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1. 发明申请

WO2004072297A2 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：WO2004072297A2
公开(公告)日：2004-08-26
申请号：PCT/US2004/002785
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： C12Q
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记。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。

2. 发明申请

WO2004072238A2 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：WO2004072238A2
公开(公告)日：2004-08-26
申请号：PCT/US2004/003284
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： C12N
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。

3. 发明申请

WO2005108994A1 FLUORESCENCE RESONANCE ENERGY TRANSFER ENZYME SUBSTRATES 审中-公开
标题翻译：荧光共振能量转移酶基质
公开(公告)号：WO2005108994A1
公开(公告)日：2005-11-17
申请号：PCT/US2005/013141
申请日：2005-04-18
申请人： AMERSHAM BIOSCIENCES CORP , KUMAR, Shiv , SOOD, Anup
发明人： KUMAR, Shiv , SOOD, Anup
IPC分类号： G01N33/542
CPC分类号： G01N33/542 , C12Q1/34
摘要： Disclosed are compounds of formula (I) wherein D 1 is a first dye moiety whose fluorescence properties may be modulated so as to be suitable as a donor or an acceptor in an energy transfer arrangement; D 2 is a second dye moiety suitable as an acceptor or a donor in an energy transfer arrangement with said first dye; L is a linking group comprises 2-200 linked atoms, wherein said linking group optionally includes an enzyme cleavage site; and M is an enzyme cleavable group chosen to modulate the fluorescence properties of D 1 . The compounds of formula (I) may be used as reporter molecules for detecting biochemical cleavage events in assays that employ fluorescence resonance energy transfer.
摘要翻译：公开了式（I）的化合物，其中D 1是第一染料部分，其荧光性质可以被调节以适合作为能量转移装置中的给体或受体; D 2是与所述第一种染料在能量转移布置中适合作为受体或供体的第二染料部分; L是包含2-200个连接原子的连接基团，其中所述连接基团任选地包括酶切割位点; M是选择调节D 1荧光性质的酶切割基团。式（I）的化合物可以用作用于检测采用荧光共振能量转移的测定中生化裂解事件的报道分子。

4. 发明申请

WO2004071155A3 SOLID PHASE SEQUENCING 审中-公开
公开(公告)号：WO2004071155A3
公开(公告)日：2004-08-26
申请号：PCT/US2004/003283
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： C12Q1/68
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.

5. 发明公开

EP0650490A1 BORONATED PHOSPHORAMIDATE COMPOUNDS 失效
标题翻译：硼化磷酸酯CONNECTIONS。
公开(公告)号：EP0650490A1
公开(公告)日：1995-05-03
申请号：EP93916854.0
申请日：1993-06-29
申请人： SPIELVOGEL, Bernard F. , SOOD, Anup
发明人： SPIELVOGEL, Bernard F. , SOOD, Anup
IPC分类号： C07F9 , C07H19 , C07H21 , C07H23
CPC分类号： C07H19/04 , C07F9/6596 , C07H21/00 , C07H23/00
摘要： A class of pharmaceutically active boronated compounds are provided. The boronated compounds include boronated phosphoramidates, and boronated nucleosides, and oligomers thereof. The compounds are boronated by an aminoalkyl substituted polyborane, carborane, metallopolyborane or metallocarborane.

6. 发明申请

WO2009124099A1 ITERATIVE STAINING OF BIOLOGICAL SAMPLES 审中-公开
标题翻译：生物样本的迭代染色
公开(公告)号：WO2009124099A1
公开(公告)日：2009-10-08
申请号：PCT/US2009/039052
申请日：2009-04-01
申请人： GENERAL ELECTRIC COMPANY , XIE, Jun , GINTY, Fiona , FILKINS, Robert, John , MONTALTO, Michael, Christopher , SOOD, Anup , FORTIN, Jeffrey, Bernard , TIAN, Wei-cheng , GERDES, Michael, J.
发明人： XIE, Jun , GINTY, Fiona , FILKINS, Robert, John , MONTALTO, Michael, Christopher , SOOD, Anup , FORTIN, Jeffrey, Bernard , TIAN, Wei-cheng , GERDES, Michael, J.
IPC分类号： G01N1/10 , B01L11/00
CPC分类号： G01N1/312
摘要： Automated methods and devices that facilitate iterative staining of biological samples from imaging applications are provided. The methods include the steps of providing a small volume flow cell containing a biological sample, applying a stain to the biological sample, combining at least two precursor reagents to form an activated destaining agent and wherein the activated destaining agent decomposition rate is greater than or similar to the destaining reaction rate, and flowing the destaining agent over the biological sample at a flow rate that is greater than the decomposition rate of the activated destaining agent. The process of staining, combining and flowing may be iteratively repeated. Also disclosed herein are devices for iterative staining of biological samples comprising a flow cell, in fluid communication with a premixer, wherein the volume capacity of the premixer is smaller than about five times the volume capacity of the flow cell.
摘要翻译：提供了促进成像应用中生物样品的迭代染色的自动化方法和装置。所述方法包括以下步骤：提供含有生物样品的小体积流动池，向生物样品施加染色，将至少两种前体试剂结合以形成活化的脱色剂，并且其中所述活化脱色剂分解速率大于或等于与脱色反应速率相关联，并使脱色剂以大于活化脱色剂分解速率的流速流过生物样品。染色，组合和流动的过程可以迭代地重复。本文还公开了用于对包含与预混合器流体连通的流动池的生物样品的迭代染色的装置，其中预混合器的体积容量小于流动池的体积容积的约五倍。

