RU2608501C2 - Детекция нуклеиновокислотной последовательности-мишени в анализе с гибридизацией сигнального олигонуклеотида, зависящей от расщепления и удлинения зондирующего и метящего олигонуклеотида (варианты) - Google Patents
Детекция нуклеиновокислотной последовательности-мишени в анализе с гибридизацией сигнального олигонуклеотида, зависящей от расщепления и удлинения зондирующего и метящего олигонуклеотида (варианты) Download PDFInfo
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| CA3049833A1 (en) * | 2016-12-23 | 2018-06-28 | Albert-Ludwigs-Universitat Freiburg | Two-piece mediator probe |
| JP6938641B2 (ja) | 2016-12-29 | 2021-09-22 | シージーン アイエヌシー | プライマーダイマー形成を減少させ、増幅効率を増加させる方法 |
| KR102408564B1 (ko) | 2017-03-28 | 2022-06-14 | 주식회사 씨젠 | 타겟 핵산 서열의 존재를 결정하기 위한 분석 시그널 |
| CN108823287B (zh) * | 2017-04-28 | 2019-04-12 | 厦门大学 | 一种检测靶核酸序列的方法 |
| WO2019045532A2 (en) | 2017-08-31 | 2019-03-07 | Seegene, Inc. | EVALUATION OF COMPONENT PERFORMANCE USING A PAIR OF DIMER FORMER PRIMERS |
| AU2018339207A1 (en) | 2017-09-28 | 2020-04-16 | Seegene, Inc. . | Method and device for analyzing target analyte in sample |
| US11401546B2 (en) | 2017-09-29 | 2022-08-02 | Seegene, Inc. | Detection of target nucleic acid sequences by PTO cleavage and extension-dependent extension assay |
| US20190112636A1 (en) * | 2017-10-16 | 2019-04-18 | ChromaCode, Inc. | Methods and compositions for nucleic acid detection |
| KR102369388B1 (ko) | 2018-01-05 | 2022-03-02 | 주식회사 씨젠 | 시료에서 M. tuberculosis, M. bovis 및 M. bovis BCG의 존재 또는 부존재를 결정하는 방법 |
| US12454720B2 (en) | 2018-04-17 | 2025-10-28 | ChromaCode, Inc. | Methods and systems for multiplex analysis |
| EP3781708B1 (en) | 2018-04-20 | 2025-01-15 | Seegene, Inc. | Method for detecting a plurality of target nucleic acid sequences in sample |
| US12203129B2 (en) | 2018-07-03 | 2025-01-21 | ChromaCode, Inc. | Formulations and signal encoding and decoding methods for massively multiplexed biochemical assays |
| EP3895170B1 (en) | 2018-12-14 | 2025-10-29 | Seegene, Inc. | Method for detecting a target analyte in a sample using an s-shaped function for a slope data set |
| AU2020256848A1 (en) * | 2020-06-30 | 2022-10-27 | Speedx Pty Ltd | Multiplex detection of nucleic acids using mixed reporters |
| CN114250275B (zh) * | 2020-09-22 | 2023-04-28 | 武汉艾米森生命科技有限公司 | 一种荧光定量pcr反应系统、pcr反应试剂盒及核酸定量检测方法 |
| CN114622000B (zh) * | 2020-12-14 | 2024-05-07 | 厦门大学 | 一种高特异性的检测靶核酸序列的方法 |
| CN112592964B (zh) * | 2020-12-17 | 2024-09-27 | 厦门大学 | 用于进行核酸多重检测的方法 |
| WO2022192758A1 (en) * | 2021-03-11 | 2022-09-15 | BioSpyder Technologies, Inc. | Tempo-span |
| KR20240058112A (ko) * | 2021-09-17 | 2024-05-03 | 주식회사 씨젠 | 합성 비자연 염기를 포함하는 태그 올리고뉴클레오타이드를 이용한 타겟 핵산 서열의 검출 |
| KR20240056605A (ko) | 2021-09-30 | 2024-04-30 | 주식회사 씨젠 | 분자진단 시스템의 샘플 처리 및 분석 방법 |
| EP4409027B1 (en) | 2021-09-30 | 2025-11-19 | Gen-Probe Incorporated | Temperature-selectable fret cassette signaling |
