Claims for Patent: 8,017,735

Summary for Patent: 8,017,735

Title:	Anti-IGFR1 antibody therapeutic combinations
Abstract:	The present invention provides combinations including a binding composition, such as an anti-IGFR1 antibody, in association with a chemotherapeutic agent. Methods for using the combinations to treat medical conditions, such as cancer, are also provided.
Inventor(s):	Wang; Yan (Scotch Plains, NJ), Pachter; Jonathan A. (Chatham, NJ), Bishop; Walter Robert (Pompton Plains, NJ)
Assignee:	Schering Corporation (Kenilworth, NJ)
Application Number:	10/993,395
Patent Claims:	1. A composition comprising: (a) one or more isolated antibodies or antigen-binding fragments thereof, that specifically bind human insulin-like growth factor receptor 1, comprising a light chain immunoglobulin amino acid sequence which comprises CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 5, CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 6 and CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 7; and a heavy chain immunoglobulin amino acid sequence which comprises CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 8 or 12, CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 9 and CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10; in association with (b) one or more chemotherapeutic agents selected from the group consisting of: lonafarnib; ##STR00066## ##STR00067## lapatinib; bevacizumab; VX-745; PD184352; temsirolimus; LY294002; LY292223; LY292696; LY293684; LY293646; wortmannin; sorafenib; ZM336372; L-779,450; ##STR00068## ##STR00069## ##STR00070## 2. The composition of claim 1 wherein (a) comprises one or more isolated antibodies or antigen-binding fragments thereof comprising a light chain immunoglobulin amino acid sequence which comprises CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 5, CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 6 and CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 7; and a heavy chain immunoglobulin amino acid sequence which comprises CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 12, CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 9 and CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10. 3. The composition of claim 2 wherein (a) comprises an isolated antibody comprising a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2 and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 4. The composition of claim 1 wherein a chemotherapeutic agent is one or more members selected from the group consisting of: lonafarnib, cetuximab, sorafenib, gefitinib, erlotinib, octreotide, and 4-hydroxytamoxifen. 5. A composition comprising: (a) a monoclonal antibody, that specifically binds human insulin-like growth factor receptor 1, comprising a light chain immunoglobulin amino acid sequence which comprises CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 5, CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 6 and CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 7; and a heavy chain immunoglobulin amino acid sequence which comprises CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 8 or 12, CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 9 and CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10; in association with (b) one or more chemotherapeutic agents selected from the group consisting of: lonafarnib; ##STR00071## ##STR00072## lapatinib; bevacizumab; VX-745; PD184352; temsirolimus; LY294002; LY292223; LY292696; LY293684; LY293646; wortmannin; sorafenib; ZM336372; L-779,450; ##STR00073## ##STR00074## ##STR00075## 6. A method for treating a cancer or a tumor expressing human Insulin-like Growth Factor Receptor-I, wherein said cancer or tumor is selected form the group consisting of: bladder cancer, Wilm's cancer, ovarian cancer, pancreatic cancer, breast cancer, prostate cancer, bone cancer, lung cancer, colorectal cancer, cervical cancer, synovial sarcoma, or a vasoactive intestinal peptide secreting tumor in a mammalian subject in need of such treatment comprising administering a therapeutically effective amount of a composition comprising: (a) one or more isolated antibodies or antigen-binding fragments thereof, that specifically bind human insulin-like growth factor receptor 1, comprising a light chain immunoglobulin amino acid sequence which comprises CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 5, CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 6 and CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 7; and a heavy chain immunoglobulin amino acid sequence which comprises CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 8 or 12, CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 9 and CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10; in association with (b) one or more chemotherapeutic agents selected from the group consisting of: lonafarnib; ##STR00076## ##STR00077## lapatinib; bevacizumab; VX-745; PD184352; temsirolimus; LY294002; LY292223; LY292696; LY293684; LY293646; wortmannin; sorafenib; ZM336372; L-779,450; ##STR00078## ##STR00079## ##STR00080## to the subject. 7. The method of claim 6 wherein (a) comprises an isolated antibody comprising a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2 and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 8. The method of claim 6 wherein a chemotherapeutic agent is one or more members selected from the group consisting of: lonafarnib; cetuximab; erlotinib; temsirolimus; sorafenib; gefitinib; fulvestrant; octreotide; bevacizumab; and 4-hydroxytamoxifen. 9. The method of claim 6 wherein the medical condition is selected from the group consisting of Wilm's cancer, pancreatic cancer, breast cancer, prostate cancer, lung cancer, and colorectal cancer. 10. The method of claim 6 wherein the antibody or fragment is administered to the subject by a parenteral route. 