CA2521127C - Polymerase inhibitor and method of using same - Google Patents
Polymerase inhibitor and method of using same Download PDFInfo
- Publication number
- CA2521127C CA2521127C CA2521127A CA2521127A CA2521127C CA 2521127 C CA2521127 C CA 2521127C CA 2521127 A CA2521127 A CA 2521127A CA 2521127 A CA2521127 A CA 2521127A CA 2521127 C CA2521127 C CA 2521127C
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- polymerase
- polymerase inhibitor
- acid sequence
- inhibitor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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Classifications
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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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
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| US45967203P | 2003-04-01 | 2003-04-01 | |
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| PCT/US2004/010029 WO2004090153A2 (en) | 2003-04-01 | 2004-04-01 | Polymerase inhibitor and method of using same |
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| CA2521127A1 CA2521127A1 (en) | 2004-10-21 |
| CA2521127C true CA2521127C (en) | 2014-05-27 |
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| CA (1) | CA2521127C (enExample) |
| WO (1) | WO2004090153A2 (enExample) |
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| US6830902B1 (en) * | 1999-07-02 | 2004-12-14 | Invitrogen Corporation | Compositions and methods for enhanced sensitivity and specificity of nucleic acid synthesis |
| CN101076608B (zh) * | 2004-10-18 | 2013-04-17 | 布兰迪斯大学 | 在pcr扩增中提高再现性和降低引物错导的试剂和方法 |
| EP2458011B1 (en) * | 2005-10-03 | 2013-07-24 | Life Technologies Corporation | Compositions, methods, and kits for amplifying nucleic acids |
| US8012694B2 (en) * | 2006-09-14 | 2011-09-06 | Immutopics, Inc. | Assay for the detection of phosphorylated PTH |
| US10865431B1 (en) * | 2008-06-17 | 2020-12-15 | Steven A Benner | Polymerase incorporation of non-standard nucleotides |
| CA2688174C (en) * | 2008-12-19 | 2018-08-07 | F. Hoffmann-La Roche Ag | Dry composition of reaction compounds with stabilized polymerase |
| EP2703501A1 (en) * | 2009-03-12 | 2014-03-05 | Brandeis University | Reagents and Methods for PCR |
| AU2010314980A1 (en) * | 2009-11-06 | 2012-05-24 | Enzymatics, Inc. | Composition and method for synthesizing a deoxyribonucleotide chain using a double stranded nucleic acid complex with a thermostable polymerase |
| US11299739B2 (en) | 2016-06-07 | 2022-04-12 | Cepheid | Thermostable polymerase inhibitor compositions and methods |
| GB201611469D0 (en) | 2016-06-30 | 2016-08-17 | Lumiradx Tech Ltd | Improvements in or relating to nucleic acid amplification processes |
| GB2569965A (en) | 2018-01-04 | 2019-07-10 | Lumiradx Uk Ltd | Improvements in or relating to amplification of nucleic acids |
| EP3818170A4 (en) * | 2018-07-02 | 2022-03-09 | Swift Biosciences, Inc. | Temperature controlled dna polymerase inhibitors |
| CN115135664A (zh) * | 2020-06-22 | 2022-09-30 | 苏州新海生物科技股份有限公司 | 一种核酸配体及其应用 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US5470974A (en) | 1985-03-15 | 1995-11-28 | Neu-Gene Development Group | Uncharged polynucleotide-binding polymers |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4996143A (en) | 1985-12-23 | 1991-02-26 | Syngene, Inc. | Fluorescent stokes shift probes for polynucleotide hybridization |
| US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
| IL86164A0 (en) | 1987-04-28 | 1988-11-15 | Tamir Biotechnology Ltd | Improved dna probes |
| JPH0344560Y2 (enExample) | 1987-08-24 | 1991-09-19 | ||
| EP0333832B1 (en) | 1987-09-22 | 1992-06-03 | Temple University | Artificial dna base pair analogues |
| US6054270A (en) | 1988-05-03 | 2000-04-25 | Oxford Gene Technology Limited | Analying polynucleotide sequences |
| US6444798B1 (en) | 1988-06-06 | 2002-09-03 | Steven Albert Benner | Chimeras of sulfur-linked oligonucleotide analogs and DNA and RNA |
