AU2011240636B2 - Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors - Google Patents
Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors Download PDFInfo
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| PT2300013T (pt) | 2008-05-21 | 2017-10-31 | Ariad Pharma Inc | Derivados de fósforo como inibidores de cinases |
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| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| EP2464954B1 (en) | 2009-08-13 | 2019-06-05 | Teleflex Life Sciences Unlimited Company | Pressure indicator |
| EP2918588B1 (en) | 2010-05-20 | 2017-05-03 | Array Biopharma, Inc. | Macrocyclic compounds as TRK kinase inhibitors |
| US20130288240A1 (en) * | 2010-05-21 | 2013-10-31 | Cell Signaling Technology, Inc. | Alk and ros kinase in cancer |
| US10549054B2 (en) | 2011-02-02 | 2020-02-04 | Teleflex Life Sciences Unlimited Company | Artificial airway |
| EP2704572B1 (en) | 2011-05-04 | 2015-12-30 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| EP2822953B9 (en) | 2012-03-06 | 2017-06-21 | Pfizer Inc | Macrocyclic derivatives for the treatment of proliferative diseases |
| AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| JP6205216B2 (ja) * | 2012-09-24 | 2017-09-27 | アークレイ株式会社 | 変異検出用プローブ、変異検出方法、薬効判定方法及び変異検出用キット |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN104513253A (zh) | 2013-10-01 | 2015-04-15 | 南京波尔泰药业科技有限公司 | 用于治疗增殖性疾病的大环化合物 |
| ES2811927T3 (es) * | 2014-04-10 | 2021-03-15 | Memorial Sloan Kettering Cancer Center | Isoforma novedosa de cinasa de linfoma anaplásico y sus usos |
| US9428812B2 (en) * | 2014-04-28 | 2016-08-30 | Insight Genetics, Inc. | Kit comprising primers for amplifying ALK kinase domain nucleic acids |
| US10799505B2 (en) | 2014-11-16 | 2020-10-13 | Array Biopharma, Inc. | Crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-A]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate |
| EP3244927A1 (en) * | 2015-01-16 | 2017-11-22 | Vedantra Pharmaceuticals Inc. | Multilamellar lipid vesicle compositions including a conjugated anaplastic lymphoma kinase (alk) variant and uses thereof |
| EP3303382A4 (en) * | 2015-05-29 | 2018-12-19 | Ignyta, Inc. | Compositions and methods for treating patients with rtk mutant cells |
| JP2018534296A (ja) | 2015-10-26 | 2018-11-22 | ロクソ オンコロジー， インコーポレイテッドＬｏｘｏ Ｏｎｃｏｌｏｇｙ， Ｉｎｃ． | Ｔｒｋ阻害薬耐性がんにおける点変異およびそれに関連する方法 |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| MX386416B (es) | 2016-04-04 | 2025-03-18 | Loxo Oncology Inc | Formulaciones liquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida. |
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| CN107885972B (zh) * | 2016-09-30 | 2021-07-27 | 广州华大基因医学检验所有限公司 | 一种基于单端测序的融合基因检测方法及其应用 |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| CN110716042A (zh) * | 2019-10-23 | 2020-01-21 | 郑州大学 | 一种用于卵巢癌早期筛查和诊断的血清蛋白标志物、试剂盒及检测方法 |
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| CN112391390A (zh) * | 2020-11-19 | 2021-02-23 | 山西大学 | 飞蝗网格蛋白重链基因及其靶向dsRNA的合成与应用 |
Family Cites Families (71)
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|---|---|---|---|---|
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| NZ201918A (en) | 1981-09-18 | 1987-04-30 | Genentech Inc | N-terminal methionyl analogues of bovine growth hormone |
| 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 |
| US4870009A (en) | 1982-11-22 | 1989-09-26 | The Salk Institute For Biological Studies | Method of obtaining gene product through the generation of transgenic animals |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4736866B1 (en) | 1984-06-22 | 1988-04-12 | Transgenic non-human mammals | |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
| EP0232967B1 (en) | 1986-01-10 | 1993-04-28 | Amoco Corporation | Competitive homogeneous assay |
| US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US5107065A (en) | 1986-03-28 | 1992-04-21 | Calgene, Inc. | Anti-sense regulation of gene expression in plant cells |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| US4873192A (en) | 1987-02-17 | 1989-10-10 | The United States Of America As Represented By The Department Of Health And Human Services | Process for site specific mutagenesis without phenotypic selection |
