CO2017003528A2 - Uso de paneles de genes mutantes de fgfr en la identificación de pacientes con cáncer que responderán al tratamiento con un inhibidor de fgfr - Google Patents

Uso de paneles de genes mutantes de fgfr en la identificación de pacientes con cáncer que responderán al tratamiento con un inhibidor de fgfr

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Publication number
CO2017003528A2
CO2017003528A2 CONC2017/0003528A CO2017003528A CO2017003528A2 CO 2017003528 A2 CO2017003528 A2 CO 2017003528A2 CO 2017003528 A CO2017003528 A CO 2017003528A CO 2017003528 A2 CO2017003528 A2 CO 2017003528A2
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CO
Colombia
Prior art keywords
fgfr
respond
treatment
cancer patients
mutant gene
Prior art date
Application number
CONC2017/0003528A
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English (en)
Inventor
Jayaprakash Karkera
Suso Jesus Platero
Original Assignee
Janssen Pharmaceutica Nv
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Publication date
Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv
Publication of CO2017003528A2 publication Critical patent/CO2017003528A2/es

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    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • 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

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)

Abstract

En la presente descripción, se describen métodos para identificar un paciente con cáncer que responderá al tratamiento con un inhibidor del receptor del factor de crecimiento de fibroblastos (FGFR) y métodos para tratar pacientes con cáncer. Los métodos implican evaluar una muestra biológica del paciente para detectar la presencia de uno o más mutantes de FGFR a partir de un panel de genes mutantes de FGFR. En la presente descripción se describen, además, estuches e iniciadores para identificar la presencia de uno o más genes mutantes de FGFR en una muestra biológica.
CONC2017/0003528A 2014-09-26 2017-04-12 Uso de paneles de genes mutantes de fgfr en la identificación de pacientes con cáncer que responderán al tratamiento con un inhibidor de fgfr CO2017003528A2 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462056159P 2014-09-26 2014-09-26
PCT/US2015/050996 WO2016048833A2 (en) 2014-09-26 2015-09-18 Use of fgfr mutant gene panels in identifying cancer patients that will be responsive to treatment with an fgfr inhibitor

Publications (1)

Publication Number Publication Date
CO2017003528A2 true CO2017003528A2 (es) 2017-07-11

Family

ID=54337343

Family Applications (1)

Application Number Title Priority Date Filing Date
CONC2017/0003528A CO2017003528A2 (es) 2014-09-26 2017-04-12 Uso de paneles de genes mutantes de fgfr en la identificación de pacientes con cáncer que responderán al tratamiento con un inhibidor de fgfr

Country Status (37)

