# US 11,208,483 B2 · CTLA-4 antibodies and uses thereof

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- Number: US 11,208,483 B2
- Document ID: US11208483B2
- Status: Granted
- Kind: B2
- Application number: 15/777,369
- Filed: 2015-11-19
- Published: 2020-08-20
- Granted: 2021-12-28
- Earliest claimed: 2015-11-19
- Assignees: Shanghai Kanda Biotechnology Co., Ltd.
- Applicants: Shanghai Kanda Biotechnology Co. Ltd
- Inventors: Zeling Cai; Yi Chen
- Web page: https://patentgrep.com/patent/US11208483B2

## CPC

- A61K 39/12: Viral antigens
- C07K 16/2818: {against CD28 or CD152}
- A61K 39/001139: {Colony stimulating factors [CSF]}
- A61K 39/292: {Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- 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
- C12N 2710/00034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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)
- 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)

## Abstract

Human antibodies which specifically bind to human CTLA-4, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

## Claims

### Claim 1

An isolated human antibody, or an antigen-binding portion thereof, that specifically binds to human CTLA-4, the antibody comprising:
a heavy chain variable region comprising three complementarity determining regions (CDRs): VHCDR1 of SEQ ID NO: 34, VHCDR2 of SEQ ID NO: 35, and VHCDR3 of SEQ ID NO: 36; and
a light chain variable region comprising three CDRs: VLCDR1 of SEQ ID NO: 25, VLCDR2 of SEQ ID NO: 26, and VLCDR3 of SEQ ID NO: 27.

### Claim 2

An isolated human antibody, or an antigen-binding portion thereof, that specifically binds to human CTLA-4, the antibody comprising:
a heavy chain variable region comprising three CDRs: VHCDR1 of SEQ ID NO: 37, VHCDR2 of SEQ ID NO: 38, and VHCDR3 of SEQ ID NO: 39; and
a light chain variable region comprising three CDRs: VLCDR1 of SEQ ID NO: 28, VLCDR2 of SEQ ID NO: 29, and VLCDR3 of SEQ ID NO: 30.

### Claim 3

An isolated human antibody, or an antigen-binding portion thereof, that specifically binds to human CTLA-4, the antibody comprising
a heavy chain variable region comprising three CDRs: VHCDR1 of SEQ ID NO: 40, VHCDR2 of SEQ ID NO: 41, and VHCDR3 of SEQ ID NO: 42; and
a light chain variable region comprising three CDRs: VLCDR1 of SEQ ID NO: 31, VLCDR2 of SEQ ID NO: 32, and VLCDR3 of SEQ ID NO: 33.

### Claim 4 (depends on 1)

The antibody of claim 1, which is an IgG1 antibody, optionally wherein the antibody is an IgG1,κ or IgG1,λ antibody.

### Claim 5 (depends on 1)

The antibody of claim 1, which is a single chain antibody (scFv).

### Claim 6 (depends on 5)

The scFv of claim 5, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 8, and a light chain variable region comprising the amino acid sequence asset forth in SEQ ID NO: 2.

### Claim 7 (depends on 1)

The antibody of claim 1, wherein the heavy chain variable region comprises:
(i) the amino acid sequence set forth in SEQ ID NO: 8,
(ii) an amino acid sequence encoded by a nucleic acid comprising the nucleotide sequence as set forth in or degenerate to SEQ ID NO: 7,
or
(iii) an amino acid sequence having at least 90% identity with (i) or (ii).

### Claim 8 (depends on 1)

The antibody of claim 1, wherein the light chain variable region comprises:
(i) the amino acid sequence set forth in SEQ ID NO: 2,
(ii) an amino acid sequence encoded by a nucleic acid comprising the nucleotide sequence as set forth in or degenerate to SEQ ID NO: 1,
or
(iii) an amino acid sequence having at least 90% identity with (i) or (ii).

### Claim 9 (depends on 1)

An isolated nucleic acid comprising a nucleotide sequence encoding the amino acid sequence of the antibody of claim 1.

### Claim 10 (depends on 1, 9)

A host cell line that produces the antibody of claim 1, wherein the host cell line is a CHO cell line that expresses the isolated nucleic acid of claim 9.

### Claim 11 (depends on 9)

The isolated nucleic acid of claim 9 comprising:
(i) the nucleotide sequence set forth in SEQ ID NO: 7,
(ii) a nucleotide sequence having at least 90% identity with (i),
(iii) a nucleotide sequence encoding h antibody heavy chain variable region amino acid sequence set forth in SEQ ID NO: 8, or
(iv) a nucleotide sequence degenerate to (i), (ii) or (iii).

### Claim 12 (depends on 9)

The isolated nucleic acid of claim 9 comprising:
(i) h nucleotide sequence set forth in SEQ ID NO: 1,
(ii) a nucleotide sequence having at least 90% identity with (i),
(iii) a nucleotide sequence encoding h antibody light chain variable region amino acid sequence set forth in SEQ ID NO: 2, or
(iv) a nucleotide sequence degenerate to (i), (ii) or (iii).

### Claim 13 (depends on 1)

A pharmaceutical composition comprising the antibody of claim 1, and a pharmaceutically acceptable carrier.

### Claim 14 (depends on 13)

The pharmaceutical composition according to claim 13, further comprising one or more additional therapeutic agents, optionally wherein the additional therapeutic agent is a chemotherapeutic agent or an immune checkpoint inhibitors.

### Claim 15 (depends on 13)

A method of treating a cancer or for stimulating a response to a pathogen in a subject, which comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 13.

### Claim 16 (depends on 15)

The method according to claim 15, further comprising administering to the subject one or more additional therapeutic agents, optionally wherein the additional therapeutic agent is a chemotherapeutic agent, an immune checkpoint inhibitors or a vaccine.

### Claim 17 (depends on 15)

The method according to claim 15, wherein the cancer is melanoma, non-small cell lung cancer, or prostate cancer.

### Claim 18 (depends on 1)

A method for activating a cell expressing CTLA-4, the method comprising contacting the antibody of claim 1 with the cell.

### Claim 19 (depends on 1)

A method for detecting in vitro or in vivo the presence of human CTLA-4 antigen in a sample, the method comprising contacting the sample with the antibody of claim 1.

### Claim 20 (depends on 13)

A method for inducing, augmenting or prolonging an immune response to an antigen in a patient, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 13, wherein the pharmaceutical composition blocks binding of human CTLA-4 to human B7 ligands, optionally wherein the antigen is a tumor antigen, or an antigen from a pathogen.