| US5080891A (en) | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| US5225326A (en) | 1988-08-31 | 1993-07-06 | Research Development Foundation | One step in situ hybridization assay |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| FR2646438B1 (fr) | 1989-03-20 | 2007-11-02 | Pasteur Institut | Procede de remplacement specifique d'une copie d'un gene present dans le genome receveur par l'integration d'un gene different de celui ou se fait l'integration |
| US5800992A (en) | 1989-06-07 | 1998-09-01 | Fodor; Stephen P.A. | Method of detecting nucleic acids |
| US6040138A (en) | 1995-09-15 | 2000-03-21 | Affymetrix, Inc. | Expression monitoring by hybridization to high density oligonucleotide arrays |
| DE69033493D1 (de) | 1989-07-25 | 2004-08-12 | Cell Genesys Inc | Homologe rekombination für universelle donorzellen und chimerische säugetierzellen |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
| IL98764A0 (en) | 1990-07-10 | 1992-07-15 | Smithkline Beecham Corp | Oxamides |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| GB9022543D0 (en) | 1990-10-17 | 1990-11-28 | Wellcome Found | Antibody production |
| KR100236506B1 (ko) | 1990-11-29 | 2000-01-15 | 퍼킨-엘머시터스인스트루먼츠 | 폴리머라제 연쇄 반응 수행 장치 |
| US5455166A (en) | 1991-01-31 | 1995-10-03 | Becton, Dickinson And Company | Strand displacement amplification |
| CA2218875C (en) | 1991-07-23 | 2000-11-07 | The Research Foundation Of State University Of New York | Improvements in the in situ pcr |
| US5756096A (en) | 1991-07-25 | 1998-05-26 | Idec Pharmaceuticals Corporation | Recombinant antibodies for human therapy |
| MX9204374A (es) | 1991-07-25 | 1993-03-01 | Idec Pharma Corp | Anticuerpo recombinante y metodo para su produccion. |
| WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| US5270184A (en) | 1991-11-19 | 1993-12-14 | Becton, Dickinson And Company | Nucleic acid target generation |
| US5545524A (en) | 1991-12-04 | 1996-08-13 | The Regents Of The University Of Michigan | Compositions and methods for chromosome region-specific probes |
| US5397703A (en) | 1992-07-09 | 1995-03-14 | Cetus Oncology Corporation | Method for generation of antibodies to cell surface molecules |
| DE69333366T2 (de) | 1992-10-30 | 2004-09-16 | The General Hospital Corp., Boston | Ein neues zellzyklus kontrollprotein |
| WO1994012520A1 (en) | 1992-11-20 | 1994-06-09 | Enzon, Inc. | Linker for linked fusion polypeptides |
| DE614989T1 (de) | 1993-02-17 | 1995-09-28 | Morphosys Proteinoptimierung | Verfahren für in vivo Selektion von Ligandenbindende Proteine. |
| US5925517A (en) | 1993-11-12 | 1999-07-20 | The Public Health Research Institute Of The City Of New York, Inc. | Detectably labeled dual conformation oligonucleotide probes, assays and kits |
| US6696548B2 (en) * | 1993-12-03 | 2004-02-24 | St. Jude Children's Research Hospital | Antibodies for recognition of alk protein tyrosine/kinase receptor |
| US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
| US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
| JP3189000B2 (ja) | 1994-12-01 | 2001-07-16 | 東ソー株式会社 | 特定核酸配列の検出方法 |
| US6091001A (en) | 1995-03-29 | 2000-07-18 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
| US5710029A (en) | 1995-06-07 | 1998-01-20 | Gen-Probe Incorporated | Methods for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product |
| GB9517780D0 (en) | 1995-08-31 | 1995-11-01 | Roslin Inst Edinburgh | Biological manipulation |
| GB9517779D0 (en) | 1995-08-31 | 1995-11-01 | Roslin Inst Edinburgh | Biological manipulation |
| US5612473A (en) | 1996-01-16 | 1997-03-18 | Gull Laboratories | Methods, kits and solutions for preparing sample material for nucleic acid amplification |
| EP0880598A4 (en) | 1996-01-23 | 2005-02-23 | Affymetrix Inc | RAPID EVALUATION OF NUCLEIC ACID ABUNDANCE DIFFERENCE, WITH A HIGH-DENSITY OLIGONUCLEOTIDE SYSTEM |
| US6121489A (en) | 1996-03-05 | 2000-09-19 | Trega Biosciences, Inc. | Selectively N-alkylated peptidomimetic combinatorial libraries and compounds therein |
| DE69738687D1 (de) | 1996-04-12 | 2008-06-26 | Phri Properties Inc | Sonden, kits und assays |
| US5830698A (en) | 1997-03-14 | 1998-11-03 | Idec Pharmaceuticals Corporation | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| DE69829402T2 (de) | 1997-10-31 | 2006-04-13 | Affymetrix, Inc. (a Delaware Corp.), Santa Clara | Expressionsprofile in adulten und fötalen organen |
