IP Library › Granted Patent US 9,765,135

Granted Patent B2

US 9,765,135 · App. 14/974,350 · Granted Sep 19, 2017

Anti-C5 antibodies

Inventors: Yoshinao Ruike (Singapore, SG); Zenjiro Sampei (Singapore, SG)

Assignee: Chugai Seiyaku Kabushiki Kaisha

C07K16/18 A61K31/519 G01N33/564 G01N33/6863 C07K2317/21 C07K2317/24 C07K2317/76 C07K2317/92 C07K2317/94 G01N2333/4716

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 9,765,135
App. No.: 14/974,350
Granted: Sep 19, 2017
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

An objective of the invention is to provide anti-C5 antibodies and methods of using the same. The invention provides anti-C5 antibodies and methods of using the same. In some embodiments, an isolated anti-C5 antibody of the present invention binds to an epitope within the β chain of C5 with a higher affinity at neutral pH than at acidic pH. The invention also provides isolated nucleic acids encoding an anti-C5 antibody of the present invention. The invention also provides host cells comprising a nucleic acid of the present invention. The invention also provides a method of producing an antibody comprising culturing a host cell of the present invention so that the antibody is produced. The invention further provides a method of producing an anti-C5 antibody comprising immunizing an animal against a polypeptide which comprises the MG1-MG2 domain of the β chain of C5. Anti-C5 antibodies of the present invention may be for use as a medicament. Anti-C5 antibodies of the present invention may be for use in treating a complement-mediated disease or condition which involves excessive or uncontrolled activation of C5. Anti-C5 antibodies of the present invention may be for use in enhancing the clearance of C5 from plasma.

Claims (109)

1. An isolated antibody that binds to C5, wherein the antibody comprises:

(a) a HVR-H1 comprising the amino acid sequence SSYYX 1 X 2 , wherein X 1 is M or V, X 2 is C or A (SEQ ID NO: 126);

(b) a HVR-H2 comprising the amino acid sequence X 1 IX 2 TGSGAX 3 YX 4 AX 5 WX 6 KG, wherein X 1 is C, A or G, X 2 is Y or F, X 3 is T, D or E, X 4 is Y, K or Q, X 5 is S, D or E, X 6 is A or V (SEQ ID NO: 127); and

(c) a HVR-H3 comprising the amino acid sequence DX 1 GYX 2 X 3 PTHAMX 4 X 5 , wherein X 1 is G or A, X 2 is V, Q or D, X 3 is T or Y, X 4 is Y or H, X 5 is L or Y (SEQ ID NO: 128);

(d) a HVR-L1 comprising the amino acid sequence X 1 ASQX 2 IX 3 SX 4 LA, wherein X 1 is Q or R, X 2 is N, Q or G, X 3 is G or S, X 4 is D, K or S (SEQ ID N: 129);

(e) a HVR-L2 comprising the amino acid sequence GASX 1 X 2 X 3 S, wherein X 1 is K, E or T, X 2 is L or T, X 3 is A, H, E or Q (SEQ ID NO: 130); and

(f) a HVR-L3 comprising the amino acid sequence QX 1 TX 2 VGSSYGNX 3 , wherein X 1 is S, C, N or T, X 2 is F or K, X 3 is A, T or H (SEQ ID NO: 131).

2. The antibody of claim 1 , further comprising a heavy chain variable domain framework FR1 comprising the amino acid sequence of SEQ ID NO: 132, 133, or 134; a FR2 comprising the amino acid sequence of SEQ ID NO: 135 or 136; a FR3 comprising the amino acid sequence of SEQ ID NO: 137, 138, or 139; and a FR4 comprising the amino acid sequence of SEQ ID NO: 140 or 141.

3. The antibody of claim 1 , further comprising a light chain variable domain framework FR1 comprising the amino acid sequence of SEQ ID NO: 142, or 143; a FR2 comprising the amino acid sequence of SEQ ID NO: 144 or 145; a FR3 comprising the amino acid sequence of SEQ ID NO: 146 or 147; and a FR4 comprising the amino acid sequence of SEQ ID NO: 148.

4. An isolated antibody that binds to C5 and comprises a VH sequence of SEQ ID NO: 10, 106, 107, 108, 109, or 110, and a VL sequence of SEQ ID NO: 20, 111, 112, or 113.

