# US 2014/0193420 A1 · Diagnosis and treatment of cancer using anti-itm2a antibody > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0193420 A1 - Document ID: US20140193420A1 - Status: Published application - Kind: A1 - Application number: 14/112,590 - Filed: 2012-04-18 - Published: 2014-07-10 - Earliest claimed: 2011-04-18 - Assignees: Chugai Seiyaku Kabushiki Kaisha; The University of Tokyo - Inventors: Hiroyuki Aburatani; Shumpei Ishikawa; Shigeto Kawai - Web page: https://patentgrep.com/patent/US20140193420A1 ## CPC - C07K 16/3061: {Blood cells} - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - G01N 33/57505: of the blood, e.g. leukaemia - G01N 33/57557: {of other specific parts of the body, e.g. brain} - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - 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 - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Disclosed is a monoclonal antibody binding to an ITM2A protein. This antibody is useful in the diagnosis, prevention, and treatment of cancer such as Ewing's sarcoma, T cell leukemia, T cell lymphoma, acute myeloid leukemia, B cell tumor, and multiple myeloma. The present invention also provides a pharmaceutical composition, a cell growth inhibitor, and an anticancer agent containing the antibody as an active ingredient, and a method for treating cancer, a method for predicting the efficacy of cancer treatment, and a method for determining the presence of cancer in a test subject using the antibody. ## Claims ### Claim 1 A monoclonal antibody binding to a fragment of an ITM2A protein having the amino acid sequence represented by SEQ ID NO: 1. ### Claim 2 (depends on 1) The antibody according to claim 1, wherein the fragment is a fragment consisting of amino acids 75 to 227 in the amino acid sequence represented by SEQ ID NO: 1. ### Claim 3 (depends on 1) The antibody according to claim 1, wherein the antibody has a cytotoxic activity. ### Claim 4 (depends on 3) The antibody according to claim 3, wherein the cytotoxic activity is an antibody-dependent cell-mediated cytotoxicity (ADCC) activity. ### Claim 5 (depends on 3) The antibody according to claim 3, wherein the cytotoxic activity is a complement-dependent cytotoxicity (CDC) activity. ### Claim 6 (depends on 1) The antibody according to claim 1, wherein the antibody is conjugated with a cytotoxic substance. ### Claim 7 (depends on 6) The antibody according to claim 6, wherein the antibody has an internalization activity. ### Claim 8 (depends on 1) The antibody according to claim 1, wherein the antibody inhibits cancer cell growth. ### Claim 9 (depends on 8) The antibody according to claim 8, wherein the cancer cell is a Ewing's sarcoma cell. ### Claim 10 (depends on 9) The antibody according to claim 9, wherein the Ewing's sarcoma cell is a cell having observable chromosomal translocation. ### Claim 11 (depends on 10) The antibody according to claim 10, wherein the chromosomal translocation is t(11;22)(q24;q12). ### Claim 12 (depends on 8) The antibody according to claim 8, wherein the cancer cell is a blood cancer cell. ### Claim 13 (depends on 12) The antibody according to claim 12, wherein the blood cancer is any of T cell leukemia, T cell lymphoma, acute myeloid leukemia, B cell tumor, and multiple myeloma. ### Claim 14 An antibody described in any of the following (1) to (26): (1) an antibody comprising an H chain having the amino acid sequence represented by SEQ ID NO: 3 as CDR1, the amino acid sequence represented by SEQ ID NO: 4 as CDR2, and the amino acid sequence represented by SEQ ID NO: 5 as CDR3; (2) an antibody comprising an L chain having the amino acid sequence represented by SEQ ID NO: 6 as CDR1, the amino acid sequence represented by SEQ ID NO: 7 as CDR2, and the amino acid sequence represented by SEQ ID NO: 8 as CDR3; (3) an antibody comprising the H chain described in (1) and the L chain described in (2); (4) an antibody comprising an H chain having the amino acid sequence represented by SEQ ID NO: 9 as CDR1, the amino acid sequence represented by SEQ ID NO: 10 as CDR2, and the amino acid sequence represented by SEQ ID