公开(公告)号：CA2720046C

公开(公告)日：2018-07-24

申请号：CA2720046

申请日：2009-03-30

Applicant: PACIFIC BIOSCIENCES CALIFORNIA INC

Inventor： CLARK SONYA ,  BIBILLO AREK ,  PELUSO PAUL ,  CHRISTIANS FRED ,  HE MOLLY ,  PARK INSIL ,  LEE HAROLD ,  BJORNSON KEITH ,  JIA LEI ,  EMIG ROBIN

IPC: C12N9/12 ,  C12N15/10 ,  C12N15/54

Abstract: Provided are compositions comprising modified recombinant polymerases that exhibit branching fractions that are less than the branching fractions of the polymerases from which they were derived, or branching fractions that are less than about 25% for a phosphate-labeled nucleotide analog. Also provided are compositions comprising modified recombinant polymerases that exhibit closed polymerase/DNA complexes with increased stability relative to the parental polymerases. Also provided are compositions comprising modified recombinant polymerases that exhibit decreased rate constants relative to the parental polymerases. Provided are methods for generating polymerases with the aforementioned phenotypes. Provided are methods of using such polymerases to make a DNA or to sequence a DNA template.

公开(公告)号：CA2738648A1

公开(公告)日：2010-04-01

申请号：CA2738648

申请日：2009-09-16

Applicant: PACIFIC BIOSCIENCES CALIFORNIA

Inventor： MAXHAM KENNETH MARK ,  SORENSON JON ,  EID JOHN ,  MARKS PATRICK ,  TRAVERS KEVIN ,  GRAY DONALD ,  EMIG ROBIN ,  CHAISSON MARK ,  FLUSBERG BENJAMIN

IPC: G01N21/00

Abstract: 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.

公开(公告)号：WO2011040971A2

公开(公告)日：2011-04-07

申请号：PCT/US2010002659

申请日：2010-09-30

Applicant: PACIFIC BIOSCIENCES CALIFORNIA ,  CLARK SONYA ,  BIBILLO AREK ,  PELUSO PAUL ,  CHRISTIANS FRED ,  HE MOLLY ,  PARK INSIL ,  LEE HAROLD ,  BJORNSON KEITH ,  JIA LEI ,  EMIG ROBIN

Inventor： CLARK SONYA ,  BIBILLO AREK ,  PELUSO PAUL ,  CHRISTIANS FRED ,  HE MOLLY ,  PARK INSIL ,  LEE HAROLD ,  BJORNSON KEITH ,  JIA LEI ,  EMIG ROBIN

IPC: C12N9/12 ,  C12N15/54 ,  C12Q1/68

CPC classification number: C12N9/1252 ,  C12Q1/6869 ,  C12Q2521/101

Abstract: Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions and/or heterologous or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties can include reduced reaction rates at one or more steps of the polymerase kinetic cycle, increased closed polymerase/DNA complex stability, enhanced metal ion coordination, reduced exonuclease activity, decreased branching fractions, 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.

Abstract translation: 提供了包含重组DNA聚合酶的组合物，其包括氨基酸取代，插入，缺失和/或异源或外源特征，其在聚合酶上赋予改进的性质以用于增强的单分子测序。 这种性质可以包括聚合酶动力学循环的一个或多个步骤的降低的反应速率，增加的闭合聚合酶/ DNA复合物稳定性，增强的金属离子配位，减少的核酸外切酶活性，降低的支化部分等。 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。

公开(公告)号：AU2009297145A1

公开(公告)日：2010-04-01

申请号：AU2009297145

申请日：2009-09-16

Applicant: PACIFIC BIOSCIENCES CALIFORNIA INC

Inventor： MAXHAM KENNETH MARK ,  SORENSON JON ,  EID JOHN ,  MARKS PATRICK ,  TRAVERS KEVIN ,  GRAY DONALD ,  EMIG ROBIN ,  CHAISSON MARK ,  FLUSBERG BENJAMIN

IPC: G01N21/00

Abstract: 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.

