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ES2569663T3 - Procedimiento de diagnóstico - Google Patents

Procedimiento de diagnóstico Download PDF

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Publication number
ES2569663T3
ES2569663T3 ES11162743.6T ES11162743T ES2569663T3 ES 2569663 T3 ES2569663 T3 ES 2569663T3 ES 11162743 T ES11162743 T ES 11162743T ES 2569663 T3 ES2569663 T3 ES 2569663T3
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Spain
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expression
gene
activity
sequence
level
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ES11162743.6T
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English (en)
Inventor
Nicholas B La Thangue
Susan Fotheringham
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Oxford University Innovation Ltd
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Oxford University Innovation Ltd
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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57496Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving intracellular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111General methods applicable to biologically active non-coding nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y305/00Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
    • C12Y305/01Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in linear amides (3.5.1)
    • C12Y305/01098Histone deacetylase (3.5.1.98), i.e. sirtuin deacetylase
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering nucleic acids [NA]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00Applications; Uses
    • C12N2320/10Applications; Uses in screening processes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2330/00Production
    • C12N2330/30Production chemically synthesised
    • C12N2330/31Libraries, arrays
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/106Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/156Polymorphic or mutational markers
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701Details
    • G01N2333/4703Regulators; Modulating activity
    • G01N2333/4706Regulators; Modulating activity stimulating, promoting or activating activity
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90Enzymes; Proenzymes
    • G01N2333/91Transferases (2.)
    • G01N2333/91045Acyltransferases (2.3)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90Enzymes; Proenzymes
    • G01N2333/914Hydrolases (3)
    • G01N2333/978Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • G01N2333/98Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/10Screening for compounds of potential therapeutic value involving cells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/52Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • General Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Hospice & Palliative Care (AREA)
  • Oncology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Plant Pathology (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)

Abstract

Un procedimiento para diagnosticar la susceptibilidad de un individuo que padece de una enfermedad al tratamiento con un inhibidor de HDAC, el procedimiento comprendiendo evaluar el nivel de expresión o actividad de un gen o sus productos de expresión, o la secuencia de un gen, en una muestra de un paciente y comparar dicho nivel de expresión o actividad o secuencia con una referencia, en donde el nivel de expresión o actividad o secuencia que es diferente a dicha referencia es indivativo de una susceptibilidad alterada al tratamiento con el inhibidor de HDAC en relación con el estado de referencia, y en donde dicho gen es hHRAD23B (rad 23B humano).

Description

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Claims (1)

  1. imagen1
ES11162743.6T 2006-03-27 2007-03-27 Procedimiento de diagnóstico Active ES2569663T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0606096.6A GB0606096D0 (en) 2006-03-27 2006-03-27 Screening method
GB0606096 2006-03-27

Publications (1)

Publication Number Publication Date
ES2569663T3 true ES2569663T3 (es) 2016-05-12

Family

ID=36384256

Family Applications (3)

Application Number Title Priority Date Filing Date
ES11162743.6T Active ES2569663T3 (es) 2006-03-27 2007-03-27 Procedimiento de diagnóstico
ES13194854.9T Active ES2607753T3 (es) 2006-03-27 2007-03-27 Procedimiento de diagnóstico
ES07732147T Active ES2376912T3 (es) 2006-03-27 2007-03-27 Procedimiento de cribado

Family Applications After (2)

Application Number Title Priority Date Filing Date
ES13194854.9T Active ES2607753T3 (es) 2006-03-27 2007-03-27 Procedimiento de diagnóstico
ES07732147T Active ES2376912T3 (es) 2006-03-27 2007-03-27 Procedimiento de cribado

Country Status (8)