| GB8827160D0 (en) | 1988-11-21 | 1988-12-29 | Apothekernes Lab | Detection & quantitative determination of rna & dna |
| GB8902689D0 (en) | 1989-02-07 | 1989-03-30 | Ici Plc | Assay method |
| US5856092A (en) | 1989-02-13 | 1999-01-05 | Geneco Pty Ltd | Detection of a nucleic acid sequence or a change therein |
| GB8920097D0 (en) | 1989-09-06 | 1989-10-18 | Ici Plc | Amplification processes |
| US6007984A (en) | 1989-11-01 | 1999-12-28 | Zeneca Limited | Detection of DNA/RNA by fluorescence polarization |
| US5412088A (en) | 1989-11-20 | 1995-05-02 | Rutgers, The State University | 6-O-substituted guanosine derivatives |
| US5763173A (en) | 1990-06-11 | 1998-06-09 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand inhibitors to DNA polymerases |
| US5693502A (en) | 1990-06-11 | 1997-12-02 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand inhibitors to DNA polymerases |
| US5874557A (en) | 1990-06-11 | 1999-02-23 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand inhibitors to DNA polymerases |
| US5552541A (en) | 1990-06-20 | 1996-09-03 | Beckman Instruments, Inc. | Haptenic probes for detecting capture polynucleotides |
| US5177064A (en) | 1990-07-13 | 1993-01-05 | University Of Florida | Targeted drug delivery via phosphonate derivatives |
| US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| US6140496A (en) | 1990-10-09 | 2000-10-31 | Benner; Steven Albert | Precursors for deoxyribonucleotides containing non-standard nucleosides |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| US6037120A (en) * | 1995-10-12 | 2000-03-14 | Benner; Steven Albert | Recognition of oligonucleotides containing non-standard base pairs |
| US5965364A (en) | 1990-10-09 | 1999-10-12 | Benner; Steven Albert | Method for selecting functional deoxyribonucleotide derivatives |
| JP3228738B2 (ja) | 1990-12-21 | 2001-11-12 | エフ，ホフマン ― ラ ロシュ アーゲー | Ｈｌａ ｄｑベータｄｎａタイピング |
| DE4129653A1 (de) | 1991-09-06 | 1993-03-11 | Boehringer Mannheim Gmbh | Verfahren zum nachweis aehnlicher nukleinsaeuren |
| US5846717A (en) | 1996-01-24 | 1998-12-08 | Third Wave Technologies, Inc. | Detection of nucleic acid sequences by invader-directed cleavage |
| US5958784A (en) | 1992-03-25 | 1999-09-28 | Benner; Steven Albert | Predicting folded structures of proteins |
| WO1994021820A1 (en) | 1993-03-17 | 1994-09-29 | City Of Hope | Nucleic acid sequences having single stranded ends |
| US6156501A (en) | 1993-10-26 | 2000-12-05 | Affymetrix, Inc. | Arrays of modified nucleic acid probes and methods of use |
| ATE247716T1 (de) | 1994-02-07 | 2003-09-15 | Beckman Coulter Inc | Ligase/polymerase-vermittelte analyse genetischer elemente von einzelnukleotid-polymorphismen und ihre verwendung in der genetischen analyse |
| US5681702A (en) | 1994-08-30 | 1997-10-28 | Chiron Corporation | Reduction of nonspecific hybridization by using novel base-pairing schemes |
| US5604097A (en) | 1994-10-13 | 1997-02-18 | Spectragen, Inc. | Methods for sorting polynucleotides using oligonucleotide tags |
| US5565340A (en) | 1995-01-27 | 1996-10-15 | Clontech Laboratories, Inc. | Method for suppressing DNA fragment amplification during PCR |
| GB9507238D0 (en) | 1995-04-07 | 1995-05-31 | Isis Innovation | Detecting dna sequence variations |
| DE69638318D1 (de) | 1995-06-07 | 2011-02-17 | Gilead Sciences Inc | Nukleinsäureliganden, die an DNA-Polymerasen binden und diese inhibieren |
| US6183967B1 (en) | 1995-06-07 | 2001-02-06 | Nexstar Pharmaceuticals | Nucleic acid ligand inhibitors to DNA polymerases |
| US5736330A (en) | 1995-10-11 | 1998-04-07 | Luminex Corporation | Method and compositions for flow cytometric determination of DNA sequences |
| US5705621A (en) | 1995-11-17 | 1998-01-06 | Isis Pharmaceuticals, Inc. | Oligomeric phosphite, phosphodiester, Phosphorothioate and phosphorodithioate compounds and intermediates for preparing same |
| WO1997035033A1 (en) | 1996-03-19 | 1997-09-25 | Molecular Tool, Inc. | Method for determining the nucleotide sequence of a polynucleotide |
