VEGF binding antibodies
The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.
1. An isolated antibody that specifically binds human VEGF, which comprises:
(a) a heavy chain consisting of SEQ ID NO:49 or SEQ ID NO:7; and
(b) a light chain consisting of SEQ ID NO:8.
2. An isolated antibody that specifically binds human vascular endothelial growth factor (VEGF), which comprises:
(a) a heavy chain CDR1 comprising NYWMH (SEQ ID NO:17), a heavy chain CDR2 comprising DINPSNGRTSYKEKFKR (SEQ ID NO:18), and a heavy chain CDR3 comprising HYDDKYYPLMDY (SEQ ID NO:19); and
(b) a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:20), a light chain CDR2 comprising AASNQGS (SEQ ID NO:21), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:22).
3. The antibody of claim 1 , which comprises:
(a) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:11; and
(b) a light chain variable region having at least 90% sequence identity to SEQ ID NO:12.
4. The antibody of claim 2 , which comprises:
(a) a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:11; and
(b) a light chain variable region having at least 95% sequence identity to SEQ ID NO:12.
5. The antibody of claim 2 , which comprises:
(a) a heavy chain variable region comprising SEQ ID NO:11; and
(b) a light chain variable region comprising SEQ ID NO:12.
6. The antibody of claim 2 , which comprises:
(a) a heavy chain variable region consisting of SEQ ID NO:11; and
(b) a light chain variable region consisting of SEQ ID NO:12.
7. The antibody of claim 1 , which is a monoclonal antibody.
8. The antibody of claim 1 , which is a recombinant antibody.
9. The antibody of claim 1 , which is a chimeric antibody.
10. The antibody of claim 1 , which is a humanized antibody.
11. The antibody of claim 1 , which is a human antibody.
12. The antibody of claim 1 , which is a bispecific antibody.
13. The antibody of claim 1 , which is an IgG1 antibody.
14. The antibody of claim 1 , which is an IgG2 antibody.
15. The antibody of claim 1 , which is an antibody fragment comprising an antigen-binding site.
16. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.