# US 2019/0375853 A1 · Use of antibody against o-acetylated gd2 ganglioside to improve the therapeutic potential of drugs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0375853 A1 - Document ID: US20190375853A1 - Status: Published application - Kind: A1 - Application number: 16/466,769 - Filed: 2017-12-05 - Published: 2019-12-12 - Earliest claimed: 2016-12-05 - Assignees: Ogd2 Pharma; Universite De Nantes; Centre National de la Recherche Scientifique (CNRS); Institut National De La Sante Et De La Recherche Medicale (Inserm); Institut De Cancerologie De L'ouest - Applicants: Ogd2 Pharma; Universite De Nantes; Centre National De La Recherche Scientifique (Cnrs); Institut National De La Sante Et De La Recherche Medicale (Inserm); Institut De Cancerologie De L'ouest - Inventors: Stéphane BIRKLE; Julien FLEURENCE; Sébastien FARAJ; Jean-Marc LE DOUSSAL; Denis COCHONNEAU; Mickaël TERME; Brigitte ASSOULINE - Web page: https://patentgrep.com/patent/US20190375853A1 ## CPC - C07K 16/3084: {against tumour-associated gangliosides} - A61K 39/39558: {against tumor tissues, cells, antigens} - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 35/04: specific for metastasis - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Disclosed is a method for delivery of an anti-cancer agent into a cell expressing the OAcGD2 ganglioside by using an antibody recognizing the OAcGD2 ganglioside. ## Claims ### Claim 1 A method for delivery of an anti-cancer agent into a cell expressing the OAcGD2 ganglioside comprising contacting the cell with at least one multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, in an amount and concentration effective to enhance uptake of the anti-cancer agent by the cell, wherein the antibody causes permeability defects within the cell membrane. ### Claim 2 A composition for delivery of an anti-cancer agent into a cell, expressing the OAcGD2 ganglioside comprising: (i) at least one anti-cancer agent, and (ii) at least one multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, wherein the at least one antibody recognizing the OAcGD2 ganglioside enhances the uptake of the at least one anti-cancer agent by the tumor cell. ### Claim 3 A multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, for use in the selective delivery into a cell expressing the OAcGD2 ganglioside of at least one anti-cancer agent to treat and/or to prevent cancer. ### Claim 4 (depends on 2) The composition according to claim 2, wherein the antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, comprises a) a light chain variable region (VL) polypeptide having the amino acid sequence SEQ ID NO:1 and b) a heavy chain variable region (VH) having the amino acid sequence SEQ ID NO:2. ### Claim 5 (depends on 2) The composition according to claim 2, wherein the antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, comprises the light chain variable region (VL) polypeptide having the amino acid sequence selected in the group comprising or consisting of SEQ ID NO:39 and SEQ ID NO: 40; and/or the heavy chain variable region (VH) having the amino acid sequence selected in the group comprising or consisting of SEQ ID NO:48, SEQ ID NO:49 SEQ ID NO:50 and SEQ ID NO:51. ### Claim 6 (depends on 2) The composition according to claim 2, wherein the functional fragment of the antibody recognizing the OAcGD2 ganglioside is in the form of single chain fragments of heavy and light chain variable regions (scFv). ### Claim 7 (depends on 2) The composition according to claim 2, wherein functional fragment of the antibody recognizing the OAcGD2 ganglioside is a single-chain part of a chimeric antigen receptor (CAR). ### Claim 8 (depends on 2) The composition according to claim 2, wherein the antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, comprises the light chain variable region (VL) polypeptide having the amino acid sequence selected in the group comprising or consisting of SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO:39 and SEQ ID NO: 40, and/or the heavy chain variable region (VH) having the amino acid sequence selected in the group comprising or consisting of SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO: 47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50 and SEQ ID NO: 51. ### Claim 9 (depends on 2) The composition according to claim 2, wherein the least one antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, comprises: a) a light chain variable region (VL) polypeptide having the amino acid sequence SEQ ID NO:14; and b) a heavy chain variable region (VH) having the amino acid sequence SEQ ID NO:15. ### Claim 10 (depends on 2) The composition according to claim 2, wherein the least one antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, comprises: a) a heavy chain comprising three heavy chain complementary regions (CDRs) having the amino acid sequences SEQ ID NO:16, SEQ ID NO:17 and SEQ ID NO:18, and a heavy chain framework sequence from an immunoglobulin heavy chain, and b) a light chain comprising three light chain complementary