# US 11,078,281 B2 · Monoclonal antibodies to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)

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- Number: US 11,078,281 B2
- Document ID: US11078281B2
- Status: Granted
- Kind: B2
- Application number: 16/987,334
- Filed: 2020-08-06
- Published: 2021-02-11
- Granted: 2021-08-03
- Earliest claimed: 2020-08-06
- Assignees: Wuxi Biologies (Shanghai) Co. Ltd.
- Applicants: WUXI Biologics (Shanghai) Co., Ltd.
- Inventors: Zhuozhi Wang; Jing Li; Gennady Gololobov; Jianqing Xu
- Web page: https://patentgrep.com/patent/US11078281B2

## CPC

- C07K 16/2818: {against CD28 or CD152}
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- A61K 2039/505: {comprising antibodies}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/565: Complementarity determining region [CDR]
- 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 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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
- 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)

## Abstract

The present invention provides CTLA-4 monoclonal antibodies, particularly humanized monoclonal antibodies specifically binding to CTLA-4 with high affinity. The present invention also provides functional monoclonal antibodies cross-reactive to CTLA-4 of human, cynomolgus monkey and mouse. The present invention further provides amino acid sequences of the antibodies of the invention, cloning or expression vectors, host cells and methods for expressing or isolating the antibodies. The epitopes of the antibodies are identified. Therapeutic compositions comprising the antibodies of the invention are also provided. The invention also provides methods for treating cancers and other diseases with anti-CTLA-4 antibodies.

## Claims

### Claim 1

An antibody or antigen binding fragment thereof, comprising a light chain variable (VL) domain and a heavy chain variable (VH) domain, wherein
the VL domain comprises a light chain complementary-determining region 1 (LCDR1) defined by SEQ ID NO: 41, LCDR2 defined by defined by SEQ ID NO: 32, and LCDR3 defined by SEQ ID NO: 22, and
the VH domain comprises a heavy chain complementary determining region 1 (HCDR1) defined by SEQ ID NO: 36, HCDR2 defined by defined by SEQ ID NO: 28, and HCDR3 defined by SEQ ID NO: 18; and
wherein the antibody or the antigen binding fragment thereof specifically binds to CTLA-4.

### Claim 2 (depends on 1)

The antibody or antigen binding fragment thereof according to claim 1, wherein the VL domain has the amino acid sequence of SEQ ID NO: 14.

### Claim 3 (depends on 1)

The antibody or antigen binding fragment thereof according to claim 1, wherein VH domain has the amino acid sequence of SEQ ID NO: 7.

### Claim 4 (depends on 1)

The antibody or antigen binding fragment thereof according to claim 1, wherein the VL domain has the amino acid sequence of SEQ ID NO: 14 and the VH domain has the amino acid sequence of SEQ ID NO: 7.

### Claim 5 (depends on 1)

The antibody or the antigen binding fragment thereof according to claim 1, wherein the antibody or the antigen binding fragment thereof is a humanized antibody.

### Claim 6 (depends on 1)

The antibody or the antigen binding fragment thereof according to claim 1, wherein the antibody or the antigen binding fragment thereof is a human antibody.

### Claim 7 (depends on 1)

The antibody or the antigen binding fragment thereof according to claim 1, wherein the antibody or the antigen binding fragment thereof inhibits CTLA-4 binding to CD80 or CD86.