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1. 发明申请

WO2004072238A3 TERMINAL-PHOSPHATE-LABELED NUCLEOTIDES WITH NEW LINKERS 审中-公开
标题翻译：带有新连接器的终端磷酸酯标记的核苷酸
公开(公告)号：WO2004072238A3
公开(公告)日：2006-05-18
申请号：PCT/US2004003284
申请日：2004-02-05
申请人： AMERSHAM BIOSCIENCES CORP , KUMAR SHIV , MCDOUGALL MARK , SOOD ANUP , NELSON JOHN , FULLER CARL , MACKLIN JOHN , MITSIS PAUL
发明人： KUMAR SHIV , MCDOUGALL MARK , SOOD ANUP , NELSON JOHN , FULLER CARL , MACKLIN JOHN , MITSIS PAUL
IPC分类号： C12Q1/68 , C12N20060101 , C12N1/00 , C12N9/00 , C12N9/22 , C12P19/34
CPC分类号： C07H19/10 , C07H19/20 , C07H21/00 , C12P19/34
摘要： The present invention describes methods of using terminal-phosphate-labeled nucleotides in the presence of a manganese salt to enhance their substrate properties towards various enzymes. Particularly described are methods of detecting a nucleic acid in a sample, based on the use of terminal-phosphate-labeled nucleotides as substrates for nucleic acid polymerases, in the presence of a manganese salt. Further provided are manganese complexes of terminal-phosphate-labeled nucleotides as well as terminal-phosphate-labeled nucleotides with new linkers with enhanced substrate properties.
摘要翻译：本发明描述了在锰盐存在下使用末端磷酸酯标记的核苷酸以增强其对各种酶的底物性质的方法。特别描述的是在锰盐存在的情况下，基于使用末端磷酸酯标记的核苷酸作为核酸聚合酶的底物，检测样品中的核酸的方法。还提供了末端磷酸酯标记的核苷酸的锰络合物以及具有增强的底物性质的新接头的末端磷酸酯标记的核苷酸。

2. 发明申请

WO2004072297A3 TERMINAL-PHOSPHATE-LABELED NUCLEOTIDES AND METHODS OF USE 审中-公开
标题翻译：终端磷酸酯标记的核苷酸和使用方法
公开(公告)号：WO2004072297A3
公开(公告)日：2007-01-18
申请号：PCT/US2004002785
申请日：2004-01-30
申请人： AMERSHAM BIOSCIENCES CORP , FULLER CARL , KUMAR SHIV , SOOD ANUP , NELSON JOHN
发明人： FULLER CARL , KUMAR SHIV , SOOD ANUP , NELSON JOHN
IPC分类号： C12Q1/68 , C07H19/10 , C07H19/20 , C07H21/00 , C12Q20060101 , C12Q1/00 , C12Q1/42 , G01N33/52 , G01N33/58
CPC分类号： C12Q1/6823 , C07H19/10 , C07H19/20 , C07H21/00 , C12Q1/6816 , C12Q1/6851 , C12Q2521/525
摘要： The present invention relates to improved methods of detecting a target using a labeled substrate or substrate analog. The methods comprise reacting the substrate or substrate analog in an enzyme-catalyzed reaction which produces a labeled moiety with independently detectable signal only when such substrate or substrate analog reacts. The present invention, in particular, describes methods of detecting a nucleic acid in a sample, based on the use of terminal-phosphate-labeled nucleotides as substrate for nucleic acid polymerases. The methods provided by this invention utilize a nucleoside polyphosphate, dideoxynucleoside polyphosphate, or deoxynucleoside polyphosphate analogue which has a colorimetric dye, chemiluminescent, or fluorescent moiety, a mass tag or an electrochemical tag attached to the terminal-phosphate. When a nucleic acid polymerase uses this analogue as a substrate, an enzyme-activatable label would be present on the inorganic polyphosphate by-product of phosphoryl transfer. Cleavage of the polyphosphate product of phosphoryl transfer via phosphatase leads to a detectable change in the label attached thereon. When the polymerase assay is performed in the presence of a phosphatase, there is provided a convenient method for real-time monitoring of DNA or RNA synthesis and detection of a target nucleic acid.
摘要翻译：本发明涉及使用标记的底物或底物类似物检测靶的改进方法。所述方法包括在酶催化的反应中使底物或底物类似物反应，其仅在这种底物或底物类似物反应时产生具有独立可检测信号的标记部分。本发明特别地描述了基于使用末端磷酸酯标记的核苷酸作为核酸聚合酶的底物来检测样品中核酸的方法。本发明提供的方法利用了具有比色染料，化学发光或荧光部分的核苷多磷酸，双脱氧核苷多聚磷酸酯或脱氧核苷多聚磷酸酯类似物，连接至末端磷酸酯的质量标签或电化学标签。当核酸聚合酶使用该类似物作为底物时，酶活性标记将存在于磷酸转移的无机多磷酸盐副产物上。通过磷酸酶切割磷酸转移的多磷酸盐产物导致附着在其上的标记物的可检测的变化。当在磷酸酶的存在下进行聚合酶测定时，提供了用于实时监测DNA或RNA合成和检测靶核酸的方便的方法。