NO: 11 as CDR3; (5) an antibody comprising an L chain having the amino acid sequence represented by SEQ ID NO: 12 as CDR1, the amino acid sequence represented by SEQ ID NO: 13 as CDR2, and the amino acid sequence represented by SEQ ID NO: 14 as CDR3; (6) an antibody comprising the H chain described in (4) and the L chain described in (5); (7) an antibody comprising an H chain having the amino acid sequence represented by SEQ ID NO: 15 as CDR1, the amino acid sequence represented by SEQ ID NO: 16 as CDR2, and the amino acid sequence represented by SEQ ID NO: 17 as CDR3; (8) an antibody comprising an L chain having the amino acid sequence represented by SEQ ID NO: 18 as CDR1, the amino acid sequence represented by SEQ ID NO: 19 as CDR2, and the amino acid sequence represented by SEQ ID NO: 20 as CDR3; (9) an antibody comprising the H chain described in (7) and the L chain described in (8); (10) an antibody comprising an H chain having the amino acid sequence represented by SEQ ID NO: 21 as CDR1, the amino acid sequence represented by SEQ ID NO: 22 as CDR2, and the amino acid sequence represented by SEQ ID NO: 23 as CDR3; (11) an antibody comprising an L chain having the amino acid sequence represented by SEQ ID NO: 24 as CDR1, the amino acid sequence represented by SEQ ID NO: 25 as CDR2, and the amino acid sequence represented by SEQ ID NO: 26 as CDR3; (12) an antibody comprising the H chain described in (10) and the L chain described in (11); (13) the antibody described in any of (1) to (12) which is a chimeric antibody; (14) the antibody described in any of (1) to (12) which is a humanized antibody; (15) the antibody described in (1) or (3), comprising the amino acid sequence represented by SEQ ID NO: 28; (16) the antibody described in (2) or (3), comprising the amino acid sequence represented by SEQ ID NO: 30; (17) the antibody described in (4) or (6), comprising the amino acid sequence represented by SEQ ID NO: 32; (18) the antibody described in (5) or (6), comprising the amino acid sequence represented by SEQ ID NO: 34; (19) the antibody described in (7) or (9), comprising the amino acid sequence represented by SEQ ID NO: 36; (20) the antibody described in (8) or (9), comprising the amino acid sequence represented by SEQ ID NO: 38; (21) the antibody described in (10) or (12), comprising the amino acid sequence represented by SEQ ID NO: 40; (22) the antibody described in (11) or (12), comprising the amino acid sequence represented by SEQ ID NO: 42; (23) the antibody described in any of (15) to (22) which is a chimeric antibody; (24) an antibody that has an amino acid sequence of an antibody described in any of (1) to (23) with a substitution, deletion, addition, and/or insertion of one or more amino acid(s) and has an activity equivalent to or a binding activity equivalent to that of the antibody; (25) an antibody capable of binding to an epitope to which a second antibody binds, wherein the second antibody is the antibody described in any of (1) to (23); and (26) an antibody capable of inhibiting the binding of a second antibody to an ITM2A protein fragment consisting of amino acids 75 to 227 in the amino acid sequence represented by SEQ ID NO: 1, wherein the second antibody is the antibody described in any of (1) to (23). ### Claim 15 (depends on 1) The antibody according to claim 1, wherein the antibody has a human constant region. ### Claim 16 (depends on 15) The antibody according to claim 15, wherein the antibody is a chimeric antibody, a humanized antibody, or a human antibody. ### Claim 17 (depends on 1) The antibody according to claim 1, wherein the antibody is deficient in fucose added to its sugar chain or has a sugar chain having bisecting GlcNAc. ### Claim 18 (depends on 1) A pharmaceutical composition comprising an antibody according to claim 1 as an active ingredient. ### Claim 19 (depends on 1) A cell growth inhibitor comprising an antibody according to claim 1 as an active ingredient. ### Claim 20 (depends on 1) An anticancer agent comprising an antibody according to claim 1 as an active ingredient. ### Claim 21 (depends on 20) The anticancer agent