公开(公告)号：CA2720046A1

公开(公告)日：2009-12-03

申请号：CA2720046

申请日：2009-03-30

Applicant: PACIFIC BIOSCIENCES CALIFORNIA

Inventor： CLARK SONYA ,  BIBILLO AREK ,  PELUSO PAUL ,  CHRISTIANS FRED ,  HE MOLLY ,  PARK INSIL ,  LEE HAROLD ,  BJORNSON KEITH ,  JIA LEI ,  EMIG ROBIN

IPC: C12N9/12 ,  C12N15/10 ,  C12N15/54

Abstract: Provided are compositions comprising modified recombinant polymerases that exhibit branching fractions that are less than the branching fractions of the polymerases from which they were derived, or branching fractions that are less than about 25% for a phosphate-labeled nucleotide analog. Also provided are compositions comprising modified recombinant polymerases that exhibit closed polymerase/DNA complexes with increased stability relative to the parental polymerases. Also provided are compositions comprising modified recombinant polymerases that exhibit decreased rate constants relative to the parental polymerases. Provided are methods for generating polymerases with the aforementioned phenotypes. Provided are methods of using such polymerases to make a DNA or to sequence a DNA template.

公开(公告)号：WO2010117470A3

公开(公告)日：2011-03-31

申请号：PCT/US2010001072

申请日：2010-04-09

Applicant: PACIFIC BIOSCIENCES CALIFORNIA ,  TURNER STEPHEN ,  FLUSBERG BENJAMIN ,  FOQUET MATHIEU ,  CALLEBAUT HANS ,  SEBRA ROBERT ,  CHAUDHURI BIDHAN ,  SORENSON JON ,  BJORNSON KEITH ,  FEHR ADRIAN ,  KORLACH JONAS ,  EMIG ROBIN

Inventor： TURNER STEPHEN ,  FLUSBERG BENJAMIN ,  FOQUET MATHIEU ,  CALLEBAUT HANS ,  SEBRA ROBERT ,  CHAUDHURI BIDHAN ,  SORENSON JON ,  BJORNSON KEITH ,  FEHR ADRIAN ,  KORLACH JONAS ,  EMIG ROBIN

IPC: C12Q1/68 ,  B82B3/00 ,  G01N33/48

CPC classification number: G01N33/48721 ,  B82Y5/00 ,  B82Y15/00 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q2565/631 ,  G01N27/447 ,  G01N27/44791 ,  C12Q2563/116 ,  C12Q2527/113

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2010036311A3

公开(公告)日：2010-06-17

申请号：PCT/US2009005169

申请日：2009-09-16

Applicant: PACIFIC BIOSCIENCES CALIFORNIA ,  MAXHAM KENNETH MARK ,  SORENSON JON ,  EID JOHN ,  MARKS PATRICK ,  TRAVERS KEVIN ,  GRAY DONALD ,  EMIG ROBIN ,  CHAISSON MARK ,  FLUSBERG BENJAMIN

Inventor： MAXHAM KENNETH MARK ,  SORENSON JON ,  EID JOHN ,  MARKS PATRICK ,  TRAVERS KEVIN ,  GRAY DONALD ,  EMIG ROBIN ,  CHAISSON MARK ,  FLUSBERG BENJAMIN

IPC: G01N21/00

CPC classification number: C12Q1/6869 ,  G01N2021/7786 ,  Y10T436/143333 ,  C12Q2525/301 ,  C12Q2533/101 ,  C12Q2537/149 ,  C12Q2565/631 ,  C12Q2525/307 ,  C12Q2525/191

Abstract: 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.

Abstract translation: 提供了用于在分析反应期间执行间歇检测的方法，装置和系统。 这种方法便于从不同的反应时间收集反应数据。 此外，此类方法可用于减少在给定反应时间下照明分析反应中一种或多种反应物的光致损伤。 在优选的实施方案中，使反应混合物经历至少一个照射和未照射的时间段并使其进行，使得照射反应混合物的时间小于光诱导的损伤阈值时间段。

公开(公告)号：WO2009145828A2

公开(公告)日：2009-12-03

申请号：PCT/US2009002003

申请日：2009-03-30

Applicant: PACIFIC BIOSCIENCES CALIFORNIA ,  BJORNSON KEITH ,  LEE HAROLD ,  KORLACH JONAS ,  TURNER STEPHEN ,  BIBILLO AREK ,  CHRISTIANS FRED ,  EMIG ROBIN ,  HE MOLLY ,  PARK INSIL ,  JIA LEI ,  FEDOROV ANDREI ,  LYLE JOHN