5. An antibody that binds to C5 and comprises a VH and VL pair selected from:

(a) a VH of SEQ ID NO:10 and a VL of SEQ ID NO:20;

(b) a VH of SEQ ID NO:107 and a VL of SEQ ID NO:111;

(d) a VH of SEQ ID NO:109 and a VL of SEQ ID NO:111;

(e) a VH of SEQ ID NO:109 and a VL of SEQ ID NO:112;

(f) a VH of SEQ ID NO:109 and a VL of SEQ ID NO:113; and

(g) a VH of SEQ ID NO:110 and a VL of SEQ ID NO:113.

6. The antibody of claim 5 , which is a full length IgG1 or IgG4 antibody.

7. An antibody that binds to C5 and comprises a VH of SEQ ID NO:106 and a VL, of SEQ ID NO:111.

8. The antibody of claim 7 , which is a full length IgG1 or IgG4 antibody.

9. An isolated antibody that binds to C5, wherein the antibody comprises:

(a) (i) a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 117;

(ii) a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 119;

(iii) a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 121;

(iv) a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122;

(v) a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 123; and

(vi) a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125;

(b) (i) a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 117;

(ii) a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 118;

(iii) a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 121;

(iv) a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122;

(v) a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 124; and

(vi) a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125;

(ii) a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 120;

(iii) a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 121;

(iv) a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122;

(v) a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 124; and

(vi) a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125; and

(d) (i) a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 54;

(ii) a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 64;

(iii) a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 74;

(iv) a HVR-L1 comprising the amino acid sequence of SEQ ID NO: 84;

(v) a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 94; and

(vi) a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 104.

10. The antibody of claim 9 , further comprising a heavy chain variable domain framework FR1 comprising the amino acid sequence of SEQ ID NO: 132, 133, or 134; a FR2 comprising the amino acid sequence of SEQ ID NO: 135 or 136; a FR3 comprising the amino acid sequence of SEQ ID NO: 137, 138, or 139; and a FR4 comprising the amino acid sequence of SEQ ID NO: 140 or 141.

11. The antibody of claim 9 , further comprising a light chain variable domain framework FR1 comprising the amino acid sequence of SEQ ID NO: 142, or 143; a FR2 comprising the amino acid sequence of SEQ ID NO: 144 or 145; a FR3 comprising the amino acid sequence of SEQ ID NO: 146 or 147; and a FR4 comprising the amino acid sequence of SEQ ID NO: 148.

12. The antibody of claim 9 , which comprises a VH selected from the group consisting of SEQ ID NO: 10, 106, 107, 108, 109, and 110.

13. The antibody of claim 9 , which comprises a VL selected from the group consisting of SEQ ID NO: 20, 111, 112, and 113.

14. The antibody of claim 9 , which is a full length IgG1 or IgG4 antibody.

15. The antibody of claim 9 , which is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO: 114.

16. The antibody of claim 9 , which is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116.

17. The antibody of claim 15 , which further comprises a CL of SEQ ID NO: 38.

18. The antibody of claim 16 , which further comprises a CL of SEQ ID NO: 38.

19. The antibody of claim 18 , which comprises a IgG4 CH sequence of SEQ ID NO: 115 and a CL of SEQ ID NO: 38.

20. The antibody of claim 18 , which comprises a IgG4 CH sequence of SEQ ID NO: 116 and a CL of SEQ ID NO: 38.

21. A pharmaceutical formulation comprising the antibody of claim 9 and a pharmaceutically acceptable carrier.

22. An isolated antibody that binds to C5, wherein the antibody comprises:

(a) a HVR-H1 comprising the amino acid sequence of SEQ ID NO: 117;

(b) a HVR-H2 comprising the amino acid sequence of SEQ ID NO: 118;

(d) a HVR-L1 comprising the amino acid sequence of SEQ ID NO): 122;

(e) a HVR-L2 comprising the amino acid sequence of SEQ ID NO: 123; and

(f) a HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125.

23. The antibody of claim 22 , further comprising a heavy chain variable domain framework FR1 comprising the amino acid sequence of SEQ ID NO: 132, 133, or 134; a FR2 comprising the amino acid sequence of SEQ ID NO: 135 or 136; a FR3 comprising the amino acid sequence of SEQ ID NO: 137, 138, or 139; and a FR4 comprising the amino acid sequence of SEQ ID NO: 140 or 141.

24. The antibody of claim 22 , further comprising a light chain variable domain framework FR1 comprising the amino acid sequence of SEQ ID NO: 142, or 143; a FR2 comprising the amino acid sequence of SEQ ID NO: 144 or 145; a FR3 comprising the amino acid sequence of SEQ ID NO: 146 or 147; and a FR4 comprising the amino acid sequence of SEQ ID NO: 148.

