CA2841900C - Ros kinase in lung cancer - Google Patents
Ros kinase in lung cancer Download PDFInfo
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- CA2841900C CA2841900C CA2841900A CA2841900A CA2841900C CA 2841900 C CA2841900 C CA 2841900C CA 2841900 A CA2841900 A CA 2841900A CA 2841900 A CA2841900 A CA 2841900A CA 2841900 C CA2841900 C CA 2841900C
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
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Priority Applications (1)
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| US20120208824A1 (en) | 2006-01-20 | 2012-08-16 | Cell Signaling Technology, Inc. | ROS Kinase in Lung Cancer |
| US9364477B2 (en) * | 2009-02-12 | 2016-06-14 | Cell Signaling Technology, Inc. | Mutant ROS expression in human cancer |
| EP3470513B1 (en) * | 2013-03-15 | 2020-05-13 | Expression Pathology, Inc. | Srm assay to indicate cancer therapy |
| WO2015103645A2 (en) * | 2014-01-06 | 2015-07-09 | Expression Pathology, Inc. | Srm assay for pd-l1 |
| WO2017153932A1 (en) | 2016-03-10 | 2017-09-14 | Novartis Ag | Strn-alk fusion as a therapeutic target in gastric cancer |
| WO2017175111A1 (en) | 2016-04-04 | 2017-10-12 | Novartis Ag | Strn-alk fusion as a therapeutic target in colorectal cancer |
| JP2020510027A (ja) * | 2017-03-08 | 2020-04-02 | アリアド ファーマシューティカルズ，インコーポレーテッド | ５−クロロ−ｎ４−［２−（ジメチルホスホリル）フェニル］−ｎ２−｛２−メトキシ−４−［４−（４−メチルピペラジン−１−イル）ピペリジン−１−イル］フェニル｝ピリミジン−２，４−ジアミンを含む医薬製剤 |
| KR101987065B1 (ko) | 2017-08-07 | 2019-06-10 | 주식회사 싸이토젠 | Eml4-alk유전자 변이 분석방법 |
| KR102167739B1 (ko) | 2018-10-31 | 2020-10-19 | 한국과학기술연구원 | Alk 또는 ros-1 인산화 효소 억제제 스크리닝을 위한 방법, 조성물 및 키트 및 방법 |
| JP7313033B2 (ja) * | 2019-03-01 | 2023-07-24 | 国立大学法人北海道大学 | Ｉｋｚｆ１遺伝子変異を検出するための核酸プローブセット及び当該プローブセットを用いたｉｋｚｆ１遺伝子変異の検出方法 |
| CN110632318B (zh) * | 2019-10-28 | 2023-04-07 | 四川大学华西医院 | Tpm3自身抗体检测试剂在制备肺癌筛查试剂盒中的用途 |
| CN111440241B (zh) * | 2020-05-31 | 2021-01-05 | 广东赛尔生物科技有限公司 | 一种包含特异性结合ros1的单克隆抗体的癌症检测试剂盒 |
Family Cites Families (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3023787A1 (de) | 1980-06-25 | 1982-01-21 | Studiengesellschaft Kohle mbH, 4330 Mülheim | Verfahren zur erhoehung der inkorporation und der expression von genetischem material in die kerne von intakten zellen mit hilfe von liposomen |
| US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
| US4474893A (en) | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4659678A (en) | 1982-09-29 | 1987-04-21 | Serono Diagnostics Limited | Immunoassay of antigens |
| NZ207394A (en) | 1983-03-08 | 1987-03-06 | Commw Serum Lab Commission | Detecting or determining sequence of amino acids |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4727022A (en) | 1984-03-14 | 1988-02-23 | Syntex (U.S.A.) Inc. | Methods for modulating ligand-receptor interactions and their application |
| DE3586772T2 (de) | 1984-07-24 | 1993-03-04 | Coselco Mimotopes Pty Ltd | Verfahren zur bestimmung von mimotopen. |
| US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
| US5756696A (en) | 1986-01-16 | 1998-05-26 | Regents Of The University Of California | Compositions for chromosome-specific staining |
| US5447841A (en) | 1986-01-16 | 1995-09-05 | The Regents Of The Univ. Of California | Methods for chromosome-specific staining |
| US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US6121424A (en) | 1991-11-25 | 2000-09-19 | Enzon, Inc. | Multivalent antigen-binding proteins |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| EP0394827A1 (en) | 1989-04-26 | 1990-10-31 | F. Hoffmann-La Roche Ag | Chimaeric CD4-immunoglobulin polypeptides |
| EP0800830A3 (en) | 1989-11-03 | 1999-03-17 | Vanderbilt University | Method of in vivo delivery of functioning foreign genes |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| ATE139258T1 (de) | 1990-01-12 | 1996-06-15 | Cell Genesys Inc | Erzeugung xenogener antikörper |
| EP1566442B1 (de) | 1990-02-01 | 2009-11-25 | Siemens Healthcare Diagnostics Products GmbH | Herstellung und Verwendung von Genbanken menschlicher Antikörper("Human-Antikörper-Bibliotheken") |
