# US 12,595,302 B2 · CLDN18.2 binding molecule > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,595,302 B2 - Document ID: US12595302B2 - Status: Granted - Kind: B2 - Application number: 17/613,440 - Filed: 2020-05-21 - Published: 2022-12-15 - Granted: 2026-04-07 - Earliest claimed: 2019-05-24 - Assignees: Sanyou Biopharmaceuticals Co., Ltd. - Applicants: Sanyou Biopharmaceuticals Co., Ltd. - Inventors: Yongcong Tan; Guojun Lang; Chao Kong; Chanjuan Liu; Min Deng; Qi Wu; Jing Zhang; Wenhai Zhang; Baoguo Fan - Web page: https://patentgrep.com/patent/US12595302B2 ## CPC - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - A61P 35/00: Antineoplastic agents - C07K 16/30: from tumour cells - A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) - A61K 2039/505: {comprising antibodies} - C07K 2317/22: from camelids, e.g. camel, llama or dromedary - 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 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® - C07K 2317/64: comprising a combination of variable region and constant region components - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/734: Complement-dependent cytotoxicity [CDC] - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - 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 - 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 Disclosed is a novel CLDN18.2 binding molecule. Also disclosed are a nucleic acid molecule encoding the CLDN18.2 binding molecule, an expression vector and a host cell for expressing the CLDN18.2 binding molecule. Further disclosed are a method for producing the CLDN18.2 binding molecule and use thereof. ## Claims ### Claim 1 A CLDN18.2 binding molecule, which is a VHH single domain antibody or a VHH-Fc antibody, wherein the VHH comprises a CDR1, a CDR2 and a CDR3 selected from the following groups, wherein: (a) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 30, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 32; (b) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 1, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 2, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 3; (c) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 1, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 2, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 6; (d) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 1, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 4, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 5; (e) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 30, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 37; (f) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 33, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 62; (g) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 33, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 37; (h) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 34, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 37; (i) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 35, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 62; (j) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 36, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 62; (k) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 38, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 62; (l) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 39, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 41, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 37; or (m) the CDR1 has the amino acid sequence as shown in SEQ ID NO: 40, the CDR2 has the amino acid sequence as shown in SEQ ID NO: 31, and the CDR3 has the amino acid sequence as shown in SEQ ID NO: 37. ### Claim 2 (depends on 1) The CLDN18.2 binding molecule of claim 1, wherein the VHH comprises any one selected from the following groups: (a) the amino acid sequence of SEQ ID NO: 7, or an amino acid sequence at least 80%, 85%, 90%, or 95% identical to SEQ ID NO: 7; and (b) the amino acid sequence shown in SEQ ID NO: 47, or an amino acid sequence at least 80%, 85%, 90%, or 95% identical to SEQ ID NO: 47. ### Claim 3 (depends on 1) The CLDN18.2 binding molecule of claim 1, wherein the VHH comprises or consists of any one of the following sequences: SEQ ID NOs: 7, 8, 9, 10, 11, 12, 13, 14, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 and 63. ### Claim 4 (depends on 1) The CLDN18.2 binding molecule of claim 1, wherein the CLDN18.2 binding molecule is a chimeric antibody comprising a VHH from camelid and an Fc domain of human IgG1 or IgG4, or a humanized antibody comprising a VHH obtained by humanizing a VHH from camelid and an Fc domain of human IgG1 or IgG4. ### Claim 5 (depends on 1) An isolated nucleic acid molecule, comprising a nucleic acid sequence encoding the CLDN18.2 binding molecule as defined in claim 1. ### Claim 6 (depends on 5) An expression vector, comprising the isolated nucleic acid molecule of claim 5. ### Claim 7 (depends on 6) A host cell, comprising the expression vector of claim 6. ### Claim 8 (depends on 1) A pharmaceutical composition, comprising the CLDN18.2 binding molecule as defined in claim 1 and a pharmaceutically acceptable carrier. ### Claim 9 (depends on 1) A method for preparing the CLDN18.2 binding molecule as defined in claim 1, comprising the steps of: (1) culturing a host cell comprising an expression vector(s) encoding the CLDN18.2 binding molecule; and (2) isolating the CLDN18.2 binding molecule from the culture supernatant. ### Claim 10 (depends on 1) A method for treating a cancer associated with CLDN18.2 in a subject, comprising: administering a therapeutically effective amount of the CLDN18.2 binding molecule as defined in claim 1 to the subject, wherein the cancer is selected from gastric cancer, pancreatic cancer and cancer of the esophagogastric junction. ### Claim 11 (depends on 10) The method of claim 10, wherein the cancer is gastric cancer. ### Claim 12 (depends on 1) A kit for treating or diagnosing a condition associated with CLDN18.2, comprising a container, wherein the container comprises the CLDN18.2 binding molecule as defined in claim 1.