CDR2); and the amino acid sequence of SEQ ID NO: 34 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 83 (H-CDR1); the amino acid sequence of SEQ ID NO: 84 (H-CDR2); and the amino acid sequence of SEQ ID NO: 85 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 16 (L-CDR1); the amino acid sequence of SEQ ID NO: 35 (L-CDR2); and the amino acid sequence of SEQ ID NO: 36 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 86 (H-CDR1); the amino acid sequence of SEQ ID NO: 87 (H-CDR2); and the amino acid sequence of SEQ ID NO: 88 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 37 (L-CDR1); the amino acid sequence of SEQ ID NO: 38 (L-CDR2); and the amino acid sequence of SEQ ID NO: 39 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 89 (H-CDR1); the amino acid sequence of SEQ ID NO: 90 (H-CDR2); and the amino acid sequence of SEQ ID NO: 91 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 40 (L-CDR1); the amino acid sequence of SEQ ID NO: 41 (L-CDR2); and the amino acid sequence of SEQ ID NO: 42 (L-CDR3).

2. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 1 comprising:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 74 (H-CDR2); and the amino acid sequence of SEQ ID NO: 75 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 78 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 164 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 78 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 167 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3).

3. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 108 and SEQ ID NO: 92, respectively;

SEQ ID NO: 109 and SEQ ID NO: 93, respectively; SEQ ID NO: 110 and SEQ ID NO: 94, respectively; SEQ ID NO: 111 and SEQ ID NO: 95, respectively; SEQ ID NO: 112 and SEQ ID NO: 96, respectively; SEQ ID NO: 113 and SEQ ID NO: 97, respectively; SEQ ID NO: 114 and SEQ ID NO: 98, respectively; SEQ ID NO: 115 and SEQ ID NO: 99, respectively; SEQ ID NO: 116 and SEQ ID NO: 100, respectively; SEQ ID NO: 117 and SEQ ID NO: 101, respectively; SEQ ID NO: 118 and SEQ ID NO: 102, respectively; SEQ ID NO: 119 and SEQ ID NO: 103, respectively; SEQ ID NO: 120 and SEQ ID NO: 104, respectively; SEQ ID NO: 121 and SEQ ID NO: 105, respectively; SEQ ID NO: 122 and SEQ ID NO: 106, respectively; SEQ ID NO: 123 and SEQ ID NO: 107, respectively; SEQ ID NO: 131 and SEQ ID NO: 125, respectively; SEQ ID NO: 133 and SEQ ID NO: 127, respectively; SEQ ID NO: 135 and SEQ ID NO: 127, respectively; SEQ ID NO: 137 and SEQ ID NO: 129, respectively; or SEQ ID NO: 139 and SEQ ID NO: 129, respectively.

4. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof comprises:

a heavy chain variable region and a light chain variable region having at least 90% identity to the amino acid sequences of SEQ ID NO: 131 and SEQ ID NO: 125, respectively;

a heavy chain variable region and a light chain variable region having at least 90% identity to the amino acid sequences of SEQ ID NO: 133 and SEQ ID NO: 127, respectively;

a heavy chain variable region and a light chain variable region having at least 90% identity to the amino acid sequences of SEQ ID NO: 135 and SEQ ID NO: 127, respectively;

a heavy chain variable region and a light chain variable region having at least 90% identity to the amino acid sequences of SEQ ID NO: 137 and SEQ ID NO: 129, respectively; or

a heavy chain variable region and a light chain variable region having at least 90% identity to the amino acid sequences of SEQ ID NO: 139 and SEQ ID NO: 129, respectively.

5. The anti-PD-1 antibody of claim 1 , wherein said antibody comprises a heavy chain constant region selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE constant regions.

6. The anti-PD-1 antibody of claim 5 , wherein the heavy chain constant region is a heavy chain constant region of an IgG1.

7. The anti-PD-1 antibody of claim 5 , wherein the heavy chain constant region is a heavy chain constant region of an IgG1 with a leucine to alanine mutation at a position corresponding to residue 235 of SEQ ID NO: 161 and at a position corresponding to residue 236 of SEQ ID NO: 161.

8. The anti-PD-1 antibody of claim 1 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4.

9. The anti-PD-1 antibody of claim 5 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4 with a serine to proline mutation at a position corresponding to residue 226 of SEQ ID NO: 143, SEQ ID NO: 147, SEQ ID NO: 149, SEQ ID NO: 153, or SEQ ID NO: 155.

10. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain constant region selected from the group consisting of kappa and lambda.

11. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof is a humanized antibody or antigen-binding fragment thereof.

12. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of a monoclonal antibody, a Fab, a F(ab′)2, a Fv and an scFv.

13. The PD-1 antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof is a monoclonal antibody.

14. A pharmaceutical composition comprising an anti-PD-1 antibody or antigen-binding fragment thereof of claim 1 , and a pharmaceutically acceptable excipient.

