US10385122B2ActiveUtilityA1

Nucleic acids encoding anti-C5 antibodies

94
Assignee: CHUGAI PHARMACEUTICAL CO LTDPriority: Dec 19, 2014Filed: Jun 27, 2018Granted: Aug 20, 2019
Est. expiryDec 19, 2034(~8.4 yrs left)· nominal 20-yr term from priority
Inventors:Yoshinao RuikeZenjiro Sampei
A61P 43/00A61P 37/02A61P 9/10A61P 9/00A61P 7/00A61P 29/00A61P 27/02A61P 25/00A61P 19/02A61P 17/00A61P 15/06A61P 13/12A61P 13/02G01N 33/6863C07K 2317/21A61K 31/519C07K 2317/24G01N 2333/4716C07K 2317/94C07K 16/18G01N 33/564C07K 2317/92C07K 2317/76A61K 2039/505C12N 15/02
94
PatentIndex Score
14
Cited by
560
References
58
Claims

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

exact text as granted — not AI-modified
What is claimed is: 
     
       1. An isolated nucleic acid or nucleic acids encoding an 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 NO: 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 nucleic acid or nucleic acids of  claim 1 , wherein the encoded antibody comprises:
 (a) 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; or 
 (b) 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. 
 
     
     
       3. The nucleic acid or nucleic acids of  claim 1 , wherein the encoded antibody is a full length IgG1 or IgG4 antibody. 
     
     
       4. The nucleic acid or nucleic acids of  claim 1 , wherein the encoded antibody is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO: 114. 
     
     
       5. The nucleic acid or nucleic acids of  claim 1 , wherein the encoded antibody is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116. 
     
     
       6. The nucleic acid or nucleic acids of  claim 4 , wherein the encoded antibody comprises a CL of SEQ ID NO: 38. 
     
     
       7. The nucleic acid or nucleic acids of  claim 5 , wherein the encoded antibody comprises a CL of SEQ ID NO: 38. 
     
     
       8. The nucleic acid or nucleic acids of  claim 7 , wherein the encoded antibody comprises a IgG4 CH sequence of SEQ ID NO: 115 and a CL of SEQ ID NO: 38. 
     
     
       9. The nucleic acid or nucleic acids of  claim 7 , wherein the encoded antibody comprises a IgG4 CH sequence of SEQ ID NO: 116 and a CL of SEQ ID NO: 38. 
     
     
       10. A vector or vectors comprising the nucleic acid or nucleic acids of  claim 1 . 
     
     
       11. A host cell comprising the vector or vectors of  claim 10 . 
     
     
       12. A method for producing an antibody, comprising culturing the host cell of  claim 11  under conditions suitable for production of the antibody. 
     
     
       13. The method of  claim 12 , which further comprises purifying the antibody. 
     
     
       14. The method of  claim 12 , wherein the host cell is a mammalian cell. 
     
     
       15. An isolated nucleic acid or nucleic acids encoding an 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; 
 (c) a HVR-H3 comprising the amino acid sequence of SEQ ID NO: 121; 
 (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. 
 
     
     
       16. The nucleic acid or nucleic acids of  claim 15 , wherein the encoded antibody comprises:
 (a) 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; or 
 (b) 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. 
 
     
     
       17. The nucleic acid or nucleic acids of  claim 15 , wherein the encoded antibody comprises a VH of SEQ ID NO: 108 or 109. 
     
     
       18. The nucleic acid or nucleic acids of  claim 15 , wherein the encoded antibody comprises a VH of SEQ ID NO: 106. 
     
     
       19. The nucleic acid or nucleic acids of  claim 15 , wherein the encoded antibody comprises a VL of SEQ ID NO: 111. 
     
     
       20. The nucleic acid or nucleic acids of  claim 15 , wherein the encoded antibody comprises a VL of SEQ ID NO: 112. 
     
     
       21. The nucleic acid or nucleic acids of  claim 15 , wherein the encoded antibody is a full length IgG1 or IgG4 antibody. 
     
     
       22. The nucleic acid or nucleic acids of  claim 15 , wherein the encoded antibody is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO: 114. 
     
     
       23. The nucleic acid or nucleic acids of  claim 15 , wherein the encoded antibody is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116. 
     
     
       24. The nucleic acid or nucleic acids of  claim 22 , wherein the encoded antibody comprises a CL of SEQ ID NO: 38. 
     
     
       25. The nucleic acid or nucleic acids of  claim 23 , wherein the encoded antibody comprises a CL of SEQ ID NO: 38. 
     
     
       26. The nucleic acid or nucleic acids of  claim 25 , wherein the encoded antibody comprises a IgG4 CH sequence of SEQ ID NO: 115 and a CL of SEQ ID NO: 38. 
     