3. 发明申请

WO2004071155A2 SOLID PHASE SEQUENCING 审中-公开
标题翻译：固相序列
公开(公告)号：WO2004071155A2
公开(公告)日：2004-08-26
申请号：PCT/US2004003283
申请日：2004-02-05
申请人： AMERSHAM BIOSCIENCES CORP , SOOD ANUP , KUMAR SHIV , NELSON JOHN , FULLER CARL
发明人： SOOD ANUP , KUMAR SHIV , NELSON JOHN , FULLER CARL
IPC分类号： C12P19/34 , C12Q1/68 , G01R29/18
CPC分类号： C12Q1/6858 , C12Q1/6874 , C12Q2565/537 , C12Q2535/125 , C12Q2521/525 , C12Q2525/101
摘要： The present invention describes methods of sequencing a nucleic acid in a sample, based on the use of terminal-phosphate-labeled nucleotides as substrates for nucleic acid polymerases. The methods provided by this invention utilize a nucleoside polyphosphate, dideoxynucleoside polyphosphate, or deoxynucleoside polyphosphate analogue which has a colorimetric dye, chemiluminescent, or fluorescent moiety, a mass tag or an electrochemical tag attached to the terminal-phosphate. When a nucleic acid polymerase uses this analogue as a substrate, an enzyme-activatable label would be present on the inorganic polyphosphate by-product of phosphoryl transfer. Cleavage of the polyphosphate product of phosphoryl transfer via phosphatase leads to a detectable change in the label attached thereon. In some instances the labeled polyphosphate may be detected directly via the label and provide information on the nucleic acid. When the polymerase assay is performed in the presence of a phosphatase, there is provided a convenient method for real-time monitoring of DNA or RNA synthesis and characterization of a target nucleic acid.
摘要翻译：本发明描述了基于使用末端磷酸酯标记的核苷酸作为核酸聚合酶的底物来测序样品中核酸的方法。本发明提供的方法利用具有比色染料，化学发光或荧光部分的核苷多磷酸，双脱氧核苷多磷酸酯或脱氧核苷多聚磷酸酯类似物，连接至末端磷酸酯的质量标签或电化学标签。当核酸聚合酶使用该类似物作为底物时，酶活性标记将存在于磷酸转移的无机多磷酸盐副产物上。通过磷酸酶切割磷酸转移的多磷酸盐产物导致附着在其上的标记物的可检测的变化。在一些情况下，标记的多磷酸盐可以通过标记物直接检测并提供关于核酸的信息。当在磷酸酶存在下进行聚合酶测定时，提供了用于实时监测DNA或RNA合成和靶核酸表征的方便的方法。

