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1. 发明授权

US5783453A Non-separation specific binding chemiluminescent assay 失效
标题翻译：非分离特异性结合化学发光测定
公开(公告)号：US5783453A
公开(公告)日：1998-07-21
申请号：US496549
申请日：1995-06-29
申请人： Eve H. Barlow , Eddie Carroll, III , Joseph E. Connolly , Michael J. Lee , Richard A. Martinelli , John T. Unger
发明人： Eve H. Barlow , Eddie Carroll, III , Joseph E. Connolly , Michael J. Lee , Richard A. Martinelli , John T. Unger
IPC分类号： G01N33/542 , G01N33/543 , G01N33/58 , C12G1/00 , G01N33/551 , G01N33/553
CPC分类号： G01N33/542 , G01N33/582
摘要： The assay described herein is predicated on an observation that when acridinium ester labeled tracers are bound to their corresponding binding conjugate immobilized on a metal oxide solid phase, the measurable chemiluminescent light emission of the labeled tracer bound to the solid phase is quenched as compared to the free fraction tracer that is unattached to the solid phase. According to the invention, a non-separation specific binding assay to detect or quantify the presence of an analyte is provided where the entire reaction mixture is flashed (including unreacted tracer) and modulated signal (because of the quench effect) is associated with a reference, thus determining the amount or presence of said analyte in said sample. Disadvantages inherent in heterogeneous assays employing multiple separations may be avoided using this non-separation method.
摘要翻译：本文所述的测定是基于以下观察结果：当吖啶酯标记的示踪剂与其固定在金属氧化物固相上的相应结合缀合物结合时，与固相结合的标记示踪剂的可测量化学发光光发射与与固相无关的游离级分示踪剂。根据本发明，提供了检测或定量分析物存在的非分离特异性结合测定法，其中整个反应混合物闪蒸（包括未反应的示踪剂）和调制信号（由于骤冷作用）与参考文献相关联，从而确定所述样品中所述分析物的量或存在。使用这种非分离方法可以避免使用多次分离的异质测定中固有的缺点。

2. 发明授权

US06083689A Sensitive immunoassays utilizing antibody conjugates with replicable DNA templates 失效
标题翻译：使用具有可复制DNA模板的抗体缀合物的敏感免疫测定
公开(公告)号：US06083689A
公开(公告)日：2000-07-04
申请号：US416571
申请日：1995-04-04
申请人： Richard A. Martinelli , Eddie Carroll, III
发明人： Richard A. Martinelli , Eddie Carroll, III
IPC分类号： G01N33/532 , C12Q1/48 , C12Q1/68 , G01N33/543 , G01N33/58 , G01N33/53 , G01N33/536
CPC分类号： G01N33/581 , C12Q1/6804 , C12Q1/682 , Y10S435/971 , Y10S435/973 , Y10S436/824 , Y10S436/828
摘要： A novel signal amplification system for immunoassays that minimizes non-specific signals is disclosed. Immunoassay methods, reagents and test kits are described for obtaining immunoassays of enhanced sensitivity. The reagents include antibody-variant DNA conjugates, wherein the variant DNA is a substrate for an RNA-dependent RNA polymerase, such as, QB replicase. Immunoassay methods to detect, or to detect and quantitate, analyte in test samples comprise transcribing the variant DNA of said antibody-DNA conjugates that are bound to analyte, to RNA, and replicating the RNA transcripts, wherein the presence or quantity of variant RNA replication products can be correlated with the presence or quantity of analyte in the test samples. Further, methods are provided to detect, or to detect and quantitate, simultaneously two or more analytes in a test sample.
摘要翻译：公开了一种用于使非特异性信号最小化的免疫测定的新型信号放大系统。描述了用于获得增强灵敏度的免疫测定的免疫测定方法，试剂和测试试剂盒。试剂包括抗体变体DNA缀合物，其中变体DNA是用于RNA依赖性RNA聚合酶的底物，例如QB复制酶。用于检测或定量测试样品中的分析物的免疫测定方法包括将与分析物结合的所述抗体-DNA缀合物的变体DNA转录成RNA并复制RNA转录物，其中变体RNA复制物的存在或数量产品可以与测试样品中分析物的存在或数量相关联。此外，提供了用于同时检测或定量测试样品中两种或更多种分析物的方法。

3. 发明授权

US5705338A Reduction of background in noncompetitive binding assays 失效
标题翻译：减少非竞争性结合测定中的背景
公开(公告)号：US5705338A
公开(公告)日：1998-01-06
申请号：US434743
申请日：1995-05-04
申请人： Uri Piran , Laurie Ann Livshin , Richard A. Martinelli , William J. Riordan , John T. Unger
发明人： Uri Piran , Laurie Ann Livshin , Richard A. Martinelli , William J. Riordan , John T. Unger
IPC分类号： C12Q1/68 , G01N33/00 , G01N33/543 , G01N33/53 , G01N33/547
CPC分类号： C12Q1/6813 , C12Q1/6834 , G01N33/54306 , G01N2033/008
摘要： Novel non-competitive assay techniques have been developed which not only improve sensitivity, but also are convenient and less susceptible to interfering factors. They are compatible with existing instruments and can be run in one or more test tubes. The analyte is reacted with labeled specific binder, after which the mixture is reacted with (1) an insoluble material attached to an analyte derivative and (2) a solid phase carrying a binder. The solid phase is then separated, and the label attached to the solid phase is measured. Variations of the procedure include the use of a reversible bridge for attaching the insoluble material to the analyte mimic and the conduct of the assay in various porous media, such as paper, chromatographic and electrophoretic media, and dipsticks.
摘要翻译：已经开发了新的非竞争性测定技术，其不仅提高灵敏度，而且方便且不易受干扰因素的影响。它们与现有仪器兼容，可以在一个或多个试管中运行。分析物与标记的特异性粘合剂反应，之后混合物与（1）与分析物衍生物连接的不溶性物质和（2）携带粘合剂的固相反应。然后分离固相，测量附着于固相的标记。方法的变化包括使用可逆桥接器将不溶性物质连接到分析物模拟物上，以及在各种多孔介质如纸张，色谱和电泳介质以及浸渍条中进行测定。

4. 发明授权

US5959095A Amplification of midivariant DNA templates 失效
公开(公告)号：US5959095A
公开(公告)日：1999-09-28
申请号：US352670
申请日：1994-12-09
申请人： Richard A. Martinelli , Jeffrey J. Donahue , John T. Unger
发明人： Richard A. Martinelli , Jeffrey J. Donahue , John T. Unger
IPC分类号： C07H21/04 , C12N15/09 , C12Q1/68 , C12P19/34 , C12Q1/70
CPC分类号： C12Q1/682 , C12Q1/6867
摘要： New methods are provided for the amplification of a midivariant DNA containing an inserted target specific nucleic acid sequence(s) to enable detection of the presence of a target nucleic acid sequence in a test sample. One method employs midivariant DNA as a template for the synthesis of RNA catalyzed by QB replicase. Two midivariant DNA/probe conjugates including a nonreplicable portion of midivariant DNA and a target specific nucleic acid sequence (probe) are described. An amplification method including the steps of hybridization and ligation of the midivariant DNA/probe conjugates followed by replication of the DNA template has enabled detection of less than 200 template molecules. In a modified amplification method one of the midivariant DNA/probe conjugates further includes a RNA polymerase promoter sequence to enable transcription of the midivariant DNA template into RNA. The sequential ligation-transcription-replication method enables the detection of a single template molecule. The detectable molecule(s) are indicative of the presence of the target nucleic acid sequences in the test sample.

