公开(公告)号：US20240067941A1

公开(公告)日：2024-02-29

申请号：US18486337

申请日：2023-10-13

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Peter VANDER HORN ,  Theo NIKIFOROV ,  Daniel MAZUR ,  Eileen TOZER ,  Mindy LANDES

IPC: C12N9/12 ,  C12Q1/686 ,  C12Q1/6869

CPC classification number: C12N9/1252 ,  C12Q1/686 ,  C12Q1/6869

Abstract: The present disclosure provides compositions, methods, kits, systems and apparatus that are useful for nucleic acid polymerization. In particular, modified polymerases and biologically active fragments thereof are provided that allow for nucleic acid amplification. In some aspects, the disclosure provides modified polymerases having lower systematic error as compared to a reference polymerase. In one aspect, the disclosure relates to modified polymerases useful for nucleic acid sequencing, genotyping, copy number variation analysis, paired-end sequencing and other forms of genetic analysis. In some aspects, the disclosure relates to modified polymerases useful for the generation of nucleic acid libraries or nucleic acid templates. In some aspects, the disclosure relates to the identification of homologous amino acid mutations that can be transferred across classes or families of polymerases to provide novel polymerases with altered properties.

公开(公告)号：US20230193223A1

公开(公告)日：2023-06-22

申请号：US17932844

申请日：2022-09-16

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Peter VANDER HORN ,  Cheng-Yao CHEN ,  Guobin LUO ,  Michael PREVITE ,  Jamshid TEMIROV ,  Theo NIKIFOROV ,  Zhaohui ZHOU ,  Hongye SUN ,  Yufang WANG ,  Stefanie Yukiko NISHIMURA ,  Hongyi WANG ,  Marian PERIS ,  Barnett ROSENBLUM ,  Michael PHELAN

IPC: C12N9/12 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q1/6872 ,  C12Q1/6804 ,  C12Q1/6818 ,  C12Q1/68

CPC classification number: C12N9/1252 ,  C12Q1/68 ,  C12Q1/6804 ,  C12Q1/6818 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q1/6872 ,  C12Y207/07007 ,  G01N2500/00

Abstract: Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.

公开(公告)号：US20200231948A1

公开(公告)日：2020-07-23

申请号：US16825788

申请日：2020-03-20

Applicant: Life Technologies Corporation

Inventor： Peter VANDER HORN ,  Cheng-Yao CHEN ,  Guobin LUO ,  Michael PREVITE ,  Jamshid TEMIROV ,  Theo NIKIFOROV ,  Zhaohui ZHOU ,  Hongye SUN ,  Yufang WANG ,  Stefanie Yukiko NISHIMURA ,  Hongyi WANG ,  Marian PERIS ,  Barnett ROSENBLUM ,  Michael PHELAN

IPC: C12N9/12 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q1/6872 ,  C12Q1/6804 ,  C12Q1/6818 ,  C12Q1/68

Abstract: Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.

公开(公告)号：US20150100247A1

公开(公告)日：2015-04-09

申请号：US14506520

申请日：2014-10-03

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Christian KOLLER ,  Marcin SIKORA ,  Peter VANDER HORN

IPC: G06F19/22 ,  G06F19/12 ,  G06F19/18

CPC classification number: G16B40/10 ,  C12Q1/6869 ,  G16B5/00 ,  G16B20/00 ,  G16B25/00 ,  G16B30/00

Abstract: A method for nucleic acid sequencing includes receiving observed or measured nucleic acid sequencing data from a sequencing instrument that receives and processes a sample nucleic acid in a termination sequencing-by-synthesis process. The method also includes generating a set of candidate sequences of bases for the observed or measured nucleic acid sequencing data by determining a predicted signal for candidate sequences using a simulation framework. The simulation framework incorporates an estimated carry forward rate (CFR), an estimated incomplete extension rate (IER), an estimated droop rate (DR), an estimated reactivated molecules rate (RMR), and an estimated termination failure rate (TFR), the RMR being greater than or equal to zero and the TFR being lesser than one. The method also includes identifying, from the set of candidate sequences of bases, one candidate sequence leading to optimization of a solver function as corresponding to the sequence for the sample nucleic acid.

