Claims for Patent: 8,574,576

Summary for Patent: 8,574,576

Title:	Humanized anti-EGFL7 antibodies and methods using same
Abstract:	The present invention concerns antibodies to EGFL7 and the uses of same.
Inventor(s):	Ye; Weilan (Foster City, CA), Dennis; Mark S. (San Carlos, CA), Fredrickson; Jill (Sunnyvale, CA)
Assignee:	Genentech, Inc. (South San Francisco, CA)
Application Number:	13/668,129
Patent Claims:	1. A method of reducing or inhibiting perfusion and permeability of a tumor which expresses EGFL7 in a subject, the method comprising administering to an individual in need of such treatment an effective amount of an anti-EGFL7 antibody, the antibody comprising a variable domain comprising the following HVR sequences: HVR-L1 comprising RTSQSLVHINXITYLH, wherein X is G or A (SEQ ID NO: 106, 241); HVR-L2 comprising RVSNRFS (SEQ ID NO: 101); HVR-L3 comprising GQSTHVPLT (SEQ ID NO: 131); HVR-H1 comprising GYTFIDYYMN (SEQ ID NO: 103); HVR-H2 comprising GDINLDNXGTHYNQKFKG (SEQ ID NO: 104, 242), wherein X is G or S; and HVR-H3 comprising AREGVYHDYDDYAMDY (SEQ ID NO: 105). 2. A method of reducing or inhibiting perfusion and permeability of a tumor which expresses EGFL7 in a subject, the method comprising administering to an individual in need of such treatment an effective amount of an anti-EGFL7 antibody, wherein the anti-EGFL7 antibody comprises the following HVR sequences: HVR-L1 comprises the amino acid sequence RTSQSLVHINAITYLH (SEQ ID NO: 241), HVR-L2 comprises the amino acid sequence RVSNRFS (SEQ ID NO: 101), HVR-L3 comprises the amino acid sequence GQSTHVPLT (SEQ ID NO: 131), HVR-H1 comprises the amino acid sequence GYTFIDYYMN (SEQ ID NO: 103), HVR-H2 comprises the amino acid sequence GDINLDNSGTHYNQKFKG (SEQ ID NO: 242), and HVR-H3 comprises the amino acid sequence AREGVYHDYDDYAMDY (SEQ ID NO: 105). 3. The method of claim 1 or 2, wherein the heavy chain comprises the following framework sequences: FR-H1 comprises EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO: 197); FR-H2 comprises WVRQAPGKGLEWX.sub.1, wherein X.sub.1 is I or V (SEQ ID NO: 228); FR-H3 comprises RX.sub.1TX.sub.2SX.sub.3DX.sub.4SX.sub.5X.sub.6TX.sub.7YX.sub.8QMNSLRAEDT- AVYYC, wherein X.sub.1 is F or V; X.sub.2 is I or L; X.sub.3 is selected from the group consisting of L, R, and V; X.sub.4 is K or N; X.sub.5 is selected from the group consisting of K, N, R, and S; X.sub.6 is N or S; X.sub.7 is selected from the group consisting of A, L, and V; and X.sub.8 is L or M (SEQ ID NO: 229); and FR-H4 comprises WGQGTLVTVSS (SEQ ID NO: 200). 4. The method of claim 3, wherein the heavy chain comprises the following framework sequences: FR-H1 comprises EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO: 197); FR-H2 comprises WVRQAPGKGLEWV (SEQ ID NO: 198); FR-H3 comprises RFTISRDX.sub.1SKNTX.sub.2YLQMNSLRAEDTAVYYCAR, wherein X.sub.1 is N or K; and X.sub.2 is selected from the group consisting of A, L, and V (SEQ ID NO: 230); and FR-H4 comprises WGQGTLVTVSS (SEQ ID NO: 200). 5. The method of claim 1 or 2, wherein the light chain comprises the following framework sequences: FR-L1 comprises DIQMTQSPSSLSASVGDRVTITC (SEQ ID NO: 201), FR-L2 comprises WYQQKPGKAPKLLIY (SEQ ID NO: 202), FR-L3 comprises GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO: 203), FR-L4 comprises FGQGTKVEIK (SEQ ID NO: 221) or FGQGTKVEIKR (SEQ ID NO: 204). 6. The method of claim 1, wherein the light chain comprises the variable domain sequence of 18F7.v6 as shown in FIG. 27 (SEQ ID NO: 193) or the variable domain sequence of 18F7.v6k as shown in FIG. 27 (SEQ ID NO: 194). 7. The method of claim 1, wherein the heavy chain comprises the variable domain sequence of 18F7.v6 as shown in FIG. 28 (SEQ ID NO: 195) or the variable domain sequence of 18F7.v6k as shown in FIG. 28 (SEQ ID NO: 196). 