5. 发明授权

US5407798A Amplification of midivariant DNA templates 失效
标题翻译：多变量DNA模板的扩增
公开(公告)号：US5407798A
公开(公告)日：1995-04-18
申请号：US15249
申请日：1993-02-05
申请人： Richard A. Martinelli , Jeffrey J. Donahue , John T. Unger
发明人： Richard A. Martinelli , Jeffrey J. Donahue , John T. Unger
IPC分类号： C07H21/04 , C12N15/09 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/682 , C12Q1/6867
摘要： New methods are provided for the amplification of a midivariant DNA containing an inserted target specific nucleic acid sequence(s) to enable detection of the presence of a target nucleic acid sequence in a test sample. One method employs midivariant DNA as a template for the synthesis of RNA catalyzed by QB replicase. Two midivariant DNA/probe conjugates including a nonreplicable portion of midivariant DNA and a target specific nucleic acid sequence (probe) are described. An amplification method including the steps of hybridization and ligation of the midivariant DNA/probe conjugates followed by replication of the DNA template has enabled detection of less than 200 template molecules. In a modified amplification method one of the midivariant DNA/probe conjugates further includes a RNA polymerase promoter sequence to enable transcription of the midivariant DNA template into RNA. The sequential ligation-transcription-replication method enables the detection of a single template molecule. The detectable molecule(s) are indicative of the presence of the target nucleic acid sequences in the test sample.
摘要翻译：提供了用于扩增含有插入的靶特异性核酸序列的多变性DNA的新方法，以便能够检测测试样品中靶核酸序列的存在。一种方法采用半变体DNA作为模板，用于合成由QB复制酶催化的RNA。描述了包括不可复制部分的变形DNA和靶特异性核酸序列（探针）的两个变异型DNA /探针缀合物。包括以下步骤的扩增方法，其中杂交和连接半变异DNA /探针缀合物，随后DNA模板的复制使得能够检测到少于200个模板分子。在修饰的扩增方法中，其中一个变体DNA /探针结合物进一步包括RNA聚合酶启动子序列，以使得能够将该变体DNA模板转录成RNA。顺序连接 - 转录复制方法能够检测单个模板分子。可检测分子指示测试样品中靶核酸序列的存在。

6. 发明授权

US6090589A Nucleic acid amplification with DNA-dependent RNA polymerase activity of RNA replicases 失效
标题翻译：核酸扩增与RNA复制酶的DNA依赖性RNA聚合酶活性
公开(公告)号：US6090589A
公开(公告)日：2000-07-18
申请号：US480041
申请日：1995-06-06
申请人： Randall L. Dimond , Steven J. Ekenberg , James R. Hartnett , Geoffrey R. Hudson , Leopoldo G. Mendoza , Katharine M. Miller , John E. Monahan , Christopher L. Jones , Mark A. Maffitt , Richard A. Martinelli , Edward E. Pahuski , James W. Schumm
发明人： Randall L. Dimond , Steven J. Ekenberg , James R. Hartnett , Geoffrey R. Hudson , Leopoldo G. Mendoza , Katharine M. Miller , John E. Monahan , Christopher L. Jones , Mark A. Maffitt , Richard A. Martinelli , Edward E. Pahuski , James W. Schumm
IPC分类号： C12N15/09 , C12Q1/68 , C07H19/00 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6867 , C12Q1/6806 , C12Q1/6853
摘要： The present invention entails methods, and kits for carrying them out, based on the discovery that an RNA replicase, such as Q.beta. replicase, has DNA-dependent RNA polymerase ("DDRP") activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2'-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase. The discovery of this DDRP activity provides methods of the invention for nucleic acid amplification wherein a nucleic acid, with a DNA segment with the sequence of an RNA that is autocatalytically replicatable by an RNA replicase, is provided as a substrate for the replicase. Assays of the invention include those wherein a nucleic acid analyte is hybridized with one or more nucleic acid probes, which include or are processed to generate a DNA segment which is amplifiable through production from the segment, catalyzed by the DDRP activity of an RNA replicase, of an autocatalytically replicatable RNA, which is autocatalytically replicated to provide an abundance of readily detectable reporter molecules.
摘要翻译：基于发现RNA复制酶，例如Qβ复制酶，具有核酸片段的DNA依赖性RNA聚合酶（“DDRP”）活性（包括DNA片段和DNA）的发现，本发明需要用于进行它们的方法和试剂盒：RNA嵌合片段，其包含2'-脱氧核糖核苷酸或其类似物，并且具有由复制酶自动催化复制的RNA序列。该DDRP活性的发现提供了用于核酸扩增的本发明的方法，其中提供具有可由RNA复制酶自动催化复制的RNA序列的DNA区段的核酸作为复制酶的底物。本发明的测定包括其中核酸分析物与一种或多种核酸探针杂交的核酸探针，其包括或被处理以产生可通过RNA复制酶的DDRP活性催化的片段产生可扩增的DNA区段，的自催化复制RNA，其自动催化复制以提供丰富的容易检测的报告分子。