25. The antibody claim 22 , which comprises a VH of SEQ ID NO: 108 or 109.

26. The antibody of claim 22 , which comprises a VH of SEQ ID NO: 106.

27. The antibody of claim 22 , which comprises a VL of SEQ ID NO: 111.

28. The antibody of claim 22 , which comprises a VL of SEQ ID NO: 112.

29. The antibody of claim 22 , which is a full length IgG1 or IgG4 antibody.

30. The antibody of claim 22 , which is a length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO: 114.

31. The antibody of claim 22 , which is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116.

32. The antibody of claim 30 , which further comprises a CL of SEQ ID NO: 38.

33. The antibody of claim 31 , which further comprises a CL of SEQ ID NO: 38.

34. The antibody of claim 33 , which comprises a IgG4 CH sequence of SEQ ID NO: 115 and a CL of SEQ ID NO: 38.

35. The antibody of claim 33 , which comprises a IgG4 CH sequence of SEQ ID NO: 116 and a CL of SEQ ID NO: 38.

36. A pharmaceutical formulation comprising the antibody of claim 22 and a pharmaceutically acceptable carrier.

37. The antibody of claim 1 , which is a full length IgG1 or IgG4 antibody.

38. The antibody of claim 1 , which is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO: 114.

39. The antibody of claim 1 , which is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116.

40. The antibody of claim 38 , which further comprises a CL of SEQ ID NO: 38.

41. The antibody of claim 39 , which further comprises a CL, of SEQ ID NO: 38.

42. The antibody of claim 41 , which comprises a IgG4 CH sequence of SEQ ID NO: 115 and a CL of SEQ ID NO: 38.

43. The antibody of claim 41 , which comprises a IgG4 CH sequence of SEQ ID NO:116 and a CL of SEQ ID NO: 38.

44. A pharmaceutical formulation comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

45. The antibody of claim 4 , which is a full length IgG1 or IgG4 antibody.

46. The antibody of claim 4 , which is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO: 114.

47. The antibody of claim 4 , which is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116.

48. The antibody of claim 46 , which further comprises a CL of SEQ ID NO: 38.

49. The antibody of claim 47 , which further comprises a CL of SEQ ID NO: 38.

50. The antibody of claim 49 , which comprises a IgG4 CH sequence of SEQ ID NO:115 and a CL of SEQ ID NO: 38.

51. The antibody of claim 49 , which comprises a IgG4 CH sequence of SEQ ID NO: 116 and a CL of SEQ ID NO: 38.

52. A pharmaceutical formulation comprising the antibody of claim 4 and a pharmaceutically acceptable carrier.

53. The antibody of claim 5 , which is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO:114.

54. The antibody of claim 5 , which is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116.

55. The antibody of claim 53 , which further comprises a CL of SEQ ID NO:38.

56. The antibody of claim 54 , which further comprises a CL of SEQ ID NO:38.

57. The antibody of claim 56 , which comprises a IgG4 CH sequence of SEQ ID NO:115 and a CL of SEQ ID NO:38.

58. The antibody of claim 56 , which comprises a IgG4 CH sequence of SEQ ID NO:116 and a CL of SEQ ID NO: 38.

59. A pharmaceutical formulation comprising the antibody of claim 5 and a pharmaceutically acceptable carrier.

60. The antibody of claim 7 , which is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO:114.

61. The antibody of claim 7 , which is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116.

62. The antibody of claim 60 , which further comprises a CL of SEQ ID NO: 38.

63. The antibody of claim 61 , which further comprises a CL of SEQ ID NO: 38.

64. The antibody of claim 63 , which comprises a IgG4 CH sequence of SEQ ID NO:115 and a CL of SEQ ID NO: 38.

65. The antibody of claim 63 , which comprises a IgG4 CH sequence of SEQ ID NO:116 and a CL of SEQ ID NO: 38.

66. A pharmaceutical formulation comprising the antibody of claim 7 and a pharmaceutically acceptable carrier.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 2, 2017

From: RUIKE, YOSHINAO; SAMPEI, ZENJIRO

To: CHUGAI SEIYAKU KABUSHIKI KAISHA

Reel/Frame 041154/0673 →

Priority Claims (1)

JP 2014-257647 · Dec 19, 2014 · national

Continuity (1)

Related Publication 20160176954A1 · Jun 23, 2016