High affinity human antibodies to human angiopoietin-2
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. An isolated antibody or antigen-binding fragment thereof that specifically binds human angiopoietin-2 (hAng-2), wherein the antibody or antigen-binding fragment thereof comprises a heavy chain CDR-1 (HCDR1) having the amino acid sequence of SEQ ID NO:4, an HCDR-2 having the amino acid sequence of SEQ ID NO:6, an HCDR-3 having the amino acid sequence of SEQ ID NO:8, a light chain CDR-1 (LCDR-1) having the amino acid sequence of SEQ ID NO:12, an LCDR-2 having the amino acid sequence of SEQ ID NO:14, and an LCDR-3 having the amino acid sequence of SEQ ID NO:16.
2. An isolated antibody or antigen-binding fragment thereof that specifically binds human angiopoietin-2 (hAng-2), wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ is NO: 18 and a light chain variable region having the amino acid sequence of SEQ NO:20.
3. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier or diluent.
4. The pharmaceutical composition of claim 3 , further comprising a vascular endothelial cell growth factor (VEGF) antagonist.
5. The pharmaceutical composition of claim 4 , wherein the VEGF antagonist is selected from the group consisting of an anti-VEGF antibody, a small molecule kinase inhibitor of a VEGF receptor and a VEGF-inhibiting fusion protein.
6. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 2 and a pharmaceutically acceptable carrier or diluent.
7. The pharmaceutical composition of claim 6 , further comprising a vascular endothelial cell growth factor (VEGF) antagonist.
8. The pharmaceutical composition of claim 7 , wherein the VEGF antagonist is selected from the group consisting of an anti-VEGF antibody, a small molecule kinase inhibitor of VEGF receptor and a VEGF-inhibiting fusion protein.
9. An isolated human antibody or antigen-binding fragment thereof comprising at least one antibody variable domain, wherein the antibody or antigen-binding fragment binds to the same epitope on hAng-2 as an antibody which comprises the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID N0:18, and the CDRs of a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO:20.
10. An isolated human antibody or antigen-binding fragment thereof comprising at least one antibody variable domain, wherein the antibody or antigen-binding fragment binds to the same epitope on hAng-2 as an antibody which comprises a heavy chain CDR-1 (HCDR1) having the amino acid sequence of SEQ ID NO:4, an HCDR-2 having the amino acid sequence of SEQ ID NO:6, an HCDR-3 having the amino acid sequence of SEQ ID NO:8, a light chain CDR-1 (LCDR-1) having the amino acid sequence of SEQ ID NO:12, an LCDR-2 having the amino acid sequence of SEQ ID NO:14, and an LCDR-3 having the amino acid sequence of SEQ ID NO:16.