7. 发明申请

WO2008064067A2 SEQUENTIAL ANALYSIS OF BIOLOGICAL SAMPLES 审中-公开
标题翻译：生物样品的序列分析
公开(公告)号：WO2008064067A2
公开(公告)日：2008-05-29
申请号：PCT/US2007/084800
申请日：2007-11-15
申请人： GENERAL ELECTRIC COMPANY , 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
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灭活荧光探针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本中的多个目标的信息。还提供了相关的套件。

8. 发明申请

WO2012038489A1 VASCULAR IMAGING AGENTS 审中-公开
标题翻译：血管成像剂
公开(公告)号：WO2012038489A1
公开(公告)日：2012-03-29
申请号：PCT/EP2011/066464
申请日：2011-09-21
申请人： GE HEALTHCARE AS , HEALEY, Andrew , BENDIKSEN, Ragnar , SOOD, Anup , BALINOV, Balin
发明人： HEALEY, Andrew , BENDIKSEN, Ragnar , SOOD, Anup , BALINOV, Balin
IPC分类号： A61K49/00
CPC分类号： A61K49/006 , A61B5/0073 , A61K49/0032 , A61K49/0054
摘要： The present invention relates to a method of in vivo optical imaging, of the blood vessels and/or blood pool of a mammalian subject, which comprises an optical imaging contrast agent. The optical imaging agents comprise conjugates of far-red or near-infrared dyes with synthetic polyethyleneglycol (PEG) polymers having a molecular weight in the range 15-45 kDa. Also disclosed are methods of treatment monitoring, methods of diagnosis and medical uses involving the contrast agents.
摘要翻译：本发明涉及哺乳动物受试者的体内光学成像，血管和/或血液池的方法，其包括光学成像造影剂。光学成像剂包括远红或近红外染料与分子量在15-45kDa范围内的合成聚乙二醇（PEG）聚合物的共轭物。还公开了治疗监测方法，诊断方法和涉及造影剂的医疗用途。

9. 发明申请

WO2011048184A1 DETECTION OF PLURALITY OF TARGETS IN BIOLOGICAL SAMPLES 审中-公开
标题翻译：检测目标在生物样本中的多样性
公开(公告)号：WO2011048184A1
公开(公告)日：2011-04-28
申请号：PCT/EP2010/065876
申请日：2010-10-21
申请人： GENERAL ELECTRIC COMPANY , GE HEALTHCARE UK LIMITED , SOOD, Anup , NELSON, John Richard , GERDES, Michael
发明人： SOOD, Anup , NELSON, John Richard , GERDES, Michael
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6816 , C12Q2600/158 , C12Q2545/101 , C12Q2537/143
摘要： Methods for detecting a plurality of targets in a biological sample are provided. The method comprises contacting the biological sample with a plurality of target-binding probes to form a plurality of target-bound probes, covalently attaching at least one of the target-bound probes to the biological sample, and observing the signals from the target-bound probes sequentially. An associated kit and device for detection of the plurality of targets 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。该方法包括使生物样品与多个靶结合探针接触以形成多个靶结合探针，将至少一个目标结合探针共价连接至生物样品，并观察来自靶标结合的信号顺序探测。还提供了用于检测多个靶的相关联的试剂盒和装置。

10. 发明申请

WO2008133729A2 SEQUENTIAL ANALYSIS OF BIOLOGICAL SAMPLES 审中-公开
标题翻译：生物样品的序列分析
公开(公告)号：WO2008133729A2
公开(公告)日：2008-11-06
申请号：PCT/US2007/084791
申请日：2007-11-15
申请人： GENERAL ELECTRIC COMPANY , 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
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。

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