Granted Patent B2

US 8,637,016 · App. 12/045,589 · Granted Jan 28, 2014

Abstract

Claims (34)

1. A method of inhibiting growth of a solid tumor in a subject that has a solid tumor that expresses EphA3 on the tumor vasculature, but has fewer than 25% of tumor cells that have detectable expression of EphA3 on the tumor cell surface, the method comprising administering an anti-EphA3 antibody that clusters and activates EphA3 to the subject, with the proviso that the anti-EphA3 antibody is not conjugated to a therapeutic agent.

2. The method of claim 1 , wherein less than 10% of the tumor cells have detectable expression of EphA3 on the cell surface.

3. The method of claim 1 , wherein the anti-EphA3 antibody competes for EphA3 binding with an antibody that has a V H region CDR1 SYWIN (SEQ ID NO:1), a V H region CDR2 DIYPGSGNTNYDEKFKR (SEQ ID NO:2), a V H region CDR3 SGYYEDFDS (SEQ ID NO:3), a V L region CDR1 RASQEISGYLG (SEQ ID NO:8), a V L region CDR2 AASTLDS (SEQ ID NO:9), and a V L region CDR3 VQYANYPYT (SEQ ID NO:10).

4. The method of claim 1 , wherein the anti-EphA3 antibody is a recombinant or chimeric antibody.

5. The method of claim 1 , wherein the anti-EphA3 antibody is a human antibody.

6. The method of claim 1 , wherein the anti-EphA3 antibody is a humanized antibody or an engineered antibody that comprises sequences from human V H - and V L -segments.

7. The method of claim 1 , wherein the anti-EphA3 antibody is a monoclonal antibody.

8. The method of claim 1 , wherein the anti-EphA3 antibody is a multivalent antibody that comprises an antibody fragment that is a Fab, a Fab′, or an Fv.

9. The method of claim 1 , wherein the anti-EphA3 antibody comprises a human Fc region.

10. The method of claim 9 , wherein the anti-EphA3 antibody comprises a human gamma 1 or gamma 3 active isotype.

11. The method of claim 10 , wherein the Fc region glycosylation lacks fucose.

12. The method of claim 1 , wherein the anti-EphA3 antibody comprises a V H region CDR1 SYWIN (SEQ ID NO:1), a V H region CDR2 DIYPGSGNTNYDEKFKR (SEQ ID NO:2), a V H region CDR3 SGYYEDFDS (SEQ ID NO:3), a V L region CDR1 RASQEISGYLG (SEQ ID NO:8), a V L region CDR2 AASTLDS (SEQ ID NO:9), and a V L region CDR3 VQYANYPYT (SEQ ID NO:10).

13. The method of claim 1 , wherein the anti-EphA3 antibody comprises:

a V H region CDR1 TYWIS (SEQ ID NO:4), a V H region CDR2 DIYPGSGNTNYDEKFQG (SEQ ID NO:5), a V H region CDR3 SGYYEEFDS (SEQ ID NO:6), a V L region CDR1 RASQGIISYLA (SEQ ID NO:11), a V L region CDR2 AASSLQS (SEQ ID NO:12), and a V L region CDR3 VQYANYPYT (SEQ ID NO:10); or

a V H region CDR1 TYWIS (SEQ ID NO:4), a V H region CDR2 DIYPGSGNTNYDEKFEG (SEQ ID NO:7), a V H region CDR3 SGYYEEFDS (SEQ ID NO:6), a V L region CDR1 RASQGIISYLA (SEQ ID NO:11), a V L region CDR2 AASSLQS (SEQ ID NO:12), and a V L region CDR3 VQYMNYPYT (SEQ ID NO:13).

14. The method of claim 1 , further comprising administering a cancer therapeutic agent.

15. The method of claim 14 , wherein the cancer therapeutic agent inhibits tubulin assembly.

16. A method of inhibiting growth of a solid tumor in subject that has a solid tumor that expresses EphA3 on tumor vasculature, but does not express detectable EphA3 on the surface of tumor cells, the method comprising administering an anti-EphA3 antibody to the patient.

17. The method of claim 16 , wherein the antibody clusters and activates EphA3.

18. A method of claim 17 , wherein the anti-EphA3 antibody competes for EphA3 binding with an antibody that has a V region CDR1 SYWIN (SEQ ID NO:1), a V H region CDR2 DIYPGSGNTNYDEKFKR (SEQ ID NO:2), a V H region CDR3 SGYYEDFDS (SEQ ID NO:3), a V L region CDR1 RASQEISGYLG (SEQ ID NO:8), a V L region CDR2 AASTLDS (SEQ ID NO:9), and a V L region CDR3 VQYANYPYT (SEQ ID NO:10).

19. The method of claim 16 , wherein the anti-EphA3 antibody is a monoclonal antibody.

20. The method of claim 16 , wherein the anti-EphA3 is a recombinant or chimeric antibody.

21. The method of claim 16 , wherein the anti-EphA3 antibody is a human antibody.

22. The method of claim 16 , wherein the anti-EphA3 antibody is a humanized antibody or an engineered antibody that comprises sequences from human V H - and V L -segments.

23. The method of claim 16 , wherein the anti-EphA3 antibody comprises a human Fc region.

24. The method of claim 23 , wherein the anti-EphA3 antibody comprises a human gamma-1 or gamma-3 active isotype.

25. The method of claim 24 , wherein the anti-EphA3 antibody Fc region glycosylation lacks fucose.

26. The method of claim 16 wherein the anti-EphA3 antibody is a multivalent antibody that comprises an antibody fragment that is a Fab, a Fab′, or an Fv.

27. The method of claim 16 , wherein the anti-EphA3 antibody has a V H region CDR1 SYWIN (SEQ ID NO:1), a V H region CDR2 DIYPGSGNTNYDEKFKR (SEQ ID NO:2), a V H region CDR3 SGYYEDFDS (SEQ ID NO:3), a V L region CDR1 RASQEISGYLG (SEQ ID NO:8), a V L region CDR2 AASTLDS (SEQ ID NO:9), and a V L region CDR3 VQYANYPYT (SEQ ID NO:10).

28. The method of claim 16 , wherein the anti-EphA3 antibody comprises:

a V H region CDR1 TYWIS (SEQ ID NO:4), a V H region CDR2 DIYPGSGNTNYDEKFQG (SEQ ID NO:5), a V H region CDR3 SGYYEEFDS (SEQ ID NO:6), a V L region CDR1 RASQGIISYLA (SEQ ID NO:11), a V L region CDR2 AASSLQS (SEQ ID NO:12), and a V L region CDR3 VQYANYPYT (SEQ ID NO:10); or

a V H region CDR1 TYWIS (SEQ ID NO:4), a V H region CDR2 DIYPGSGNTNYDEKFEG (SEQ ID NO:7), a V H region CDR3 SGYYEEFDS (SEQ ID NO:6), a V L region CDR1 RASQGIISYLA (SEQ ID NO:11), a V L region CDR2 AASSLQS (SEQ ID NO:12), and a V L region CDR3 VQYMNYPYT (SEQ ID NO:13).

29. The method of claim 16 , further comprising administering a cancer therapeutic agent.

30. The method of claim 29 , wherein the cancer therapeutic agent inhibits tubulin assembly and further, wherein anti-EphA3 antibody clusters and activates EphA3.

Assignments (12)