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1. 发明授权

US08999676B2 Recombinant polymerases for improved single molecule sequencing 有权
标题翻译：用于改进单分子测序的重组聚合酶
公开(公告)号：US08999676B2
公开(公告)日：2015-04-07
申请号：US13176697
申请日：2011-07-05
申请人： Robin Emig , Lei Jia , Satwik Kamtekar , Erik Miller , Colleen Cutcliffe , Walter Lee
发明人： Robin Emig , Lei Jia , Satwik Kamtekar , Erik Miller , Colleen Cutcliffe , Walter Lee
IPC分类号： C12N15/54 , C12N9/00 , C12N9/12 , C12Q1/68
CPC分类号： C12N9/1252 , C12N9/1241 , C12P19/34 , C12Q1/6869
摘要： Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties can include enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased thermostability, increased accuracy, increased speed, increased readlength, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.
摘要翻译：提供了包含重组DNA聚合酶的组合物，其包括赋予聚合酶修饰性质以增强单分子测序的氨基酸取代，插入，缺失和/或外源特征。这种性质可以包括增强的金属离子配位，降低的核酸外切酶活性，在聚合酶动力学循环的一个或多个步骤中降低的反应速率，降低的支化部分，改变的辅因子选择性，增加的产率，增加的热稳定性，增加的准确度，增加的速度，增加的读长度，等等。还提供了编码具有上述表型的聚合酶的核酸，以及使用这种聚合酶制备DNA或顺序DNA模板的方法。

2. 发明授权

US08383369B2 Intermittent detection during analytical reactions 有权
公开(公告)号：US08383369B2
公开(公告)日：2013-02-26
申请号：US12561221
申请日：2009-09-16
申请人： Kenneth Mark Maxham , Jon Sorenson , John Eid , Patrick Marks , Kevin Travers , Donald Gray , Robin Emig , Mark Chaisson , Benjamin Flusberg
发明人： Kenneth Mark Maxham , Jon Sorenson , John Eid , Patrick Marks , Kevin Travers , Donald Gray , Robin Emig , Mark Chaisson , Benjamin Flusberg
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： G01N21/6452 , C12Q1/6869 , G01N21/6428 , G01N2201/0635 , Y10T436/143333 , C12Q2525/119 , C12Q2521/125 , C12Q2537/149
摘要： Methods, devices, and systems for performing intermittent detection during analytical reactions are provided. Such methods facilitate collection of reaction data from disparate reaction times. Further, such methods are useful for reducing photo-induced damage of one or more reactants in an illuminated analytical reaction at a given reaction time. In preferred embodiments, the reaction mixture is subjected to at least one illuminated and non-illuminated period and allowed to proceed such that the time in which the reaction mixture is illuminated is less than a photo-induced damage threshold period.

3. 发明授权

US08014961B2 Integrated systems and methods for diversity generation and screening 有权
标题翻译：用于多样化生成和筛选的综合系统和方法
公开(公告)号：US08014961B2
公开(公告)日：2011-09-06
申请号：US11677505
申请日：2007-02-21
申请人： Steven H. Bass , Simon Christopher Davis , Phillip A. Patten , Matthew Tobin , Jeremy S. Minshull , Mark Welch , Claus Gustafsson , Brian Carr , Stephan J. Jenne , Sun Ai Raillard , Andreas Crameri , Willem P. C. Stemmer , Robin Emig , Pascal Longchamp , Stanley Goldman , Lorraine J. Giver , Joseph A. Affholter
发明人： Steven H. Bass , Simon Christopher Davis , Phillip A. Patten , Matthew Tobin , Jeremy S. Minshull , Mark Welch , Claus Gustafsson , Brian Carr , Stephan J. Jenne , Sun Ai Raillard , Andreas Crameri , Willem P. C. Stemmer , Robin Emig , Pascal Longchamp , Stanley Goldman , Lorraine J. Giver , Joseph A. Affholter
IPC分类号： G01N33/48
CPC分类号： C12N15/1031 , B01J19/0046 , B01J2219/00378 , B01J2219/00585 , B01J2219/00659 , B01J2219/00675 , B01J2219/00689 , B01J2219/00695 , B01J2219/007 , B01J2219/00722 , B82Y30/00 , C12N15/1027 , C40B60/04 , G06F19/18 , Y02A90/22
摘要： Integrated systems and methods for diversity generation and screening are provided. The systems use common fluid and array handling components to provide nucleic acid diversification, transcription, translation, product screening and subsequent diversification reactions.
摘要翻译：提供了用于多样化生成和筛选的集成系统和方法。该系统使用普通液体和阵列处理组分来提供核酸多样化，转录，翻译，产物筛选和随后的多样化反应。

