Methods for treating cancer by administering an anti-Ang-2 antibody
The present invention provides antibodies that bind to angiopoietin-2 (Ang-2) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human Ang-2. The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more Ang-2 biological activities including angiogenesis.
1. A method for treating a tumor, the method comprising administering to a patient in need of such treatment a pharmaceutical composition comprising a therapeutically effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds human angiopoietin-2 (hAng-2) but does not substantially bind hAng-1, wherein the antibody or antigen binding fragment comprises the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO: 18 and the CDRs of a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO: 20.
2. The method of claim 1 , wherein the antibody or antigen binding fragment comprises a heavy chain CDR1 (HCDR1) having the amino acid sequence of SEQ ID NO: 4, an HCDR2 having the amino acid sequence of SEQ ID NO: 6, an HCDR3 having the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 (LCDR1) having the amino acid sequence of SEQ ID NO: 12, a LCDR2 having the amino acid sequence of SEQ ID NO: 14, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.
3. The method of claim 1 , wherein the antibody or antigen binding fragment binds an epitope on hAng-2 (SEQ ID NO: 518) comprising an amino acid selected from the group consisting of F-469, Y-475 and S-480.
4. The method of claim 1 , wherein the antibody or antigen binding fragment binds an epitope on hAng-2 comprising amino acids F-469, Y-475 and S-480.
5. The method of claim 1 , wherein the tumor is present in ovary, colon, or liver of the patient.
6. The method of claim 1 further comprising administering a second therapeutic agent.
7. The method of claim 6 , wherein the second therapeutic agent is selected from the group consisting of an anti-VEGF (vascular endothelial growth factor) antibody, a small molecule kinase inhibitor of VEGF receptor and a VEGF-inhibiting fusion protein.
8. The method of claim 7 , wherein the second therapeutic agent is aflibercept or bevacizumab.
9. A method of treating an advanced solid tumor malignancy, the method comprising administering to a patient in need of such treatment a pharmaceutical composition comprising a therapeutically effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds human angiopoietin-2 (hAng-2) but does not substantially bind hAng-1, wherein the antibody or antigen binding fragment comprises the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO: 18 and the CDRs of a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO: 20.
10. The method of claim 9 , wherein the antibody or antigen binding fragment comprises a heavy chain CDR1 (HCDR1) having the amino acid sequence of SEQ ID NO: 4, an HCDR2 having the amino acid sequence of SEQ ID NO: 6, an HCDR3 having the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 (LCDR1) having the amino acid sequence of SEQ ID NO: 12, a LCDR2 having the amino acid sequence of SEQ ID NO: 14, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.
11. The method of claim 9 , wherein the antibody or antigen binding fragment binds an epitope on hAng-2 (SEQ ID NO: 518) comprising an amino acid selected from the group consisting of F-469, Y-475 and S-480.
12. The method of claim 9 further comprising administering a second therapeutic agent.
13. The method of claim 12 , wherein the second therapeutic agent is an anti-angiogenic agent.
14. The method of claim 13 , wherein the anti-angiogenic agent is selected from the group consisting of an anti-VEGF (vascular endothelial growth factor) antibody, a small molecule kinase inhibitor of VEGF receptor and a VEGF-inhibiting fusion protein.
15. The method of claim 14 , wherein the anti-angiogenic agent is aflibercept or bevacizumab.
16. The method of claim 15 , wherein the advanced solid tumor malignancy is present in the ovary, colon or liver of the patient.
17. The method of claim 16 , wherein the advanced solid tumor malignancy is resistant to conventional therapy.
18. The method of claim 17 , wherein the advanced solid tumor malignancy is advanced platinum-resistant ovarian cancer.
19. A method of inhibiting angiogenesis in an advanced solid tumor, the method comprising administering to a patient in need of such treatment a pharmaceutical composition comprising a therapeutically effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds human angiopoietin-2 (hAng-2) but does not substantially bind hAng-1, wherein the antibody or antigen binding fragment comprises the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO: 18 and the CDRs of a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO: 20.
20. The method of claim 19 , wherein the antibody or antigen binding fragment comprises a heavy chain CDR1 (HCDR1) having the amino acid sequence of SEQ ID NO: 4, an HCDR2 having the amino acid sequence of SEQ ID NO: 6, an HCDR3 having the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 (LCDR1) having the amino acid sequence of SEQ ID NO: 12, a LCDR2 having the amino acid sequence of SEQ ID NO: 14, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.
21. The method of claim 19 , wherein the antibody or antigen binding fragment binds an epitope on hAng-2 (SEQ ID NO: 518) comprising an amino acid selected from the group consisting of F-469, Y-475 and S-480.
22. The method of claim 19 further comprising administering a second anti-angiogenic agent.
23. The method of claim 22 , wherein the second anti-angiogenic agent is selected from the group consisting of an anti-VEGF (vascular endothelial growth factor) antibody, a small molecule kinase inhibitor of VEGF receptor and a VEGF-inhibiting fusion protein.
24. The method of claim 23 , wherein the second anti-angiogenic agent is aflibercept or bevacizumab.
25. The method of 24 , wherein the advanced solid tumor is present in ovary, colon or liver of the patient.
26. The method of claim 25 , wherein the tumor is advanced platinum-resistant ovarian cancer.