Country Link
US (2) US20160090633A1 (es)
EP (2) EP4063516A1 (es)
JP (3) JP6766037B2 (es)
KR (2) KR20220162823A (es)
CN (2) CN107002141B (es)
AR (1) AR102345A1 (es)
AU (2) AU2015321626B2 (es)
BR (1) BR112017006088A2 (es)
CA (1) CA2962075A1 (es)
CO (1) CO2017003528A2 (es)
CR (1) CR20170104A (es)
DK (1) DK3198033T3 (es)
EA (1) EA037920B1 (es)
EC (1) ECSP17025787A (es)
ES (1) ES2912567T3 (es)
GT (1) GT201700059A (es)
HR (1) HRP20220496T1 (es)
HU (1) HUE058219T2 (es)
IL (2) IL251264B (es)
JO (1) JO3681B1 (es)
LT (1) LT3198033T (es)
MA (1) MA40761B1 (es)
MX (2) MX2017003954A (es)
MY (1) MY194567A (es)
NI (1) NI201700035A (es)
PH (1) PH12017500556A1 (es)
PL (1) PL3198033T3 (es)
PT (1) PT3198033T (es)
RS (1) RS63178B1 (es)
SG (1) SG11201702381QA (es)
SI (1) SI3198033T1 (es)
SV (1) SV2017005415A (es)
TW (1) TWI706136B (es)
UA (1) UA122564C2 (es)
UY (1) UY36325A (es)
WO (1) WO2016048833A2 (es)
ZA (1) ZA201702899B (es)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014051022A1 (ja) 2012-09-27 2014-04-03 中外製薬株式会社 Fgfr3融合遺伝子およびそれを標的とする医薬
JP6731254B2 (ja) * 2014-01-24 2020-07-29 公益財団法人がん研究会 新規融合体及びその検出法
AU2015238301B2 (en) 2014-03-26 2020-06-25 Astex Therapeutics Ltd Combinations
JOP20200201A1 (ar) 2015-02-10 2017-06-16 Astex Therapeutics Ltd تركيبات صيدلانية تشتمل على n-(3.5- ثنائي ميثوكسي فينيل)-n'-(1-ميثيل إيثيل)-n-[3-(ميثيل-1h-بيرازول-4-يل) كينوكسالين-6-يل]إيثان-1.2-ثنائي الأمين
US10478494B2 (en) * 2015-04-03 2019-11-19 Astex Therapeutics Ltd FGFR/PD-1 combination therapy for the treatment of cancer
KR20180118719A (ko) * 2016-03-04 2018-10-31 다이호야쿠힌고교 가부시키가이샤 악성 종양 치료용 제제 및 조성물
US11883404B2 (en) 2016-03-04 2024-01-30 Taiho Pharmaceuticals Co., Ltd. Preparation and composition for treatment of malignant tumors
JOP20190280A1 (ar) 2017-06-02 2019-12-02 Janssen Pharmaceutica Nv مثبطات fgfr2 لعلاج سرطان الأوعية الصفراوية
KR20210064274A (ko) * 2018-09-21 2021-06-02 얀센 파마슈티카 엔.브이. 담관암종의 치료
MX2021011926A (es) 2019-03-29 2021-11-03 Janssen Pharmaceutica Nv Inhibidores de fgfr tirosina cinasa para el tratamiento de carcinoma urotelial.
BR112021019203A2 (pt) 2019-03-29 2021-11-30 Janssen Pharmaceutica Nv Inibidores de tirosina quinase fgfr para o tratamento de carcinoma urotelial
MX2021014524A (es) * 2019-05-31 2022-05-19 Qed Therapeutics Inc Metodos para tratar canceres del sistema urinario.
CN110241183B (zh) * 2019-06-13 2022-10-28 南京世和基因生物技术股份有限公司 一种fgfr融合基因的检测方法、试剂盒以及探针库
WO2021050100A1 (en) * 2019-09-09 2021-03-18 Zepto Life Technology, LLC Systems and methods for detecting genetic variation in nucleic acids
BR112022005224A2 (pt) 2019-09-26 2022-06-14 Janssen Pharmaceutica Nv Uso de inibidores de fgfr em cânceres alterados geneticamente por fgfr para melhorar a resposta do paciente a inibidores de ponto de verificação imune em configurações de tratamento sequenciais
KR20220140781A (ko) 2020-02-12 2022-10-18 얀센 파마슈티카 엔.브이. 고위험 비근침윤성 방광암 치료를 위한 fgfr 티로신 키나제 억제제
TW202140012A (zh) 2020-02-12 2021-11-01 比利時商健生藥品公司 用於治療尿路上皮癌的fgfr酪胺酸激酶抑制劑和抗pd1藥劑
CA3175356A1 (en) * 2020-04-15 2021-10-21 Jared LOPES Immunostimulatory agents in combination with angiogenesis inhibitors
CN111440790A (zh) * 2020-05-08 2020-07-24 公安部物证鉴定中心 唾液斑迹dna和rna同时提取的方法
WO2022053697A1 (en) 2020-09-14 2022-03-17 Janssen Pharmaceutica Nv Fgfr inhibitor combination therapies
CN112143815B (zh) * 2020-11-25 2021-02-26 江苏申基生物科技有限公司 一种用于检测人fgfr2基因融合突变的核酸组合物、试剂盒及检测方法
TW202313038A (zh) 2021-05-19 2023-04-01 比利時商健生藥品公司 用於治療晚期實性瘤之fgfr酪胺酸激酶抑制劑
TW202333720A (zh) 2021-10-12 2023-09-01 美商塔里斯生物醫學有限責任公司 用於膀胱內施用的厄達替尼調配物及系統
TW202400174A (zh) 2022-02-18 2024-01-01 美商塔里斯生物醫學有限責任公司 用於膀胱內施用的Erdafitinib調配物及滲透系統