according to claim 20, wherein the cancer to be treated is Ewing's sarcoma. ### Claim 22 (depends on 21) The anticancer agent according to claim 21, wherein the Ewing's sarcoma has observable chromosomal translocation. ### Claim 23 (depends on 22) The anticancer agent according to claim 22, wherein the chromosomal translocation is t(11;22)(q24;q12). ### Claim 24 (depends on 20) The anticancer agent according to claim 20, wherein the cancer cell is a blood cancer cell. ### Claim 25 (depends on 24) The anticancer agent according to claim 24, wherein the blood cancer is any of T cell leukemia, T cell lymphoma, acute myeloid leukemia, B cell tumor, and multiple myeloma. ### Claim 26 (depends on 1) A method for treating cancer, comprising administering an antibody according to claim 1. ### Claim 27 (depends on 26) The method according to claim 26, wherein the cancer to be treated is Ewing's sarcoma. ### Claim 28 (depends on 27) The method according to claim 27, wherein the Ewing's sarcoma has observable chromosomal translocation. ### Claim 29 (depends on 28) The method according to claim 28, wherein the chromosomal translocation is t(11;22)(q24;q12). ### Claim 30 (depends on 26) The method according to claim 26, wherein the cancer cell is a blood cancer cell. ### Claim 31 (depends on 30) The method according to claim 30, wherein the blood cancer is any of T cell leukemia, T cell lymphoma, acute myeloid leukemia, B cell tumor, and multiple myeloma. ### Claim 32 (depends on 1) A method for predicting the efficacy of cancer treatment by the administration of an antibody according to claim 1, comprising the step of detecting the expression level of an ITM2A in a biological sample collected from a test subject. ### Claim 33 (depends on 32) The method according to claim 32, wherein an ITM2A protein in the sample collected from a test subject is detected. ### Claim 34 (depends on 33) The method according to claim 33, wherein the detection of the ITM2A protein is performed using an antibody binding to the ITM2A protein. ### Claim 35 (depends on 32) The method according to claim 32, wherein the cancer to be treated is Ewing's sarcoma. ### Claim 36 (depends on 35) The method according to claim 35, wherein the Ewing's sarcoma has observable chromosomal translocation. ### Claim 37 (depends on 36) The method according to claim 36, wherein the chromosomal translocation is t(11;22)(q24;q12). ### Claim 38 (depends on 35) The method according to claim 35, wherein the cancer cell is a blood cancer cell. ### Claim 39 (depends on 38) The method according to claim 38, wherein the blood cancer is any of T cell leukemia, T cell lymphoma, acute myeloid leukemia, B cell tumor, and multiple myeloma. ### Claim 40 A method for determining the presence of cancer in a test subject, comprising detecting an ITM2A protein in a sample collected from the test subject. ### Claim 41 A method for determining the presence of cancer in a test subject, comprising the following steps: (a) providing a sample collected from the test subject; and (b) detecting an ITM2A protein contained in the sample of step (a) using an antibody binding to the ITM2A protein. ### Claim 42 A method for determining the presence of cancer in a test subject, comprising the following steps: (a) administering, to the test subject, a radioisotope-labeled antibody having a binding activity to an ITM2A protein; and (b) detecting the accumulation of the radioisotope. ### Claim 43 (depends on 40) The diagnosis method according to claim 40, wherein the cancer whose presence is to be determined is Ewing's sarcoma. ### Claim 44 (depends on 43) The method according to claim 43, wherein the Ewing's sarcoma has observable chromosomal translocation. ### Claim 45 (depends on 44) The method according to claim 44, wherein the chromosomal translocation is t(11;22)(q24;q12). ### Claim 46 (depends on 40) The method according to claim 40, wherein the cancer is blood cancer. ### Claim 47 (depends on 46) The method according to claim 46, wherein the blood cancer is any of T cell leukemia, T cell lymphoma, acute myeloid leukemia, B cell tumor, and multiple myeloma.