Anti-HER2 antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-10179820-B2
Application number	US-201615296454-A
Country	US
Kind code	B2
Filing date	Oct 18, 2016
Priority date	Sep 12, 2014
Publication date	Jan 15, 2019
Grant date	Jan 15, 2019

Abstract

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

First claim

What is claimed is:

1. A method of detecting human HER2 in a biological sample comprising contacting the biological sample with an anti-HER2 antibody under conditions permissive for binding of the anti-HER2 antibody to a naturally occurring human HER2, and detecting whether a complex is formed between the anti-HER2 antibody and a naturally occurring human HER2 in the biological sample, wherein the anti-HER2 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 method for detecting a HER2-positive cancer comprising (i) administering a labeled anti-HER2 antibody to a subject having or suspected of having a HER2-positive cancer, wherein the labeled anti-HER2 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 and (ii) detecting the labeled anti-HER2 antibody in the subject, wherein detection of the labeled anti-HER2 antibody indicates a HER2-positive cancer in the subject.

3. The method of claim 1 , wherein the anti-HER2 antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 11.

4. The method of claim 1 , wherein the anti-HER2 antibody comprises a light chain variable region comprising the sequence of SEQ ID NO: 10.

5. The method of claim 1 , wherein the anti-HER2 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.

6. The method of claim 1 , wherein the anti-HER2 antibody is an IgG1, IgG2a or IgG2b antibody.

7. The method of claim 1 , wherein the anti-HER2 antibody comprises a κ light chain.

8. The method of claim 7 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

9. The method 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.

10. The method 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.

11. The method of claim 1 , wherein the anti-HER2 antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 19 or SEQ ID NO: 24.

12. The method of claim 1 , wherein the anti-HER2 antibody comprises a light chain comprising the sequence of SEQ ID NO: 18 or SEQ ID NO: 23.

13. The method of claim 1 , wherein the anti-HER2 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.

14. The method of claim 2 , wherein the anti-HER2 antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 11.

15. The method of claim 2 , wherein the anti-HER2 antibody comprises a light chain variable region comprising the sequence of SEQ ID NO: 10.

16. The method of claim 2 , wherein the anti-HER2 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.

17. The method of claim 2 , wherein the anti-HER2 antibody is an IgG1, IgG2a or IgG2b antibody.

18. The method of claim 2 , wherein the anti-HER2 antibody comprises a κ light chain.

19. The method of claim 18 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

20. The method of claim 2 , 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.

21. The method of claim 2 , 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.

22. The method of claim 2 , wherein the anti-HER2 antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 19 or SEQ ID NO: 24.

23. The method of claim 2 , wherein the anti-HER2 antibody comprises a light chain comprising the sequence of SEQ ID NO: 18 or SEQ ID NO: 23.

24. The method of claim 2 , wherein the anti-HER2 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.

25. The method of claim 2 , wherein the labeled anti-HER2 antibody comprises an anti-HER2 antibody conjugated to a positron emitter.

26. The method of claim 25 , wherein the positron emitter is 89 Zr.

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