Anti-il-4 antibodies and bispecific antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2016207995-A1
Application number	US-201514858251-A
Country	US
Kind code	A1
Filing date	Sep 18, 2015
Priority date	Apr 5, 2013
Publication date	Jul 21, 2016
Grant date	—

Abstract

The invention provides anti-IL-4 antibodies and bispecific antibodies and methods of using the same.

First claim

1 . A multispecific antibody comprising an antigen-binding domain that comprises a first VH/VL unit that specifically binds IL-4 and a second VH/VL unit that specifically binds IL-13, wherein the antibody:
a) inhibits binding of IL-4 to IL-4 receptor alpha (IL-4Rα), b) inhibits IL-4-induced proliferation of cells in vitro, and/or c) inhibits IL-13-induced proliferation of cells in vitro.

2 . The multispecific antibody of claim 1 , wherein the first VH/VL unit comprises HVR-H3 comprising the amino acid sequence of SEQ ID NO: 14, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 17, and HVR-H2 comprising the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 18.

3 . The multispecific antibody of claim 1 or claim 2 , wherein the first VH/VL unit comprises HVR-H1 comprising the amino acid sequence of SEQ ID NO: 12, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 18, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 14.

4 . The multispecific antibody of any one of claims 1 to 3 , wherein the first VH/VL unit comprises HVR-L1 comprising the amino acid sequence of SEQ ID NO: 15, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 16, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 17.

5 . The multispecific antibody of any one of claims 1 to 4 , wherein the first VH/VL unit comprises (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 9; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10; or (c) a VH sequence as in (a) and a VL sequence as in (b).

6 . The multispecific antibody of any one of claims 1 to 5 , wherein the first VH/VL unit comprises a VH sequence selected from SEQ ID NOs: 1 and 3 to 9.

7 . The multispecific antibody of any one of claims 1 to 6 , wherein the first VH/VL unit comprises a VL sequence selected from SEQ ID NOs: 2, 10, and 11.

8 . The multispecific antibody of claim 1 , wherein the first VH/VL unit comprises the VH sequence of SEQ ID NO: 9 and the VL sequence of SEQ ID NO: 10.

9 . The multispecific antibody of any one of claims 1 to 8 , wherein the second VH/VL unit comprises:
a) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 23, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26, and HVR-H2 comprising the amino acid sequence of SEQ ID NO: 22; or
b) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 52, HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and HVR-H2 comprising the amino acid sequence of SEQ ID NO: 51.

10 . The multispecific antibody of any one of claims 1 to 9 , wherein the second VH/VL unit comprises:
a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 21 or the amino acid sequence of SEQ ID NO: 60, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 22, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 23; or
b) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 50, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 51, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 52.

11 . The multispecific antibody of any one of claims 1 to 10 , wherein the second VH/VL unit comprises:
a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 24, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 25, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26; or
b) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 53, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 54, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55.

12 . The multispecific antibody of any one of claims 1 to 11 , wherein the second VH/VL unit comprises:
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;
c) a VH sequence as in (a) and a VL sequence as in (b);
d) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 49;
e) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 48;
f) a VH sequence as in (d) and a VL sequence as in (e).

13 . The multispecific antibody of any one of claims 1 to 12 , wherein the second VH/VL unit comprises the VH sequence of SEQ ID NO: 19, 56, or 49.

14 . The multispecific antibody of any one of claims 1 to 13 , wherein the second VH/VL unit comprises the VL sequence of SEQ ID NO: 20, 57, or 48.

15 . The multispecific antibody of any one of claims 1 to 14 , wherein the second VH/VL unit comprises the VH sequence of SEQ ID NO: 19 or 56 and the VL sequence of SEQ ID NO: 20 or 57; or the VH sequence of SEQ ID NO: 49 and the VL sequence of SEQ ID NO: 48.

16 . The multispecific antibody of any one of claims 1 to 15 , wherein the antibody competes for binding to IL-4 with an antibody comprising a VH sequence of SEQ ID NO: 9 and a VL sequence of SEQ ID NO: 10.

17 . The multispecific antibody of any one of claims 1 to 16 , wherein the antibody competes for binding to IL-13 with an antibody comprising a VH sequence of SEQ ID NO: 19 and a VL sequence of SEQ ID NO: 20, or with an antibody comprising a VH sequence of SEQ ID NO: 49 and a VL sequence of SEQ ID NO: 48.

18 . The multispecific antibody of any one of claims 1 to 17 , wherein the antibody binds an epitope within amino acids 77 to 89 of SEQ ID NO: 29, or within amino acids 82 to 89 of SEQ ID NO: 29.

19 . A multispecific antibody comprising a first VH/VL unit that specifically binds IL-4 and a second VH/VL unit that specifically binds IL-13, wherein the first VH/VL unit comprises the VH sequence of SEQ ID NO: 9 and the VL sequence of SEQ ID NO: 10, and the second VH/VL unit comprises the VH sequence of SEQ ID NO: 19 and the VL sequence of SEQ ID NO: 20.

20 . The multispecific antibody of any one of the preceding claims, wherein the antibody is an IgG antibody.

21 . The multispecific antibody of claim 20 , wherein the antibody is an IgG1 or IgG4 antibody.

22 . The multispecific antibody of claim 21 , wherein the antibody is an IgG4 antibody.

23 . The multispecific antibody of any one of the preceding claims, wherein the antibody comprises a first heavy chain constant region and a second heavy chain constant region, wherein the first heavy chain constant region comprises a knob mutation and the second heavy chain constant region comprises a hole mutation.

24 . The multispecific antibody of claim 23 , wherein the first heavy chain constant region is fused to the heavy chain variable region portion of a VH/VL unit that binds IL-4.

25 . The multispecific antibody of claim 23 or claim 24 , wherein the second heavy chain constant region is fused to the heavy chain variable region portion of a VH/VL unit that binds IL-13.

26 . The multispecific antibody of claim 23 , wherein the first heavy chain constant region is fused to the heavy chain variable region portion of a VH/VL unit that binds IL-13.

27 . The multispecific antibody of claim 23 or claim 26 , wherein the second heavy chain constant region is fused to the heavy chain variable region portion of a VH/VL unit that binds IL-4.

28 . The multispecific antibody of any one of claims 23 to 27 , wherein the antibody is an IgG1 antibody and wherein the knob mutation comprises a T366W mutatio

Assignees

• Genentech Inc

Inventors

• Yansura Daniel G
• Chiang Nancy Y
• Dennis Mark S
• Dillon Michael
• Fuh Germaine G
• Nakamura Gerald R
• Spiess Christoph
• Wu Lawren C
• Zhang Yin

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P7/10

  Antioedematous agents; Diuretics · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P31/10

  Antimycotics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title