Patents by Inventor Theo Nikiforov

Theo Nikiforov has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 11015220
    Abstract: Disclosed herein are conjugates comprising a biomolecule linked to a label that have biological activity and are useful in a wide variety of biological applications. For example, provided herein are polymerase-nanoparticle conjugates including a polymerase linked to a nanoparticle, wherein the conjugate has polymerase activity. Such conjugates can exhibit reduced aggregation and improved stochiometries wherein the average biomolecule:nanoparticle ratio approaches or equals 1:1. Also disclosed herein are improved methods for preparing such conjugates, and methods and systems for using such conjugates in biological applications such as nucleotide incorporation, primer extension and single molecule sequencing.
    Type: Grant
    Filed: September 6, 2018
    Date of Patent: May 25, 2021
    Assignee: Life Technologies Corporation
    Inventors: Theo Nikiforov, Daniel Mazur, Xinzhan Peng, Tommie Lloyd Lincecum, Yuri Belosludtsev, Howard Reese, Dmitriy Gremyachinskiy, Roman Rozhkov, John Mauro, Joseph Beechem, Eric Tulsky, Imad Naasani, Kari Haley, Joseph Treadway
  • Patent number: 11008612
    Abstract: Provided herein are systems and methods for nucleotide incorporation reactions. The systems comprise polymerases having altered nucleotide incorporation kinetics and are linked to an energy transfer donor moiety, and nucleotide molecules linked with at least one energy transfer acceptor moiety. The donor and acceptor moieties undergo energy transfer when the polymerase and nucleotide are proximal to each other during nucleotide binding and/or nucleotide incorporation. As the donor and acceptor moieties undergo energy transfer, they generate an energy transfer signal which can be associated with nucleotide binding or incorporation. Detecting a time sequence of the generated signals, or the change in the signals, can be used to determine the order of the incorporated nucleotides, and can therefore be used to deduce the sequence of the target molecule.
    Type: Grant
    Filed: September 6, 2018
    Date of Patent: May 18, 2021
    Assignee: Life Technologies Corporation
    Inventors: Joseph Beechem, Theo Nikiforov, Vi-En Choong, Xinzhan Peng, Guobin Luo, Cheng-Yao Chen, Michael Previte
  • Publication number: 20210040543
    Abstract: The present disclosure provides methods and systems for sequencing nucleic acid molecules in a manner that enables higher sequencing accuracy. Methods and systems provided herein may enable sequences that may have low-accuracy reads, such as homopolymer sequences or other repeating sequences, to be determined at a higher accuracy and efficiency.
    Type: Application
    Filed: July 23, 2020
    Publication date: February 11, 2021
    Inventors: Eliane TREPAGNIER, Mark PRATT, Theo NIKIFOROV, Gilad ALMOGY
  • Publication number: 20200318170
    Abstract: The disclosure provides methods for sequencing nucleic acids using, including with nucleotide analogs and subsequently appended labels.
    Type: Application
    Filed: March 18, 2020
    Publication date: October 8, 2020
    Inventors: Linda LEE, Steven MENCHEN, Theo NIKIFOROV, Gilad ALMOGY, Florian OBERSTRASS
  • Publication number: 20200299655
    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.
    Type: Application
    Filed: June 5, 2020
    Publication date: September 24, 2020
    Inventors: Peter VANDER HORN, Daniel MAZUR, Theo NIKIFOROV, Mindy LANDES, Eileen TOZER
  • Publication number: 20200277580
    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.
    Type: Application
    Filed: April 16, 2020
    Publication date: September 3, 2020
    Inventors: Peter VANDER HORN, Theo NIKIFOROV, Guobin LUO, Mindy LANDES, Daniel MAZUR, Eileen TOZER, Tommie LINCECUM
  • Publication number: 20200231948
    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.
    Type: Application
    Filed: March 20, 2020
    Publication date: July 23, 2020
    Inventors: 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
  • Patent number: 10676724
    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.
    Type: Grant
    Filed: February 7, 2019
    Date of Patent: June 9, 2020
    Assignee: LIFE TECHNOLOGIES CORPORATION
    Inventors: Peter Vander Horn, Daniel Mazur, Theo Nikiforov, Mindy Landes, Eileen Tozer
  • Patent number: 10633641
    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.
