Material and methods for treating or preventing HER-3 associated diseases

1. A method of treating a cancer expressing a HER-3 polypeptide comprising the sequence of SEQ ID NO: 389 in a human subject, comprising administering to the subject a first agent and a second agent, wherein said first agent is an isolated antibody or antigen-binding fragment thereof which binds to HER-3, comprising:

a heavy chain amino acid sequence that comprises a CDRH1 having the sequence of SEQ ID NO: 256, a CDRH2 having the sequence of SEQ ID NO: 282, and a CDRH3 having the sequence of SEQ ID NO: 315; and a light chain amino acid sequence that comprises a CDRL1 having the sequence of SEQ ID NO: 340, a CDRL2 having the sequence of SEQ ID NO: 344, and a CDRL3 having the sequence of SEQ ID NO: 387;

and wherein said second agent is lapatinib.

2. The method of claim 1 , wherein said first agent is an isolated antibody or antigen-binding fragment thereof that binds to HER-3, and comprises the heavy chain amino acid sequence of SEQ ID NO: 70 and the light chain amino acid sequence of SEQ ID NO: 72.

3. The method of claim 1 , wherein said isolated antibody or antigen-binding fragment thereof is directed against the extracellular domain of HER-3.

4. The method of claim 1 , wherein said antibody or antigen-binding fragment thereof is a monoclonal antibody, a recombinant antibody, a human antibody, a chimeric antibody, a multispecific antibody, a single chain antibody, or a diabody.

5. The method of claim 4 , wherein the antibody-binding fragment is selected from a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, and a Fv fragment.

6. The method of claim 4 , wherein said antibody or antigen-binding fragment thereof is of the IgG1-, IgG2-, IgG3-, or IgG4-type.

7. The method of claim 1 , wherein said antibody or antigen-binding fragment thereof is coupled to a radioisotope, a radionuclide, a non-radio isotope, a toxin, or a therapeutic or chemotherapeutic group.

8. The method of claim 7 , wherein said antibody or antigen-binding fragment thereof is coupled to a radioisotope, a radionuclide, or a non-radio isotope.

9. The method of claim 7 , wherein said therapeutic or chemotherapeutic group is calicheamicin, auristatin-PE, geldanamycin, maytansine, or a DM1.

10. The method of claim 1 , comprising administering a further therapeutic agent and/or radiation therapy.

11. The method of claim 10 , wherein the further therapeutic agent is an anti-neoplastic agent.

12. The method of claim 11 , wherein the anti-neoplastic agent is an anti-tumor antibody or a chemotherapeutic agent.

13. The method of claim 12 , wherein the chemotherapeutic agent is selected from the group consisting of capecitabine, anthracycline, doxorubicin, cyclophosphamide, paclitaxel, docetaxel, cisplatin, gemcitabine, and carboplatin.

14. The method of claim 1 , wherein said first agent and said second agent are administered by intravenous, subcutaneous, intramuscular, or oral administration.

15. The method of claim 1 , wherein said cancer is selected from the group consisting of breast cancer, ovarian cancer, prostate cancer, colon cancer, renal cancer, lung cancer, pancreatic cancer, epidermoid carcinoma, fibrosarcoma, melanoma, head and neck cancer, nasopharyngeal carcinoma, and squamous cell carcinoma.

16. The method of claim 15 , comprising administering said first agent at a dose of about 1 to about 20 mg/kg body weight, at least once every 6 weeks.

17. The method of claim 15 , comprising administering said second agent at a dose of about 1 to about 20 mg/kg body weight, at least once every 6 weeks.

18. The method of claim 15 , further comprising, after the administering, monitoring the therapeutic outcome.

19. The method of claim 8 , wherein said isotope is 3 H, 14 C, 15 N, 35 S, 90 Y, 99 Tc, 111 In, 125 I, 131 I or 2 D.

20. The method of claim 2 , wherein the cancer is breast cancer.