7. 发明授权

US06677140B2 Nucleic acid amplification with DNA-dependent RNA polymerase activity of RNA replicases 失效
标题翻译：核酸扩增与RNA复制酶的DNA依赖性RNA聚合酶活性
公开(公告)号：US06677140B2
公开(公告)日：2004-01-13
申请号：US10071057
申请日：2002-02-07
申请人： Randall L. Dimond , Steven J. Ekenberg , James R. Hartnett , Geoffrey R. Hudson , Leopoldo G. Mendoza , Katharine M. Miller , John E. Monahan , Christopher L. Jones , Mark A. Maffitt , Richard A. Martinelli , Edward E. Pahuski , James W. Schumm
发明人： Randall L. Dimond , Steven J. Ekenberg , James R. Hartnett , Geoffrey R. Hudson , Leopoldo G. Mendoza , Katharine M. Miller , John E. Monahan , Christopher L. Jones , Mark A. Maffitt , Richard A. Martinelli , Edward E. Pahuski , James W. Schumm
IPC分类号： C12P1934
CPC分类号： C12Q1/6867 , C12Q1/6806 , C12Q1/6853 , C12Q2521/501 , C12Q2521/325 , C12Q2521/119 , C12Q2521/107 , C12Q2563/137 , C12Q2531/149 , C12Q2525/121
摘要： The present invention entails methods and kits for carrying them out based on the discovery that an RNA replicase, such as Q&bgr; replicase, has DNA-dependent RNA polymerase (“DDRP”) activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2′-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase.
摘要翻译：本发明涉及用于携带RNA的复制酶如Qbeta复制酶具有核酸片段的DNA依赖性RNA聚合酶（“DDRP”）活性的发现的方法和试剂盒，包括DNA片段和DNA：RNA嵌合其包含2'-脱氧核糖核苷酸或其类似物，并且具有由复制酶自动催化复制的RNA序列。

8. 发明申请

US20100159455A1 RECEPTOR FAMILY PROFILING 审中-公开
标题翻译：受体家族简介
公开(公告)号：US20100159455A1
公开(公告)日：2010-06-24
申请号：US12441672
申请日：2007-09-18
申请人： Tanya Landsman , David J. Livingston , Richard A. Martinelli , Yumei Huang , Benjamin Adam Seigal , Dingxue Yan , James M. Coull , Andrew M. Stern
发明人： Tanya Landsman , David J. Livingston , Richard A. Martinelli , Yumei Huang , Benjamin Adam Seigal , Dingxue Yan , James M. Coull , Andrew M. Stern
IPC分类号： C12Q1/68
CPC分类号： G01N33/542 , C12Q1/6804 , G01N33/566 , G01N2333/71 , C12Q2565/101 , C12Q2563/179 , C12Q2563/131
摘要： The invention provides compositions and methods, e.g., assay technologies and their use in biodetection and diagnostics. More particularly, the invention provides compositions and methods based on nucleic acid-templated chemistry in biodetection and profiling of receptors (and their families) and proteins (and their families), and the use of same in diagnostics.
摘要翻译：本发明提供组合物和方法，例如测定技术及其在生物检测和诊断中的应用。更具体地，本发明提供了基于生物检测和受体（及其家族）和蛋白质（及其家族）的生物检测和分析的核酸模板化学的组合物和方法，以及其在诊断中的用途。