| DE4002897A1 (de) | 1990-02-01 | 1991-08-08 | Behringwerke Ag | Herstellung und verwendung von genbanken synthetischer menschlicher antikoerper ("synthetische human-antikoerper-bibliotheken") |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5491224A (en) | 1990-09-20 | 1996-02-13 | Bittner; Michael L. | Direct label transaminated DNA probe compositions for chromosome identification and methods for their manufacture |
| DK0590058T3 (da) | 1991-06-14 | 2004-03-29 | Genentech Inc | Humaniseret heregulin-antistof |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| EP0746609A4 (en) | 1991-12-17 | 1997-12-17 | Genpharm Int | NON-HUMAN TRANSGENIC ANIMALS CAPABLE OF PRODUCING HETEROLOGOUS ANTIBODIES |
| AU4769893A (en) | 1992-07-17 | 1994-02-14 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for treatment of animal diseases |
| US6710174B2 (en) | 2001-09-13 | 2004-03-23 | Isis Pharmaceuticals, Inc. | Antisense inhibition of vascular endothelial growth factor receptor-1 expression |
| IL108367A0 (en) | 1993-01-27 | 1994-04-12 | Hektoen Inst For Medical Resea | Antisense polynzcleotide inhibition of human growth factor-sensitive cancer cells |
| US6340674B1 (en) | 1993-03-26 | 2002-01-22 | Thomas Jefferson University | Method of inhibiting the proliferation and causing the differentiation of cells with IGF-1 receptor antisense oligonucleotides |
| US5480971A (en) | 1993-06-17 | 1996-01-02 | Houghten Pharmaceuticals, Inc. | Peralkylated oligopeptide mixtures |
| US5529925A (en) | 1993-12-03 | 1996-06-25 | St. Jude Children's Research Hospital | Nucleic acid sequences and fusion proteins present in human t(2;5) lymphoma |
| EP0744958B1 (en) | 1994-01-31 | 2003-06-25 | Trustees Of Boston University | Polyclonal antibody libraries |
| US6074642A (en) | 1994-05-02 | 2000-06-13 | Alexion Pharmaceuticals, Inc. | Use of antibodies specific to human complement component C5 for the treatment of glomerulonephritis |
| US5753613A (en) | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
| US5820873A (en) | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| US5783683A (en) | 1995-01-10 | 1998-07-21 | Genta Inc. | Antisense oligonucleotides which reduce expression of the FGFRI gene |
| US5675063A (en) | 1995-02-28 | 1997-10-07 | Loyola University Of Chicago | Immortalized rabbit hybridoma fusion partner |
| EP0859841B1 (en) | 1995-08-18 | 2002-06-19 | MorphoSys AG | Protein/(poly)peptide libraries |
| US6395713B1 (en) | 1997-07-23 | 2002-05-28 | Ribozyme Pharmaceuticals, Inc. | Compositions for the delivery of negatively charged molecules |
| US6617162B2 (en) | 2001-12-18 | 2003-09-09 | Isis Pharmaceuticals, Inc. | Antisense modulation of estrogen receptor alpha expression |
| AU1922999A (en) | 1997-12-16 | 1999-07-05 | Baylor College Of Medicine | Needle-free injection of formulated nucleic acid molecules |
| US7300753B2 (en) | 1998-09-04 | 2007-11-27 | John Rush | Immunoaffinity isolation of modified peptides from complex mixtures |
| US7198896B2 (en) | 1998-09-04 | 2007-04-03 | Cell Signaling Technology, Inc. | Immunoaffinity isolation of modified peptides from complex mixtures |
| US6573043B1 (en) | 1998-10-07 | 2003-06-03 | Genentech, Inc. | Tissue analysis and kits therefor |
| CA2365625A1 (en) | 1999-03-10 | 2000-09-14 | Phogen Limited | Delivery of substances to cells |
| US7662793B2 (en) | 1999-06-18 | 2010-02-16 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from a Pol III promoter |
| US7829693B2 (en) | 1999-11-24 | 2010-11-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
| DE60140676D1 (de) | 2000-03-30 | 2010-01-14 | Massachusetts Inst Technology | Mediatoren von rns-interferenz, die rns-sequenzspezifisch sind |
| AU2001288437C1 (en) | 2000-09-09 | 2009-05-21 | The Research Foundation Of State University Of New York | Method and compositions for isolating metastatic cancer cells, and use in measuring metastatic potential of a cancer thereof |
| CZ308053B6 (cs) | 2000-12-01 | 2019-11-27 | Max Planck Gesellschaft | Izolovaná molekula dvouřetězcové RNA, způsob její výroby a její použití |
| GEP20084484B (en) | 2001-01-05 | 2008-09-25 | Pfizer | Antibodies to insulin-like growth factor i receptor |
| CA2447612A1 (en) | 2001-05-17 | 2002-11-28 | The Public Health Research Institute Of The City Of New York, Inc. | Selection of target sites for antisense attack of rna |