| EP4421814A4 (en) | 2021-10-21 | 2025-11-12 | Seegene Inc | APPROVAL AND METHOD FOR READING A POSITIVE/NEGATIVE RESULT WITH RESPECT TO A TARGET TEST SUBSTANCE IN A SAMPLE |
| CN114134219A (zh) * | 2021-12-14 | 2022-03-04 | 广州市金圻睿生物科技有限责任公司 | 一种多重核酸检测系统及其制备方法与应用 |
| CN114032337B (zh) * | 2021-12-14 | 2024-08-02 | 广州市金圻睿生物科技有限责任公司 | 一种呼吸道病原体检测试剂盒及其制备方法与应用 |
| WO2023214843A1 (ko) | 2022-05-06 | 2023-11-09 | 주식회사 씨젠 | 핵산 검출 카트리지 |
| KR20250022719A (ko) | 2022-06-15 | 2025-02-17 | 주식회사 씨젠 | 기술 문서를 생성하는 방법 및 장치 |
| EP4553489A1 (en) | 2022-07-05 | 2025-05-14 | Seegene, Inc. | Method for obtaining approximate signal for each of multiple target analytes, and computer device for performing same |
| US20250336479A1 (en) | 2022-07-29 | 2025-10-30 | Seegene, Inc | Apparatus and method for providing interface for setting threshold value of parameter |
| KR20240028084A (ko) | 2022-08-24 | 2024-03-05 | 주식회사 멀티렉스 | 표지자가 결합된 태그 프로브 및 이의 용도 |
| KR20250086619A (ko) | 2022-10-14 | 2025-06-13 | 주식회사 씨젠 | 상이한 tm 값을 가지는 2개의 프로브를 이용하여 샘플 내 타겟 핵산을 검출하는 방법 |
| WO2024085731A1 (ko) | 2022-10-20 | 2024-04-25 | 주식회사 씨젠 | 타겟 핵산 분자 검출용 시약 개발에 필요한 복수 개의 세부 성능 실험 가이딩 및 실험 결과 기록서 정리 방법 |
| EP4621068A1 (en) | 2022-11-16 | 2025-09-24 | Seegene, Inc. | Detection of target nucleic acid by quenching-pto cleavage and extension (q-ptoce) assay |
| WO2024128878A1 (ko) | 2022-12-15 | 2024-06-20 | 주식회사 씨젠 | 형광 데이터의 분석 알고리즘에 대한 성능 비교 결과를 디스플레이하는 장치 및 방법 |
| AU2024230052A1 (en) * | 2023-02-28 | 2025-08-14 | Seegene, Inc. | Detection of target nucleic acid by lpho-assisted pto cleavage and extension assay |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7381532B2 (en) * | 1999-10-29 | 2008-06-03 | Stratagene California | Compositions and methods for the detection of a nucleic acid using a cleavage reaction |
| US20080160535A1 (en) * | 1997-12-15 | 2008-07-03 | Somalogic, Inc. | Methods and Reagents for Detecting Target Binding by Nucleic Acid Ligands |
| WO2011078441A1 (en) * | 2009-12-21 | 2011-06-30 | Seegene, Inc. | Tsg primer target detection |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| US5541311A (en) | 1992-12-07 | 1996-07-30 | Third Wave Technologies, Inc. | Nucleic acid encoding synthesis-deficient thermostable DNA polymerase |
| US5538848A (en) | 1994-11-16 | 1996-07-23 | Applied Biosystems Division, Perkin-Elmer Corp. | Method for detecting nucleic acid amplification using self-quenching fluorescence probe |
| ATE414167T1 (de) | 1996-11-29 | 2008-11-15 | Third Wave Tech Inc | Fen-1 endonukleasen, gemische und spaltmethoden |
| GB9812768D0 (en) | 1998-06-13 | 1998-08-12 | Zeneca Ltd | Methods |
| US6322980B1 (en) | 1999-04-30 | 2001-11-27 | Aclara Biosciences, Inc. | Single nucleotide detection using degradation of a fluorescent sequence |
| JP4724380B2 (ja) | 1999-04-20 | 2011-07-13 | 独立行政法人産業技術総合研究所 | 核酸の測定方法に用いる核酸プローブおよびデータを解析する方法 |
| US7585632B2 (en) | 1999-10-29 | 2009-09-08 | Hologic, Inc. | Compositions and methods for the detection of a nucleic acid using a cleavage reaction |