    Type: Grant
    Filed: April 23, 2018
    Date of Patent: April 28, 2020
    Assignee: Life Technologies Corporation
    Inventors: Peter Vander Horn, Theo Nikiforov, Guobin Luo, Mindy Landes, Daniel Mazur, Eileen Tozer, Tommie Lloyd Lincecum
  • Patent number: 10597642
    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.
    Type: Grant
    Filed: August 30, 2017
    Date of Patent: March 24, 2020
    Assignee: Life Technologies Corporation
    Inventors: 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
  • Publication number: 20200017846
    Abstract: In some embodiments, the disclosure relates generally to methods as well as related compositions, systems, kits and apparatus comprising linking proteins to target compounds and/or to locations of interest using tethers. For example, the tether can be used to link the protein to a target compound, for example, to link an enzyme to a substrate. Similarly, the tether can be used to link the protein at or near a desired location on a surface. In one group of embodiments, the tether includes a polynucleotide and the target compound or location on the surface includes another polynucleotide that is capable of hybridizing to the tether. In such embodiments, the tether can be used to link the protein to the target compound or location using nucleic acid hybridization.
    Type: Application
    Filed: August 15, 2019
    Publication date: January 16, 2020
    Inventors: John DAVIDSON, Theo NIKIFOROV, Guobin LUO
  • Publication number: 20200002688
    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.
    Type: Application
    Filed: February 7, 2019
    Publication date: January 2, 2020
    Inventors: Peter VANDER HORN, Daniel Mazur, Theo Nikiforov, Mindy Landes, Eileen Tozer
  • Patent number: 10508306
    Abstract: In some embodiments, methods for obtaining sequence information from a nucleic acid template linked to a support include hybridizing a first primer to a template strand linked to a support, sequencing a portion of the nucleic acid template, thereby forming an extended first primer product that is complementary to a portion of the nucleic acid template, In some embodiments, the method further includes introducing a nick into a portion of the template strand that is hybridized to the extended first primer product, degrading a portion of the template strand from the nick using a degrading agent, where a portion of the extended first primer remains hybridized to an undegraded portion of the template strand, and sequencing at least some of the single-stranded portion of the extended first primer by synthesis.
    Type: Grant
    Filed: September 6, 2018
    Date of Patent: December 17, 2019
    Assignee: LIFE TECHNOLOGIES CORPORATION
    Inventors: Jason Myers, Zhoutao Chen, Devin Dressman, Theo Nikiforov
  • Publication number: 20190345549
    Abstract: The present disclosure provide systems, compositions, methods, reagents, kits and products for extending a nucleic acid that includes incorporating a nucleotide residue at a terminus of a nucleic acid using a polymerase enzyme and at least one nucleotide, wherein the at least one nucleotide includes a thiophosphate moiety, and wherein the at least one nucleotide is resistant to hydrolysis by phosphatase. In some embodiments, the nucleotide incorporation can be conducted in the presence of a phosphatase. In some embodiments, the nucleotide incorporation can be conducted in the presence of at least on chelation moiety that is configured to bind an orthophosphate moiety.
    Type: Application
    Filed: May 23, 2019
    Publication date: November 14, 2019
    Inventors: Steven MENCHEN, Theo NIKIFOROV, Barnett ROSENBLUM
  • Publication number: 20190284597
    Abstract: In some embodiments, the disclosure relates generally to methods, as well as related compositions and kits for recombinase-mediated nucleic acid amplification, such as recombinase-polymerase amplification (RPA), of a nucleic acid template using at least one blocked primer that contains a 5? domain, at least one nucleotide that is cleavable by an RNase H enzyme, a 3? domain, wherein the primer is not extendable by a polymerase, and wherein the 3? domain has a length of 7-100 nucleotides, for example 10-30 nucleotides. These methods and the use of a blocked primer reduce or eliminate non-specific amplification products, such as primer dimers, which are generated in RPA reactions.
