Anti-HER2 antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-10556966-B2
Application number	US-201816170819-A
Country	US
Kind code	B2
Filing date	Oct 25, 2018
Priority date	Sep 12, 2014
Publication date	Feb 11, 2020
Grant date	Feb 11, 2020

Abstract

The invention provides anti-HER2 antibodies and immunoconjugates and methods of using the same.

First claim

What is claimed is:

1. An isolated nucleic acid encoding an antibody that binds to HER2, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:15; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:16; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:17; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:12; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:13; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:14.

2. A host cell comprising the nucleic acid of claim 1 .

3. A method of producing an antibody comprising culturing the host cell of claim 2 so that the antibody is produced.

4. An isolated nucleic acid encoding an antibody that binds to HER2, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:15; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:20; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:17; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:12; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:13; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:14.

5. A host cell comprising the nucleic acid of claim 4 .

6. A method of producing an antibody comprising culturing the host cell of claim 5 so that the antibody is produced.

7. An isolated nucleic acid encoding an antibody that binds to HER2, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:15; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:21; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:17; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:12; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:13; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:14.

8. A host cell comprising the nucleic acid of claim 7 .

9. A method of producing an antibody comprising culturing the host cell of claim 8 so that the antibody is produced.

10. An isolated nucleic acid encoding an antibody that binds to HER2, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:15; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:8; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:22; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:12; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:13; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:14.

11. A host cell comprising the nucleic acid of claim 10 .

12. A method of producing an antibody comprising culturing the host cell of claim 11 so that the antibody is produced.

13. The nucleic acid of claim 1 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

14. The nucleic acid of claim 1 , wherein the antibody comprises a κ light chain.

15. The nucleic acid of claim 1 , wherein the anti-HER2 antibody comprises a heavy chain comprising at least one mutation in the heavy chain constant region selected from A118C and S400C.

16. The nucleic acid of claim 1 , wherein the anti-HER2 antibody comprises a light chain comprising at least one mutation in the light chain constant region selected from K149C and V205C.

17. The nucleic acid of claim 4 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

18. The nucleic acid of claim 4 , wherein the antibody comprises a κ light chain.

19. The nucleic acid of claim 4 , wherein the anti-HER2 antibody comprises a heavy chain comprising at least one mutation in the heavy chain constant region selected from A118C and S400C.

20. The nucleic acid of claim 4 , wherein the anti-HER2 antibody comprises a light chain comprising at least one mutation in the light chain constant region selected from K149C and V205C.

21. The nucleic acid of claim 7 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

22. The nucleic acid of claim 7 , wherein the antibody comprises a κ light chain.

23. The nucleic acid of claim 7 , wherein the anti-HER2 antibody comprises a heavy chain comprising at least one mutation in the heavy chain constant region selected from A118C and S400C.

24. The nucleic acid of claim 7 , wherein the anti-HER2 antibody comprises a light chain comprising at least one mutation in the light chain constant region selected from K149C and V205C.

25. The nucleic acid of claim 10 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

26. The nucleic acid of claim 10 , wherein the antibody comprises a κ light chain.

27. The nucleic acid of claim 10 , wherein the anti-HER2 antibody comprises a heavy chain comprising at least one mutation in the heavy chain constant region selected from A118C and S400C.

28. The nucleic acid of claim 10 , wherein the anti-HER2 antibody comprises a light chain comprising at least one mutation in the light chain constant region selected from K149C and V205C.

29. An isolated nucleic acid encoding an antibody that binds to HER2, wherein the antibody comprises:
(i) a heavy chain variable region comprising the sequence of SEQ ID NO: 11 and a light chain variable region comprising the sequence of SEQ ID NO: 10; or
(ii) a heavy chain comprising the sequence of SEQ ID NO: 19 or SEQ ID NO: 24 and a light chain comprising the sequence of SEQ ID NO: 18 or SEQ ID NO: 23.

30. A host cell comprising the nucleic acid of claim 29 .

31. A method of producing an antibody comprising culturing the host cell of claim 30 so that the antibody is produced.

32. The nucleic acid of claim 29 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

33. The nucleic acid of claim 29 , wherein the antibody comprises a κ light chain.

34. The nucleic acid of claim 29 , wherein the anti-HER2 antibody comprises a heavy chain comprising at least one mutation in the heavy chain constant region selected from A118C and S400C.

35. The nucleic acid of claim 29 , wherein the anti-HER2 antibody comprises a light chain comprising at least one mutation in the light chain constant region selected from K149C and V205C.

36. The nucleic acid of claim 29 , wherein the anti-HER2 antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 19 and a light chain comprising the sequence of SEQ ID NO: 18.

37. A host cell comprising the nucleic acid of claim 36 .

38. A method of producing an antibody comprising culturing the host cell of claim 37 so that the antibody is produced.

39. The nucleic acid of claim 29 , wherein the anti-HER2 antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 24 and a light chain comprising the sequence of SEQ ID NO: 18.

40. A host cell comprising the nucleic acid of claim 39 .

41. A method of producing an antibody comprising culturing the host cell of claim 40 so that the antibody is produced.

42. The nucleic acid of claim 29 , wherein the anti-HER2 antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 19 and a light chain comprising the sequence of SEQ ID NO: 23.

43. A host cell comprising the nucleic acid of claim 42 .

44. A method of producing an antibody comprising culturing the host cell of claim 43 so that the ant

Assignees

• Genentech Inc

Inventors

• Chen Xiaocheng
• Dennis Mark
• Junutula Jagath Reddy
• Phillips Gail Lewis
• Pillow Thomas Harden
• Sliwkowski Mark X

Classifications

• A61P43/00

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

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/57515

  of the breast · CPC title

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title