Patents by Inventor Denis A. MALYSHEV

Denis A. MALYSHEV 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).

  • Publication number: 20220144875
    Abstract: Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3?-O-oxime moiety such as with a reagent having an —ONH2 moiety to produce a nucleotide having a 3?-O—NH2 moiety such as wherein the reagent having the —ONH2 moiety further comprises alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, or (heteroalicyclyl)alkyl.
    Type: Application
    Filed: September 17, 2021
    Publication date: May 12, 2022
    Inventors: Denis Malyshev, Aaron W. Feldman
  • Publication number: 20220136045
    Abstract: A method of characterizing a nucleic acid that includes steps of (a) contacting a primer-template nucleic acid hybrid with a polymerase and a mixture of nucleotides to produce an extended primer hybrid and to form a stabilized ternary complex including the extended primer hybrid, the polymerase and a nucleotide cognate of the next base in the template, wherein the mixture contains nucleotide cognates of four different base types, wherein the nucleotide cognate of the first base type has a reversible terminator, and wherein nucleotide cognates of the second, third and fourth base types are extendable; (b) detecting the stabilized ternary complex to distinguish the next base from other base types in the template; and (c) determining the presence of a base multiplet in the template nucleic acid, the base multiplet including the first base type followed by the next base.
    Type: Application
    Filed: August 2, 2021
    Publication date: May 5, 2022
    Inventors: Denis Malyshev, Arnold Oliphant
  • Publication number: 20220106628
    Abstract: A method for identifying a nucleic acid template that include (a) providing a plurality of primer-template hybrids, wherein a first hybrid of the plurality includes a first template hybridized to a first primer, and wherein a second hybrid of the plurality includes a second template hybridized to a second primer, the second primer having a ternary complex inhibitor moiety at the 3? end; (b) delivering polymerases and nucleotides to the plurality, whereby the first hybrid binds a polymerase and nucleotide to form a stabilized ternary complex and whereby the second hybrid does not bind a polymerase and nucleotide to form a stabilized ternary complex; and (c) detecting the stabilized ternary complex to identify the first template.
    Type: Application
    Filed: October 15, 2021
    Publication date: April 7, 2022
    Applicant: Omniome, Inc.
    Inventors: Hari K.K. SUBRAMANIAN, Chad FLEISCHER, Denis MALYSHEV
  • Patent number: 11180520
    Abstract: Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3?-O-oxime moiety such as with a reagent having an —ONH2 moiety to produce a nucleotide having a 3?-O—NH2 moiety such as wherein the reagent having the —ONH2 moiety further comprises alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, or (heteroalicyclyl)alkyl.
    Type: Grant
    Filed: September 10, 2020
    Date of Patent: November 23, 2021
    Assignee: OMNIOME, INC.
    Inventors: Denis Malyshev, Aaron W. Feldman
  • Patent number: 11180794
    Abstract: A method for identifying a nucleic acid template that includes (a) providing a plurality of primer-template hybrids, wherein a first hybrid of the plurality includes a first template hybridized to a first primer, and wherein a second hybrid of the plurality includes a second template hybridized to a second primer, the second primer having a ternary complex inhibitor moiety at the 3? end; (b) delivering polymerases and nucleotides to the plurality, whereby the first hybrid binds a polymerase and nucleotide to form a stabilized ternary complex and whereby the second hybrid does not bind a polymerase and nucleotide to form a stabilized ternary complex; and (c) detecting the stabilized ternary complex to identify the first template.
    Type: Grant
    Filed: October 18, 2019
    Date of Patent: November 23, 2021
    Assignee: OMNIOME, INC.
    Inventors: Hari K. K. Subramanian, Chad Fleischer, Denis Malyshev
  • Publication number: 20210070795
    Abstract: Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3?-O-oxime moiety with a reagent having the structure R2-ONH2 to produce a nucleotide having a 3?-O—NH2 moiety, wherein R2 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, or an optionally substituted variant thereof.
    Type: Application
    Filed: September 10, 2020
    Publication date: March 11, 2021
    Inventors: Denis Malyshev, Aaron W. Feldman
  • Patent number: 10626138
    Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.