| US6020135A (en) | 1998-03-27 | 2000-02-01 | Affymetrix, Inc. | P53-regulated genes |
| WO2000001850A2 (en) | 1998-07-02 | 2000-01-13 | Gen-Probe Incorporated | Molecular torches |
| US6573043B1 (en) | 1998-10-07 | 2003-06-03 | Genentech, Inc. | Tissue analysis and kits therefor |
| US6453242B1 (en) | 1999-01-12 | 2002-09-17 | Sangamo Biosciences, Inc. | Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites |
| US6303305B1 (en) | 1999-03-30 | 2001-10-16 | Roche Diagnostics, Gmbh | Method for quantification of an analyte |
| US6541205B1 (en) | 1999-05-24 | 2003-04-01 | Tosoh Corporation | Method for assaying nucleic acid |
| US20030198627A1 (en) | 2001-09-01 | 2003-10-23 | Gert-Jan Arts | siRNA knockout assay method and constructs |
| CA2524572C (en) | 2003-05-01 | 2018-07-10 | Gen-Probe Incorporated | Oligonucleotides comprising a molecular switch having enhanced sensitivity to the presence of a mismatch |
| US20080051419A1 (en) | 2006-07-26 | 2008-02-28 | Pfizer Inc. | Amine derivatives useful as anticancer agents |
| US8063225B2 (en) | 2006-08-14 | 2011-11-22 | Chembridge Corporation | Tricyclic compound derivatives useful in the treatment of neoplastic diseases, inflammatory disorders and immunomodulatory disorders |
| CA2598893C (en) | 2006-10-11 | 2012-04-10 | Astellas Pharma Inc. | Eml4-alk fusion gene |
| EP2042191B1 (en) * | 2007-09-28 | 2013-01-02 | Roberto Chiarle | Anaplastic Lymphoma Kinase (ALK) as oncoantigen for lymphoma vaccination |
| WO2009103061A2 (en) * | 2008-02-15 | 2009-08-20 | The Children's Hospital Of Philadelphia | Methods and compositions for identifying, diagnosing, and treating neuroblastoma |
| TWI518325B (zh) * | 2010-02-04 | 2016-01-21 | 自治醫科大學 | 對ａｌｋ抑制劑具有先抗性或後抗性癌症的識別、判斷和治療 |
-
2010
- 2010-04-15 US US12/761,050 patent/US8383793B2/en not_active Expired - Fee Related
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2011
- 2011-04-13 KR KR1020127029988A patent/KR20130064067A/ko not_active Withdrawn
- 2011-04-13 BR BR112012026239A patent/BR112012026239A2/pt not_active IP Right Cessation
- 2011-04-13 EP EP11721840.4A patent/EP2558490B1/en not_active Not-in-force
- 2011-04-13 AU AU2011240636A patent/AU2011240636B2/en not_active Ceased
- 2011-04-13 CN CN201180023776.XA patent/CN103201286B/zh not_active Expired - Fee Related
- 2011-04-13 CA CA2796306A patent/CA2796306A1/en not_active Abandoned
- 2011-04-13 RU RU2012148450/10A patent/RU2012148450A/ru not_active Application Discontinuation
- 2011-04-13 JP JP2013505074A patent/JP6223822B2/ja not_active Expired - Fee Related
- 2011-04-13 WO PCT/US2011/032204 patent/WO2011130340A1/en not_active Ceased
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2013
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-
2016
- 2016-10-03 JP JP2016195911A patent/JP2017018141A/ja active Pending
Non-Patent Citations (3)
| Title |
|---|
| DATABASE UniProt [Online] 19 January 2010 (2010-01-19), "RecName: Full= Tyrosine-protein kinase receptor; EC=2.7.10.1 ;", XP000002656286, retrieved from EBI accession no. UNIPROT:D1 MAM0 Database accession no. D1 MAMO * |
| ISABELLE JANOUEIX-LEROSEY ET AL: "Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma", NATURE, vol. 455, no. 7215, 16 October 2008 (2008-10-16), pages 967-970, * |
| YAEL P. MOSSE ET AL: "Identification of ALK as a major familial neuroblastoma predisposition gene", NATURE, vol. 455, no. 7215, 16 October 2008 (2008-10-16), pages 930-935, * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011130340A1 (en) | 2011-10-20 |
| BR112012026239A2 (pt) | 2018-06-26 |
| US20110256546A1 (en) | 2011-10-20 |
| KR20130064067A (ko) | 2013-06-17 |
| AU2011240636A1 (en) | 2012-11-15 |
| CN103201286B (zh) | 2017-05-03 |
| JP2013534804A (ja) | 2013-09-09 |
| EP2558490A1 (en) | 2013-02-20 |
| RU2012148450A (ru) | 2014-05-20 |
| EP2558490B1 (en) | 2016-12-14 |
| CN103201286A (zh) | 2013-07-10 |
| CA2796306A1 (en) | 2011-10-20 |
| JP6223822B2 (ja) | 2017-11-01 |
| US8383793B2 (en) | 2013-02-26 |
| JP2017018141A (ja) | 2017-01-26 |
| US20130244893A1 (en) | 2013-09-19 |
| US9458508B2 (en) | 2016-10-04 |
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