| US6893819B1 (en) | 2000-11-21 | 2005-05-17 | Stratagene California | Methods for detection of a nucleic acid by sequential amplification |
| US7118860B2 (en) | 1999-10-29 | 2006-10-10 | Stratagene California | Methods for detection of a target nucleic acid by capture |
| AU7125401A (en) * | 2000-05-19 | 2001-12-03 | David J Marshall | Materials and methods for detection of nucleic acids |
| US7678541B2 (en) * | 2000-11-21 | 2010-03-16 | Hologic, Inc. | Methods and compositions for the detection of a nucleic acid using a non-invasive cleavage reaction |
| US7309573B2 (en) | 2000-11-21 | 2007-12-18 | Stratagene California | Methods for detection of a nucleic acid by sequential amplification |
| US9261460B2 (en) * | 2002-03-12 | 2016-02-16 | Enzo Life Sciences, Inc. | Real-time nucleic acid detection processes and compositions |
| WO2003033741A1 (en) | 2001-10-16 | 2003-04-24 | Aclara Biosciences, Inc. | Universal e-tag primer and probe compositions and methods |
| GB0205455D0 (en) | 2002-03-07 | 2002-04-24 | Molecular Sensing Plc | Nucleic acid probes, their synthesis and use |
| US8206904B2 (en) | 2002-12-18 | 2012-06-26 | Third Wave Technologies, Inc. | Detection of nucleic acids |
| WO2005010199A2 (en) | 2003-07-16 | 2005-02-03 | Geneohm Sciences, Inc. | Invasive cleavage reaction with electrochemical readout |
| US20050142595A1 (en) | 2003-11-07 | 2005-06-30 | U.S. Genomics, Inc. | Intercalator FRET donors or acceptors |
| JP4851188B2 (ja) | 2003-12-19 | 2012-01-11 | 日鉄環境エンジニアリング株式会社 | 核酸測定用新規混合物、及びそれを用いる核酸の新規測定方法並びにそれらに用いる核酸プローブ |
| CA2497324A1 (en) | 2004-02-17 | 2005-08-17 | Affymetrix, Inc. | Methods for fragmenting and labelling dna |
| US20060029954A1 (en) * | 2004-06-30 | 2006-02-09 | Applera Corporation | Compositions and methods for identifying nucleotides in polynucleotide sequences |
| WO2006004949A1 (en) | 2004-06-30 | 2006-01-12 | Applera Corporation | Compositions and methods for detecting and quantitating polynucleotide sequences |
| CA2609328A1 (en) | 2005-05-26 | 2006-11-30 | The Trustees Of Boston University | Quantification of nucleic acids and proteins using oligonucleotide mass tags |
| WO2007011946A2 (en) * | 2005-07-15 | 2007-01-25 | Applera Corporation | Detection of nucleic acid amplification |
| WO2008083261A1 (en) * | 2006-12-29 | 2008-07-10 | Applera Corporation | Systems and methods for detecting nucleic acids |
| US20080193940A1 (en) * | 2006-12-29 | 2008-08-14 | Applera Corporation, Applied Biosystems Group | Systems and methods for detecting nucleic acids |
| FI20075124A0 (fi) | 2007-02-21 | 2007-02-21 | Valtion Teknillinen | Menetelmä ja testikitti nukleotidivariaatioiden toteamiseksi |
| KR20090067334A (ko) | 2007-12-21 | 2009-06-25 | 주식회사 씨젠 | 핵산 중합효소의 뉴클레아제 활성을 이용한 타깃핵산분자의 검출방법 |
| MX2010010161A (es) | 2008-03-15 | 2011-03-21 | Hologic Inc Star | Composiciones y metodos para el analisis de moleculas de acido nucleico durante reacciones de amplificacion. |