     
       27. The nucleic acid or nucleic acids of  claim 25 , wherein the encoded antibody comprises a IgG4 CH sequence of SEQ ID NO: 116 and a CL of SEQ ID NO: 38. 
     
     
       28. A vector or vectors comprising the nucleic acid or nucleic acids of  claim 15 . 
     
     
       29. A host cell comprising the vector or vectors of  claim 28 . 
     
     
       30. A method for producing an antibody, comprising culturing the host cell of  claim 29  under conditions suitable for production of the antibody. 
     
     
       31. The method of  claim 30 , which further comprises purifying the antibody. 
     
     
       32. The method of  claim 30 , wherein the host cell is a mammalian cell. 
     
     
       33. An isolated nucleic acid or nucleic acids encoding 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; 
 (c) a VH of SEQ ID NO:108 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. 
 
     
     
       34. The nucleic acid or nucleic acids of  claim 33 , wherein the encoded antibody is a full length IgG1 or IgG4 antibody. 
     
     
       35. The nucleic acid or nucleic acids of  claim 33 , wherein the encoded antibody is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO: 114. 
     
     
       36. The nucleic acid or nucleic acids of  claim 33 , wherein the encoded antibody is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116. 
     
     
       37. The nucleic acid or nucleic acids of  claim 35 , wherein the encoded antibody comprises a CL of SEQ ID NO: 38. 
     
     
       38. The nucleic acid or nucleic acids of  claim 36 , wherein the encoded antibody comprises a CL of SEQ ID NO: 38. 
     
     
       39. The nucleic acid or nucleic acids of  claim 38 , wherein the encoded antibody comprises a IgG4 CH sequence of SEQ ID NO: 115 and a CL of SEQ ID NO: 38. 
     
     
       40. The nucleic acid or nucleic acids of  claim 38 , wherein the encoded antibody comprises a IgG4 CH sequence of SEQ ID NO: 116 and a CL of SEQ ID NO: 38. 
     
     
       41. A vector or vectors comprising the nucleic acid or nucleic acids of  claim 33 . 
     
     
       42. A host cell comprising the vector or vectors of  claim 41 . 
     
     
       43. A method for producing an antibody, comprising culturing the host cell of  claim 42  under conditions suitable for production of the antibody. 
     
     
       44. The method of  claim 43 , which further comprises purifying the antibody. 
     
     
       45. The method of  claim 43 , wherein the host cell is a mammalian cell. 
     
     
       46. An isolated nucleic acid or nucleic acids encoding an antibody that binds to C5 and comprises a VH of SEQ ID NO:106 and a VL of SEQ ID NO:111. 
     
     
       47. The nucleic acid or nucleic acids of  claim 46 , wherein the encoded antibody is a full length IgG1 or IgG4 antibody. 
     
     
       48. The nucleic acid or nucleic acids of  claim 46 , wherein the encoded antibody is a full length antibody and comprises a IgG1 CH variant sequence of SEQ ID NO: 114. 
     
     
       49. The nucleic acid or nucleic acids of  claim 46 , wherein the encoded antibody is a full length antibody and comprises a IgG4 CH sequence of SEQ ID NO: 35, 115, or 116. 
     
     
       50. The nucleic acid or nucleic acids of  claim 48 , wherein the encoded antibody comprises a CL of SEQ ID NO: 38. 
     
     
       51. The nucleic acid or nucleic acids of  claim 49 , wherein the encoded antibody comprises a CL of SEQ ID NO: 38. 
     
     
       52. The nucleic acid or nucleic acids of  claim 51 , wherein the encoded antibody comprises a IgG4 CH sequence of SEQ ID NO: 115 and a CL of SEQ ID NO: 38. 
     
     
       53. The nucleic acid or nucleic acids of  claim 51 , wherein the encoded antibody comprises a IgG4 CH sequence of SEQ ID NO: 116 and a CL of SEQ ID NO: 38. 
     
     
       54. A vector or vectors comprising the nucleic acid or nucleic acids of  claim 46 . 
     
     
       55. A host cell comprising the vector or vectors of  claim 54 . 
     
     
       56. A method for producing an antibody, comprising culturing the host cell of  claim 55  under conditions suitable for production of the antibody. 
     
     
       57. The method of  claim 56 , which further comprises purifying the antibody. 
     
     
       58. The method of  claim 56 , wherein the host cell is a mammalian cell.

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