Antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-10017577-B2
Application number	US-201615181618-A
Country	US
Kind code	B2
Filing date	Jun 14, 2016
Priority date	Jun 15, 2015
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

The invention provides immunoconjugates and methods of using the same.

First claim

What is claimed is:

1. An immunoconjugate comprising a structure selected from:

wherein p is from 1 to 4 and Ab is an antibody that binds Ly6E comprising an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 6, and an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 7; an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 8; an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 3; an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 4; and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 5.

2. The immunoconjugate of claim 1 , wherein Ab is an antibody that binds Ly6E comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 2 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 1.

3. The immunoconjugate of claim 1 , wherein the antibody is a monoclonal antibody.

4. The immunoconjugate of claim 1 , wherein the antibody is a humanized or chimeric antibody.

5. The immunoconjugate of claim 1 , wherein the antibody is an antibody fragment that binds to Ly6E.

6. The immunoconjugate of claim 1 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

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

8. The immunoconjugate of claim 7 , wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 77 or 79.

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

10. The immunoconjugate of claim 9 , wherein the antibody comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO: 76 or 78.

11. The immunoconjugate of claim 1 , wherein the antibody comprises a K149C mutation in the light chain constant region.

12. The immunoconjugate of claim 11 , wherein the light chain constant region comprises the amino acid sequence of SEQ ID NO: 78.

13. The immunoconjugate of claim 1 , wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 10 and a light chain comprising the sequence of SEQ ID NO: 9.

14. The immunoconjugate of claim 1 , wherein p ranges from 1 to about 2.

15. The immunoconjugate of claim 1 , wherein p is about 2.

16. An immunoconjugate comprising the structure:

wherein Ab is an antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises the sequence of SEQ ID NO: 10 and the light chain comprises the sequence of SEQ ID NO: 9; and p is 1 to about 2.

17. The immunoconjugate of claim 16 , wherein p is about 2.

18. A pharmaceutical formulation comprising the immunoconjugate of claim 1 and a pharmaceutically acceptable carrier.

19. A method of treating a Ly6E-positive cancer comprising administering to an individual with a Ly6E-positive cancer an effective amount of the pharmaceutical formulation of claim 18 .

20. The method of claim 19 , wherein the cancer is selected from breast cancer, metastatic breast cancer, Her2 negative breast cancer, triple negative breast cancer, pancreatic cancer, colon cancer, colorectal cancer, melanoma, ovarian cancer, non-small cell lung cancer, and gastric cancer.

21. A method of inhibiting proliferation of a Ly6E-positive cell, comprising exposing the Ly6E-positive cell to an immunoconjugate of claim 1 under conditions permissive for binding of the immunoconjugate to an antigen on the surface of the cell, thereby inhibiting proliferation of the cell.

22. The immunoconjugate of claim 2 , wherein the antibody is a monoclonal antibody.

23. The immunoconjugate of claim 2 , wherein the antibody is an antibody fragment that binds to Ly6E.

24. The immunoconjugate of claim 2 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

25. The immunoconjugate of claim 2 , wherein the antibody comprises at least one mutation in the heavy chain constant region selected from A 118C and S400C.

26. The immunoconjugate of claim 25 , wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 77 or 79.

27. The immunoconjugate of claim 2 , wherein the antibody comprises at least one mutation in the light chain constant region selected from K149C and V205C.

28. The immunoconjugate of claim 27 , wherein the antibody comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO: 76 or 78.

29. The immunoconjugate of claim 2 , wherein the antibody comprises a K149C mutation in the light chain constant region.

30. The immunoconjugate of claim 29 , wherein the light chain constant region comprises the amino acid sequence of SEQ ID NO: 78.

31. The immunoconjugate of claim 2 , wherein p ranges from 1 to about 2.

32. The immunoconjugate of claim 2 , wherein p is about 2.

33. A pharmaceutical formulation comprising the immunoconjugate of claim 2 and a pharmaceutically acceptable carrier.

34. A method of treating a Ly6E-positive cancer comprising administering to an individual with a Ly6E-positive cancer an effective amount of the pharmaceutical formulation of claim 33 .

35. The method of claim 34 , wherein the cancer is selected from breast cancer, metastatic breast cancer, Her2 negative breast cancer, triple negative breast cancer, pancreatic cancer, colon cancer, colorectal cancer, melanoma, ovarian cancer, non-small cell lung cancer, and gastric cancer.

36. A pharmaceutical formulation comprising the immunoconjugate of claim 16 and a pharmaceutically acceptable carrier.

37. A method of treating a Ly6E-positive cancer comprising administering to an individual with a Ly6E-positive cancer an effective amount of the pharmaceutical formulation of claim 36 .

38. The method of claim 37 , wherein the cancer is selected from breast cancer, metastatic breast cancer, Her2 negative breast cancer, triple negative breast cancer, pancreatic cancer, colon cancer, colorectal cancer, melanoma, ovarian cancer, non-small cell lung cancer, and gastric cancer.

Assignees

• Genentech Inc

Inventors

• Polakis Paul
• DRAGOVICH Peter
• Pillow Thomas Harden
• Yu Shang-Fan

Classifications

• C07K16/3023

  Lung · CPC title

• C07K2317/515

  Complete light chain, i.e. VL + CL · CPC title

• C07K16/32

  against translation products of oncogenes · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title