Claims for Patent: 8,454,960

Summary for Patent: 8,454,960

Title:	Multispecific antibody targeting and multivalency through modular recognition domains
Abstract:	Antibodies containing one or more modular recognition domains (MRDs) that can be used to target the antibodies to specific sites are described. The use of antibodies containing one or more modular recognition domains to treat disease, and methods of making antibodies containing one or more modular recognition domains are also described.
Inventor(s):	Barbas, III; Carlos F. (La Jolla, CA)
Assignee:	The Scripps Research Institute (La Jolla, CA)
Application Number:	13/135,754
Patent Claims:	1. A complex comprising an antibody and at least one modular recognition domain (MRD), wherein the MRD competitively inhibits binding of angiopoietin-2 (Ang2) to a polypeptide consisting of the amino acid sequence of SEQ ID NO:8 or SEQ ID NO: 21, wherein the antibody is (a) murine, (b) chimeric, (c) humanized, or (d) human, and wherein the antibody binds to a cell surface tumor antigen. 2. The complex of claim 1, wherein the antibody is multispecific. 3. The complex of claim 1, wherein the antibody is an IgG. 4. The complex of claim 1, wherein the antibody binds to a target selected from the group consisting of an integrin, insulin-like growth factor-I receptor (IGF-IR), a CD20, epidermal growth factor receptor (EGFR), ErbB2 receptor, ErbB3 receptor, and tumor associated surface antigen epithelial cell adhesion molecule (Ep-CAM). 5. The complex of claim 1, wherein the antibody binds to the same epitope as trastuzumab, cetuximab, or panitumumab. 6. The complex of claim 1, wherein the MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain. 7. The complex of claim 6, wherein a first MRD is located on (c) the C-terminus of the antibody heavy chain and a second MRD is located on (d) the C-terminus of the antibody light chain. 8. The complex of claim 1, wherein the antibody and the MRD are operably linked through a linker peptide. 9. The complex of claim 8, wherein the linker comprises a sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:19. 10. The complex of claim 1, wherein the antibody and the at least one MRD bind to their targets simultaneously. 11. The complex of claim 1, wherein the antibody comprises at least two MRDs. 12. The complex of claim 11, wherein the two MRDs are homo-multimeric. 13. The complex of claim 11, wherein the two MRDs are hetero-multimeric. 14. The complex of claim 13, wherein the hetero-multimeric MRDs bind to different targets. 15. The complex of claim 11, wherein the two MRDs are located on the same antibody terminus or on different antibody termini. 16. The complex of claim 11, wherein the complex is capable of binding to the antibody target and two MRD targets simultaneously. 17. The complex of claim 1, wherein the antibody comprises at least three MRDs. 18. The complex of claim 17, wherein the antibody and the three MRDs bind to their targets simultaneously. 19. The complex of claim 1, wherein the antibody comprises at least four MRDs. 20. The complex of claim 19, wherein the antibody and the four MRDs bind to their targets simultaneously. 21. The complex of claim 1, wherein the complex has ADCC activity. 22. A fusion polypeptide comprising an antibody heavy chain and an MRD, wherein the MRD competitively inhibits binding of Ang2 to a polypeptide consisting of the amino acid sequence of SEQ ID NO:8 or SEQ ID NO: 21, wherein the antibody is (a) murine, (b) chimeric, (c) humanized, or (d) human, and wherein the antibody binds to a cell surface tumor antigen. 23. A fusion polypeptide comprising an antibody light chain and an MRD, wherein the MRD competitively inhibits binding of Ang2 to a polypeptide consisting of the amino acid sequence of SEQ ID NO:8 or SEQ ID NO: 21, wherein the antibody is (a) murine, (b) chimeric, (c) humanized, or (d) human, and wherein the antibody can bind to a cell surface tumor antigen. 24. A pharmaceutical composition comprising the complex of claim 1. 25. A method for inhibiting the growth of a cell comprising contacting the cell with the complex of claim 1. 26. A method for inhibiting angiogenesis in a patient comprising administering to said patient a therapeutically effective amount of the complex of claim 1. 27. The complex of claim 1, wherein the complex further comprises a MRD consisting of the animo acid sequence of SEQ ID NO: 7-11, 21, 23, 24, 26, 27, 29, 30, 32, 33, or 34. 28. The complex of claim 1, wherein the antibody binds to the same epitope as trastuzumab. 29. The complex of claim 27, wherein the antibody binds to the same epitope as trastuzumab. 30. The complex of claim 29, wherein the antibody is trastuzumab. 31. The complex of claim 3, wherein the IgG is an IgG1. 32. A complex comprising an antibody and at least one modular recognition domain (MRD), wherein the MRD binds to Ang2 and consists of the amino acid sequence of SEQ ID NO: 7-12, 21, 23, 24, 26, 27, 29, 30, or 32-34, and wherein the antibody binds to the same epitope as trastuzumab.

Details for Patent 8,454,960

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2028-01-03
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2028-01-03
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2028-01-03
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2028-01-03
Amgen, Inc.	VECTIBIX	panitumumab	Injection	125147	09/27/2006		2028-01-03