Country Link
US (3) US8784806B2 (es)
EP (3) EP2005162B1 (es)
JP (2) JP5528103B2 (es)
AT (1) ATE537445T1 (es)
DK (2) DK2733491T3 (es)
ES (3) ES2569663T3 (es)
GB (1) GB0606096D0 (es)
WO (1) WO2007110623A2 (es)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2777924T3 (es) 2004-05-23 2020-08-06 Hmi Medical Innovations Llc Moduladores de teramuteína
CA2596210C (en) 2005-02-03 2014-07-08 Topotarget Uk Limited Combination therapies using hdac inhibitors
ES2380887T3 (es) 2005-05-13 2012-05-21 Topotarget Uk Limited Formulaciones farmacéuticas de inhibidores de la HDAC
US8828392B2 (en) 2005-11-10 2014-09-09 Topotarget Uk Limited Histone deacetylase (HDAC) inhibitors (PXD101) for the treatment of cancer alone or in combination with chemotherapeutic agent
GB0606096D0 (en) 2006-03-27 2006-05-03 Cbmm Sa Screening method
EP2203421B1 (en) 2007-09-25 2014-05-07 TopoTarget UK Limited Methods of synthesis of certain n-hydroxy-3-(3-phenylsulfamoyl-phenyl)-acrylamide compounds
BR112015022737A2 (pt) * 2013-03-11 2018-04-24 Pioneer Hi-Bred International, Inc construto de polinucleotídeo recombinante, célula vegetal, planta, semente, método para regular expressão
GB201306339D0 (en) * 2013-04-08 2013-05-22 Isis Innovation Biomarkers for prognosis
GB2524519B (en) * 2014-03-25 2019-11-06 Pelago Bioscience AB Methods for identifying a biomarker indicative of a reduced drug response using a thermal shift assay
ES2702432B2 (es) 2017-08-31 2019-08-05 Venegas Pedro Manuel Medina Método y dispositivo para el análisis de ácidos nucleicos
IL318095A (en) * 2022-07-27 2025-02-01 E Therapeutics Plc Double-stranded nucleic acid compounds that inhibit ZPI
CN116949169B (zh) * 2023-07-31 2024-02-06 山东大学齐鲁医院 Smek1在缺血性脑卒中诊治中的应用

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050123896A1 (en) * 2001-10-25 2005-06-09 Benz Christopher C. Screening system for modulators of her2 mediated transcription and her2 modulators identified thereby
US20030186903A1 (en) 2001-11-23 2003-10-02 Isis Pharmaceuticals Inc. Antisense modulation of MyD88 expression
WO2003066885A2 (en) * 2002-02-08 2003-08-14 Novartis Ag Method for screening for compounds having hdac inhibitory activity
US20040132825A1 (en) * 2002-03-04 2004-07-08 Bacopoulos Nicholas G. Methods of treating cancer with HDAC inhibitors
DE60334247D1 (de) * 2002-11-27 2010-10-28 Irm Llc Verfahren und zusammensetzungen zur apoptoseinduktion in krebszellen
WO2004074478A1 (ja) 2003-02-19 2004-09-02 Astellas Pharma Inc. ヒストンデアセチラーゼ阻害剤の抗腫瘍効果の予測方法
CN1964714B (zh) * 2003-08-29 2011-09-28 Hdac默克研究有限责任公司 辛二酰苯胺异羟肟酸和吉西他滨在制备用于治疗癌症的药物中的用途
GB0401876D0 (en) 2004-01-28 2004-03-03 Vereniging Het Nl Kanker I New use for cancer antigen
US8193332B2 (en) * 2004-04-09 2012-06-05 Genecare Research Institute Co., Ltd. Cancer cell-specific apoptosis-inducing agents that target chromosome stabilization-associated genes
CN1985007A (zh) 2004-04-15 2007-06-20 罗斯塔英法美蒂克斯有限责任公司 鉴定介导活细胞对药物响应的基因的方法
EP1769242A2 (en) 2004-07-19 2007-04-04 Schering Corporation Myd88 as a therapeutic target for cancer
EP2395109A1 (en) * 2004-12-08 2011-12-14 Aventis Pharmaceuticals Inc. Method for measuring resistance or sensitivity to docetaxel
US7985538B2 (en) 2006-02-23 2011-07-26 Yale University Drug resistance and methods of reversing
GB0606096D0 (en) 2006-03-27 2006-05-03 Cbmm Sa Screening method

Also Published As

Publication number Publication date
WO2007110623A3 (en) 2008-12-04
DK2005162T3 (da) 2012-03-05
WO2007110623A2 (en) 2007-10-04
EP2365335B1 (en) 2016-01-27
JP5528103B2 (ja) 2014-06-25
US9347103B2 (en) 2016-05-24
EP2005162B1 (en) 2011-12-14
EP2733491A1 (en) 2014-05-21
JP6017367B2 (ja) 2016-10-26
JP2009531051A (ja) 2009-09-03
ES2376912T3 (es) 2012-03-20
EP2365335A2 (en) 2011-09-14
US10012652B2 (en) 2018-07-03
US20090311244A1 (en) 2009-12-17
EP2733491B1 (en) 2016-09-21
ES2607753T3 (es) 2017-04-03
DK2733491T3 (en) 2017-01-09
JP2013178260A (ja) 2013-09-09
ATE537445T1 (de) 2011-12-15
GB0606096D0 (en) 2006-05-03
EP2005162A2 (en) 2008-12-24
US20170219594A1 (en) 2017-08-03
US20140369999A1 (en) 2014-12-18
US8784806B2 (en) 2014-07-22
EP2365335A3 (en) 2011-12-28

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