Anti-HER2 antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-9518118-B2
Application number	US-201514851001-A
Country	US
Kind code	B2
Filing date	Sep 11, 2015
Priority date	Sep 12, 2014
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

Abstract

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

First claim

What is claimed is:

1. An isolated 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. The antibody of claim 1 , wherein the antibody comprises 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.

3. The antibody of claim 1 , which is a monoclonal antibody.

4. The antibody of claim 1 , which is a humanized or chimeric antibody.

5. The antibody of claim 1 , which is an antibody fragment that binds HER2.

6. The antibody of claim 1 , wherein HER2 is human HER2 comprising amino acids 23 to 1255 of SEQ ID NO: 1.

7. The antibody of claim 1 , wherein the antibody binds to extracellular domain I of HER2.

8. The antibody of claim 7 , wherein extracellular domain I of HER2 has the sequence of SEQ ID NO: 35.

9. The antibody of claim 1 , which is an IgG1, IgG2a or IgG2b antibody.

10. The antibody of claim 1 , wherein the antibody comprises at least one mutation in the heavy chain constant region selected from A118C and S400C.

11. The antibody of claim 1 , wherein the antibody comprises at least one mutation in the light chain constant region selected from K149C and V205C.

12. The antibody of claim 1 , wherein the antibody comprises:
a) a heavy chain comprising the sequence of SEQ ID NO: 19 and a light chain comprising the sequence of SEQ ID NO: 18; or
b) a heavy chain comprising the sequence of SEQ ID NO: 19 and a light chain comprising the sequence of SEQ ID NO: 23; or
c) a heavy chain comprising the sequence of SEQ ID NO: 24 and a light chain comprising the sequence of SEQ ID NO: 18.

13. The antibody of claim 1 , wherein the antibody comprises the heavy chain constant region of SEQ ID NO: 28.

14. The antibody of claim 1 , wherein the antibody comprises the light chain constant region of SEQ ID NO: 25.

15. An isolated antibody that binds to HER2, wherein the 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.

16. An isolated antibody that binds to HER2, wherein the 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.

17. An immunoconjugate comprising the antibody of claim 1 and a cytotoxic agent.

18. The antibody of claim 1 conjugated to a label.

19. The antibody of claim 18 , wherein the label is a positron emitter.

20. The antibody of claim 19 , wherein the positron emitter is 89 Zr.

21. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable region comprising a sequence at least 95% identical to the sequence of SEQ ID NO: 11 and a light chain variable region comprising a sequence at least 95% identical to the sequence of SEQ ID NO: 10.

22. The antibody of claim 2 , which is an IgG1, IgG2a or IgG2b antibody.

23. The antibody of claim 22 , wherein the antibody comprises at least one mutation in the heavy chain constant region selected from A118C and S400C.

24. The antibody of claim 22 , wherein the antibody comprises at least one mutation in the light chain constant region selected from K149C and V205C.

25. The antibody of claim 22 , wherein the antibody comprises a K149C mutation in the light chain constant region.

26. The antibody of claim 21 , which is an IgG1, IgG2a or IgG2b antibody.

27. The antibody of claim 26 , wherein the antibody comprises at least one mutation in the heavy chain constant region selected from A118C and S400C.

28. The antibody of claim 26 , wherein the antibody comprises at least one mutation in the light chain constant region selected from K149C and V205C.

29. The antibody of claim 26 , wherein the antibody comprises a K149C mutation in the light chain constant region.

Assignees

• Genentech Inc

Inventors

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

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• G01N33/57515

  of the breast · CPC title

• G01N33/5759

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