4. 发明申请

US20100331194A1 NANOPORE SEQUENCING DEVICES AND METHODS 有权
标题翻译： NANOPORE顺序设备和方法
公开(公告)号：US20100331194A1
公开(公告)日：2010-12-30
申请号：US12757789
申请日：2010-04-09
申请人： Stephen Turner , Benjamin Flusberg , Mathieu Foquet , Hans Callebaut , Robert Sebra , Bidhan Chaudhuri , Jon Sorenson , Keith Bjornson , Adrian Fehr , Jonas Korlach , Robin Emig
发明人： Stephen Turner , Benjamin Flusberg , Mathieu Foquet , Hans Callebaut , Robert Sebra , Bidhan Chaudhuri , Jon Sorenson , Keith Bjornson , Adrian Fehr , Jonas Korlach , Robin Emig
IPC分类号： C40B20/00 , C40B60/10 , H01L21/30
CPC分类号： G01N33/48721 , B82Y5/00 , B82Y15/00 , C12Q1/6869 , C12Q1/6874 , C12Q2565/631 , G01N27/447 , G01N27/44791 , C12Q2563/116 , C12Q2527/113
摘要： The invention relates to devices and methods for nanopore sequencing. The invention includes arrays of nanopores having incorporated electronic circuits, for example, in CMOS. In some cases, the arrays of nanopores comprise resistive openings for isolating the electronic signals for improved sequencing. Methods for controlling translocation of through the nanopore are disclosed.
摘要翻译：本发明涉及纳米孔测序的装置和方法。本发明包括纳入电子电路的纳米孔阵列，例如在CMOS中。在一些情况下，纳米孔阵列包括用于隔离电子信号的电阻开口以改善测序。公开了通过纳米孔控制易位的方法。

5. 发明申请

US20100075327A1 INTERMITTENT DETECTION DURING ANALYTICAL REACTIONS 有权
标题翻译：分析反应期间的间接检测
公开(公告)号：US20100075327A1
公开(公告)日：2010-03-25
申请号：US12561221
申请日：2009-09-16
申请人： Kenneth Mark Maxham , Jon Sorenson , John Eid , Patrick Marks , Kevin Travers , Donald Gray , Robin Emig , Mark Chaisson , Benjamin Flusberg
发明人： Kenneth Mark Maxham , Jon Sorenson , John Eid , Patrick Marks , Kevin Travers , Donald Gray , Robin Emig , Mark Chaisson , Benjamin Flusberg
IPC分类号： C12Q1/68 , G01N21/76 , G01N33/00
CPC分类号： G01N21/6452 , C12Q1/6869 , G01N21/6428 , G01N2201/0635 , Y10T436/143333 , C12Q2525/119 , C12Q2521/125 , C12Q2537/149
摘要： Methods, devices, and systems for performing intermittent detection during analytical reactions are provided. Such methods facilitate collection of reaction data from disparate reaction times. Further, such methods are useful for reducing photo-induced damage of one or more reactants in an illuminated analytical reaction at a given reaction time. In preferred embodiments, the reaction mixture is subjected to at least one illuminated and non-illuminated period and allowed to proceed such that the time in which the reaction mixture is illuminated is less than a photo-induced damage threshold period.
摘要翻译：提供了在分析反应期间执行间歇检测的方法，装置和系统。这种方法有助于从不同的反应时间收集反应数据。此外，这样的方法可用于在给定的反应时间下降低照明分析反应中一种或多种反应物的光诱导损伤。在优选的实施方案中，将反应混合物经受至少一个照明和非照射期，并允许进行，使得反应混合物被照射的时间小于光诱导的损伤阈值期。

