CN107148481A - 用于确定患有braf‑阳性癌症的患者为braf抑制剂非响应者且为mapk/erk抑制剂响应者的工具和方法 - Google Patents
用于确定患有braf‑阳性癌症的患者为braf抑制剂非响应者且为mapk/erk抑制剂响应者的工具和方法 Download PDFInfo
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- C12Q—MEASURING 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- 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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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING 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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING 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
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| EP14176944.8 | 2014-07-14 | ||
| EP14176944 | 2014-07-14 | ||
| PCT/EP2015/065986 WO2016008853A1 (en) | 2014-07-14 | 2015-07-13 | Means and methods for identifying a patient having a braf-positive cancer as a non-responder to a braf inhibitor and as a responder to an mapk/erk inhibitor |
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| EP (1) | EP3169797B2 (enExample) |
| JP (1) | JP7036594B2 (enExample) |
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| CA (1) | CA2953732C (enExample) |
| ES (1) | ES2751925T5 (enExample) |
| WO (1) | WO2016008853A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111020033A (zh) * | 2019-12-24 | 2020-04-17 | 中山大学达安基因股份有限公司 | 多重检测braf基因突变的试剂盒及方法 |
| CN112795647A (zh) * | 2019-11-14 | 2021-05-14 | 北京肿瘤医院(北京大学肿瘤医院) | 一种肿瘤标志物及其应用 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX393780B (es) | 2017-01-17 | 2025-03-24 | Heparegenix Gmbh | Inhibidores de proteina cinasa para promover la regeneracion hepatica o reducir o prevenir la muerte de hepatocitos |
| WO2018213302A1 (en) * | 2017-05-16 | 2018-11-22 | Biomed Valley Discoveries, Inc. | Compositions and methods for treating cancer with atypical braf mutations |
| EP4359781A4 (en) * | 2021-06-23 | 2025-05-14 | Royal Melbourne Institute of Technology | CONDUCTOMETRIC SENSOR FOR DETECTING A NUCLEIC ACID AND ITS DETECTION METHOD |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012058532A2 (en) * | 2010-10-28 | 2012-05-03 | Yale University | Methods and compositions for assessing and treating cancer |
| WO2012068562A2 (en) * | 2010-11-19 | 2012-05-24 | The Regents Of The University Of California | Compositions and methods for detection and treatment of b-raf inhibitor-resistant melanomas |
| US20120252015A1 (en) * | 2011-02-18 | 2012-10-04 | Bio-Rad Laboratories | Methods and compositions for detecting genetic material |
| CN103402517A (zh) * | 2010-11-19 | 2013-11-20 | 葛兰素史密斯克莱知识产权（第2号）有限公司 | 使用braf抑制剂的治疗方法 |
| US20140018405A1 (en) * | 2012-07-11 | 2014-01-16 | Boehringer Ingelheim International Gmbh | Anticancer Compounds |
| US20140018372A1 (en) * | 2012-07-11 | 2014-01-16 | Boehringer Ingelheim International Gmbh | Crystalline form of a indolinone derivative and its use |
| CA2886397A1 (en) * | 2012-09-26 | 2014-04-03 | Insight Genetics, Inc. | Methods and compositions relating to next generation sequencing for genetic testing in alk related cancers |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103911428B (zh) * | 2009-03-27 | 2016-02-24 | 生命技术公司 | 用于检测等位基因变体的方法、组合物和试剂盒 |
| WO2012061683A2 (en) | 2010-11-05 | 2012-05-10 | Glaxosmithkline Llc | Methods for treating cancer |
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2015
- 2015-07-13 CN CN201580038260.0A patent/CN107148481A/zh active Pending
- 2015-07-13 EP EP15734713.9A patent/EP3169797B2/en active Active
- 2015-07-13 US US15/326,344 patent/US20190194757A1/en not_active Abandoned
- 2015-07-13 CA CA2953732A patent/CA2953732C/en active Active
- 2015-07-13 JP JP2017522732A patent/JP7036594B2/ja active Active
- 2015-07-13 WO PCT/EP2015/065986 patent/WO2016008853A1/en not_active Ceased
- 2015-07-13 ES ES15734713T patent/ES2751925T5/es active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012058532A2 (en) * | 2010-10-28 | 2012-05-03 | Yale University | Methods and compositions for assessing and treating cancer |
| WO2012068562A2 (en) * | 2010-11-19 | 2012-05-24 | The Regents Of The University Of California | Compositions and methods for detection and treatment of b-raf inhibitor-resistant melanomas |
| CN103402517A (zh) * | 2010-11-19 | 2013-11-20 | 葛兰素史密斯克莱知识产权（第2号）有限公司 | 使用braf抑制剂的治疗方法 |
| US20120252015A1 (en) * | 2011-02-18 | 2012-10-04 | Bio-Rad Laboratories | Methods and compositions for detecting genetic material |
| US20140018405A1 (en) * | 2012-07-11 | 2014-01-16 | Boehringer Ingelheim International Gmbh | Anticancer Compounds |
| US20140018372A1 (en) * | 2012-07-11 | 2014-01-16 | Boehringer Ingelheim International Gmbh | Crystalline form of a indolinone derivative and its use |
| CA2886397A1 (en) * | 2012-09-26 | 2014-04-03 | Insight Genetics, Inc. | Methods and compositions relating to next generation sequencing for genetic testing in alk related cancers |
Non-Patent Citations (4)
| Title |
|---|
| EMANUELA ROMANO等: "Identification of Multiple Mechanisms of Resistance to Vemurafenib in a Patient With BRAFV600E-mutated Cutaneous Melanoma Successfully Rechallenged After Progression", 《CLIN CANCER RES》 * |
| JAMES G GREGER等: "Combinations of BRAF, MEK, and PI3K/mTOR Inhibitors Overcome Acquired Resistance to the BRAF Inhibitor GSK2118436 Dabrafenib, Mediated by NRAS or MEK Mutations", 《MOL CANCER THER》 * |
| RAMIN NAZARIAN等: "Melanomas Acquire Resistance to B-RAF(V600E) Inhibition by RTK or N-RAS Upregulation", 《NATURE》 * |
| 陈德高: "NRAS突变的黑色素瘤分子机制研究进展", 《科技视界》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112795647A (zh) * | 2019-11-14 | 2021-05-14 | 北京肿瘤医院(北京大学肿瘤医院) | 一种肿瘤标志物及其应用 |
| CN112795647B (zh) * | 2019-11-14 | 2022-08-16 | 北京肿瘤医院(北京大学肿瘤医院) | 一种肿瘤标志物及其应用 |
| CN111020033A (zh) * | 2019-12-24 | 2020-04-17 | 中山大学达安基因股份有限公司 | 多重检测braf基因突变的试剂盒及方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016008853A1 (en) | 2016-01-21 |
| CA2953732A1 (en) | 2016-01-21 |
| JP2017529094A (ja) | 2017-10-05 |
| EP3169797A1 (en) | 2017-05-24 |
| EP3169797B2 (en) | 2025-02-19 |
| ES2751925T5 (en) | 2025-05-13 |
| ES2751925T3 (es) | 2020-04-02 |
| US20190194757A1 (en) | 2019-06-27 |
| JP7036594B2 (ja) | 2022-03-15 |
| EP3169797B1 (en) | 2019-08-21 |
| CA2953732C (en) | 2023-09-26 |
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