    Type: Grant
    Filed: August 8, 2014
    Date of Patent: April 21, 2020
    Assignees: THE SCRIPPS RESEARCH INSTITUTE NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT NIH DIVISION OF EXTRAMURAL INVENTIONS AND TECHNOLOGY RESOURCES (DEITR)
    Inventors: Floyd E. Romesberg, Denis A. Malyshev, Lingjun Li, Thomas Lavergne, Zhengtao Li
  • Publication number: 20200095591
    Abstract: A recombinantly expressed nucleotide triphosphate transporter efficiently imports the triphosphates of unnatural nucleotides into cells, and the endogenous cellular machinery incorporates those nucleotides into cellular nucleic acids. UBPs can therefore form within the cell's nucleic acids. Moreover, neither the presence of the unnatural triphosphates nor the replication of the UBP represents a significant growth burden. The UBP is not efficiently excised by nucleic acid repair pathways, and therefore can be retained as long as the unnatural triphosphates are available in the growth medium. Thus, the resulting cell is the first organism to stably propagate an expanded genetic alphabet.
    Type: Application
    Filed: October 2, 2019
    Publication date: March 26, 2020
    Inventors: Floyd E. ROMESBERG, Denis A. MALYSHEV
  • Publication number: 20200040027
    Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.
    Type: Application
    Filed: July 22, 2019
    Publication date: February 6, 2020
    Inventors: Floyd E. ROMESBERG, Denis A. MALYSHEV, Lingjun LI, Thomas LAVERGNE, Zhengtao LI
  • Publication number: 20200032317
    Abstract: A method for identifying a nucleotide in a primed template nucleic acid, including the steps of (a) providing a vessel having a primed template nucleic acid, polymerase and a nucleotide cognate of a first base type; (b) examining the vessel for a stabilized ternary complex including the polymerase and the nucleotide cognate of the first base type bound at a base position of the primed template nucleic acid; (c) delivering a nucleotide cognate of a second base type to the vessel, whereby the vessel retains the primed template nucleic acid and the polymerase from step (b); (d) examining the vessel for a stabilized ternary complex including the polymerase and the nucleotide cognate of the second base type bound at the base position of the primed template nucleic acid; and (e) identifying the type of nucleotide at the base position of the primed template nucleic acid.
    Type: Application
    Filed: July 22, 2019
    Publication date: January 30, 2020
    Applicant: Omniome, Inc.
    Inventors: Brittany A. ROHRMAN, Denis MALYSHEV, Morassa Mohseni MIDDLETON, Arnold OLIPHANT
  • Publication number: 20200032322
    Abstract: A method for identifying a nucleic acid template that include (a) providing a plurality of primer-template hybrids, wherein a first hybrid of the plurality includes a first template hybridized to a first primer, and wherein a second hybrid of the plurality includes a second template hybridized to a second primer, the second primer having a ternary complex inhibitor moiety at the 3? end; (b) delivering polymerases and nucleotides to the plurality, whereby the first hybrid binds a polymerase and nucleotide to form a stabilized ternary complex and whereby the second hybrid does not bind a polymerase and nucleotide to form a stabilized ternary complex; and (c) detecting the stabilized ternary complex to identify the first template.
    Type: Application
    Filed: October 18, 2019
    Publication date: January 30, 2020
    Applicant: Omniome, Inc.
    Inventors: Hari SUBRAMANIAN, Chad FLEISCHER, Denis MALYSHEV
  • Publication number: 20200024597
    Abstract: Disclosed herein are methods, compositions and kits for the synthesis of proteins which comprises unnatural amino acids that utilize a mutant tRNA.
    Type: Application
    Filed: September 20, 2019
    Publication date: January 23, 2020
    Inventors: Jerod Ptacin, Denis Malyshev, Carolina Caffaro
  • Publication number: 20200017540
    Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.
    Type: Application
    Filed: August 8, 2019
    Publication date: January 16, 2020
    Inventors: Floyd E. ROMESBERG, Denis A. MALYSHEV, Lingjun LI, Thomas LAVERGNE, Zhengtao LI
  • Publication number: 20200010885
    Abstract: A method for determining the presence of an allele, including (a) binding a polymerase to a double stranded nucleic acid that includes a primer hybridized to a template, the template including a first allele of a locus; (b) adding a nucleotide to the primer via catalytic activity of the polymerase, thereby producing an extended nucleic acid; (c) dissociating the polymerase from the extended nucleic acid; (d) detecting dissociation of the polymerase from the extended nucleic acid; and (e) comparing the dissociation of the polymerase from the extended nucleic acid to dissociation of the polymerase from a second double stranded nucleic acid, the second double stranded nucleic acid including a primer hybridized to the same position of the locus as the primer of the extended nucleic acid.