    Type: Application
    Filed: June 9, 2017
    Publication date: September 19, 2019
    Inventors: Hua YU, Theo NIKIFOROV, Abraham ROSENBAUM
  • Patent number: 10385329
    Abstract: In some embodiments, the disclosure relates generally to methods as well as related compositions, systems, kits and apparatus comprising linking proteins to target compounds and/or to locations of interest using tethers. For example, the tether can be used to link the protein to a target compound, for example, to link an enzyme to a substrate. Similarly, the tether can be used to link the protein at or near a desired location on a surface. In one group of embodiments, the tether includes a polynucleotide and the target compound or location on the surface includes another polynucleotide that is capable of hybridizing to the tether. In such embodiments, the tether can be used to link the protein to the target compound or location using nucleic acid hybridization.
    Type: Grant
    Filed: October 17, 2017
    Date of Patent: August 20, 2019
    Assignee: LIFE TECHNOLOGIES CORPORATION
    Inventors: John Davidson, Theo Nikiforov, Guobin Luo
  • Patent number: 10344325
    Abstract: The present disclosure provide systems, compositions, methods, reagents, kits and products for extending a nucleic acid that includes incorporating a nucleotide residue at a terminus of a nucleic acid using a polymerase enzyme and at least one nucleotide, wherein the at least one nucleotide includes a thiophosphate moiety, and wherein the at least one nucleotide is resistant to hydrolysis by phosphatase. In some embodiments, the nucleotide incorporation can be conducted in the presence of a phosphatase. In some embodiments, the nucleotide incorporation can be conducted in the presence of at least on chelation moiety that is configured to bind an orthophosphate moiety.
    Type: Grant
    Filed: November 10, 2015
    Date of Patent: July 9, 2019
    Assignee: Life Technologies Corporation
    Inventors: Steven Menchen, Theo Nikiforov, Barnett Rosenblum
  • Patent number: 10240134
    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.
    Type: Grant
    Filed: April 7, 2017
    Date of Patent: March 26, 2019
    Assignee: LIFE TECHNOLOGIES CORPORATION
    Inventors: Peter Vander Horn, Daniel Mazur, Theo Nikiforov, Mindy Landes, Eileen Tozer
  • Publication number: 20190062829
    Abstract: Provided herein are systems and methods for nucleotide incorporation reactions. The systems comprise polymerases having altered nucleotide incorporation kinetics and are linked to an energy transfer donor moiety, and nucleotide molecules linked with at least one energy transfer acceptor moiety. The donor and acceptor moieties undergo energy transfer when the polymerase and nucleotide are proximal to each other during nucleotide binding and/or nucleotide incorporation. As the donor and acceptor moieties undergo energy transfer, they generate an energy transfer signal which can be associated with nucleotide binding or incorporation. Detecting a time sequence of the generated signals, or the change in the signals, can be used to determine the order of the incorporated nucleotides, and can therefore be used to deduce the sequence of the target molecule.
    Type: Application
    Filed: September 6, 2018
    Publication date: February 28, 2019
    Inventors: Joseph BEECHEM, Theo NIKIFOROV, Vi-En CHOONG, Xinzhan PENG, Guobin LUO, Cheng-Yao CHEN, Michael PREVITE
  • Publication number: 20190062830
    Abstract: Disclosed herein are conjugates comprising a biomolecule linked to a label that have biological activity and are useful in a wide variety of biological applications. For example, provided herein are polymerase-nanoparticle conjugates including a polymerase linked to a nanoparticle, wherein the conjugate has polymerase activity. Such conjugates can exhibit reduced aggregation and improved stochiometries wherein the average biomolecule:nanoparticle ratio approaches or equals 1:1. Also disclosed herein are improved methods for preparing such conjugates, and methods and systems for using such conjugates in biological applications such as nucleotide incorporation, primer extension and single molecule sequencing.
    Type: Application
    Filed: September 6, 2018
    Publication date: February 28, 2019
    Inventors: Theo NIKIFOROV, Daniel MAZUR, Xinzhan PENG, Tommie Lloyd LINCECUM, Yuri BELOSLUDTSEV, Howard REESE, Dmitriy GREMYACHINSKIY, Roman ROZHKOV, John MAURO, Joseph BEECHEM, Eric TULSKY, Imad NAASANI, Kari HALEY, Joseph TREADWAY