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8101359B2 (en) * 2002-10-01 2012-01-24 Epigenomics Ag Method for determining risk of relapse of breast cancer following tamoxifen adjuvant therapy
GB0512324D0 (en) 2005-06-16 2005-07-27 Novartis Ag Organic compounds
EP1659175A1 (en) * 2004-11-18 2006-05-24 Institut Curie Alterations in seborrheic keratoses and their applications
BRPI0611375A2 (pt) 2005-05-23 2010-08-31 Novartis Ag formas cristalinas e outras de sais de ácido láctico de 4-amino-5-flúor-3-[6-(4-metilpiperazin-1-il)-1h-benzimid azol-2-il]-1h-quinolin-2-ona
US20090247576A1 (en) * 2005-11-22 2009-10-01 Eisai R & D Management Co., Ltd. Anti-tumor agent for multiple myeloma
WO2007067968A2 (en) 2005-12-08 2007-06-14 Novartis Ag Effects of inhibitors of fgfr3 on gene transcription
EP1918376A1 (en) 2006-11-03 2008-05-07 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. FGFR4 promotes cancer cell resistance in response to chemotherapeutic drugs
US8163923B2 (en) 2007-03-14 2012-04-24 Advenchen Laboratories, Llc Spiro substituted compounds as angiogenesis inhibitors
US8071338B2 (en) * 2007-08-08 2011-12-06 Roche Molecular Systems, Inc. Suppression of amplification using an oligonucleotide and a polymerase significantly lacking 5′-3′ nuclease activity
GB201007286D0 (en) 2010-04-30 2010-06-16 Astex Therapeutics Ltd New compounds
GB201020179D0 (en) * 2010-11-29 2011-01-12 Astex Therapeutics Ltd New compounds
CN102293770A (zh) * 2011-05-25 2011-12-28 温州医学院 新型成纤维细胞生长因子受体酪氨酸激酶抑制剂
CN102319224B (zh) * 2011-07-27 2013-03-20 赛乐医药科技(上海)有限公司 复方甲氧那明的速释-缓释渗透泵制剂
WO2013026027A1 (en) * 2011-08-18 2013-02-21 Nestec S.A. Compositions and methods for detecting allelic variants
US20130096021A1 (en) * 2011-09-27 2013-04-18 Arul M. Chinnaiyan Recurrent gene fusions in breast cancer
AR088941A1 (es) 2011-11-23 2014-07-16 Bayer Ip Gmbh Anticuerpos anti-fgfr2 y sus usos
WO2013088191A1 (en) * 2011-12-12 2013-06-20 Institut National De La Sante Et De La Recherche Medicale (Inserm) Antagonist of the fibroblast growth factor receptor 3 (fgfr3) for use in the treatment or the prevention of skeletal disorders linked with abnormal activation of fgfr3
MX349120B (es) * 2012-02-28 2017-07-12 Astellas Pharma Inc Compuesto heterociclico aromatico que contiene nitrogeno.
US9254288B2 (en) * 2012-05-07 2016-02-09 The Translational Genomics Research Institute Susceptibility of tumors to tyrosine kinase inhibitors and treatment thereof
GB201209609D0 (en) * 2012-05-30 2012-07-11 Astex Therapeutics Ltd New compounds
CN104619840A (zh) * 2012-07-05 2015-05-13 日本国立癌症研究中心 Fgfr2融合基因
EP2877854B1 (en) * 2012-07-24 2022-09-07 The Trustees of Columbia University in the City of New York Fgfr-tacc fusion proteins and methods thereof
RU2015102194A (ru) * 2012-07-27 2016-09-20 Дженентек, Инк. Способы лечения связанных с fgfr3 состояний
WO2014051022A1 (ja) * 2012-09-27 2014-04-03 中外製薬株式会社 Fgfr3融合遺伝子およびそれを標的とする医薬
US11230589B2 (en) * 2012-11-05 2022-01-25 Foundation Medicine, Inc. Fusion molecules and uses thereof
WO2014113729A2 (en) * 2013-01-18 2014-07-24 Foundation Mecicine, Inc. Methods of treating cholangiocarcinoma

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AU2015321626A1 (en) 2017-04-06
RS63178B1 (sr) 2022-06-30
SI3198033T1 (sl) 2022-06-30
JP7051920B2 (ja) 2022-04-11
DK3198033T3 (da) 2022-04-11
CR20170104A (es) 2017-05-31
AU2015321626B2 (en) 2021-12-16
HRP20220496T1 (hr) 2022-05-27
JP2020124192A (ja) 2020-08-20
UY36325A (es) 2016-04-01
LT3198033T (lt) 2022-05-10
JP6766037B2 (ja) 2020-10-07
MA40761B1 (fr) 2022-04-29
TW201619609A (zh) 2016-06-01
EP4063516A1 (en) 2022-09-28
SG11201702381QA (en) 2017-04-27
MX2022006536A (es) 2022-07-11
SV2017005415A (es) 2017-07-03
MX2017003954A (es) 2017-12-14
PT3198033T (pt) 2022-05-25
WO2016048833A3 (en) 2016-05-19
IL251264A0 (en) 2017-05-29
GT201700059A (es) 2019-08-21
CN107002141B (zh) 2021-11-02
ZA201702899B (en) 2019-06-26
US20190078166A1 (en) 2019-03-14
ECSP17025787A (es) 2018-07-31
CN113957146A (zh) 2022-01-21
EA037920B1 (ru) 2021-06-07
UA122564C2 (uk) 2020-12-10
BR112017006088A2 (pt) 2017-12-19
PL3198033T3 (pl) 2022-08-29
AR102345A1 (es) 2017-02-22
PH12017500556A1 (en) 2017-08-30
JP2022109910A (ja) 2022-07-28
JP2017529090A (ja) 2017-10-05
ES2912567T3 (es) 2022-05-26
TWI706136B (zh) 2020-10-01
HUE058219T2 (hu) 2022-07-28
CN107002141A (zh) 2017-08-01
KR20220162823A (ko) 2022-12-08
NI201700035A (es) 2017-06-22
IL251264B (en) 2022-04-01
KR20170062495A (ko) 2017-06-07
EA201790716A1 (ru) 2017-10-31
AU2021277633A1 (en) 2021-12-23
IL291633A (en) 2022-05-01
CA2962075A1 (en) 2016-03-31
EP3198033B1 (en) 2022-02-16
WO2016048833A2 (en) 2016-03-31
KR102470456B1 (ko) 2022-11-23
MA40761A (fr) 2017-08-01
EP3198033A2 (en) 2017-08-02
JO3681B1 (ar) 2020-08-27
MY194567A (en) 2022-12-02
US20160090633A1 (en) 2016-03-31

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