regions (CDRs) having the amino acid sequences SEQ ID NO:19, SEQ ID NO:20 and SEQ ID NO:21, and a light chain framework sequence from an immunoglobulin light chain. ### Claim 11 (depends on 2) The composition according to claim 2, said antibody is an immunoconjugate. ### Claim 12 (depends on 2) The composition according to claim 2, wherein the at least one anti-cancer agent is selected from the group comprising or consisting of anti-cancer agents such as alkylating agents, anti-metabolites, anti-tumor antibodies, anti-tumor antibiotics, topoisomerase inhibitors, mitotic inhibitors, tyrosine kinase inhibitors, corticosteroids, hormones or hormone-like drugs, cytokines, nucleoside analogs, nucleic acids, such double-stranded synthetic short RNA molecules (miRNAs) or synthetic DNA/RNA-like oligonucleotides (ASOs). ### Claim 13 (depends on 2) The composition according to claim 2, wherein the at least one anti-cancer agent is unable to cross the cell membrane of cancer cells by itself. ### Claim 14 (depends on 3) The antibody for use according to claim 3, wherein cancer expressing the OAcGD2 ganglioside is selected from the group comprising or consisting of neuroblastoma, glioma, retinoblastoma, Ewing's family of tumors, sarcoma, small cell lung cancer, breast cancer, melanoma, metastatic renal carcinoma, head and neck cancer and hematological cancers. ### Claim 15 (depends on 14) The antibody for use according to claim 14, wherein the at least one anti-cancer agent is selected from the group comprising or consisting of cyclophosphamide, doxorubicin, topotecan, irinotecan, temozolomide (TMZ), retinoic acid (RA), 5-Fluorouracil (5-FU), fludarabine, carboplatin and cisplatin. ### Claim 16 (depends on 3) The antibody for use according to claim 3, wherein the at least one anti-cancer agent is temozolomide, topotecan, irinotecan, fludarabine, cyclophosphamide or a mixture thereof and the cancer expressing the OAcGD2 ganglioside is neuroblastoma. ### Claim 17 A method of increasing the efficacy of a cancer expressing the OAcGD2 ganglioside treatment comprising an anti-cancer agent, comprising administering to a patient in need thereof an effective amount of a composition comprising: (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one antibody recognizing the OAcGD2 ganglioside, and a functional fragment or a derivative thereof. ### Claim 18 A method of increasing sensitivity to an anti-cancer agent in a patient suffering from a cancer expressing the OAcGD2 ganglioside, comprising administering to a patient in need thereof an effective amount of a composition comprising: (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one antibody recognizing the OAcGD2 ganglioside, and a functional fragment or a derivative thereof. ### Claim 19 A method of preventing or delaying development of cancer resistant to an anti-cancer agent in a patient suffering from a cancer expressing the OAcGD2 ganglioside, comprising administering to a patient in need thereof an effective amount of a composition comprising: (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one antibody recognizing the OAcGD2 ganglioside, and a functional fragment or a derivative thereof. ### Claim 20 An in vitro/ex vivo method of identifying synergistic combination of (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons and, (ii) at least one multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof comprising the steps of: a) incubating primary tumor cells or cancer cell lines cells expressing the O-acetylated form of GD2 ganglioside in vitro with a composition comprising at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons and, (ii) at least one antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, and b) measuring the CI50 index according to the method as disclosed by Chou and Talalay, wherein a CI50 below 1 is indicative of synergism. ### Claim 21 A kit suitable for treating cancer expressing OAcGD2 ganglioside comprising (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one multimeric antibody recognizing the OAcGD2 ganglioside, and a functional fragment or a derivative thereof. ### Claim 22 A method for enhancing intracellular uptake of an anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons in a cell expressing the O-acetylated form of GD2 ganglioside, comprising administering an effective amount of a multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof. ### Claim 23 A method of treating a refractory or relapsed cancer in a patient suffering from a cancer expressing the OAcGD2 ganglioside, comprising administering to a patient in need thereof an effective amount of a composition comprising: (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, wherein said cancer is refractory to or is in relapse after a first line cancer treatment comprising one or more anti-cancer agent selected from the group consisting of alkylating agents, antimetabolites, anti-tumor antibiotics, topoisomerase inhibitors, mitotic inhibitors, tyrosine kinase inhibitors and nucleoside analogs.