Treatment of renal cell carcinoma with anti-CD70 antibody-drug conjugates

Patent metadata

Field	Value
Publication number	US-9345785-B2
Application number	US-63560709-A
Country	US
Kind code	B2
Filing date	Dec 10, 2009
Priority date	Feb 20, 2003
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

Disclosed are anti-CD70 antibodies and derivatives thereof conjugated to cytotoxic, therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody- and antibody derivative-drug conjugates. Also disclosed are methods, for the treatment of CD70-expressing a cancer, comprising administering to a subject the disclosed pharmaceutical compositions.

First claim

What is claimed is:

1. A method for the treatment of a CD70-expressing renal cell carcinoma in a human subject, the method comprising:
administering to the subject, in an amount effective for the treatment thereof, an antibody-drug conjugate comprising an antibody that specifically binds to CD70, wherein the antibody is a mouse antibody comprising a heavy chain variable region having the amino acid sequence set forth in residues 20 to 137 of SEQ ID NO:2, and a light chain variable region having the amino acid sequence set forth in residues 21 to 132 of SEQ ID NO:12, or a chimeric or humanized form of the mouse antibody, and wherein:
(i) the drug is a cytotoxic agent that is a DNA minor groove binding agent, an alkylating agent, or an anti-tubulin agent, and
(ii) the antibody-drug conjugate is internalized into cells, where it exerts a cytotoxic effect.

2. The method of claim 1 , wherein the antibody is a humanized antibody.

3. The method of claim 1 , wherein the antibody is a chimeric antibody.

4. The method of claim 1 , wherein the antibody is multivalent.

5. The method of claim 1 , wherein the cytotoxic agent is selected from the group consisting of an auristatin, a DNA minor groove alkylating agent, an enediyne, a lexitropsin, a duocarmycin, a taxane, a dolastatin, a maytansinoid, and a vinca alkaloid.

6. The method of claim 1 , wherein the cytotoxic agent is a DNA minor groove binding agent.

7. The method of claim 1 , wherein the cytotoxic agent is an anti-tubulin agent.

8. The method of claim 7 , wherein the cytotoxic agent is AFP or MMAE.

9. The method of claim 1 , wherein the antibody is conjugated to the cytotoxic agent via a linker.

10. The method of claim 9 , wherein the linker is cleavable under intracellular conditions.

11. The method of claim 10 , wherein the cleavable linker is cleavable by an intracellular protease.

12. The method of claim 11 , wherein the linker comprises a dipeptide.

13. The method of claim 12 , wherein the dipeptide is val-cit or phe-lys.

14. The method of claim 10 , wherein the cleavable linker is hydrolyzable at a pH of less than 5.5.

15. The method of claim 14 , wherein the hydrolyzable linker is a hydrazone linker.

16. The method of claim 10 , wherein the cleavable linker is a disulfide linker.

17. The method of claim 1 , wherein the antibody is a humanized antibody comprising H1, H2, H3, L1, L2 and L3 complementarity-determining regions having, respectively, the amino acid sequences set forth in SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10; SEQ ID NO:16, SEQ ID NO:18, and SEQ ID NO:20, respectively.

18. A method for the treatment of a CD70-expressing renal cell carcinoma in a human subject, the method comprising:
administering to the subject, in an amount effective for the treatment thereof, an antibody-drug conjugate comprising an antibody that specifically binds to CD70, wherein the antibody is a mouse antibody comprising a heavy chain variable region having the amino acid sequence set forth in residues 20 to 137 of SEQ ID NO:22, and a light chain variable region having the amino acid sequence set forth in residues 21 to 132 of SEQ ID NO:32, or a chimeric or humanized form of the mouse antibody, and wherein:
(i) the drug is a cytotoxic agent that is a DNA minor groove binding agent, an alkylating agent, or an anti-tubulin agent, and
(ii) the antibody-drug conjugate is internalized into cells, where it exerts a cytotoxic effect.

19. The method of claim 18 , wherein the antibody is a humanized antibody comprising H1, H2, H3, L1, L2 and L3 complementarity-determining regions having, respectively, the amino acid sequences set forth in SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30; SEQ ID NO:36, SEQ ID NO:38, and SEQ ID NO:40, respectively.

20. The method of claim 18 , wherein the antibody is a humanized antibody.

21. The method of claim 18 , wherein the antibody is a chimeric antibody.

22. The method of claim 18 , wherein the antibody is multivalent.

23. The method of claim 18 , wherein the cytotoxic agent is selected from the group consisting of an auristatin, a DNA minor groove alkylating agent, an enediyne, a lexitropsin, a duocarmycin, a taxane, a dolastatin, a maytansinoid, and a vinca alkaloid.

24. The method of claim 18 , wherein the cytotoxic agent is an anti-tubulin agent.

25. The method of claim 24 , wherein the cytotoxic agent is AFP or MMAE.

26. The method of claim 18 , wherein the antibody is conjugated to the cytotoxic agent via a linker.

27. The method of claim 26 , wherein the linker is cleavable under intracellular conditions.

28. The method of claim 27 , wherein the cleavable linker is cleavable by an intracellular protease.

29. The method of claim 28 , wherein the linker comprises a dipeptide.

30. The method of claim 29 , wherein the dipeptide is val-cit or phe-lys.

31. The method of claim 27 , wherein the cleavable linker is hydrolyzable at a pH of less than 5.5.

32. The method of claim 31 , wherein the hydrolyzable linker is a hydrazone linker.

33. The method of claim 27 , wherein the cleavable linker is a disulfide linker.

34. The method of claim 18 , wherein the cytotoxic agent is a DNA minor groove binding agent.

Assignees

• Law Che-Leung
• Wahl Alan F
• Scholler Nathalie
• Pestano Linda A
• Seattle Genetics Inc

Inventors

• Law Che-Leung
• Wahl Alan F
• Scholler Nathalie
• Pestano Linda A

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/06

  for tuberculosis · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P5/16

  for decreasing, blocking or antagonising the activity of the thyroid hormones · CPC title