HUMANIZED AND AFFINITY MATURED ANTIBODIES TO FcRH5 AND METHODS OF USE

Patent metadata

Field	Value
Publication number	US-2016368985-A1
Application number	US-201615184690-A
Country	US
Kind code	A1
Filing date	Jun 16, 2016
Priority date	Jun 16, 2015
Publication date	Dec 22, 2016
Grant date	—

Abstract

The present invention relates to anti-FcRH5 antibodies, including anti-FcRH5 antibodies comprising an FcRH5 binding domain and a CD3 binding domain (e.g., FcRH5 T cell-dependent bispecific (TDB) antibodies), and methods of using the same.

First claim

1 . An anti-Fc Receptor-like 5 (FcRH5) antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising the following six hypervariable regions (HVRs):
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

2 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (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: 12; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 23.

3 . The anti-FcRH5 antibody of claim 2 , wherein the binding domain comprises (a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 104; (b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 105; or (c) a VH domain as in (a) and a VL domain as in (b).

4 . The anti-FcRH5 antibody of claim 2 , wherein the antibody further comprises the following heavy chain variable region framework regions (FRs):
(a) an FR-H1 comprising the amino acid sequence of SEQ ID NO: 52; (b) an FR-H2 comprising the amino acid sequence of SEQ ID NO: 54; (c) an FR-H3 comprising the amino acid sequence of SEQ ID NO: 46; and (d) an FR-H4 comprising the amino acid sequence of SEQ ID NO: 47.

5 . The anti-FcRH5 antibody of claim 4 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 104.

6 . The anti-FcRH5 antibody of claim 2 , wherein the antibody further comprises the following light chain variable region FRs:
(a) an FR-L1 comprising the amino acid sequence of SEQ ID NO: 48; (b) an FR-L2 comprising the amino acid sequence of SEQ ID NO: 57; (c) an FR-L3 comprising the amino acid sequence of SEQ ID NO: 50; and (d) an FR-L4 comprising the amino acid sequence of SEQ ID NO: 51.

7 . The anti-FcRH5 antibody of claim 6 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO: 105.

8 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising (a) a VH domain comprising an amino acid sequence of SEQ ID NO: 104 and (b) a VL domain comprising an amino acid sequence of SEQ ID NO: 105.

9 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (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: 10; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 23.

10 . The anti-FcRH5 antibody of claim 9 , wherein the binding domain comprises (a) a VH domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 106; (b) a VL domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 107; or (c) a VH domain as in (a) and a VL domain as in (b).

11 . The anti-FcRH5 antibody of claim 9 , wherein the antibody further comprises the following heavy chain variable region FRs:
(a) an FR-H1 comprising the amino acid sequence of SEQ ID NO: 53; (b) an FR-H2 comprising the amino acid sequence of SEQ ID NO: 54; (c) an FR-H3 comprising the amino acid sequence of SEQ ID NO: 46; and (d) an FR-H4 comprising the amino acid sequence of SEQ ID NO: 47.

12 . The anti-FcRH5 antibody of claim 11 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 106.

13 . The anti-FcRH5 antibody of claim 9 , wherein the antibody further comprises the following light chain variable region FRs:
(a) an FR-L1 comprising the amino acid sequence of SEQ ID NO: 48; (b) an FR-L2 comprising the amino acid sequence of SEQ ID NO: 57; (c) an FR-L3 comprising the amino acid sequence of SEQ ID NO: 50; and (d) an FR-L4 comprising the amino acid sequence of SEQ ID NO: 51.

14 . The anti-FcRH5 antibody of claim 13 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO: 107.

15 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising (a) a VH domain comprising an amino acid sequence of SEQ ID NO: 106 and (b) a VL domain comprising an amino acid sequence of SEQ ID NO: 107.

16 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (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: 11; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 15; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 20.

17 - 22 . (canceled)

23 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (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: 12; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 21.

24 - 29 . (canceled)

30 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (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: 12; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 17; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 22.

31 - 36 . (canceled)

37 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (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: 13; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 16; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 21.

38 - 43 . (canceled)

44 . An anti-FcRH5 antibody, wherein the anti-FcRH5 antibody comprises a binding domain comprising the following six HVRs:
(a) an HVR-H1 comprising th

Assignees

• Genentech Inc

Inventors

• Hotzel Isidro
• Junttila Teemu T
• Li Ji
• Scheer Justin
• Dicara Danielle
• Ellerman Diego
• Spiess Christoph
• Carter Paul J

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title