9. 发明授权

US06369207B1 Nucleic acid amplification with DNA-dependent RNA polymerase activity of RNA replicases 失效
公开(公告)号：US06369207B1
公开(公告)日：2002-04-09
申请号：US09396001
申请日：1999-09-14
申请人： Randall L. Dimond , Steven J. Ekenberg , James R. Hartnett , Geoffrey R. Hudson , Leopoldo G. Mendoza , Katharine M. Miller , John E. Monahan , Christopher L. Jones , Mark A. Maffitt , Richard A. Martinelli , Edward E. Pahuski , James W. Schumm
发明人： Randall L. Dimond , Steven J. Ekenberg , James R. Hartnett , Geoffrey R. Hudson , Leopoldo G. Mendoza , Katharine M. Miller , John E. Monahan , Christopher L. Jones , Mark A. Maffitt , Richard A. Martinelli , Edward E. Pahuski , James W. Schumm
IPC分类号： C07H1900
CPC分类号： C12Q1/6867 , C12Q1/6806 , C12Q1/6853 , C12Q2521/501 , C12Q2521/325 , C12Q2521/119 , C12Q2521/107 , C12Q2563/137 , C12Q2531/149 , C12Q2525/121
摘要： The present invention entails methods, and kits for carrying them out, based on the discovery that an RNA replicase, such as Q&bgr; replicase, has DNA-dependent RNA polymerase (“DDRP”) activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2′-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase. The discovery of this DDRP activity provides methods of the invention for nucleic acid amplification wherein a nucleic acid, with a DNA segment with the sequence of an RNA that is autocatalytically replicatable by an RNA replicase, is provided as a substrate for the replicase. The replicase catalyzes synthesis, from the DNA segment, of the RNA, which the replicase then autocatalytically replicates. The invention entails use of the amplification methods in detecting nucleic acid analytes, as in nucleic acid probe hybridization assays. Such assays of the invention include those wherein a nucleic acid analyte is hybridized with one or more nucleic acid probes, which include or are processed to generate a DNA segment which is amplifiable through production from the segment, catalyzed by the DDRP activity of an RNA replicase, of an autocatalytically replicatable RNA, which is autocatalytically replicated to provide an abundance of readily detectable reporter molecules. The invention permits replacement of an RNA, that is autocatalytically replicatable with an RNA replicase and employed as a reporter or label in prior art assays, such as nucleic acid probe hybridization assays or immunoassays, with a nucleic acid comprising a DNA segment with the same base sequence as the RNA. The invention also includes the methods of the invention with Mn+2, Co+2, or Zn+2 in the solutions in which the DDRP activity occurs.

10. 发明申请

US20100159446A1 Detection Assays and Use Thereof 审中-公开
标题翻译：检测分析及其用途
公开(公告)号：US20100159446A1
公开(公告)日：2010-06-24
申请号：US12176798
申请日：2008-07-21
申请人： Lawrence A. Haff , Yumei Huang , Richard A. Martinelli , Benjamin A. Seigal , David J. Livingston , Wei-Chuan Sun
发明人： Lawrence A. Haff , Yumei Huang , Richard A. Martinelli , Benjamin A. Seigal , David J. Livingston , Wei-Chuan Sun
IPC分类号： C12Q1/68
CPC分类号： C12Q1/485 , C12Q1/6804 , G01N2333/705 , G01N2333/91215 , G01N2333/95 , G01N2500/02 , C12Q2565/101 , C12Q2563/179
摘要： The invention provides compositions and methods for the detection and/or quantification of biological targets (e.g., nucleic acids and proteins) by the nucleic acid-templated creation of one or more reaction products, for example, epitopes, enzyme substrates, enzyme activators, and ligands. The reaction products can be detected and/or quantitated after signal amplification using an amplification system.
摘要翻译：本发明提供用于通过核酸模板产生一种或多种反应产物，例如表位，酶底物，酶活化剂和/或生物学靶标的检测和/或定量生物学靶标（例如核酸和蛋白质）的组合物和方法配体。可以使用扩增系统在信号放大后检测和/或定量反应产物。

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