# US 12,180,282 B2 · Anti-PD-L1 antibodies

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- Number: US 12,180,282 B2
- Document ID: US12180282B2
- Status: Granted
- Kind: B2
- Application number: 17/200,374
- Filed: 2021-03-12
- Published: 2021-09-02
- Granted: 2024-12-31
- Earliest claimed: 2015-08-06
- Assignees: WUXI Biologics (Shanghai) Co., Ltd.; Wuxi Biologics Ireland Limited
- Applicants: Wuxi Biologics (Shanghai) Co. Ltd.; Wuxi Biologics Ireland Limited
- Inventors: Yong Zheng; Jing Li; Zhisheng Chen
- Web page: https://patentgrep.com/patent/US12180282B2

## CPC

- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- A61P 31/12: Antivirals
- A61P 37/04: Immunostimulants
- G01N 33/6893: {related to diseases not provided for elsewhere}
- A61K 2039/505: {comprising antibodies}
- A61P 35/00: Antineoplastic agents
- C07K 2317/21: from primates, e.g. man
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/70: characterized by effect upon binding to a cell or to an antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

A vector comprising the isolated polynucleotide of claim 1.

### Claim 3 (depends on 2)

An isolated host cell comprising the vector of claim 2.

### Claim 4 (depends on 3)

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.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 1)

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.

### Claim 10 (depends on 1)

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.

### Claim 11 (depends on 1)

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.

### Claim 12 (depends on 1)

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.

### Claim 13 (depends on 1)

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

### Claim 14 (depends on 13)

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

### Claim 15 (depends on 1)

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.

### Claim 16 (depends on 1)

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.

### Claim 17 (depends on 1)

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

### Claim 18 (depends on 1)

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