| US9234232B2 (en) * | 2008-07-31 | 2016-01-12 | Oxitec Limited | Multiplex amplification and detection |
| CN104673888B (zh) * | 2008-08-15 | 2017-09-19 | 卡斯凯德生物体系股份有限公司 | 检测核酸 |
| GB0818355D0 (en) * | 2008-10-08 | 2008-11-12 | Smart Patents Ltd | Universal beverage container marker |
| CN102216472A (zh) | 2008-11-13 | 2011-10-12 | 里博克斯艾克斯有限公司 | Rna检测方法 |
| EP2256215A1 (en) | 2009-04-30 | 2010-12-01 | Steffen Mergemeier | Assay system using a nuclease activity of a nucleic acid polymerase |
| EP2248915B1 (en) | 2009-05-05 | 2013-09-18 | Qiagen GmbH | Detection of multiple nucleic acid sequences in a reaction cartridge |
| WO2011027966A2 (en) * | 2009-09-03 | 2011-03-10 | Seegene, Inc. | Td probe and its uses |
| EP2569449A4 (en) | 2010-05-14 | 2013-12-04 | Life Technologies Corp | IDENTIFICATION OF NUCLEIC ACIDS |
| MX352460B (es) | 2011-01-11 | 2017-11-24 | Seegene Inc | Detección de secuencias de ácido nucleico objetivo mediante ensayo de escisión y extensión del pto. |
| JP5852222B2 (ja) | 2011-03-29 | 2016-02-03 | シージーン アイエヌシー | Ｐｔｏ切断及び延長−依存的切断によるターゲット核酸配列の検出 |
| KR20130101952A (ko) | 2012-02-02 | 2013-09-16 | 주식회사 씨젠 | Ｐｔｏ 절단과 연장-의존적 혼성화를 이용한 타겟 핵산서열의 검출 |
-
2012
- 2012-03-20 KR KR1020120028429A patent/KR20130101952A/ko active Pending
- 2012-07-03 AU AU2012368436A patent/AU2012368436B2/en active Active
- 2012-07-03 EP EP12867064.3A patent/EP2809797B1/en active Active
- 2012-07-03 CN CN201610320413.7A patent/CN106011234B/zh active Active
- 2012-07-03 CA CA2862488A patent/CA2862488C/en active Active
- 2012-07-03 MX MX2014009403A patent/MX361903B/es active IP Right Grant
- 2012-07-03 KR KR1020147022148A patent/KR101832867B1/ko active Active
- 2012-07-03 BR BR112014018940-4A patent/BR112014018940B1/pt active IP Right Grant
- 2012-07-03 JP JP2014555469A patent/JP6005180B2/ja active Active
- 2012-07-03 WO PCT/KR2012/005281 patent/WO2013115442A1/en not_active Ceased
- 2012-07-03 SG SG11201404349YA patent/SG11201404349YA/en unknown
- 2012-07-03 US US14/374,567 patent/US9868980B2/en active Active
- 2012-07-03 CN CN201280071069.2A patent/CN104145029B/zh active Active
- 2012-07-03 RU RU2014133695A patent/RU2608501C2/ru active
-
2014
- 2014-07-23 IL IL233773A patent/IL233773B/en active IP Right Grant
- 2014-07-24 ZA ZA2014/05463A patent/ZA201405463B/en unknown
- 2014-07-30 NO NO20140948A patent/NO20140948A1/no not_active Application Discontinuation
-
2016
- 2016-07-13 AU AU2016204887A patent/AU2016204887B2/en active Active
-
2017
- 2017-12-27 US US15/854,891 patent/US10731203B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080160535A1 (en) * | 1997-12-15 | 2008-07-03 | Somalogic, Inc. | Methods and Reagents for Detecting Target Binding by Nucleic Acid Ligands |
| US7381532B2 (en) * | 1999-10-29 | 2008-06-03 | Stratagene California | Compositions and methods for the detection of a nucleic acid using a cleavage reaction |
| WO2011078441A1 (en) * | 2009-12-21 | 2011-06-30 | Seegene, Inc. | Tsg primer target detection |
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