Abstract translation: 用于核酸测序的方法包括接收来自测序仪器的观测或测量的核酸测序数据，所述测序仪器在终止测序合成过程中接收和处理样品核酸。 该方法还包括通过使用模拟框架确定候选序列的预测信号来产生用于观察或测量的核酸测序数据的一组候选碱基序列。 模拟框架包含估计结转率（CFR），估计不完全扩展率（IER），估计下降率（DR），估计的再活化分子率（RMR）和估计的终止失败率（TFR）， RMR大于或等于零，TFR小于1。 该方法还包括从候选碱基序列的集合中鉴定出一个候选序列，导致解析函数的优化对应于样品核酸的序列。

公开(公告)号：US20150094211A1

公开(公告)日：2015-04-02

申请号：US14502201

申请日：2014-09-30

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Peter VANDER HORN ,  Daniel MAZUR ,  Theo NIKIFOROV ,  Mindy LANDES ,  Eileen TOZER

IPC: C12N9/12 ,  C12Q1/68

CPC classification number: C12N9/1252 ,  C12Q1/686 ,  C12Q1/6869

Abstract: The present disclosure provides compositions, methods, kits, systems and apparatus that are useful for nucleic acid polymerization. In particular, modified polymerases and biologically active fragments thereof are provided that allow for nucleic acid amplification. In some aspects, the disclosure provides modified polymerases having lower systematic error as compared to a reference polymerase. In one aspect, the disclosure relates to modified polymerases useful for nucleic acid sequencing, genotyping, copy number variation analysis, paired-end sequencing and other forms of genetic analysis. In some aspects, the disclosure relates to modified polymerases useful for the generation of nucleic acid libraries or nucleic acid templates. In some aspects, the disclosure relates to the identification of homologous amino acid mutations that can be transferred across classes or families of polymerases to provide novel polymerases with altered properties.

Abstract translation: 本公开提供了可用于核酸聚合的组合物，方法，试剂盒，系统和装置。 特别地，提供了允许核酸扩增的修饰的聚合酶及其生物活性片段。 在一些方面，本公开提供与参考聚合酶相比具有较低系统误差的修饰聚合酶。 一方面，本公开涉及可用于核酸测序，基因分型，拷贝数变异分析，配对末端测序和其他形式遗传分析的修饰聚合酶。 在一些方面，本公开涉及可用于产生核酸文库或核酸模板的修饰聚合酶。 在一些方面，本公开涉及可以跨越聚合酶的类或家族转移的同源氨基酸突变的鉴定，以提供具有改变的性质的新型聚合酶。

公开(公告)号：US20240425921A1

公开(公告)日：2024-12-26

申请号：US18787313

申请日：2024-07-29

Applicant: LIFE TECHNOLOGIES CORPORATION ,  ONE LAMBDA, INC.

Inventor： Rui PEI ,  Peter VANDER HORN ,  Hong MA ,  Ito WAKEFIELD

IPC: C12Q1/6876 ,  C12Q1/6804 ,  C12Q1/6806 ,  C12Q1/6844

Abstract: Methods, systems, and devices for analyzing a sample for the presence of a target protein are provided. A sample can be processed, the processing generating an amplification product of a template nucleic acid formed in response to a target protein being present in the sample. The amplification product can be contacted with a detection probe to generate a second product comprising a labeled nucleic acid. A lateral flow substrate can be contacted with the second product, the lateral flow substrate comprising a capture moiety configured to bind the labeled nucleic acid. The methods can be carried out in one or more chambers of a single device or multiple devices. Detection probe bound to amplicons of the template nucleic acid captured on the lateral flow substrate can be read visually or using a sensor.

公开(公告)号：US20220162573A1

公开(公告)日：2022-05-26

申请号：US17645146

申请日：2021-12-20

Applicant: Life Technologies Corporation

Inventor： Peter VANDER HORN ,  Theo NIKIFOROV ,  Guobin LUO ,  Mindy LANDES ,  Daniel MAZUR ,  Eileen TOZER ,  Tommie LINCECUM

IPC: C12N9/12 ,  C12Q1/6844 ,  C12Q1/686

Abstract: The present disclosure provides compositions, methods, kits, systems and apparatus that are useful for nucleic acid polymerization. In particular, modified polymerases and biologically active fragment thereof are provided that allow for nucleic acid amplification. In one aspect, the disclosure relates to modified polymerases useful for nucleic acid sequencing, genotyping, copy number variation analysis, paired-end sequencing and other forms of genetic analysis. In some aspects, the disclosure relates to modified polymerases useful for the generation of nucleic acid libraries or nucleic acid templates for use in various downstream processes. In some aspects, the disclosure relates to the identification of homologous amino acid mutations that can be transferred across classes or families of polymerases to provide novel polymerases with altered catalytic properties. In some aspects, the disclosure provides modified polymerases having enhanced catalytic properties as compared to a reference polymerase.