4. 发明申请

WO2008133729A3 SEQUENTIAL ANALYSIS OF BIOLOGICAL SAMPLES WITH INTERMEDIATE BLEACHING OF FLUORESCENCE DETECTOR 审中-公开
标题翻译：生物样品的序贯分析与荧光检测器的中间漂白
公开(公告)号：WO2008133729A3
公开(公告)日：2009-01-08
申请号：PCT/US2007084791
申请日：2007-11-15
申请人： GEN ELECTRIC , SOOD ANUP , GERDES MICHAEL J , PANG ZHENGYU , GINTY FIONA , MONTALTO MICHAEL CHRISTOPHER , LARSEN MELINDA
发明人： SOOD ANUP , GERDES MICHAEL J , PANG ZHENGYU , GINTY FIONA , MONTALTO MICHAEL CHRISTOPHER , LARSEN MELINDA
IPC分类号： G01N33/68 , C12Q1/68
CPC分类号： G01N33/53 , C12Q1/68 , G01N33/542 , G01N33/582 , Y10T436/143333
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets adhered to a solid support, binding at least one fluorescent probe to one or more target present in the sample, and observing a signal from the fluorescent probe. The method further includes the steps of oxidizing the bound fluorescent probe with a solution containing an oxidizing agent that substantially inactivates the fluorescent probe, binding at least one fluorescent probe to one or more target present in the sample, and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探测生物样品中多个靶标的方法。所述方法包括以下步骤：提供包含粘附到固体支持物上的多个靶的生物样品，将至少一个荧光探针结合到样品中存在的一个或多个靶，并观察来自荧光探针的信号。所述方法还包括以下步骤：用含有基本上灭活荧光探针的氧化剂的溶液氧化结合的荧光探针，将至少一种荧光探针结合到样品中存在的一种或多种靶，并观察来自荧光探针的信号。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件。

5. 发明申请

WO2008064067A3 METHOD FOR THE SEQUENTIAL ANALYSIS OF DIFFERENT COMPONENTS IN A SINGLE BIOLOGICAL SAMPLE AND REAGENTS THEREFOR 审中-公开
标题翻译：单一生物样品和试剂中不同成分的顺序分析方法
公开(公告)号：WO2008064067A3
公开(公告)日：2008-07-10
申请号：PCT/US2007084800
申请日：2007-11-15
申请人： GEN ELECTRIC , PANG ZHENGYU , FILKINS ROBERT JOHN , MONTALTO MICHAEL CHRISTOPHER , GINTY FIONA , GERDES MICHAEL J , CAN ALI , BRESNAHAN MAUREEN ANN , SOOD ANUP
发明人： PANG ZHENGYU , FILKINS ROBERT JOHN , MONTALTO MICHAEL CHRISTOPHER , GINTY FIONA , GERDES MICHAEL J , CAN ALI , BRESNAHAN MAUREEN ANN , SOOD ANUP
IPC分类号： G01N33/50 , C12Q1/68
CPC分类号： G01N33/582 , C12Q1/6816 , G01N33/542 , C12Q2545/101 , C12Q2527/125
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets, binding at least one fluorescent probe to one or more target present in the sample, and binding at least at least one control probe to one or more target present in the sample. The methods include the steps of observing a signal from the fluorescent probe and a control signal from the control probe and applying to the sample a basic solution containing an oxidizing agent that selectively inactivates the fluorescent probe and not the control probe. The methods further include the steps of binding at least one fluorescent probe to one or more target present in the sample and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探索生物样品中多个靶标的方法。所述方法包括以下步骤：提供含有多个靶标的生物样品，将至少一种荧光探针结合至样品中存在的一种或多种靶标，以及将至少一种对照探针结合至样品中存在的一种或多种靶标。所述方法包括以下步骤：观察来自荧光探针的信号和来自对照探针的控制信号，并向样品施加含有选择性地使荧光探针失活而不是对照探针的氧化剂的碱性溶液。所述方法还包括将至少一种荧光探针结合到样品中存在的一种或多种目标物并观察来自荧光探针的信号的步骤。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样品中的多个靶的信息。还提供了相关的套件。

