# US 12,006,372 B2 · Anti-GARP antibody

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- Number: US 12,006,372 B2
- Document ID: US12006372B2
- Status: Granted
- Kind: B2
- Application number: 17/361,137
- Filed: 2021-06-28
- Published: 2022-01-13
- Granted: 2024-06-11
- Earliest claimed: 2015-09-24
- Assignees: Daiichi Sankyo Company, Limited
- Applicants: Daiichi Sankyo Company, Limited
- Inventors: Kazuki Satoh; Kazuki Hirahara; Ichiro Watanabe; Masato Amano
- Web page: https://patentgrep.com/patent/US12006372B2

## CPC

- C07K 16/32: against translation products of oncogenes
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C12N 1/20: Bacteria; Culture media therefor
- C12N 5/10: Cells modified by introduction of foreign genetic material
- C12N 5/12: Fused cells, e.g. hybridomas
- C12N 15/02: Preparation of hybrid cells by fusion of two or more cells, e.g. protoplast fusion {(monoclonal antibodies C07K16/00; apparatus for cell fusion C12M)}
- A61K 2039/505: {comprising antibodies}
- A61P 35/00: Antineoplastic agents
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to an antibody that binds to GARP and is useful as a therapeutic agent for a tumor, and a method for treating a tumor using the aforementioned antibody. It is an object of the present invention to provide an antibody, which inhibits the function of Treg in a tumor and is thereby used as a pharmaceutical product having therapeutic effects, a method for treating a tumor using the aforementioned antibody, and the like. An anti-GARP antibody that binds to GARP and exhibits inhibitory activity to Treg function and exhibits ADCC activity is obtained, and moreover a pharmaceutical composition for use in tumor therapy, comprising the aforementioned antibody, etc. is obtained.

## Claims

### Claim 1

An antibody that specifically binds Glycoprotein-A Repetitions Predominant (GARP) comprising,
a) CDRH1 consisting of the amino acid sequence at amino acid positions 26 to 35 of SEQ ID NO: 2,
b) CDRH2 consisting of the amino acid sequence at amino acid positions 50 to 66 of SEQ ID NO: 2,
c) CDRH3 consisting of the amino acid sequence at amino acid positions 99 to 107 of SEQ ID NO: 2,
d) CDRL1 consisting of the amino acid sequence at amino acid positions 23 to 36 of SEQ ID NO: 3,
e) CDRL2 consisting of the amino acid sequence at amino acid positions 52 to 58 of SEQ ID NO: 3 and
f) CDRL3 consisting of the amino acid sequence at amino acid positions 91 to 101 of SEQ ID NO: 3.

### Claim 2 (depends on 1)

The antibody of claim 1, comprising:
a heavy chain variable region consisting of the amino acid sequence at amino acid positions 1 to 118 of SEQ ID NO: 2, and a light chain variable region consisting of the amino acid sequence at amino acid positions 1 to 112 of SEQ ID NO: 3.

### Claim 3 (depends on 1)

The antibody of claim 1, comprising a human constant region.

### Claim 4 (depends on 1)

The antibody of claim 1, comprising
a heavy chain consisting of the amino acid sequence of SEQ ID NO: 2, and a light chain consisting of the amino acid sequence of SEQ ID NO: 3.

### Claim 5 (depends on 1)

The antibody of claim 1 which is humanized.

### Claim 6 (depends on 1)

A method for treating a tumor, which comprises administering the antibody of claim 1 to an individual having a tumor.

### Claim 7 (depends on 6)

The method of claim 6, wherein the tumor is a cancer.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising the antibody of claim 1.

### Claim 9

An antibody that specifically binds Glycoprotein-A Repetitions Predominant (GARP) comprising,
a) CDRH1 consisting of the amino acid sequence at amino acid positions 26 to 35 of SEQ ID NO: 4,
b) CDRH2 consisting of the amino acid sequence at amino acid positions 50 to 66 of SEQ ID NO: 4,
c) CDRH3 consisting of the amino acid sequence at amino acid positions 99 to 112 of SEQ ID NO: 4,
d) CDRL1 consisting of the amino acid sequence at amino acid positions 23 to 36 of SEQ ID NO: 5,
e) CDRL2 consisting of the amino acid sequence at amino acid positions 52 to 58 of SEQ ID NO: 5 and
f) CDRL3 consisting of the amino acid sequence at amino acid positions 91 to 100 of SEQ ID NO: 5.

### Claim 10 (depends on 9)

The antibody of claim 9, comprising:
a heavy chain variable region consisting of the amino acid sequence at amino acid positions 1 to 123 of SEQ ID NO: 4, and a light chain variable region consisting of the amino acid sequence at amino acid positions 1 to 111 of SEQ ID NO: 5.

### Claim 11 (depends on 9)

The antibody of claim 9, comprising a human constant region.

### Claim 12 (depends on 9)

The antibody of claim 9, comprising
a heavy chain consisting of the amino acid sequence of SEQ ID NO: 4, and a light chain consisting of the amino acid sequence of SEQ ID NO: 5.

### Claim 13 (depends on 9)

The antibody of claim 9 which is humanized.

### Claim 14 (depends on 9)

A method for treating a tumor, which comprises administering the antibody of claim 9 to an individual having a tumor.

### Claim 15 (depends on 14)

The method of claim 14, wherein the tumor is a cancer.

### Claim 16 (depends on 9)

A pharmaceutical composition comprising the antibody of claim 9.

### Claim 17

An antibody that specifically binds Glycoprotein-A Repetitions Predominant (GARP) comprising,
a) CDRH1 consisting of the amino acid sequence at amino acid positions 45 to 54 of SEQ ID NO: 29,
b) CDRH2 consisting of the amino acid sequence at amino acid positions 69 to 77 of SEQ ID NO: 29,
c) CDRH3 consisting of the amino acid sequence at amino acid positions 117 to 128 of SEQ ID NO: 29,
d) CDRL1 consisting of the amino acid sequence at amino acid positions 44 to 54 of SEQ ID NO: 31,
e) CDRL2 consisting of the amino acid sequence at amino acid positions 70 to 76 of SEQ ID NO: 31 and
f) CDRL3 consisting of the amino acid sequence at amino acid positions 109 to 117 of SEQ ID NO: 31.

### Claim 18 (depends on 17)

The antibody of claim 17, comprising:
a heavy chain variable region consisting of the amino acid sequence at amino acid positions 20 to 139 of SEQ ID NO: 29, and a light chain variable region consisting of the amino acid sequence at amino acid positions 21 to 129 of SEQ ID NO: 31.

### Claim 19 (depends on 17)

The antibody of claim 17, comprising a human constant region.

### Claim 20 (depends on 17)

The antibody of claim 17, comprising
a heavy chain consisting of the amino acid sequence at amino acid positions 20 to 469 of SEQ ID NO: 29 and a light chain consisting of the amino acid sequence at amino acid positions 21 to 234 of SEQ ID NO: 31.

### Claim 21 (depends on 17)

The antibody of claim 17 which is humanized.

### Claim 22 (depends on 17)

A method for treating a tumor, which comprises administering the antibody of claim 17 to an individual having a tumor.

### Claim 23 (depends on 22)

The method of claim 22, wherein the tumor is a cancer.

### Claim 24 (depends on 17)

A pharmaceutical composition comprising the antibody of claim 17.
