# US 12,600,774 B2 · Monoclonal antibodies against CLDN18.2 and Fc-engineered versions thereof

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- Number: US 12,600,774 B2
- Document ID: US12600774B2
- Status: Granted
- Kind: B2
- Application number: 18/262,987
- Filed: 2022-05-30
- Published: 2025-09-04
- Granted: 2026-04-14
- Earliest claimed: 2021-05-31
- Assignees: Shijiazhuang Yiling Pharmaceutical Co., Ltd.
- Applicants: Shijiazhuang Yiling Pharmaceutical Co., Ltd.
- Inventors: Zhenhua Jia
- Web page: https://patentgrep.com/patent/US12600774B2

## CPC

- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- A61P 35/00: Antineoplastic agents
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/71: Decreased effector function due to an Fc-modification
- C07K 2317/72: Increased effector function due to an Fc-modification
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- C07K 2317/77: Internalization into the cell
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided is a panel of monoclonal antibodies which specifically bind to CLDN18.2 and do not specifically bind to CLDN18.1, and optionally have an engineered Fc region.

## Claims

### Claim 1

A monoclonal antibody which specifically binds to CLDN18.2, comprising:
(1) a heavy chain complementarity determining region 1 (HCDR1) as set forth in SEQ ID NO: 17, a HCDR2 as set forth in SEQ ID NO: 18, a HCDR3 as set forth in SEQ ID NO: 19, a light chain complementarity determining region 1 (LCDR1) as set forth in SEQ ID NO: 20, a LCDR2 as set forth in SEQ ID NO: 21, and a LCDR3 as set forth in SEQ ID NO: 22;
(2) a HCDR1 as set forth in SEQ ID NO: 41, a HCDR2 as set forth in SEQ ID NO: 42, a HCDR3 as set forth in SEQ ID NO: 43, a LCDR1 as set forth in SEQ ID NO: 44, a LCDR2 as set forth in SEQ ID NO: 45, and a LCDR3 as set forth in SEQ ID NO: 46;
(3) a HCDR1 as set forth in SEQ ID NO: 47, a HCDR2 as set forth in SEQ ID NO: 48, a HCDR3 as set forth in SEQ ID NO: 49, a LCDR1 as set forth in SEQ ID NO: 50, a LCDR2 as set forth in SEQ ID NO: 51, and a LCDR3 as set forth in SEQ ID NO: 52; or
(4) a HCDR1 as set forth in SEQ ID NO: 53, a HCDR2 as set forth in SEQ ID NO: 54, a HCDR3 as set forth in SEQ ID NO: 55, a LCDR1 as set forth in SEQ ID NO: 56, a LCDR2 as set forth in SEQ ID NO: 57, and a LCDR3 as set forth in SEQ ID NO: 58.

### Claim 2 (depends on 1)

The monoclonal antibody according to claim 1, comprising: a VH as set forth in SEQ ID NO: 3 and a VL as set forth in SEQ ID NO: 4.

### Claim 3 (depends on 1)

The monoclonal antibody according to claim 1, which comprises a human IgG heavy chain constant region and/or a human kappa light chain constant region.

### Claim 4 (depends on 1)

The monoclonal antibody according to claim 1, which is an antigen-binding antibody fragment selected from the group consisting of a Fab fragment, a Fab′ fragment, a F(ab′) 2 fragment, a scFv fragment, and a diabody.

### Claim 5 (depends on 1)

The monoclonal antibody according to claim 1, which is naked or conjugated.

### Claim 6 (depends on 3)

The monoclonal antibody according to claim 3, wherein the monoclonal antibody is Fc-engineered to comprise one or more mutations in the Fc region.

### Claim 7 (depends on 6)

The monoclonal antibody according to claim 6, wherein the one or more mutations in the Fc region are one or more mutations that increase or decrease binding to an Fc receptor and/or effector function.

### Claim 8 (depends on 7)

The monoclonal antibody according to claim 7, wherein the one or more mutations in the Fc region are one or more substitutions selected from the group consisting of L235V, F243L, R292P, Y300L and P396L.

### Claim 9 (depends on 6)

The monoclonal antibody according to claim 6, which comprises an engineered human IgG1 heavy chain constant region as set forth in SEQ ID NO: 40.

### Claim 10 (depends on 1)

An isolated nucleic acid encoding the monoclonal antibody according to claim 1.

### Claim 11 (depends on 1)

A method of producing the monoclonal antibody according to claim 1 by culturing a host cell comprising a nucleic acid encoding the monoclonal antibody under conditions to produce the antibody.

### Claim 12 (depends on 1)

A composition comprising the monoclonal antibody according to claim 1.

### Claim 13 (depends on 7)

The monoclonal antibody according to claim 7, wherein the effector function is ADCC and/or CDC.

### Claim 14 (depends on 2)

The monoclonal antibody according to claim 2, which comprises a human IgG1 heavy chain constant region as set forth in SEQ ID NO: 9 and a human kappa light chain constant region as set forth in SEQ ID NO: 10.

### Claim 15 (depends on 2)

The monoclonal antibody according to claim 2, which comprises an engineered human IgG1 heavy chain constant region as set forth in SEQ ID NO: 40, and a human kappa light chain constant region as set forth in SEQ ID NO: 10.

### Claim 16 (depends on 15)

An isolated nucleic acid encoding the monoclonal antibody according to claim 15.

### Claim 17 (depends on 15)

A method of producing the monoclonal antibody according to claim 15 by culturing a host cell comprising a nucleic acid encoding the monoclonal antibody under conditions to produce the antibody.

### Claim 18 (depends on 15)

A composition comprising the monoclonal antibody according to claim 15.