| US5780233A (en) | 1996-06-06 | 1998-07-14 | Wisconsin Alumni Research Foundation | Artificial mismatch hybridization |
| US6124092A (en) | 1996-10-04 | 2000-09-26 | The Perkin-Elmer Corporation | Multiplex polynucleotide capture methods and compositions |
| US6482590B1 (en) | 1996-12-20 | 2002-11-19 | Aventis Behring Gmbh | Method for polynucleotide amplification |
| US7101672B2 (en) | 1998-05-05 | 2006-09-05 | Third Wave Technologies, Inc. | Target-dependent reactions using structure-bridging oligonucleotides |
| JP4185185B2 (ja) | 1997-05-08 | 2008-11-26 | 征夫 軽部 | 部分二重鎖ｄｎａを利用したｄｎａの検出方法 |
| US5928869A (en) | 1997-05-30 | 1999-07-27 | Becton, Dickinson And Company | Detection of nucleic acids by fluorescence quenching |
| WO1999022030A1 (en) | 1997-10-28 | 1999-05-06 | The Regents Of The University Of California | Dna polymorphism identity determination using flow cytometry |
| GB9725197D0 (en) | 1997-11-29 | 1998-01-28 | Secr Defence | Detection system |
| JP4471494B2 (ja) | 1998-05-14 | 2010-06-02 | ルミネックス コーポレイション | ダイオードレーザをベースとした測定装置 |
| AU754952B2 (en) | 1998-06-24 | 2002-11-28 | Illumina, Inc. | Decoding of array sensors with microspheres |
| US6200757B1 (en) | 1999-01-19 | 2001-03-13 | Dade Behring Inc. | Method for controlling the extension of an oligonucleotide |
| US6274353B1 (en) | 1999-09-22 | 2001-08-14 | Genecopoeia, Inc. | Method and compositions for improved polynucleotide synthesis |
| US6528254B1 (en) | 1999-10-29 | 2003-03-04 | Stratagene | Methods for detection of a target nucleic acid sequence |
| US6509157B1 (en) * | 1999-11-05 | 2003-01-21 | Roche Molecular Systems, Inc | 3 blocked nucleic acid amplification primers |
| WO2001051669A2 (en) | 2000-01-15 | 2001-07-19 | Genelabs Technologies, Inc. | Nucleic acid binding assay and selection method |
| WO2001075139A1 (en) | 2000-04-03 | 2001-10-11 | Biolink Partners, Inc. | Reversible chemical modification of nucleic acids and improved method for nucleic acid hybridization |
| AU7125401A (en) | 2000-05-19 | 2001-12-03 | David J Marshall | Materials and methods for detection of nucleic acids |
| CA2425747C (en) | 2000-10-14 | 2012-01-24 | Eragen Biosciences, Inc. | Solid support assay systems and methods utilizing non-standard bases |
| ES2311638T5 (es) | 2001-11-28 | 2011-09-08 | Bio-Rad Laboratories, Inc. | Métodos de uso de polimerasas mejoradas. |
| US20030194705A1 (en) | 2002-03-01 | 2003-10-16 | Schroth Gary P. | Methods of using unnatural nucleobases for decoding |
| US7282333B2 (en) | 2003-10-20 | 2007-10-16 | Promega Corporation | Methods and compositions for nucleic acid analysis |
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2004
- 2004-04-01 EP EP04758726.6A patent/EP1615942B1/en not_active Expired - Lifetime
- 2004-04-01 US US10/551,705 patent/US7820808B2/en active Active
- 2004-04-01 CA CA2521127A patent/CA2521127C/en not_active Expired - Lifetime
- 2004-04-01 JP JP2006509580A patent/JP4567673B2/ja not_active Expired - Lifetime
- 2004-04-01 WO PCT/US2004/010029 patent/WO2004090153A2/en not_active Ceased
- 2004-04-01 AU AU2004227353A patent/AU2004227353B2/en not_active Expired
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2010
- 2010-09-17 US US12/884,575 patent/US8313932B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
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| AU2004227353A1 (en) | 2004-10-21 |
| WO2004090153A3 (en) | 2005-06-23 |
| CA2521127A1 (en) | 2004-10-21 |
| EP1615942B1 (en) | 2016-03-16 |
| US20110104678A1 (en) | 2011-05-05 |
| WO2004090153A2 (en) | 2004-10-21 |
| EP1615942A2 (en) | 2006-01-18 |
| EP1615942A4 (en) | 2009-03-25 |
| JP2006521824A (ja) | 2006-09-28 |
| JP4567673B2 (ja) | 2010-10-20 |
| US8313932B2 (en) | 2012-11-20 |
| AU2004227353B2 (en) | 2010-02-25 |
| US20080108124A1 (en) | 2008-05-08 |
| US7820808B2 (en) | 2010-10-26 |
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