Anti-PD-L1 antibodies

Patent metadata

Field	Value
Publication number	US-10981995-B2
Application number	US-201615749783-A
Country	US
Kind code	B2
Filing date	Aug 5, 2016
Priority date	Aug 6, 2015
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

Abstract

The present disclosure provides monoclonal antibodies against protein programmed cell death 1 ligand (PD-L1), which can block the binding of PD-L1 to PD-1, and therefore block the inhibitory function of PD-L1 on PD-1 expressing T cells. The antibodies of disclosure provide very potent agents for the treatment of multiple cancers via modulating human immune function.

First claim

What is claimed is:

1. An isolated anti-PD-L1 antibody or an antigen binding fragment, comprising:
a) a heavy chain variable region comprising SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 5; and a light chain variable region comprising SEQ ID NO: 7, SEQ ID NO: 9, and SEQ ID NO: 11;
b) a heavy chain variable region comprising SEQ ID NO: 13, SEQ ID NO: 15, and SEQ ID NO: 17; a light chain variable region comprising SEQ ID NO: 19, SEQ ID NO: 21, and SEQ ID NO: 23;
c) a heavy chain variable region comprising SEQ ID NO: 25, SEQ ID NO: 27, and SEQ ID NO: 29; a light chain variable region comprising SEQ ID NO: 31, SEQ ID NO: 33, and SEQ ID NO: 35; or
d) a heavy chain variable region comprising SEQ ID NO: 37, SEQ ID NO: 39, and SEQ ID NO: 41, and a light chain variable region comprising SEQ ID NO: 19, SEQ ID NO:
21, and SEQ ID NO: 23.

2. The antibody or an antigen binding fragment thereof of claim 1 , comprising a heavy chain variable region selected from the group consisting of: SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51 and SEQ ID NO: 55.

3. The antibody or an antigen binding fragment thereof of claim 1 , comprising a light chain variable region selected from the group consisting of: SEQ ID NO: 45, SEQ ID NO: 49 and SEQ ID NO: 53.

4. The antibody or an antigen binding fragment thereof of claim 1 , comprising:
a) a heavy chain variable region comprising SEQ ID NO: 43; and a light chain variable region comprising SEQ ID NO: 45;
b) a heavy chain variable region comprising SEQ ID NO: 47; and a light chain variable region comprising SEQ ID NO: 49;
c) a heavy chain variable region comprising SEQ ID NO: 51; and a light chain variable region comprising SEQ ID NO: 53; or d) a heavy chain variable region comprising SEQ ID NO: 55; and a light chain variable region comprising SEQ ID NO: 49.

5. The antibody or an antigen binding fragment thereof of claim 1 , capable of specifically binding to human PD-L1 at an Kd value no more than 10 −8 M as measured by plasmon resonance binding assay.

6. The antibody or an antigen binding fragment thereof of claim 1 , which binds to monkey PD-L1 at an EC50 of no more than 1 OnM, or no more than 1 nM, and/or does not bind to mouse PD-L1.

7. The antibody or an antigen binding fragment thereof of claim 1 , capable of inhibiting binding of human or monkey PD-L1 to its receptor at an IC50 of no more than 100 nM.

8. The antibody or an antigen binding fragment thereof of claim 1 , which does not substantially bind to PD-L2.

9. The antibody or an antigen binding fragment thereof of claim 1 , which does not mediate ADCC or CDC or both.

10. The antibody or an antigen binding fragment thereof of claim 1 , which is a fully human monoclonal antibody.

11. The antibody or an antigen binding fragment thereof of claim 10 , wherein the fully human monoclonal antibody is produced by a transgenic rat.

12. The antibody or an antigen binding fragment thereof of claim 1 , capable of blocking binding of human PD-L1 to its receptor and thereby providing at least one of the following activities:
a) inducing production of IL-2 in CD4 + T cells;
b) inducing production of IFNγ in CD4 + T cells;
c) inducing proliferation of CD4 + T cells; and
d) reversing T reg's suppressive function.

13. The antibody or antigen-binding fragment thereof of claim 1 , which is a camelized single domain antibody, a diabody, a scFv, an scFv dimer, a BsFv, a dsFv, a (dsFv)2, a dsFv-dsFv', an Fv fragment, a Fab, a Fab', a F(ab')2, a ds diabody, a nanobody, a domain antibody, or a bivalent domain antibody.

14. The antibody or antigen-binding fragment thereof of claim 1 , further comprising an immunoglobulin constant region.

15. The antibody or antigen-binding fragment thereof of claim 1 , further comprising a conjugate.

16. A kit comprising the antibody or antigen-binding fragment thereof of claim 1 .

17. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 and one or more pharmaceutically acceptable carriers.

Assignees

• Wuxi Biologics Shanghai Co Ltd
• Wuxi Biologics Ireland Ltd
• Wuxi Biologies Ireland Ltd
• Wuxi Biologies Shanghai Co Ltd

Inventors

• Zheng Yong
• Li Jing
• Chen Zhisheng

Classifications

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/70

  characterized by effect upon binding to a cell or to an antigen · CPC title