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Gene Overexpressed in Cancer

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Gene Overexpressed in Cancer (19) & (11) EP 2 311 468 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 20.04.2011 Bulletin 2011/16 A61K 31/711 (2006.01) C07K 14/82 (2006.01) C07K 16/30 (2006.01) C12Q 1/68 (2006.01) (2006.01) (21) Application number: 10178204.3 G01N 33/574 (22) Date of filing: 06.08.2004 (84) Designated Contracting States: • Ishikawa, Shumpei AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Tokyo 113-0032 (JP) HU IE IT LI LU MC NL PL PT RO SE SI SK TR • Fukumoto, Shin-ichi Tokyo 155-0031 (JP) (30) Priority: 08.08.2003 JP 2003290704 • Shimamura, Takahiro Tokyo 151-0072 (JP) (62) Document number(s) of the earlier application(s) in • Kamimura, Naoko accordance with Art. 76 EPC: Tokyo 171-0021 (JP) 04771625.3 / 1 652 923 • Guo, Ying qui Tokyo 157-0067 (JP) (71) Applicants: • Yamamoto, Shogo • Perseus Proteomics Inc. Tokyo 140-0015 (JP) Tokyo 153-0041 (JP) • Ito, Yukio • Chugai Seiyaku Kabushiki Kaisha Tokyo 153-0041 (JP) Kita-ku • Ito, Hirotaka Tokyo 115-8543 (JP) Shizuoka 412-8513 (JP) • Aburatani, Hiroyuki • Ohtomo, Toshihiko Musashino-shi, Shizuoka 412-8513 (JP) Tokyo 180-0003 (JP) (74) Representative: Vossius & Partner (72) Inventors: Siebertstrasse 4 • Aburatani, Hiroyuki 81675 München (DE) Tokyo 180-0003 (JP) • Hippo, Yoshitaka Remarks: Tokyo 201-0004 (JP) This application was filed on 22-09-2010 as a • Taniguchi, Hirokazu divisional application to the application mentioned Tokyo 154-0003 (JP) under INID code 62. • Chen, Yong xin Tokyo 157-0067 (JP) (54) Gene overexpressed in cancer (57) Disclosed are a protein encoded by a gene hav- quence represented by any of SEQ ID NOs: 1 to 65 or a ing a nucleotide sequence represented by any of SEQ nucleotide sequence complementary thereto. The gene ID NOs: 1 to 65 or a fragment thereof, an antibody rec- and the protein of the invention is useful for diagnosing ognizing the protein or antigen- binding fragment thereof, and treating cancer. and a polynucleotide having a sequence comprising at least 12 consecutive nucleotides of a nucleotide se- 68 A1 4 11 11 3 EP 2 Printed by Jouve, 75001 PARIS (FR) EP 2 311 468 A1 Description Technical Field 5 [0001] The present invention relates to a cancer-associated gene, a protein encoded by the gene, and an antibody recognizing this protein. The gene, protein and antibody of the present invention can be used in diagnosis and treatment of cancer and development of a therapeutic drug of cancer. Background Art 10 [0002] Heretofore, a number of genes have been found whose expression level changes as being associated with malignant transformation of cells and antigens that can be used as a cancer marker, and numerous studies on such genes have been carried out. However, it is still difficult to specifically detect or treat a specific cancer. Therefore, in th is technical field, identification of another cancer-associated gene or protein that can be used in diagnosis and treatment 15 of cancer has been demanded. [0003] There are prior art documents related to the present invention: EP 1033401; US 2002022248; US 2002042096; US 200208150; US 6337195; US 6362321; WO 9738098; WO 9920764; WO 9929729; WO 0006698; WO 0012702; WO 0034477; WO 0036107; WO 0037643; WO 0055174; WO 0055320; WO 0055351; WO 0055633; WO 0058473; WO 0073509; WO 0100828; WO 0109317; WO 0121653; WO 0122920; WO 0151513; WO 0151628; WO 0154733; 20 WO 0155355; WO 0157058; WO 0159111; WO 0160860; WO 0164835; WO 0164886; WO 0166719; WO 0170976; WO 0173027; WO 0175177; WO 0177168; WO 0192578; WO 0194629; WO 0200677; WO 0200889; WO 0200939; WO 0204514; WO 0210217; WO D212280; WO 0220598; WO 0229086; WO 0229103; WO 0258534; WO 0260317; and WO 0264797. [0004] An object of the present invention is to provide a gene and a protein that can be used as an agent for diagnosing 25 and treating cancer. Disclosure of the invention [0005] The present inventors have found that the expression of specific genes is elevated in a cancer tissue, and have 30 completed the present invention. The present invention provides a protein encoded by a gene having a nucleotide sequence represented by any of SEQ ID NOs : 1 to 65 or a fragment thereof. [0006] In one aspect, the present invention provides a gene having a nucleotide sequence represented by any of SEQ ID NOs: 1, 2, 28, 29, 30, 31, 32, 51, 52, 60 and 61, a protein encoded by the gene or a fragment thereof. The gene preferably has a nucleotide sequence represented by any of SEQ ID NOs: 1, 2, 28, 29, 30, 31 and 32, more preferably 35 has a nucleotide sequence represented by SEQ ID NO: 1 or 2. [0007] Such a protein or a fragment is useful as a composition for diagnosing or treating lung cancer. [0008] In another aspect, the present invention provides a gene having a nucleotide sequence represented by any of SEQ ID NOs : 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 22, 23, 24, 25, 26, 27, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 53, 54 and 55, a protein encoded by the gene or a fragment thereof. The gene preferably has a nucleotide sequence represented 40 by any of SEQ ID NOs: 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 22, 23, 24, 25 and 26. [0009] Such a protein or a fragment is useful as a composition for diagnosing or treating stomach cancer. [0010] In another aspect, the present invention provides a gene having a nucleotide sequence represented by any of SEQ ID NOs: 3, 7, 20, 21, 46, 47, 48, 49 and 50, a protein encoded by the gene or a fragment thereof. The gene preferably has a nucleotide sequence represented by any of SEQ ID NOs: 3, 7, 20, 21, 46, 49 and 50, more preferably 45 has a nucleotide sequence represented by any of SEQ ID NOs: 3, 7, 20 and 21. [0011] Such a protein or a fragment is useful as a composition for diagnosing or treating large bowel cancer. [0012] In another aspect, the present invention provides a gene having a nucleotide sequence represented by any of SEQ ID NOs: 14, 15, 16, 17, 18, 19, 43, 44, 45, 56, 57, 58, 59, 62, 63, 64 and 65, a protein encoded by the gene or a fragment thereof. The gene preferably has a nucleotide sequence represented by any of SEQ ID NOs: 14, 15, 16, 17, 50 18, 19, 45, 56, 57, 58, 64 and 65, more preferably has a nucleotide sequence represented by any of SEQ ID NOs: 14, 15, 16, 17, 18, 19, 64 and 65. [0013] Such a protein or a fragment is useful as a composition for diagnosing or treating liver cancer. [0014] In a composition of the present invention, the gene preferably has a nucleotide sequence represented by any of SEQ ID NOs: 1, 9, 10, 14, 20, 22, 24, 25, 26, 27, 28, 29, 32, 38, 39, 40, 44, 51, 52, 53, 54 and 58, more preferably 55 has a nucleotide sequence represented by any of SEQ ID NOs: 1, 9, 10, 14, 20, 22, 24, 25 and 26. [0015] In addition, in a composition of the present invention, the gene preferably has a nucleotide sequence represented by any of SEQ ID NOs: 2, 3, 4, 5, 6, 7, 8, 11, 12, 13, 15, 16, 17, 18, 19, 21, 23, 30, 31, 33, 34, 35, 36, 37, 41, 42, 43, 45, 46, 47, 48, 49, 50, 55, 56, 57, 59, 60, 61, 62 and 63, more preferably has a nucleotide sequence represented by 2 EP 2 311 468 A1 any of SEQ ID NOs: 2, 3, 4, 5, 6, 7, 8, 11, 12, 13, 15, 16, 17, 18, 19, 21 and 23. [0016] In another aspect, the present invention provides a cell or a vector that expresses the above- mentioned gene or a fragment thereof. Such a cell or a vector is useful for producing a protein of the present invention, producing an antibody against the protein, as well as diagnosing or treating cancer and the like. 5 [0017] In still another aspect, the present invention provides a protein having an amino acid sequence represented by any of SEQ ID NOs: 66 to 123 or a fragment thereof. Such a protein or a fragment thereof is useful as an antigen for producing an antibody or is useful for diagnosing or treating cancer. [0018] In still another aspect, the present invention provides an antibody recognizing the above-mentioned protein or a fragment thereof or an antigen-binding fragment thereof. The present invention also provides a cell producing such 10 an antibody. [0019] In still another aspect, the present invention provides a polynucleotide having a nucleotide sequence repre- sented by any of SEQ ID NOs : 1 to 65 or a nucleotide sequence complementary thereto, and a polynucleotide that can hybridize under high stringent conditions to any of these polynucleotides. [0020] Further, the present invention provides a polynucleotide having a sequence comprising at least 12 consecutive 15 nucleotides of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 65 or a nucleotide sequence complementary thereto, and an oligonucleotide with a length of at least 12 nucleotides that can hybridize under high stringent conditions to a polynucleotide having a nucleotide sequence represented by any of SEQ ID NOs: 1 to 65. [0021] Such a polynucleotide is useful for diagnosis of cancer, production of a protein, and as a primer, an antisense and siRNA for inhibiting gene expression.
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