Nucleic acids encoding anti-C5 antibodies

Patent metadata

Field	Value
Publication number	US-10385122-B2
Application number	US-201816019752-A
Country	US
Kind code	B2
Filing date	Jun 27, 2018
Priority date	Dec 19, 2014
Publication date	Aug 20, 2019
Grant date	Aug 20, 2019

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.

First claim

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 I

Assignees

• Chugai Pharmaceutical Co Ltd

Inventors

• Ruike Yoshinao
• Sampei Zenjiro

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title