11. A method for treating a cancer or a tumor expressing human Insulin-like Growth Factor Receptor-I, wherein said cancer or tumor is selected form the group consisting of: bladder cancer, Wilm's cancer, ovarian cancer, pancreatic cancer, breast cancer, prostate cancer, bone cancer, lung cancer, colorectal cancer, cervical cancer, synovial sarcoma, or a vasoactive intestinal peptide secreting tumor, in a mammalian subject in need of such treatment, comprising administering a therapeutically effective amount of a composition comprising: (a) a monoclonal antibody, that specifically binds human insulin-like growth factor receptor 1, comprising a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2 and a heavy chain immunoglobulin comprising amino acids 20-137 of SEQ ID NO: 4; in association with (b) one or more chemotherapeutic agents selected from the group consisting of: lonafarnib; cetuximab; erlotinib; rapamycin; temsirolimus; sorafenib; gefitinib; fulvestrant; octreotide; bevacizumab; and 4-hydroxytamoxifen to the subject. 12. The method of claim 11 wherein the medical condition is selected from the group consisting of Wilm's cancer, pancreatic cancer, breast cancer, prostate cancer, lung cancer, and colorectal cancer. 13. The composition of claim 5 wherein a chemotherapeutic agent is lonafarnib; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 14. The composition of claim 5 wherein a chemotherapeutic agent is cetuximab; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 15. The composition of claim 5 wherein a chemotherapeutic agent is temsirolimus; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 16. The composition of claim 5 wherein a chemotherapeutic agent is sorafenib; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 17. The composition of claim 5 wherein a chemotherapeutic agent is gefitinib; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 18. The composition of claim 5 wherein a chemotherapeutic agent is bevacizumab; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 19. The composition of claim 5 wherein a chemotherapeutic agent is octreotide; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 20. The composition of claim 5 wherein a chemotherapeutic agent is 4-hydroxytamoxifen; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 21. The method of claim 6 wherein (a) comprises one or more isolated antibodies or antigen-binding fragments thereof comprising a light chain immunoglobulin amino acid sequence which comprises CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 5, CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 6 and CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 7; and a heavy chain immunoglobulin amino acid sequence which comprises CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 12, CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 9 and CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 10. 22. A composition comprising (a) one or more antibodies or antigen-binding fragments thereof, that specifically bind human insulin-like growth factor receptor 1, comprising a light chain immunoglobulin which comprises the amino acids 20-128 of the amino acid sequence set forth in SEQ ID NO: 2; or a heavy chain immunoglobulin which comprises amino acids 20-137 of the amino acid sequence set forth in SEQ ID NO: 4; or both; in association with (b) one or more chemotherapeutic agents selected from the group consisting of lonafarnib; ##STR00081## ##STR00082## bevacizumab; VX-745; PD184352; temsirolimus; LY294002; LY292223; LY292696; LY293684; LY293646; wortmannin; sorafenib; ZM336372; L-779,450; ##STR00083## ##STR00084## ##STR00085## 23. The composition of claim 5 wherein a chemotherapeutic agent is erlotinib; and wherein the monoclonal antibody comprises a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4. 24. The method of claim 12 wherein the medical condition is selected from the group consisting of Wilm's cancer, pancreatic cancer, breast cancer, prostate cancer, lung cancer, and colorectal cancer. 25. The method of claim 24 wherein the antibody is administered to the subject by a parenteral route. 26. The composition of claim 5 wherein the heavy chain immunoglobulin is linked to a .gamma.1 immunoglobulin constant region and the light chain immunoglobulin is linked to a .kappa. immunoglobulin constant region. 27. The composition of claim 1 wherein (a) comprises an isolated antibody comprising a light chain immunoglobulin comprising amino acids 20-128 of SEQ ID NO: 2, linked to a .kappa. immunoglobulin constant region; and a heavy chain immunoglobulin comprising amino acids of 20-137 of SEQ ID NO: 4 linked to a .gamma.1 immunoglobulin constant region. 28. The composition of claim 27 wherein the chemotherapeutic agent is bevacizumab. 29. The method of claim 12 wherein the medical condition is colorectal cancer, lung cancer or breast cancer and the chemotherapeutic agent is bevacizumab. 30. The method of claim 24 wherein the chemotherapeutic agent is lonafarnib. 31. The method of claim 24 wherein the chemotherapeutic agent is bevacizumab. 32. The method of claim 24 wherein the chemotherapeutic agent is temsirolimus. 33. The method of claim 24 wherein the chemotherapeutic agent is sorafenib. 34. The method of claim 24 wherein the chemotherapeutic agent is cetuximab. 35. The method of claim 24 wherein the chemotherapeutic agent is erlotinib. 36. The method of claim 24 wherein the chemotherapeutic agent is rapamycin. 37. The method of claim 24 wherein the chemotherapeutic agent is gefitinib. 38. The method of claim 24 wherein the chemotherapeutic agent is fulvestrant. 39. The method of claim 24 wherein the chemotherapeutic agent is octreotide. 40. The method of claim 24 wherein the chemotherapeutic agent is 4-hydroxytamoxifen. 41. The method of claim 11 wherein the medical condition is colorectal cancer, lung cancer or breast cancer.

Details for Patent 8,017,735

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2023-11-21
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2023-11-21
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2023-11-21