    Type: Application
    Filed: February 14, 2018
    Publication date: January 9, 2020
    Applicant: OMNIOME, INC.
    Inventors: Denis MALYSHEV, Sean STROMBERG
  • Patent number: 10513706
    Abstract: A recombinantly expressed nucleotide triphosphate transporter efficiently imports the triphosphates of unnatural nucleotides into cells, and the endogenous cellular machinery incorporates those nucleotides into cellular nucleic acids. UBPs can therefore form within the cell's nucleic acids. Moreover, neither the presence of the unnatural triphosphates nor the replication of the UBP represents a significant growth burden. The UBP is not efficiently excised by nucleic acid repair pathways, and therefore can be retained as long as the unnatural triphosphates are available in the growth medium. Thus, the resulting cell is the first organism to stably propagate an expanded genetic alphabet.
    Type: Grant
    Filed: April 9, 2015
    Date of Patent: December 24, 2019
    Assignee: The Scripps Research Institute
    Inventors: Floyd E. Romesberg, Denis A. Malyshev
  • Publication number: 20190367974
    Abstract: A method for identifying a nucleotide in a template nucleic acid by (a) providing a plurality of primer-template nucleic acid hybrids, wherein the primers have an extendable 3? end; (b) contacting the plurality with: (i) blocked nucleotides to produce a first subset of the primer-template nucleic acid hybrids that include a blocked nucleotide at the 3? end, and (ii) a ternary complex inhibitor to produce a second subset of the primer-template nucleic acid hybrids that include a ternary complex inhibitor; (c) forming ternary complexes that each include a polymerase, a primer-template nucleic acid hybrid of the first subset, and a cognate nucleotide; and (d) detecting the ternary complexes, thereby identifying a nucleotide in the template nucleic acid.
    Type: Application
    Filed: April 12, 2019
    Publication date: December 5, 2019
    Applicant: Omniome, Inc.
    Inventors: Chad FLEISCHER, Denis MALYSHEV
  • Publication number: 20190241945
    Abstract: A method of characterizing a nucleic acid that includes steps of (a) contacting a primer-template nucleic acid hybrid with a polymerase and a mixture of nucleotides to produce an extended primer hybrid and to form a stabilized ternary complex including the extended primer hybrid, the polymerase and a nucleotide cognate of the next base in the template, wherein the mixture contains nucleotide cognates of four different base types, wherein the nucleotide cognate of the first base type has a reversible terminator, and wherein nucleotide cognates of the second, third and fourth base types are extendable; (b) detecting the stabilized ternary complex to distinguish the next base from other base types in the template; and (c) determining the presence of a base multiplet in the template nucleic acid, the base multiplet including the first base type followed by the next base.
    Type: Application
    Filed: February 1, 2019
    Publication date: August 8, 2019
    Inventors: Denis Malyshev, Arnold Oliphant
  • Publication number: 20170369871
    Abstract: Disclosed herein are methods, composition and kits for the synthesis of proteins which comprises unnatural amino acids that utilize a mutant tRNA, wherein the mutant tRNA comprises a mutant anticodon sequence. And an additional method comprises generating nucleic acids that contain an expanded genetic alphabet.
    Type: Application
    Filed: January 12, 2016
    Publication date: December 28, 2017
    Inventors: Jerod PTACIN, Denis A. MALYSHEV, Carolina CAFFARO
  • Publication number: 20170029829
    Abstract: A recombinantly expressed nucleotide triphosphate transporter efficiently imports the triphosphates of unnatural nucleotides into cells, and the endogenous cellular machinery incorporates those nucleotides into cellular nucleic acids. UBPs can therefore form within the cell's nucleic acids. Moreover, neither the presence of the unnatural triphosphates nor the replication of the UBP represents a significant growth burden. The UBP is not efficiently excised by nucleic acid repair pathways, and therefore can be retained as long as the unnatural triphosphates are available in the growth medium. Thus, the resulting cell is the first organism to stably propagate an expanded genetic alphabet.
    Type: Application
    Filed: April 9, 2015
    Publication date: February 2, 2017
    Applicant: The Scripps Research Institute
    Inventors: Floyd E. ROMESBERG, Denis A. MALYSHEV
  • Publication number: 20160168187
    Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.
    Type: Application
    Filed: August 8, 2014
    Publication date: June 16, 2016
    Applicant: Synthorx, Inc.
    Inventors: Floyd E. ROMESBERG, Denis A. MALYSHEV, Lingjun LI, Thomas LAVERGNE, Zhengtao LI