ANTI-CD79b ANTIBODIES AND METHODS OF USE

Patent metadata

Field	Value
Publication number	US-2016159906-A1
Application number	US-201514960015-A
Country	US
Kind code	A1
Filing date	Dec 4, 2015
Priority date	Dec 5, 2014
Publication date	Jun 9, 2016
Grant date	—

Abstract

The invention provides anti-CD79b antibodies and methods of using the same.

First claim

1 . An isolated anti-CD79b antibody, wherein the antibody comprises a CD79b binding domain comprising the following six hypervariable regions (HVRs):
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 5; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 8; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

2 . The anti-CD79b antibody of claim 1 , wherein the CD79b binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 3; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 6; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

3 . The anti-CD79b antibody of claim 1 , wherein the CD79b binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 4; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 7; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

4 . The anti-CD79b antibody of claim 2 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:17, 21, 23, 25, 27 or 29; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:18, 22, 24, 26, 28, or 30; or (c) a VH sequence as in (a) and a VL sequence as in (b).

5 . The anti-CD79b antibody of claim 3 comprising a VH sequence of SEQ ID NO: 17, 21, 23, 25, 27 or 29.

6 . The anti-CD79b antibody of claim 3 comprising a VL sequence of SEQ ID NO: 18, 22, 24, 26, 28, or 30.

7 . The anti-CD79b antibody of claim 3 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:19; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:20; or (c) a VH sequence as in (a) and a VL sequence as in (b).

8 . The anti-CD79b antibody of claim 3 , comprising a VH sequence of SEQ ID NO:19.

9 . The anti-CD79b antibody of claim 8 , comprising a VL sequence of SEQ ID NO:20.

10 . The anti-CD79b antibody of claim 1 , wherein the CD79b binding domain binds to SEQ ID NO:63.

11 . The anti-CD79b antibody of claim 10 , wherein the CD79b binding domain binds human CD79b with a Kd of less than about 25 nM as a dual arm, bivalent IgG antibody, e.g., less than about any of 10 nM or 5 nM.

12 . The antibody of claim 11 , wherein the CD79b binding domain binds human CD79b binds a B cell at an EC 50 of less than about 1.5 ug/mL in a monovalent format, e.g., less than about 1 ug/mL, 0.75 ug/mL, 0.5 ug/mL or less than 0.25 ug/mL.

13 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is a monoclonal, human, humanized, or chimeric antibody.

14 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is an IgG antibody.

15 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is an antibody fragment that binds CD79b.

16 . The anti-CD79b antibody of claim 15 , wherein the anti-CD79b antibody fragment is a Fab, Fab′-SH, Fv, scFv, and/or (Fab′) 2 fragment.

17 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is a full-length antibody.

18 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody comprises an aglycosylation site mutation.

19 . The anti-CD79b antibody of claim 18 , wherein the aglycosylation site mutation is a substitution mutation.

20 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody comprises reduced effector function.

21 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody comprises a substitution mutation is at amino acid residue N297, L234, L235, and/or D265 according to EU numbering.

22 . The anti-CD79b antibody of claim 21 , wherein the substitution mutation is selected from the group consisting of N297G, N297A, L234A, L235A, and D265A according to EU numbering.

23 . The anti-CD79b antibody of claim 21 , wherein the antibody comprises an N297G substitution mutation at amino acid residue 297 according to EU numbering.

24 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is a monospecific antibody (e.g., bivalent, dual arm antibody).

25 . The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is a multispecific antibody.

26 . The anti-CD79b antibody of claim 25 , wherein the multispecific antibody comprises a CD3 binding domain.

27 . The anti-CD79b antibody of claim 26 , wherein the CD3 binding domain binds to a human CD3 polypeptide or a cynomolgus monkey (cyno) CD3 polypeptide.

28 . The anti-CD79b antibody of claim 27 , wherein the human CD3 polypeptide or the cyno CD3 polypeptide is a human CDR polypeptide or a cyno CDR polypeptide, respectively.

29 . The anti-CD79b antibody of claim 27 , wherein the human CD3 polypeptide or the cyno CD3 polypeptide is a human CD3y polypeptide or a cyno CD3y polypeptide, respectively.

30 . The anti-CD79b antibody of claim 26 , wherein the CD3 binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:45; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:46; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:47; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:48; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:49; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:50.

31 . The anti-CD79b antibody of claim 26 , wherein the CD3 binding domain comprises (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:59; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:60; or (c) a VH sequence as in (a) and a VL sequence as in (b).

32 . The anti-CD79b antibody of claim 26 , wherein the CD3 binding domain comprises a VH sequence of SEQ ID NO:59.

33 . The anti-CD79b antibody of claim 32 , wherein the CD3 binding domain comprises a VL sequence of SEQ ID NO:60.

34 . The anti-CD79b antibody of claim 26 , wherein the CD3 binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:39; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:40; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:41; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:42; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:43; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:44.

35 . The anti-CD79b antibody of claim 26 , wherein the CD3 binding domain comprises (

Assignees

• Genentech Inc

Inventors

• Sun Liping L
• Chen Yvonne Man-Yee
• Dennis Mark S
• Ebens Jr Allen J
• Polson Andrew

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

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

• A61P37/02

  Immunomodulators · CPC title