6. 发明申请

US20090286245A1 TWO SLOW-STEP POLYMERASE ENZYME SYSTEMS AND METHODS 有权
标题翻译：两个慢步聚合酶酶系统和方法
公开(公告)号：US20090286245A1
公开(公告)日：2009-11-19
申请号：US12414191
申请日：2009-03-30
申请人： Keith Bjornson , Harold Lee , Jonas Korlach , Stephen Turner , Arek Bibillo , Fred Christians , Robin Emig , Molly He , Insil Park , Lei Jia , Andrei Fedorov , John Lyle
发明人： Keith Bjornson , Harold Lee , Jonas Korlach , Stephen Turner , Arek Bibillo , Fred Christians , Robin Emig , Molly He , Insil Park , Lei Jia , Andrei Fedorov , John Lyle
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6869 , C12Q1/6874 , C12Q2527/125 , C12Q2527/119 , C12Q2527/101 , C12Q2565/1015 , C12Q2527/137 , C12Q2521/101
摘要： Compositions, kits, methods and systems for nucleotide sequencing comprising producing polymerase reactions that exhibit two kinetically observable steps within an observable phase of the polymerase reaction. Two slow step systems can be produced, for example, by selecting the appropriate polymerase enzyme, polymerase reaction conditions including cofactors, and polymerase reaction substrates including the primed template and nucleotides.
摘要翻译：用于核苷酸测序的组合物，试剂盒，方法和系统，其包括产生聚合酶反应，其在聚合酶反应的可观察期内显示两个动力学可观察步骤。可以通过例如选择合适的聚合酶，包括辅因子的聚合酶反应条件和包括引发的模板和核苷酸的聚合酶反应底物来产生两个缓慢的步骤系统。

7. 发明授权

US07462469B2 Integrated system for diversity generation and screening 失效
标题翻译：用于多样化生成和筛选的综合系统
公开(公告)号：US07462469B2
公开(公告)日：2008-12-09
申请号：US10154936
申请日：2002-05-23
申请人： Steven H. Bass , S. Christopher Davis , Phillip A. Patten , Matthew Tobin , Jeremy Minshull , Mark Welch , Claes Gustafsson , Brian Carr , Stephane Jenne , Sun Ai Raillard , Andreas Crameri , Willem P. C. Stemmer , Robin Emig , Pascal Longchamp , Stanley Goldman , Lorraine J. Giver , Joseph A. Affholter
发明人： Steven H. Bass , S. Christopher Davis , Phillip A. Patten , Matthew Tobin , Jeremy Minshull , Mark Welch , Claes Gustafsson , Brian Carr , Stephane Jenne , Sun Ai Raillard , Andreas Crameri , Willem P. C. Stemmer , Robin Emig , Pascal Longchamp , Stanley Goldman , Lorraine J. Giver , Joseph A. Affholter
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： C12N15/1031 , B01J19/0046 , B01J2219/00378 , B01J2219/00585 , B01J2219/00659 , B01J2219/00675 , B01J2219/00689 , B01J2219/00695 , B01J2219/007 , B01J2219/00722 , B82Y30/00 , C12N15/1027 , C40B60/04 , G06F19/18 , Y02A90/22
摘要： Integrated systems and methods for diversity generation and screening are provided. The systems use common fluid and array handling components to provide nucleic acid diversification, transcription, translation, product screening and subsequent diversification reactions.
摘要翻译：提供了用于多样化生成和筛选的集成系统和方法。该系统使用普通液体和阵列处理组分来提供核酸多样化，转录，翻译，产物筛选和随后的多样化反应。