15. An isolated polynucleotide encoding a heavy chain variable region and/or a light chain variable region of claim 3 .

16. An expression vector comprising a polynucleotide according to claim 15 .

17. An isolated host cell comprising an expression vector according to claim 16 .

18. The isolated host cell of claim 17 , wherein the cell is a mammalian cell.

19. A method of manufacturing an antibody comprising the steps of:

culturing an isolated host cell comprising an expression vector comprising an isolated polynucleotide encoding a heavy chain variable region according to claim 3 and an expression vector comprising an isolated polynucleotide encoding a light chain variable region according to claim 3 under conditions that allow formation of an antibody; and

recovering said antibody.

20. The method of claim 19 , further comprising the step of purifying said antibody.

21. The method of claim 19 , further comprising the step of formulating said antibody into a pharmaceutical composition.

22. An anti-PD-1 antibody or antigen-binding fragment thereof comprising a heavy chain variable region comprising the amino acid sequence of any one of SEQ NO: 131, SEQ NO: 133, SEQ NO: 135, SEQ NO: 137 or SEQ NO: 139 and a light chain variable region comprising the amino acid sequence of any one of SEQ NO: 125, SEQ NO: 127 or SEQ NO: 129.

23. An anti-PD-1 antibody or antigen-binding fragment thereof comprising:

a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 131 and SEQ ID NO: 125, respectively;

a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 133 and SEQ ID NO: 127, respectively;

a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 135 and SEQ ID NO: 127, respectively;

a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 137 and SEQ ID NO: 129, respectively; or

a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 139 and SEQ ID NO: 129, respectively.

24. The anti-PD-1 antibody of claim 23 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4.

25. The anti-PD-1 antibody of claim 23 comprising a heavy chain constant region of an IgG4 with a serine to proline mutation at a position corresponding to residue 226 of SEQ ID NO: 143, SEQ ID NO: 147, SEQ ID NO: 149, SEQ ID NO: 153, or SEQ ID NO: 155.

26. An isolated polynucleotide encoding a heavy chain variable region and/or a light chain variable region of claim 23 .

27. An expression vector comprising a polynucleotide according to claim 26 .

28. An isolated host cell comprising an expression vector according to claim 27 .

29. The isolated host cell of claim 28 , wherein the cell is a mammalian cell.

30. A method of manufacturing an antibody comprising the steps of:

culturing an isolated host cell comprising an expression vector comprising an isolated polynucleotide encoding a heavy chain variable region according to claim 23 and an expression vector comprising an isolated polynucleotide encoding a light chain variable region according to claim 23 under conditions that allow formation of an antibody; and

recovering said antibody.

31. An anti-PD-1 antibody comprising:

a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 143 and SEQ ID NO: 141, respectively;

a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 147 and SEQ ID NO: 145, respectively;

a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 149 and SEQ ID NO: 145, respectively;

a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 153 and SEQ ID NO: 151, respectively; or

a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 155 and SEQ ID NO: 151, respectively.

32. An isolated polynucleotide encoding a heavy chain and/or a light chain according to claim 31 .

33. An expression vector comprising a polynucleotide according to claim 32 .

34. An isolated host cell comprising an expression vector according to claim 33 .

35. The isolated host cell of claim 34 , wherein the cell is a mammalian cell.

36. A method of manufacturing an antibody comprising the steps of:

culturing an isolated host cell comprising an expression vector comprising an isolated polynucleotide encoding a heavy chain according to claim 31 and an expression vector comprising an isolated polynucleotide encoding a light chain according to claim 31 under conditions that allow formation of an antibody; and

recovering said antibody.

37. The method of claim 36 , further comprising the step of purifying said antibody.

38. The method of claim 36 , further comprising the step of formulating said antibody into a pharmaceutical composition.

39. An anti-PD-1 antibody or antigen-binding fragment thereof comprising:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76, SEQ ID NO: 78, or SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 164 or SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 31, SEQ ID NO: 166, or SEQ ID NO: 167 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3).

40. An anti-PD-1 antibody or antigen-binding fragment thereof comprising:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 164 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

73 (H-CDR1); the amino acid sequence of SEQ ID NO: 78 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),

or

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 167 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3).

41. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 40 comprising:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 164 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3).

42. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 40 comprising:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3).

43. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 40 comprising:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 78 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3).

44. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 40 comprising:

a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and

a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 167 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3).

45. The anti-PD-1 antibody of claim 40 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4.

46. The anti-PD-1 antibody of claim 40 comprising a heavy chain constant region of an IgG4 with a serine to proline mutation at a position corresponding to residue 226 of SEQ ID NO: 143, SEQ ID NO: 147, SEQ ID NO: 149, SEQ ID NO: 153, or SEQ ID NO: 155.

47. An anti-PD-1 antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 131 and SEQ ID NO: 125, respectively.

48. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 47 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4.

49. An anti-PD-1 antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 133 and SEQ ID NO: 127, respectively.

50. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 49 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4.

