公开(公告)号：AU2006330947B2

公开(公告)日：2012-04-12

申请号：AU2006330947

申请日：2006-12-21

Applicant: PACIFIC BIOSCIENCES CALIFORNIA INC

Inventor： BIBILLO AREK ,  MITSIS PAUL ,  PHAM THANG ,  CHRISTIANS FRED C ,  MURPHY DEVON ,  PARK INSIL ,  HANZEL DAVID K ,  LYLE JOHN ,  RANK DAVID R ,  CLARK SONYA ,  PELUSO PAUL ,  OTTO GEOFF

IPC: C12Q1/68

Abstract: Compositions that include polymerases with features for improving entry of nucleotide analogues into active site regions and for coordinating with the nucleotide analogues in the active site region are provided. Methods of making the polymerases and of using the polymerases in sequencing and DNA replication and amplification as well as kinetic models of polymerase activity and computer-implemented methods of using the models are also provided.

公开(公告)号：CA2623042A1

公开(公告)日：2007-04-12

申请号：CA2623042

申请日：2006-09-28

Applicant: PACIFIC BIOSCIENCES CALIFORNIA

Inventor： BIBILLO AREK ,  XU YUE ,  WEGENER JEFFREY

IPC: C07H19/00 ,  C07H21/00

Abstract: Labeled nucleotide analogs used in place of naturally occurring nucleoside triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions, and various analyses based thereon, including DNA sequencing, single base identification, hybridization assays and others.

公开(公告)号：WO2008051530A3

公开(公告)日：2008-12-18

申请号：PCT/US2007022459

申请日：2007-10-22

Applicant: PACIFIC BIOSCIENCES CALIFORNIA ,  RANK DAVID R ,  BIBILLO AREK ,  HANZEL DAVID K ,  PELUSO PAUL ,  WEGENER JEFF

Inventor： RANK DAVID R ,  BIBILLO AREK ,  HANZEL DAVID K ,  PELUSO PAUL ,  WEGENER JEFF

IPC: C12N9/12 ,  C12N9/00

CPC classification number: C12N9/1252 ,  C12P19/34

Abstract: Compositions that include DNA polymerases having increased residence times for nucleotide analogues, particularly modified recombinant F29-type DNA polymerases with such increased residence times, are provided. Methods of making the polymerases and of using the polymerases in sequencing and DNA amplification are also provided. Compositions including a-thiophosphate nucleotide analogues with four or more phosphate groups are described, as are methods for determining the sequence of nucleic acid molecules using such analogues.

Abstract translation: 提供了包括具有增加的核苷酸类似物停留时间的DNA聚合酶的组合物，特别是具有增加的停留时间的修饰的重组F29-型DNA聚合酶。 还提供了在测序和DNA扩增中制备聚合酶和使用聚合酶的方法。 描述了包含具有四个或更多个磷酸基团的α-硫代磷酸核苷酸类似物的组合物，以及使用此类类似物确定核酸分子序列的方法。

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：AU2009251883A1

公开(公告)日：2009-12-03

申请号：AU2009251883

申请日：2009-03-30

Applicant: PACIFIC BIOSCIENCES CALIFORNIA

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

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 polymerase. 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：CA2715385A1

公开(公告)日：2009-08-20

申请号：CA2715385

申请日：2009-02-12

Applicant: PACIFIC BIOSCIENCES CALIFORNIA

Inventor： BJORNSON KEITH ,  BIBILLO AREK ,  SEBO LUBOMIR

IPC: C12Q1/68 ,  G01N33/50

Abstract: Compositions, methods, substrates and systems for use in analysis of single molecule reactions and particularly single molecule nucleic acid sequence analysis. Compositions that include non-reactive, distinguishable or undetectable competitive substrates for the reaction system of interest are provided, as well as their use in systems and substrates for such applications, such compounds typically preferably polyphosphate chains or analogous structures.

公开(公告)号：AU2006297104A1

公开(公告)日：2007-04-12

申请号：AU2006297104

申请日：2006-09-28

Applicant: PACIFIC BIOSCIENCES CALIFORNIA INC

Inventor： BIBILLO AREK ,  WEGENER JEFFEY ,  XU YUE

IPC: C07H19/00 ,  C07H21/00

Abstract: Labeled nucleotide analogs used in place of naturally occurring nucleoside triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions, and various analyses based thereon, including DNA sequencing, single base identification, hybridization assays and others.

公开(公告)号：AU2007309504B2

公开(公告)日：2012-09-13

申请号：AU2007309504

申请日：2007-10-22

Applicant: PACIFIC BIOSCIENCES CALIFORNIA INC

Inventor： PELUSO PAUL ,  RANK DAVID R ,  BIBILLO AREK ,  WEGENER JEFF ,  HANZEL DAVID K

IPC: C12N9/12 ,  C12N9/00

Abstract: Compositions that include DNA polymerases having increased residence times for nucleotide analogues, particularly modified recombinant Φ29-type DNA polymerases with such increased residence times, are provided. Methods of making the polymerases and of using the polymerases in sequencing and DNA amplification are also provided. Compositions including α-thiophosphate nucleotide analogues with four or more phosphate groups are described, as are methods for determining the sequence of nucleic acid molecules using such analogues.

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：CA2666517A1

公开(公告)日：2008-05-02

申请号：CA2666517

申请日：2007-10-22

Applicant: PACIFIC BIOSCIENCES CALIFORNIA

Inventor： BIBILLO AREK ,  HANZEL DAVID K ,  RANK DAVID R ,  PELUSO PAUL ,  WEGENER JEFF

IPC: C12N9/12 ,  C12N15/00 ,  C12P19/34 ,  C12Q1/68

Abstract: Compositions that include DNA polymerases having increased residence time s for nucleotide analogues, particularly modified recombinant .PHI.29-type D NA polymerases with such increased residence times, are provided. Methods of making the polymerases and of using the polymerases in sequencing and DNA a mplification are also provided. Compositions including .alpha.-thiophosphate nucleotide analogues with four or more phosphate groups are described, as a re methods for determining the sequence of nucleic acid molecules using such analogues.