Anti-ErbB3 antibodies and uses thereof
The present invention provides antibodies that bind to ErbB3 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human ErbB3. In certain embodiments, the antibodies of the present invention block the interaction of ErbB3 with an ErbB3 ligand such as neuregulin 1. The antibodies of the invention are useful for the treatment of various cancers.
1. A method for extending or prolonging the survival of a subject afflicted with a cancer expressing ErbB3 and one or more of EGFR, HER2, ErbB4, EGFRvIII, VEGF and DLL4, the method comprising administering to the subject (i) a therapeutically effective amount of an anti-ErbB3 antibody or an antigen binding fragment thereof and (ii) a therapeutically effective amount of a second component selected from an anti-EGFR antibody or an antigen-binding fragment thereof, a small molecule inhibitor of EGFR activity, an anti-HER2 antibody or an antigen-binding fragment thereof, an anti-ErbB4 antibody or an antigen-binding fragment thereof, an anti-EGFRvIII antibody or an antigen-binding fragment thereof, a VEGF antagonist, an anti-VEGF antibody or an antigen-binding fragment thereof, a small molecule kinase inhibitor of VEGF receptor, or an anti-DLL4 antibody or an antigen-binding fragment thereof;
wherein the anti-ErbB3 antibody or an antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) comprising the amino acid sequence of SEQ ID NOs: 324, 326 and 328, respectively, and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) comprising the amino acid sequence of SEQ ID NOs: 332, 334 and 336, respectively.
2. The method of claim 1 , wherein the anti-ErbB3antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:322, and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:330.
3. The method of claim 1 , wherein the anti-EGFR antibody is selected from cetuximab, panitumumab, an antigen-binding fragment of cetuximab or an antigen-binding fragment of panitumumab.
4. The method of claim 1 , wherein the small molecule inhibitor of EGFR activity is selected from erlotinib or gefitinib.
5. The method of claim 1 , wherein the VEGF antagonist is a VEGF-Trap.
6. The method of claim 1 , wherein the anti-VEGF antibody is selected from bevacizumab or an antigen-binding fragment of bevacizumab.
7. The method of claim 1 , wherein the small molecule kinase inhibitor of VEGF receptor is selected from sunitinib, sorafenib, or pazopanib.
8. The method of claim 1 , wherein the anti-ErbB3 antibody or antigen-binding fragment thereof and the second component are administered to the subject in separate dosage forms.
9. The method of claim 8 , wherein the separate dosage forms are administered to the subject simultaneously.
10. The method of claim 8 , wherein the separate dosage forms are administered to the subject sequentially.
11. The method of claim 1 , wherein the anti-ErbB3 antibody or antigen-binding fragment thereof and the second component are administered to the subject in a single dosage form.
12. The method of claim 2 , wherein the anti-ErbB3 antibody or antigen-binding fragment thereof and the second component are administered to the subject in separate dosage forms.