6. 发明申请

WO2010094698A2 SWITCHABLE AFFINITY BINDERS 审中-公开
标题翻译：可切换的亲和力绑定
公开(公告)号：WO2010094698A2
公开(公告)日：2010-08-26
申请号：PCT/EP2010051967
申请日：2010-02-17
申请人： GEN ELECTRIC , GE HEALTHCARE UK LTD , SOOD ANUP , DULGAR-TULLOCH AARON , KOVACS ERNEST WILLIAM , LOGHIN EVELINA ROXANA
发明人： SOOD ANUP , DULGAR-TULLOCH AARON , KOVACS ERNEST WILLIAM , LOGHIN EVELINA ROXANA
IPC分类号： C12N5/00 , A61K47/48
CPC分类号： G01N33/5375 , C12N2539/10 , G01N33/54333
摘要： Methods and kits for binding and releasing biological targets, comprising, a binder comprising an environmentally reactive molecular switch that can switch between a high affinity state, to bind the target, to a low affinity state, to release the target.
摘要翻译：用于结合和释放生物靶标的方法和试剂盒，其包含包含环境反应性分子开关的结合剂，所述结合剂可以在高亲和力状态之间切换，以将靶标结合至低亲和力状态，以释放靶标。

7. 发明申请

WO2004020604A3 ALLELE SPECIFIC PRIMER EXTENSION 审中-公开
标题翻译： ALLELE特定的PRIMER扩展
公开(公告)号：WO2004020604A3
公开(公告)日：2004-08-12
申请号：PCT/US0327286
申请日：2003-08-29
申请人： AMERSHAM BIOSCIENCES CORP
发明人： SOOD ANUP , KUMAR SHIV , FULLER CARL , NELSON JOHN , MACKLIN JOHN
IPC分类号： C12N15/09 , C12Q1/42 , C12Q1/44 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6869 , C12Q1/6823 , C12Q2600/156 , C12Q2535/125 , C12Q2525/125 , C12Q2521/125 , C12Q2565/301 , C12Q2525/101
摘要： A method of characterizing a nucleic acid sample is provided that includes the steps of: (a) conducting a DNA polymerase reaction that includes the reaction of a template, an allele specific primer, at least one terminal phosphate-labeled nucleotide, DNA polymerase, and optionally an enzyme having 3' ? 5' exonuclease activity when the primer is non-hydrolyzable, which reaction results in the production of labeled polyphosphate; (b) permitting the labeled polyphosphate to react with a phosphatase to produce a detectable species; (c) detecting the detectable species; and (d) characterizing the nucleic acid sample based on such detection.
摘要翻译：提供了表征核酸样品的方法，其包括以下步骤：（a）进行DNA聚合酶反应，其包括模板，等位基因特异性引物，至少一个末端磷酸酯标记的核苷酸，DNA聚合酶和任选地具有3' 5'核酸外切酶活性，该反应导致标记多磷酸盐的产生; （b）允许标记的多磷酸酯与磷酸酶反应以产生可检测的物质; （c）检测可检测物种; 和（d）基于这种检测来表征核酸样品。

8. 发明申请

WO2004020602A3 TERMINAL PHOSPHATE BLOCKED NUCLEOSIDE POLYPHOSPHATES 审中-公开
标题翻译：磷酸盐封闭的核苷酸多磷酸盐
公开(公告)号：WO2004020602A3
公开(公告)日：2004-05-13
申请号：PCT/US0327284
申请日：2003-08-29
申请人： AMERSHAM BIOSCIENCES CORP
发明人： SOOD ANUP , KUMAR SHIV , FULLER CARL , NELSON JOHN
IPC分类号： C12N15/09 , C07H21/00 , C07H21/02 , C07H21/04 , C12N20060101 , C12P19/34 , C12Q1/68
CPC分类号： C12Q1/686 , C12Q2525/186 , C12Q2531/119
摘要： The present invention describes terminal phosphate blocked nucleoside polyphosphates that are stable at high temperature and their use in nucleic acid amplification and analysis. Current invention further describes charge modified terminal phosphate blocked nucleoside polyphosphates for improved incorporation and direct loading of nucleic acid sequencing reactions onto separating media.
摘要翻译：本发明描述了在高温下稳定的末端磷酸封端的核苷多磷酸盐及其在核酸扩增和分析中的用途。本发明进一步描述了电荷修饰的末端磷酸封端的核苷多磷酸酯，用于改善引入并将核酸测序反应直接加载到分离介质上。