公开(公告)号：US20210371834A1

公开(公告)日：2021-12-02

申请号：US17445047

申请日：2021-08-13

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Peter VANDER HORN ,  Daniel MAZUR ,  Theo NIKIFOROV ,  Mindy LANDES ,  Eileen TOZER

IPC: C12N9/12 ,  C12Q1/686 ,  C12Q1/6869

Abstract: The present disclosure provides compositions, methods, kits, systems and apparatus that are useful for nucleic acid polymerization. In particular, modified polymerases and biologically active fragments thereof are provided that allow for nucleic acid amplification. In some aspects, the disclosure provides modified polymerases having lower systematic error as compared to a reference polymerase. In one aspect, the disclosure relates to modified polymerases useful for nucleic acid sequencing, genotyping, copy number variation analysis, paired-end sequencing and other forms of genetic analysis. In some aspects, the disclosure relates to modified polymerases useful for the generation of nucleic acid libraries or nucleic acid templates. In some aspects, the disclosure relates to the identification of homologous amino acid mutations that can be transferred across classes or families of polymerases to provide novel polymerases with altered properties.

公开(公告)号：US20200002688A1

公开(公告)日：2020-01-02

申请号：US16270129

申请日：2019-02-07

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Peter VANDER HORN ,  Daniel Mazur ,  Theo Nikiforov ,  Mindy Landes ,  Eileen Tozer

IPC: C12N9/12 ,  C12Q1/686 ,  C12Q1/6869

Abstract: The present disclosure provides compositions, methods, kits, systems and apparatus that are useful for nucleic acid polymerization. In particular, modified polymerases and biologically active fragments thereof are provided that allow for nucleic acid amplification. In some aspects, the disclosure provides modified polymerases having lower systematic error as compared to a reference polymerase. In one aspect, the disclosure relates to modified polymerases useful for nucleic acid sequencing, genotyping, copy number variation analysis, paired-end sequencing and other forms of genetic analysis. In some aspects, the disclosure relates to modified polymerases useful for the generation of nucleic acid libraries or nucleic acid templates. In some aspects, the disclosure relates to the identification of homologous amino acid mutations that can be transferred across classes or families of polymerases to provide novel polymerases with altered properties.

公开(公告)号：US20160097091A1

公开(公告)日：2016-04-07

申请号：US14856220

申请日：2015-09-16

Applicant: LIFE TECHNOLOGIES CORPORATION ,  LIFE TECHNOLOGIES GmbH

Inventor： Wolfgang HINZ ,  Peter VANDER HORN ,  Earl HUBBELL ,  Christian WOEHLER

IPC: C12Q1/68

CPC classification number: C12Q1/6869 ,  C12Q1/6874 ,  C12Q2535/113 ,  C12Q2565/519

Abstract: In some embodiments, the disclosure relates generally to methods, as well as compositions, systems, kits and apparatuses, for performing nucleotide incorporation, comprising: (a) providing a surface including one or more reaction sites containing a polymerase and a nucleic acid template that has, or is hybridized to, an extendible end; (b) performing a first nucleotide flow by contacting one or more of the reaction sites with a first solution including one or more types of terminator nucleotide; (c) incorporating at least one type of terminator nucleotide at the extendible end of the nucleic acid template contained within at least one of the reaction sites using the polymerase; and (d) detecting a non-optical signal indicating the nucleotide incorporation using a sensor that is attached or operatively linked to the at least one reaction site.

Abstract translation: 在一些实施方案中，本公开一般涉及用于进行核苷酸掺入的方法以及组合物，系统，试剂盒和装置，其包括：（a）提供包含一个或多个含有聚合酶和核酸模板的反应位点的表面，所述反应位点 已经或被杂交到可延伸的一端; （b）通过使一个或多个所述反应位点与包含一种或多种类型的终止子核苷酸的第一溶液接触来进行第一核苷酸流; （c）使用所述聚合酶在至少一个所述反应位点内的所述核酸模板的可延伸末端掺入至少一种类型的终止子核苷酸; 和（d）使用附着或可操作地连接至少一个反应位点的传感器检测表示核苷酸掺入的非光学信号。