| US20040209832A1 (en) | 2001-11-30 | 2004-10-21 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US20030170891A1 (en) | 2001-06-06 | 2003-09-11 | Mcswiggen James A. | RNA interference mediated inhibition of epidermal growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| AU2002314495A1 (en) | 2001-06-20 | 2003-01-02 | Prochon Biotech Ltd. | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
| WO2003016861A2 (en) | 2001-08-14 | 2003-02-27 | President And Fellows Of Harvard College | Absolute quantification of proteins and modified forms thereof by multistage mass spectrometry |
| US20030219839A1 (en) | 2001-09-20 | 2003-11-27 | Katherine Bowdish | Anti-PDGF antibodies and methods for producing engineered antibodies |
| US6734017B2 (en) | 2001-09-28 | 2004-05-11 | Isis Pharmaceuticals, Inc. | Antisense modulation of vascular endothelial growth factor receptor-2 expression |
| DE10230997A1 (de) | 2001-10-26 | 2003-07-17 | Ribopharma Ag | Medikament zur Erhöhung der Wirksamkeit eines Rezeptor-vermittelt Apoptose in Tumorzellen auslösenden Arzneimittels |
| CA2485691A1 (en) | 2002-05-20 | 2003-12-04 | Abgenix, Inc. | Treatment of renal carcinoma using antibodies against the egfr |
| CN105884893A (zh) | 2002-07-18 | 2016-08-24 | 莫鲁斯有限公司 | 抗体混合物的重组生产 |
| US20040023390A1 (en) | 2002-08-05 | 2004-02-05 | Davidson Beverly L. | SiRNA-mediated gene silencing with viral vectors |
| CN1705753A (zh) * | 2002-09-30 | 2005-12-07 | 肿瘤疗法科学股份有限公司 | 非小细胞肺癌的诊断方法 |
| WO2004063355A2 (en) | 2003-01-10 | 2004-07-29 | Protein Design Labs, Inc. | Novel methods of diagnosis of metastatic cancer, compositions and methods of screening for modulators of matastatic cancer |
| EP1603948A1 (en) | 2003-03-14 | 2005-12-14 | Pharmacia Corporation | Antibodies to igf-i receptor for the treatment of cancers |
| US20050214301A1 (en) | 2004-03-24 | 2005-09-29 | Cell Signaling Technology, Inc. | Antibodies specific for BCR-ABL fusion protein and uses thereof |
| DE602006018354D1 (de) | 2005-12-05 | 2010-12-30 | Pfizer Prod Inc | Verfahren zur behandlung von abnormalem zellwachstum |
| US20120208824A1 (en) | 2006-01-20 | 2012-08-16 | Cell Signaling Technology, Inc. | ROS Kinase in Lung Cancer |
| DK2671954T3 (en) | 2006-01-20 | 2018-08-13 | Cell Signaling Technology Inc | Translocation and mutant ROS kinase in human non-small cell lung carcinoma |
| US20100143918A1 (en) | 2007-01-19 | 2010-06-10 | Cell Signaling Technology, Inc. | Translocation and mutant ros kinase in human non-small cell lung carcinoma |
| US8383799B2 (en) | 2006-01-20 | 2013-02-26 | Cell Signaling Technology, Inc. | Translocation and mutant ROS kinase in human non-small cell lung carcinoma |
| EP2016089B1 (en) * | 2006-04-14 | 2014-01-15 | Cell Signaling Technology, Inc. | Gene defects and mutant alk kinase in human solid tumors |
| EP2450437B1 (en) | 2006-04-14 | 2017-05-17 | Cell Signaling Technology, Inc. | Gene defects and mutant ALK kinase in human solid tumors |
| CA2598893C (en) | 2006-10-11 | 2012-04-10 | Astellas Pharma Inc. | Eml4-alk fusion gene |
| SG177225A1 (en) | 2006-12-01 | 2012-01-30 | Agency Science Tech & Res | Cancer-related protein kinases |
| JP5769968B2 (ja) | 2007-10-18 | 2015-08-26 | セル・シグナリング・テクノロジー・インコーポレイテツド | ヒト非小細胞肺癌における転座および変異ｒｏｓキナーゼ |
| EP2255190A4 (en) | 2008-02-12 | 2011-05-04 | Brigham & Womens Hospital | FISH TEST FOR EML4-ALK FUSION IN LUNG CANCER |
| GB2467901A (en) | 2009-02-12 | 2010-08-18 | Norgine Bv | 3',6'-dihydroxy-5(6)-nitrospiro[2-benzofuran-3,9'-xanthene]-1-one mixt. by reacting 4-nitrophthalic acid/anhydride & benzene-1,3-diol in methanesulphonic acid |
| US9364477B2 (en) * | 2009-02-12 | 2016-06-14 | Cell Signaling Technology, Inc. | Mutant ROS expression in human cancer |
| RS57045B1 (sr) * | 2009-05-08 | 2018-05-31 | Astellas Pharma Inc | Jedinjenje diamino heterocikličnog karboksamida |
| US20130288240A1 (en) * | 2010-05-21 | 2013-10-31 | Cell Signaling Technology, Inc. | Alk and ros kinase in cancer |
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2011
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2012
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