# US 11,993,655 B2 · Anti-PD-L1 antibody and use thereof

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- Number: US 11,993,655 B2
- Document ID: US11993655B2
- Status: Granted
- Kind: B2
- Application number: 17/046,265
- Filed: 2018-08-27
- Published: 2021-12-09
- Granted: 2024-05-28
- Earliest claimed: 2018-04-09
- Assignees: Oricell Therapeutics Co., Ltd.
- Applicants: Oricell Therapeutics Co., Ltd.
- Inventors: Bohua Li; Huajing Wang; Xiaowen He
- Web page: https://patentgrep.com/patent/US11993655B2

## CPC

- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C12N 15/1037: {Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display}
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61P 35/00: Antineoplastic agents
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C12N 5/10: Cells modified by introduction of foreign genetic material
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C40B 40/02: Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
- A61K 2039/505: {comprising antibodies}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/75: Agonist effect on 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60)

## Abstract

An antibody that binds to the PD-L1 protein or CD137 protein, an antigen-binding fragment or a variant thereof, as well as a bispecific antibody that can bind to both the PD-L1 protein and the CD137 protein. The bispecific antibody has a strong ability to specifically recognize the PD-L1 protein and the CD137 protein, and can enhance T-cell activity. The antibody or the antigen-binding fragment or the variant thereof and the bispecific antibody may be used in the prevention and treatment of tumors.

## Claims

### Claim 1

An antibody or an antigen binding fragment thereof capable of binding to PD-L1 protein, comprising a light chain variable region VL which comprises LCDRI-3 and a heavy chain variable region VH which comprises HCDRI-3, wherein said antibody or antigen binding fragment thereof comprises amino acid sequences selected from any one of the following groups:
(a) LCDR1: SEQ ID NO:54, LCDR2: SEQ ID NO:60, LCDR3: SEQ ID NO:63, HCDR1: SEQ ID NO:46, HCDR2: SEQ ID NO:48 and HCDR3: SEQ ID NO:50;
(b) LCDR1: SEQ ID NO:55, LCDR2: SEQ ID NO:60, LCDR3: SEQ ID NO:64, HCDR1: SEQ ID NO:47, HCDR2: SEQ ID NO:48 and HCDR3: SEQ ID NO: 51;
(c) LCDR1: SEQ ID NO:55, LCDR2: SEQ ID NO:60, LCDR3: SEQ ID NO:64, HCDR1: SEQ ID NO:47, HCDR2: SEQ ID NO:48 and HCDR3: SEQ ID NO:52;
(d) LCDRI: SEQ ID NO:56, LCDR2: SEQ ID NO:61, LCDR3: SEQ ID NO:64, HCDR1: SEQ ID NO:47, HCDR2: SEQ ID NO:48 and HCDR3: SEQ ID NO:52;
(e) LCDRI: SEQ ID NO:57, LCDR2: SEQ ID NO:61, LCDR3: SEQ ID NO:64, HCDRI: SEQ ID NO:47, HCDR2: SEQ ID NO:48 and HCDR3: SEQ ID NO:52; and
(f) LCDR1: SEQ ID NO:58, LCDR2: SEQ ID NO:61, LCDR3: SEQ ID NO:64, HCDRI: SEQ ID NO:47, HCDR2: SEQ ID NO:48 and HCDR3: SEQ ID NO:52.

### Claim 2 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, wherein said heavy chain variable region VH comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 9, SEQ ID NO: 31 and SEQ ID NO: 35, and said light chain variable region VL comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 11, SEQ ID NO: 33, SEQ ID NO: 37, SEQ ID NO: 39 and SEQ ID NO: 41.

### Claim 3 (depends on 1)

The antibody or antigen binding fragment thereof of claim 1, comprising an antibody light chain or a fragment thereof and an antibody heavy chain or a fragment thereof, wherein said antibody light chain or fragment thereof comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 8, SEQ ID NO: 15, SEQ ID NO: 34, SEQ ID NO: 38, SEQ ID NO: 40 and SEQ ID NO: 42, and said antibody heavy chain or fragment thereof comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 13, SEQ ID NO: 32 and SEQ ID NO: 36.

### Claim 4 (depends on 1)

A bispecific antibody, comprising a first targeting moiety that specifically binds to a PD-L1 protein, wherein the first targeting moiety comprises the antibody or antigen binding fragment thereof of claim 1.

### Claim 5 (depends on 4)

The bispecific antibody of claim 4, comprising a second targeting moiety that specifically binds to a CD137 protein, wherein the second targeting moiety comprises an antibody or an antigen binding fragment thereof, wherein the antibody that binds to CD137 comprises an antibody light chain or fragment thereof which comprises LCDR1-3 sequentially comprising SEQ ID NOs: 80-82 and an antibody heavy chain or fragment thereof which comprises HCDR1-3 sequentially comprising SEQ ID NOs: 77-79.

### Claim 6 (depends on 5)

The bispecific antibody of claim 5, wherein the antibody that binds to the CD137 protein comprises an scFv, and wherein the scFv comprises the amino acid sequence of SEQ ID NO: 83.

### Claim 7 (depends on 5)

The bispecific antibody of claim 5, comprising a first polypeptide chain comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 30, SEQ ID NO: 43, and SEQ ID NO: 44; and a second polypeptide chain comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 15 and SEQ ID NO: 34, wherein the first polypeptide chain comprises a heavy chain variable region of the antibody that binds to the PD-L1 protein, a heavy chain variable region of the antibody that binds to the CD137 protein, and a light chain variable region of the antibody that binds to the CD137 protein, and wherein the second polypeptide chain comprises a light chain variable region of the antibody that binds to the PD-L1 protein.

### Claim 8 (depends on 7)

The bispecific antibody of claim 7, wherein, in the first polypeptide chain, the heavy chain variable region of the antibody that binds to the PD-L1 protein is located at an N-terminus of the heavy chain variable region of the antibody that binds to the CD137 protein, and the heavy chain variable region of the antibody that binds to the CD137 protein is located at an N-terminus of the light chain variable region of the antibody that binds to the CD137 protein.

### Claim 9 (depends on 1)

An isolated nucleic acid molecule which encodes the antibody or antigen binding fragment thereof of claim 1.

### Claim 10 (depends on 4)

An isolated nucleic acid molecule which encodes the bispecific antibody of claim 4.

### Claim 11 (depends on 9)

A vector, comprising the molecule of claim 9.

### Claim 12 (depends on 9)

A cell, comprising the molecule of claim 9 or a vector comprising the molecule.

### Claim 13 (depends on 1)

A pharmaceutical composition, comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable adjuvant.

### Claim 14 (depends on 4)

A pharmaceutical composition, comprising the bispecific antibody of claim 4 and a pharmaceutically acceptable adjuvant.

### Claim 15 (depends on 1)

A method of treating a tumor, the method comprising administering the antibody or antigen binding fragment thereof of claim 1.

### Claim 16 (depends on 4)

A method of treating a tumor, the method comprising administering the bispecific antibody of claim 4.

### Claim 17 (depends on 1)

A method of inhibiting the binding of a PD-L1 protein to a PD-1 protein, the method comprising administering the antibody or antigen binding fragment thereof of claim 1.

### Claim 18 (depends on 4)

A method of inhibiting the binding of a PD-L1 protein to a PD-1 protein, the method comprising administering the bispecific antibody of claim 4.