8. 发明授权

US08603741B2 Single molecule sequencing with two distinct chemistry steps 有权
标题翻译：具有两个不同化学步骤的单分子测序
公开(公告)号：US08603741B2
公开(公告)日：2013-12-10
申请号：US13022926
申请日：2011-02-08
申请人： Robin Emig , Lei Jia , Jeremiah Hanes , Lubomir Sebo
发明人： Robin Emig , Lei Jia , Jeremiah Hanes , Lubomir Sebo
IPC分类号： C12Q1/68 , C07H19/04
CPC分类号： C12Q1/6869 , C07H19/10 , C07H19/11 , C07H19/20 , C07H19/213 , C12Q1/6874 , C12Q2521/301 , C12Q2525/186 , C12Q2563/107 , C12Q2537/157 , C12Q2521/319 , C12Q2521/525
摘要： Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3′ hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3′ hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3′ hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
摘要翻译：提供了用于核酸测序的方法，组合物和系统，其中连续掺入核苷酸使用两个不同的化学步骤。在选择性切割活性的存在下，可以将多个在其3'羟基上具有标记的离去基团的核苷酸类似物依次加入到生长链中，该选择性裂解活性优选在其引入后优先切割3'羟基离去基团。选择性切割剂可以包含核酸外切酶活性，并且核酸外切酶活性可以是聚合酶相关的外切核酸酶活性。在可切割聚磷酸酯部分和3'羟基离去基团上具有标记的核苷酸类似物可以提供核苷酸类似物掺入特征的信号。具有照明光学器件，收集光学元件和底物的系统在标记被并入生长的核酸链中观察信号，允许对模板核酸进行测序。

9. 发明授权

US08501922B2 CIS reactive oxygen quenchers integrated into linkers 有权
公开(公告)号：US08501922B2
公开(公告)日：2013-08-06
申请号：US12367411
申请日：2009-02-06
申请人： Geoffrey Otto , Gene Shen , Xiangxu Kong , Robin Emig
发明人： Geoffrey Otto , Gene Shen , Xiangxu Kong , Robin Emig
IPC分类号： C07H21/04 , C12Q1/68
CPC分类号： C12Q1/48 , C07H21/00 , C12Q1/68 , C12Q1/686
摘要： The present invention provides methods and compositions for performing illuminated reactions, particularly sequencing reactions, while mitigating and/or preventing photodamage to reactants that can result from prolonged illumination. In particular, the invention provides methods and compositions for incorporating photoprotective agents into conjugates comprising reporter molecules and nucleoside polyphosphates.

10. 发明授权

US08133672B2 Two slow-step polymerase enzyme systems and methods 有权
标题翻译：两个慢步聚合酶系统和方法
公开(公告)号：US08133672B2
公开(公告)日：2012-03-13
申请号：US12414191
申请日：2009-03-30
申请人： Keith Bjornson , Harold Lee , Jonas Korlach , Stephen Turner , Arek Bibillo , Fred Christians , Robin Emig , Molly He , Insil Park , Lei Jia , Andrei Fedorov , John Lyle
发明人： Keith Bjornson , Harold Lee , Jonas Korlach , Stephen Turner , Arek Bibillo , Fred Christians , Robin Emig , Molly He , Insil Park , Lei Jia , Andrei Fedorov , John Lyle
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6869 , C12Q1/6874 , C12Q2527/125 , C12Q2527/119 , C12Q2527/101 , C12Q2565/1015 , C12Q2527/137 , C12Q2521/101
摘要： Compositions, kits, methods and systems for nucleotide sequencing comprising producing polymerase reactions that exhibit two kinetically observable steps within an observable phase of the polymerase reaction. Two slow step systems can be produced, for example, by selecting the appropriate polymerase enzyme, polymerase reaction conditions including cofactors, and polymerase reaction substrates including the primed template and nucleotides.
摘要翻译：用于核苷酸测序的组合物，试剂盒，方法和系统，其包括产生聚合酶反应，其在聚合酶反应的可观察期内显示两个动力学可观察步骤。可以通过例如选择合适的聚合酶，包括辅因子的聚合酶反应条件和包括引发的模板和核苷酸的聚合酶反应底物来产生两个缓慢的步骤系统。

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