Multispecific antibodies
The invention provides multispecific antibodies and methods of making and using such antibodies.
1. An isolated antibody, wherein said antibody comprises HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3, wherein each, in order, comprises the sequence of SEQ ID NO:1, 2, 3, 4, 5, and 6, and wherein said antibody specifically binds HER2 and VEGF.
2. An isolated antibody, wherein said antibody comprises HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3, wherein each, in order, comprises the sequence of SEQ ID NO:1, 2, 3, 7, 8, and 9, and wherein said antibody specifically binds HER2 and VEGF.
3. The antibody of claim 1 or 2 , wherein said antibody is a monoclonal antibody.
4. The antibody of claim 1 or 2 , wherein said antibody is an IgG antibody.
5. The antibody of claim 1 or 2 , wherein at least a portion of the framework sequence is a human consensus framework sequence.
6. The antibody of claim 1 or 2 , wherein said antibody binds human or murine VEGF with a nanomolar affinity.
7. The antibody of claim 6 , wherein said antibody binds human and murine VEGF with a nanomolar affinity.
8. The antibody of claim 1 or 2 , wherein said antibody binds HER2 with a nanomolar affinity.
9. The antibody of claim 1 or 2 , wherein said antibody inhibits VEGF-induced cell proliferation and proliferation of a HER2 expressing cell relative to a control.
10. The antibody of claim 1 or 2 , wherein said antibody inhibits VEGF binding to VEGF receptor 2 (VEGFR2).
11. A fragment of the antibody of claim 1 or 2 , wherein said fragment specifically binds HER2 and VEGF.
12. The fragment of claim 11 , wherein said fragment is a Fab fragment or a single chain variable fragment (scFv).
13. The antibody fragment of claim 11 , wherein said fragment binds human or murine VEGF with a nanomolar affinity.
14. The antibody fragment of claim 13 , wherein said fragment binds human and murine VEGF with a nanomolar affinity.
15. The antibody fragment of claim 11 , wherein said fragment binds HER2 with a nanomolar affinity.
16. The antibody fragment of claim 11 , wherein said fragment inhibits VEGF-induced cell proliferation and proliferation of a HER2 expressing cell relative to a control.
17. The antibody fragment of claim 11 , wherein said fragment inhibits VEGF binding to VEGF receptor 2 (VEGFR2).