Anti-PD-L1 antibodies

Patent metadata

Field	Value
Publication number	US-12180282-B2
Application number	US-202117200374-A
Country	US
Kind code	B2
Filing date	Mar 12, 2021
Priority date	Aug 6, 2015
Publication date	Dec 31, 2024
Grant date	Dec 31, 2024

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 polynucleotide encoding for an anti-PD-L1 antibody or an antigen binding fragment thereof 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; and 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; and 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. A vector comprising the isolated polynucleotide of claim 1 .

3. An isolated host cell comprising the vector of claim 2 .

4. A method of expressing the antibody or antigen binding fragment thereof, comprising culturing the host cell of claim 3 under the condition at which the polynucleotide encoding for the anti-PD-L1 antibody or antigen binding fragment thereof is expressed.

5. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof comprises 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.

6. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof comprises a light chain variable region selected from the group consisting of: SEQ ID NO: 45, SEQ ID NO: 49 and SEQ ID NO: 53.

7. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof comprises:
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.

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

9. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof binds to monkey PD-L1 at an EC50 of no more than 10 nM, or no more than 1 nM, and/or does not bind to mouse PD-L1.

10. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof is capable of inhibiting binding of human or monkey PD-L1 to its receptor at an IC50 of no more than 100 nM.

11. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof does not substantially bind to PD-L2.

12. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof does not mediate ADCC or CDC or both.

13. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof is a fully human monoclonal antibody.

14. The isolated polynucleotide of claim 13 , wherein the fully human monoclonal antibody is produced by a transgenic rat.

15. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment is capable of blocking binding of human PD-L1 to its receptor and thereby provides 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.

16. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof 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.

17. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof comprises an immunoglobulin constant region.

18. The isolated polynucleotide of claim 1 , wherein the anti-PD-L1 antibody or an antigen binding fragment thereof further comprises a conjugate.

Assignees

• Wuxi Biologics Shanghai Co Ltd
• Wuxi Biologics Ireland 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

• C07K2317/565

  Complementarity determining region [CDR] · CPC title