51. An anti-PD-1 antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 135 and SEQ ID NO: 127, respectively.

52. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 51 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4.

53. An anti-PD-1 antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 137 and SEQ ID NO: 129, respectively.

54. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 53 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4.

55. An anti-PD-1 antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 139 and SEQ ID NO: 129, respectively.

56. The anti-PD-1 antibody or antigen-binding fragment thereof of claim 55 , wherein the heavy chain constant region is a heavy chain constant region of an IgG4.

57. An anti-PD- 1 antibody comprising a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 143 and SEQ ID NO: 141, respectively.

58. A pharmaceutical composition comprising the anti-PD-1 antibody of claim 57 and a pharmaceutically acceptable excipient.

59. The anti-PD-1 antibody of claim 57 , wherein the antibody consists of a heavy chain and a light chain consisting of the amino acid sequences of SEQ ID NO: 143 and SEQ ID NO: 141, respectively.

60. An isolated polynucleotide encoding a heavy chain and/or a light chain of claim 57 .

61. An expression vector comprising a polynucleotide according to claim 60 .

62. An isolated host cell comprising an expression vector according to claim 61 .

63. An anti-PD-1 antibody comprising a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 147 and SEQ ID NO: 145, respectively.

64. A pharmaceutical composition comprising the anti-PD-1 antibody of claim 63 and a pharmaceutically acceptable excipient.

65. The anti-PD-1 antibody of claim 63 , wherein the antibody consists of a heavy chain and a light chain consisting of the amino acid sequences of SEQ ID NO: 147 and SEQ ID NO: 145, respectively.

66. An isolated polynucleotide encoding a heavy chain and/or a light chain of claim 63 .

67. An expression vector comprising a polynucleotide according to claim 66 .

68. An isolated host cell comprising an expression vector according to claim 67 .

69. An anti-PD-1 antibody comprising a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 149 and SEQ ID NO: 145, respectively.

70. A pharmaceutical composition comprising the anti-PD-1 antibody of claim 69 and a pharmaceutically acceptable excipient.

71. The anti-PD-1 antibody of claim 69 , wherein the antibody consists of a heavy chain and a light chain consisting of the amino acid sequences of SEQ ID NO: 149 and SEQ ID NO: 145, respectively.

72. An isolated polynucleotide encoding a heavy chain and/or a light chain of claim 69 .

73. An expression vector comprising a polynucleotide according to claim 72 .

74. An isolated host cell comprising an expression vector according to claim 73 .

75. An anti-PD-1 antibody comprising a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 153 and SEQ ID NO: 151, respectively.

76. A pharmaceutical composition comprising the anti-PD-1 antibody of claim 75 and a pharmaceutically acceptable excipient.

77. The anti-PD-1 antibody of claim 75 , wherein the antibody consists of a heavy chain and a light chain consisting of the amino acid sequences of SEQ ID NO: 153 and SEQ ID NO: 151, respectively.

78. An isolated polynucleotide encoding a heavy chain and/or a light chain of claim 75 .

79. An expression vector comprising a polynucleotide according to claim 78 .

80. An isolated host cell comprising an expression vector according to claim 79 .

81. An anti-PD-1 antibody comprising a heavy chain and a light chain comprising the amino acid sequences of SEQ ID NO: 155 and SEQ ID NO: 151, respectively.

82. A pharmaceutical composition comprising the anti-PD-1 antibody of claim 81 and a pharmaceutically acceptable excipient.

83. The anti-PD-1 antibody of claim 81 , wherein the antibody consists of a heavy chain and a light chain consisting of the amino acid sequences of SEQ ID NO: 155 and SEQ ID NO: 151, respectively.

84. An isolated polynucleotide encoding a heavy chain and/or a light chain of claim 81 .

85. An expression vector comprising a polynucleotide according to claim 84 .

86. An isolated host cell comprising an expression vector according to claim 85 .

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2022
From: BOEHRINGER INGELHEIM PHARMACEUTICALS INC.
To: BOEHRINGER INGELHEIM INTERNATIONAL GMBH
Reel/Frame 059326/0803 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2022
From: BLAIR, DAVID A.; GARAFFA, NICOLE K.; GUPTA, PANKAJ; GUPTA, PRIYANKA; HAN, FEI; KARLAK, AARON TIMOTHY; LIU, DONGMEI; LORENZ, IVO; MBOW, MOUHAMADOU LAMINE; MORENO-GARCIA, MIGUEL E.; MOZDZIERZ, JOSEPH A.; RALPH, KERRY L.M.; SHAABAN, ABDULSALAM; WHITE, DELLA M.; WU, HELEN HAIXIA; YANG, GUANGWEI
To: BOEHRINGER INGELHEIM PHARMACEUTICALS INC.
Reel/Frame 059453/0543 →
Continuity (3)
Provisional Application 63039686 · Jun 16, 2020
Provisional Application 63029962 · May 26, 2020
Related Publication 20210380696A1 · Dec 9, 2021
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