IP Library Granted Patent US 8,404,811
Granted Patent B2
US 8,404,811 · App. 12/776,259 · Granted Mar 26, 2013

Humanized anti-EGFL7 antibodies and methods using same

Inventors: Weilan Ye (Foster City, CA); Mark Dennis (San Carlos, CA); Jill Fredrickson (Sunnyvale, CA)
Assignee: Genentech, Inc.
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Quick Facts
Patent No.
US 8,404,811
App. No.
12/776,259
Granted
Mar 26, 2013
Kind
B2
Abstract

The present invention concerns antibodies to EGFL7 and the uses of same.

Claims (29)

1. An isolated anti-EGFL7 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 GDINLDNXGTHYNOKFKG (SEQ ID NO: 104, 242), wherein X is G or S; and

HVR-H3 comprising AREGVYHDYDDYAMDY (SEQ ID NO: 105).

2. An isolated anti-EGFL7 antibody comprising a variable domain, wherein 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 antibody 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 1 , wherein X 1 is I or V (SEQ ID NO: 228); FR-H3 comprises RX 1 TX 2 SX 3 DX 4 SX 5 X 6 TX 7 YX 8 QMNSLRAEDTAVYYC, wherein X 1 is F or V; X 2 is I or L; X 3 is selected from the group consisting of L, R, and V; X 4 is K or N; X 5 is selected from the group consisting of K, N, R, and S; X 6 is N or S; X 7 is selected from the group consisting of A, L, and V; and X 8 is L or M (SEQ ID NO: 229); and FR-H4 comprises WGQGTLVTVSS (SEQ ID NO: 200).

4. The antibody 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 1 SKNTX 2 YLQMNSLRAEDTAVYYCAR, wherein X 1 is N or K; and X 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 antibody 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 antibody of claim 1 , wherein the light chain comprises the variable domain sequence of 18F7.v6 as shown in FIG. 27 (SEQ ID NO: 193).

7. The antibody of claim 1 , wherein the light chain comprises the variable domain sequence of 18F7.v6k as shown in FIG. 27 (SEQ ID NO: 194).

8. The antibody of claim 1 , wherein the heavy chain comprises the variable domain sequence of 18F7.v6 as shown in FIG. 28 (SEQ ID NO: 195).

9. The antibody of claim 1 , wherein the heavy chain comprises the variable domain sequence of 18F7.v6k as shown in FIG. 28 (SEQ ID NO: 196).

10. The antibody 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).

11. The antibody 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).

12. The antibody of claim 1 or 2 , wherein at least a portion of the framework sequence is a human consensus framework sequence.

13. The antibody of claim 12 , comprising human is subgroup 1 consensus framework sequence.

14. The antibody of claim 12 , comprising heavy chain human subgroup III consensus framework sequence.

15. The antibody of claim 1 or 2 , wherein said antibody is a bispecific antibody.

16. The antibody of claim 15 , wherein said bispecific antibody binds to vascular endothelial growth factor (VEGF).

17. The antibody of claim 16 , where said bispecific antibody binds to the same VEGF epitope as bevacizumab or ranibizumab.

18. A composition comprising the antibody of claim 1 .

19. The composition of claim 18 , wherein the composition comprises a carrier.

20. The composition of claim 18 or 19 , which is a pharmaceutical composition.

21. A composition comprising the antibody of claim 2 .

22. The composition of claim 21 , wherein the composition comprises a carrier.

23. The composition of claim 22 , which is a pharmaceutical composition.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 25, 2011
From: GENENTECH, INC.
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 026021/0516 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 21, 2010
From: YE, WEILAN; DENNIS, MARK; FREDRICKSON, JILL
To: GENENTECH, INC.
Reel/Frame 024422/0744 →
Continuity (2)
Provisional Application 61176817 · May 8, 2009
Related Publication 20100285009A1 · Nov 11, 2010