8. The method of claim 1, wherein the light chain comprises the variable domain sequence of 18F7.v6 as shown in FIG. 27 (SEQ ID NO: 193) and the heavy chain comprises the variable domain sequence of 18F7.v6 as shown in FIG. 28 (SEQ ID NO: 195). 9. The method of claim 1, wherein the light chain comprises the variable domain sequence of 18F7.v6k as shown in FIG. 27 (SEQ ID NO: 194) and the heavy chain comprises the variable domain sequence of 18F7.v6k as shown in FIG. 28 (SEQ ID NO: 196). 10. The method of claim 1 or 2, wherein at least a portion of the framework sequence is a human consensus framework sequence. 11. The method of claim 10, comprising human .kappa. subgroup 1 consensus framework sequence or heavy chain human subgroup III consensus framework sequence. 12. The method of claim 1 or 2, wherein said antibody is a bispecific antibody. 13. The method of claim 12, wherein said bispecific antibody binds to vascular endothelial growth factor (VEGF). 14. The method of claim 13, wherein said bispecific antibody binds to the same epitope as bevacizumab or ranibizumab. 15. The method of claim 14, wherein said bispecific antibody binds to the same epitope as bevacizumab. 16. The method of claim 1 or 2, wherein the tumor is selected from the group consisting of breast, colorectal, lung, esophageal, bladder, ovarian, pancreatic, and hepatocellular tumor. 17. The method of claim 16, wherein the tumor is a colorectal or lung tumor. 18. The method of claim 1 or 2, further comprising administering to the individual an effective amount of a second medicament, wherein the anti-EGFL7 antibody is a first medicament. 19. The method of claim 18, wherein the second medicament is another antibody, a chemotherapeutic agent, a cytotoxic agent, an anti-angiogenic agent, an immunosuppressive agent, a prodrug, a cytokine, a cytokine antagonist, cytotoxic radiotherapy, a corticosteroid, an anti-emetic, a cancer vaccine, an analgesic, or a growth-inhibitory agent. 20. The method of claim 19, wherein the second medicament is an anti-VEGF antibody. 21. The method of claim 20, where the second medicament is bevacizumab or ranibizumab. 22. The method of claim 21, wherein the second medicament is bevacizumab. 23. The method of claim 22, further comprising administering to the individual an effective amount of a further medicament, wherein the anti-EGFL7 antibody is a first medicament and an anti-VEGF antibody is the second medicament. 24. The method of claim 23, wherein the further medicament is a chemotherapeutic agent. 25. The method of claim 24, wherein the chemotherapeutic agent is FOLFOX. 26. The method of claim 24, wherein the chemotherapeutic agent is carboplatin and paclitaxel. 27. The method of claim 18, further comprising administering to the individual an effective amount of a further medicament, wherein the anti-EGFL7 antibody is a first medicament and an anti-VEGF antibody is the second medicament. 28. The method of claim 27, wherein the further medicament is a chemotherapeutic agent. 29. The method of claim 28, wherein the chemotherapeutic agent is FOLFOX. 30. The method of claim 28, wherein the chemotherapeutic agent is carboplatin and paclitaxel.

Details for Patent 8,574,576

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2039-02-26
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	06/30/2006		2039-02-26
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	08/10/2012		2039-02-26
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	10/13/2016		2039-02-26
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	03/20/2018		2039-02-26