9. 发明申请

WO2008133728A3 SEQUENTIAL ANALYSIS OF BIOLOGICAL SAMPLES WITH INTERMEDIATE BLEACHING OF FLUORESCENCE DETECTOR 审中-公开
标题翻译：生物样品的序贯分析与荧光检测器的中间漂白
公开(公告)号：WO2008133728A3
公开(公告)日：2009-01-22
申请号：PCT/US2007084786
申请日：2007-11-15
申请人： GEN ELECTRIC , SOOD ANUP , GERDES MICHAEL J , TREYNOR THOMAS PIRRIE , PANG ZHENGYU
发明人： SOOD ANUP , GERDES MICHAEL J , TREYNOR THOMAS PIRRIE , PANG ZHENGYU
IPC分类号： G01N33/68 , C12Q1/68
CPC分类号： G01N33/581 , G01N33/6803
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a sample containing multiple targets, binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample, and reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator. The methods include the steps of observing a signal from the fluorescent signal generator and applying to the sample a solution containing an oxidizing agent that substantially inactivates both the fluorescent signal generator and the enzyme. The methods further include the steps of binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample of step, reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator; and observing a signal from the fluorescent signal generator. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探测生物样品中多个靶标的方法。所述方法包括以下步骤：提供含有多个靶标的样品，将至少一种具有与酶偶联的结合剂的探针结合至样品中存在的一种或多种靶标，以及使结合的探针与偶联于荧光信号发生器。所述方法包括以下步骤：观察来自荧光信号发生器的信号，并向样品施加含有基本上灭活荧光信号发生器和酶的氧化剂的溶液。所述方法还包括以下步骤：将具有与酶偶联的粘合剂的至少一种探针与步骤样品中存在的一种或多种靶结合，使结合的探针与耦合到荧光信号发生器的酶底物反应; 并观察来自荧光信号发生器的信号。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件。

10. 发明申请

WO2008133727A3 SEQUENTIAL ANALYSIS OF BIOLOGICAL SAMPLES WITH BLEACHING OF INTERMEDIATE FLUORESCENT SIGNALS 审中-公开
标题翻译：中间荧光信号漂白生物样品的顺序分析
公开(公告)号：WO2008133727A3
公开(公告)日：2009-01-22
申请号：PCT/US2007084783
申请日：2007-11-15
申请人： GEN ELECTRIC , FILKINS ROBERT JOHN , MONTALTO MICHAEL CHRISTOPHER , SOOD ANUP , GERDES MICHAEL J , SEEL MAXIMILIAN LEWIS
发明人： FILKINS ROBERT JOHN , MONTALTO MICHAEL CHRISTOPHER , SOOD ANUP , GERDES MICHAEL J , SEEL MAXIMILIAN LEWIS
IPC分类号： G01N33/542
CPC分类号： G01N33/53 , C12Q1/68 , G01N33/542 , G01N33/582 , Y10T436/143333
摘要： Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.
摘要翻译：提供了用于检测生物样品中多个靶的方法。所述方法包括使样品与第一探针接触; 将第一探针物理地绑定到第一靶; 观察来自第一探针的第一信号; 施用化学试剂来修饰第一信号; 使样品与第二探针接触; 将第二探针物理地绑定到第二靶上; 并观察来自第二探测器的第二信号。本文公开的方法还提供绑定，观察，信号修改的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件和设备。

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