Inventor： BJORNSON KEITH ,  LEE HAROLD ,  KORLACH JONAS ,  TURNER STEPHEN ,  BIBILLO AREK ,  CHRISTIANS FRED ,  EMIG ROBIN ,  HE MOLLY ,  PARK INSIL ,  JIA LEI ,  FEDOROV ANDREI ,  LYLE JOHN

IPC: C12Q1/68 ,  C12N9/12 ,  C12Q1/48

CPC classification number: C12Q1/6869 ,  C12Q1/6874 ,  C12Q2527/125 ,  C12Q2527/119 ,  C12Q2527/101 ,  C12Q2565/1015 ,  C12Q2527/137 ,  C12Q2521/101

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2011040971A3

公开(公告)日：2011-11-03

申请号：PCT/US2010002659

申请日：2010-09-30

Applicant: PACIFIC BIOSCIENCES CALIFORNIA ,  CLARK SONYA ,  BIBILLO AREK ,  PELUSO PAUL ,  CHRISTIANS FRED ,  HE MOLLY ,  PARK INSIL ,  LEE HAROLD ,  BJORNSON KEITH ,  JIA LEI ,  EMIG ROBIN

Inventor： CLARK SONYA ,  BIBILLO AREK ,  PELUSO PAUL ,  CHRISTIANS FRED ,  HE MOLLY ,  PARK INSIL ,  LEE HAROLD ,  BJORNSON KEITH ,  JIA LEI ,  EMIG ROBIN

IPC: C12N9/12 ,  C12N15/54 ,  C12Q1/68

CPC classification number: C12N9/1252 ,  C12Q1/6869 ,  C12Q2521/101

Abstract: Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions and/or heterologous or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties can include reduced reaction rates at one or more steps of the polymerase kinetic cycle, increased closed polymerase/DNA complex stability, enhanced metal ion coordination, reduced exonuclease activity, decreased branching fractions, 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.

公开(公告)号：WO2009145820A2

公开(公告)日：2009-12-03

申请号：PCT/US2009001974

申请日：2009-03-30

Applicant: PACIFIC BIOSCIENCES CALIFORNIA ,  CLARK SONYA ,  BIBILLO AREK ,  PELUSO PAUL ,  CHRISTIANS FRED ,  HE MOLLY ,  PARK INSIL ,  LEE HAROLD ,  BJORNSON KEITH ,  JIA LEI ,  EMIG ROBIN

Inventor： CLARK SONYA ,  BIBILLO AREK ,  PELUSO PAUL ,  CHRISTIANS FRED ,  HE MOLLY ,  PARK INSIL ,  LEE HAROLD ,  BJORNSON KEITH ,  JIA LEI ,  EMIG ROBIN

IPC: C12N9/12 ,  C12N15/10 ,  C12N15/54

CPC classification number: C12N9/1252 ,  C12Q1/6844 ,  C12Q1/6869 ,  C12Q2521/101

Abstract: Provided are compositions comprising modified recombinant polymerases that exhibit branching fractions that are less than the branching fractions of the polymerases from which they were derived, or branching fractions that are less than about 25% for a phosphate-labeled nucleotide analog. Also provided are compositions comprising modified recombinant polymerases that exhibit closed polymerase/DNA complexes with increased stability relative to the parental polymerases. Also provided are compositions comprising modified recombinant polymerases that exhibit decreased rate constants relative to the parental polymerases. Provided are methods for generating polymerases with the aforementioned phenotypes. Provided are methods of using such polymerases to make a DNA or to sequence a DNA template.

Abstract translation: 提供了包含修饰的重组聚合酶的组合物，其表现出小于其衍生自其的聚合酶的支化部分的支化部分，或对于磷酸酯标记的核苷酸类似物的支化部分小于约25％。 还提供了包含修饰的重组聚合酶的组合物，其表现出相对于亲本聚合酶具有增加的稳定性的闭合的聚合酶/ DNA复合物。 还提供了包含修饰的重组聚合酶的组合物，其相对于亲本聚合酶表现出降低的速率常数。 提供了产生具有上述表型的聚合酶的方法。 提供使用这种聚合酶制备DNA或顺序DNA模板的方法。