IP Library › Granted Patent US 9,518,118
Granted Patent B2
US 9,518,118 · App. 14/851,001 · Granted Dec 13, 2016

Anti-HER2 antibodies and immunoconjugates

Inventors: Xiaocheng Chen (Burlingame, CA); Mark Dennis (San Carlos, CA); Jagath Reddy Junutula (Fremont, CA); Gail Lewis Phillips (San Carlos, CA); Thomas Harden Pillow (San Francisco, CA); Mark X. Sliwkowski (San Carlos, CA)
Assignee: Genentech, Inc.
C07K16/2863A61K39/3955A61K47/48369A61K47/48407A61K47/48561A61K47/48584A61K47/48615C07K16/32G01N33/57415G01N33/57446C07K2317/24C07K2317/34C07K2317/51C07K2317/515C07K2317/56C07K2317/565C07K2317/73C07K2317/92G01N2333/82
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Quick Facts
Patent No.
US 9,518,118
App. No.
14/851,001
Granted
Dec 13, 2016
Kind
B2
Abstract

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

Claims (32)

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.

Continuity (2)
Provisional Application 62049594 · Sep 12, 2014
Related Publication 20160096893A1 · Apr 7, 2016