# US 2010/0166779 A1 · Monoclonal Antibodies Against Claudin-18 for Treatment of Cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2010/0166779 A1 - Document ID: US20100166779A1 - Status: Published application - Kind: A1 - Application number: 12/601,488 - Filed: 2008-05-27 - Published: 2010-07-01 - Earliest claimed: 2007-05-29 - Assignees: Ganymed Pharmaceuticals AG; Johannes Gutenberg-Universitat - Inventors: Ugur Sahin; Ozlem Tureci; Gunda Brandenburg; Dirk Usener - Web page: https://patentgrep.com/patent/US20100166779A1 ## CPC - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - A61P 35/00: Antineoplastic agents - A61P 35/04: specific for metastasis - A61P 37/04: Immunostimulants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/30: from tumour cells - C07K 16/3046: {Stomach, Intestines} - A61K 2039/505: {comprising antibodies} - 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 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/734: Complement-dependent cytotoxicity [CDC] - 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 The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing CLD1 8, including tumor-related diseases such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, cancer of the gallbladder, and the metastases thereof. ## Claims ### Claim 1 An antibody having the ability of binding to CLD18 and mediating killing or inhibition of proliferation of cells expressing CLD18. ### Claim 2 (depends on 1) The antibody of claim 1 which binds to CLD18A1 and CLD18A2. ### Claim 3 (depends on 1) The antibody of claim 1 which binds to CLD18A2 but not to CLD18A1. ### Claim 4 (depends on 1) The antibody of claim 1 wherein said killing of cells or inhibition of proliferation is induced by binding of said antibody to CLD18 expressed by said cells. ### Claim 5 (depends on 1) The antibody of claim 1 wherein said killing of cells or inhibition of proliferation is induced by binding of said antibody to CLD18A2 expressed by said cells. ### Claim 6 (depends on 1) The antibody of claim 1 wherein said killing of cells or inhibition of proliferation is not induced by binding of said antibody to CLD18A1 expressed by said cells. ### Claim 7 (depends on 1) The antibody of claim 1 wherein said cells expressing CLD18 are tumor cells or cancer cells. ### Claim 8 (depends on 7) The antibody of claim 7 wherein the cancer cells are selected from the group consisting essentially of tumorigenic gastric cancer cells, esophageal cancer cells, pancreatic cancer cells and lung cancer cells. ### Claim 9 (depends on 1) The antibody of claim 1 which mediates said killing of cells by inducing complement dependent cytotoxicity (CDC) mediated lysis, antibody dependent cellular cytotoxicity (ADCC) mediated lysis, apoptosis, homotypic adhesion, or phagocytosis. ### Claim 10 (depends on 1) The antibody of claim 1 which mediates said killing of cells by inducing CDC mediated lysis or ADCC mediated lysis. ### Claim 11 (depends on 1) The antibody of claim 1 which does not induce CDC mediated lysis of said cells. ### Claim 12 (depends on 9) The antibody of claim 9 wherein said ADCC mediated lysis takes place in the presence of effector cells selected from the group consisting essentially of monocytes, mononuclear cells, NK cells and PMNs. ### Claim 13 (depends on 9) The antibody of claim 9 wherein said phagocytosis is by macrophages. ### Claim 14 (depends on 1) The antibody of claim 1 which is a monoclonal, chimeric or humanized antibody, or a fragment of an antibody. ### Claim 15 (depends on 1) The antibody of claim 1 selected from the group consisting essentially of an IgG1, an IgG2, preferably IgG2a and IgG2b, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, a secretory IgA, an IgD, and an IgE antibody. ### Claim 16 (depends on 2) The antibody of claim 2 wherein CLD18A2 has the amino acid sequence according to SEQ ID NO:2. ### Claim 17 (depends on 2) The antibody of claim 2 wherein CLD18A1 has the amino acid sequence according to SEQ ID NO: 8. ### Claim 18 (depends on 1) The antibody of claim 1 which binds to native epitopes of CLD18 present on the surface of living cells. ### Claim 19 (depends on 1) The antibody of claim 1 which is specific for cancer cells, preferably stomach cancer cells. ### Claim 20 (depends on 1) The antibody of claim 1 wherein said CLD18 is expressed on the surface of said cells. ### Claim 21 (depends on 1) The antibody of claim 1 which is obtainable by a method comprising the step of immunizing an animal with a protein or peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, 4, 6, 16, 18, 20-23, 26-31, 151, 153, and 155-157, or an immunogenic fragment or derivative thereof, or a nucleic acid or host cell expressing said protein or peptide, or immunogenic fragment thereof. ### Claim 22 An antibody produced by a clone deposited under the accession no. DSM ACC2737, DSM ACC2738, DSM ACC2739, DSM ACC2740, DSM ACC2741, DSM ACC2742, DSM ACC2743, DSM ACC2745, DSM ACC2746, DSM ACC2747, DSM ACC2748, DSM ACC2808, DSM ACC2809, or DSM ACC2810. ### Claim 23 (depends on 1, 22) A hybridoma capable of producing the antibody of claim 1 or 22. ### Claim 24 A hybridoma deposited under the accession no. DSM ACC2737, DSM ACC2738, DSM ACC2739, DSM ACC2740, DSM ACC2741, DSM ACC2742, DSM ACC2743, DSM ACC2745, DSM ACC2746, DSM ACC2747, DSM ACC2748, DSM ACC2808, DSM ACC2809, or DSM ACC2810. ### Claim 25 (depends on 1) The antibody of claim 1 wherein said antibody is conjugated to a therapeutic agent. ### Claim 26 (depends on 25) The antibody of claim 25 wherein the therapeutic agent is a toxin, a radioisotope, a drug or a cytotoxic agent. ### Claim 27 (depends on 1) A pharmaceutical composition comprising the antibody of claim 1, and a pharmaceutically acceptable carrier. ### Claim 28 (depends on 1) A method of inhibiting growth, killing, or inhibiting metastatic spread of cells expressing CLD18, comprising contacting the cells with an effective amount of the antibody of claim 1. ### Claim at position 29 29-30. (canceled) ### Claim 31 (depends on 1) A method of treating or preventing a disease or disorder involving cells expressing CLD18, comprising administering to a subject the antibody of claim 1 and a pharmaceutically acceptable carrier. ### Claim 32 (depends on 31) The method of claim 31 wherein the disease or disorder is a tumor-related disease. ### Claim 33 (depends on 32) The method of claim 32 wherein the tumor-related disease is selected from the group consisting essentially of gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, gallbladder cancer and the metastasis thereof. ### Claim 34 (depends on 32) The method of claim 32 wherein the tumor-related disease is Krukenberg tumor, peritoneal metastasis or lymph node metastasis. ### Claim 35 (depends on 28, 31) The method of claim 28 or 31, wherein said CLD18 is CLD18A2. ### Claim 36 (depends on 28, 31) The method of claim 28 or 31 wherein said CLD18 is expressed on the surface of said cells.