JP7091325B2 - チオール含有切断試薬および酸化的洗浄液 - Google Patents
チオール含有切断試薬および酸化的洗浄液 Download PDFInfo
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- JP7091325B2 JP7091325B2 JP2019522971A JP2019522971A JP7091325B2 JP 7091325 B2 JP7091325 B2 JP 7091325B2 JP 2019522971 A JP2019522971 A JP 2019522971A JP 2019522971 A JP2019522971 A JP 2019522971A JP 7091325 B2 JP7091325 B2 JP 7091325B2
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- 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
- 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
- C12Q1/6869—Methods for sequencing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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| US15/457,344 | 2017-03-13 | ||
| US15/457,344 US11421264B2 (en) | 2015-11-06 | 2017-03-13 | Thiol-containing cleave reagents and oxidative wash |
| PCT/US2017/058908 WO2018085156A1 (en) | 2016-11-04 | 2017-10-28 | Thiol-containing cleave reagents and oxidative wash |
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| JP2019536448A JP2019536448A (ja) | 2019-12-19 |
| JP2019536448A5 JP2019536448A5 (enExample) | 2020-11-12 |
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| CN113453692A (zh) * | 2019-01-08 | 2021-09-28 | 奇异基因组学系统公司 | 核苷酸可裂解接头和其用途 |
| GB2580963C (en) * | 2019-02-01 | 2025-09-03 | Hemispherian As | Cancer therapies |
| CN114031476B (zh) * | 2021-11-23 | 2023-12-08 | 北京中医药大学 | 一种将甲硫基亚甲基氧衍生物转化为羟基化合物的绿色方法 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000226399A (ja) | 1999-02-04 | 2000-08-15 | Isis Pharmaceut Inc | オリゴマ―化合物を合成するための改善された方法 |
| JP2003511386A (ja) | 1999-10-05 | 2003-03-25 | キアテク アーベー | ヒドロキシル基を保護するための化合物及びその使用方法 |
| US20030092763A1 (en) | 1999-11-10 | 2003-05-15 | Snezna Rogelj | Method for induction of L-selectin shedding |
| JP2005511058A (ja) | 2001-12-04 | 2005-04-28 | ソレックサ リミテッド | 標識ヌクレオチド |
| JP2005521422A (ja) | 2002-04-04 | 2005-07-21 | バイオタージ アクチボラゲット | 新しい方法 |
| US20140045175A1 (en) | 2009-04-23 | 2014-02-13 | Intelligent Biosystems, Inc. | Hydroxymethyl Linkers For Labeling Nucleotides |
| US20150140561A1 (en) | 2013-11-20 | 2015-05-21 | Roche Diagnostics Operations, Inc. | Compound for sequencing by synthesis |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| NO873956L (no) * | 1986-09-25 | 1988-03-28 | Bp Chem Int Ltd | Rensemidler inneholdende peroksyder for fremstilling av flyktige sulfider. |
| US6046039A (en) * | 1998-08-19 | 2000-04-04 | Battelle Memorial Institute | Methods for producing partially digested restriction DNA fragments and for producing a partially modified PCR product |
| US6566059B1 (en) * | 1998-10-01 | 2003-05-20 | Variagenics, Inc. | Method for analyzing polynucleotides |
| US6440705B1 (en) * | 1998-10-01 | 2002-08-27 | Vincent P. Stanton, Jr. | Method for analyzing polynucleotides |
| US8481259B2 (en) * | 2007-02-05 | 2013-07-09 | Intelligent Bio-Systems, Inc. | Methods and devices for sequencing nucleic acids in smaller batches |
| US8101353B2 (en) * | 2007-12-18 | 2012-01-24 | Advanced Analytical Technologies, Inc. | System and method for nucleotide sequence profiling for sample identification |
| KR101107315B1 (ko) * | 2009-09-29 | 2012-01-20 | 한국과학기술연구원 | ３′―하이드록실기에 형광을 띄는 장애그룹이 부착된 뉴클레오시드 삼인산을 가역적 종결자로서 이용한 ｄｎａ 염기서열 분석 방법 |
| WO2012149472A2 (en) * | 2011-04-27 | 2012-11-01 | Ignite Institute For Individualized Health | Methods, compositions, and kits for treating and preventing neurological conditions |
| WO2015006811A2 (en) * | 2013-07-19 | 2015-01-22 | The Walter And Eliza Hall Institute Of Medical Research | Diagnostic methods |
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2017
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- 2017-10-28 EP EP17868018.7A patent/EP3535407B1/en active Active
- 2017-10-28 WO PCT/US2017/058908 patent/WO2018085156A1/en not_active Ceased
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Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000226399A (ja) | 1999-02-04 | 2000-08-15 | Isis Pharmaceut Inc | オリゴマ―化合物を合成するための改善された方法 |
| JP2003511386A (ja) | 1999-10-05 | 2003-03-25 | キアテク アーベー | ヒドロキシル基を保護するための化合物及びその使用方法 |
| US20030092763A1 (en) | 1999-11-10 | 2003-05-15 | Snezna Rogelj | Method for induction of L-selectin shedding |
| JP2005511058A (ja) | 2001-12-04 | 2005-04-28 | ソレックサ リミテッド | 標識ヌクレオチド |
| JP2005521422A (ja) | 2002-04-04 | 2005-07-21 | バイオタージ アクチボラゲット | 新しい方法 |
| US20140045175A1 (en) | 2009-04-23 | 2014-02-13 | Intelligent Biosystems, Inc. | Hydroxymethyl Linkers For Labeling Nucleotides |
| US20150140561A1 (en) | 2013-11-20 | 2015-05-21 | Roche Diagnostics Operations, Inc. | Compound for sequencing by synthesis |
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| Publication number | Publication date |
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| JP2019536448A (ja) | 2019-12-19 |
| EP3535407A1 (en) | 2019-09-11 |
| EP3535407B1 (en) | 2021-06-02 |
| CN110506121A (zh) | 2019-11-26 |
| WO2018085156A1 (en) | 2018-05-11 |
| EP3535407A4 (en) | 2020-06-24 |
| CA3041055A1 (en) | 2018-05-11 |
| AU2017354876A1 (en) | 2019-06-20 |
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