Anti-factor D antibodies and conjugates

Patent metadata

Field	Value
Publication number	US-10407510-B2
Application number	US-201615335847-A
Country	US
Kind code	B2
Filing date	Oct 27, 2016
Priority date	Oct 30, 2015
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

The invention provides anti-Factor D antibodies and conjugates and methods of using the same.

First claim

What is claimed is:

1. An isolated antibody that binds to Factor D, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence SYYMY (SEQ ID NO: 15); (b) HVR-H2 comprising the amino acid sequence X 4 INPX 5 X 6 GX 7 TNFNEKFKS (SEQ ID NO: 111), wherein X 4 is selected from E and W; X 5 is selected from T and Y; X 6 is selected from S and Q; and X 7 is selected from G, D, and E; (c) HVR-H3 comprising the amino acid sequence EGGFAY (SEQ ID NO: 25); (d) HVR-L1 comprising the amino acid sequence KASQNVDTDVA (SEQ ID NO:9); (e) HVR-L2 comprising the amino acid sequence SASSRX 1 S (SEQ ID NO: 108), wherein X 1 is selected from Y, K, and R; and (f) HVR-L3 comprising the amino acid sequence QQYX 3 NYPLT (SEQ ID NO: 110), wherein X 3 is selected from N and E.

2. The antibody of claim 1 , wherein the antibody comprises the sequence X 2 SASSRX 1 S (SEQ ID NO: 109), wherein X 1 is selected from Y, K, and R; X 2 is selected from Y, R, S, K, and Q.

3. The antibody of claim 2 , wherein X 2 is R.

4. The antibody of claim 2 , wherein X 1 is Y.

5. The antibody of claim 1 , wherein the antibody comprises HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 16 and 18 to 24, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising an amino acid sequence selected from SEQ ID NOs: 10 to 12, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13or 14.

6. The antibody of claim 1 , wherein the antibody comprises:
a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 16, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
b) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 20, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
c) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 18, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
d) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 19, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
e) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 21, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
f) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2comprising the amino acid sequence of SEQ ID NO: 22, HVR-H3comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
g) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 23, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
h) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 16, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
i) HVR-H1comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 16, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 12, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13;
j) HVR-H1comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 16, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 14; or
k) HVR-H1comprising the amino acid sequence of SEQ ID NO: 15, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 24, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 25, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 13.

7. The antibody of claim 1 , wherein the amino acid at position 49 of the light chain according to Kabat numbering is arginine (R).

8. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, and 63.

9. The antibody of claim 1 , wherein the antibody comprises a light chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, and 62.

10. The antibody of claim 1 , wherein the antibody comprises:
a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 35 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 34;
b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 39 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 38;
c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 33 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32;
d) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 45 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 44;
e) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 47 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 46;
f) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 49 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 48;
g) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 29 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28;
h) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 31 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30;
i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 37 and a light chain variable region comprising the amino acid seq

Assignees

• Genentech Inc

Inventors

• Kelley Robert F
• Shatz Whitney
• Tesar Devin
• Scheer Justin M
• Dion Michelle

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P27/10

  for accommodation disorders, e.g. myopia · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• C07K2317/90

  characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin · CPC title

• A61K39/39591 Primary

  Stabilisation, fragmentation · CPC title