Patents by Inventor Lubomir Sebo

Lubomir Sebo 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: 20170145495
    Abstract: Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
    Type: Application
    Filed: November 21, 2016
    Publication date: May 25, 2017
    Inventors: Lubomir SEBO, Honey OSUNA, Stephen YUE, Yuri LAPIN
  • Publication number: 20170145502
    Abstract: Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
    Type: Application
    Filed: November 21, 2016
    Publication date: May 25, 2017
    Inventors: Gene SHEN, Stephen YUE, Lubomir SEBO, Louis BROGLEY
  • Patent number: 9587275
    Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
    Type: Grant
    Filed: September 8, 2015
    Date of Patent: March 7, 2017
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
  • Patent number: 9447464
    Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
    Type: Grant
    Filed: November 5, 2013
    Date of Patent: September 20, 2016
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
  • Publication number: 20160237279
    Abstract: Multimeric protected fluorescent reagents and their methods of synthesis are provided. The reagents are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The reagents contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements. The reagents also contain coupling elements connect monomeric compounds into multimeric forms, thereby increasing brightness.
    Type: Application
    Filed: February 4, 2016
    Publication date: August 18, 2016
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Frank ZHENG, Jeremiah HANES, Gene SHEN, Louis BROGLEY, Stephen YUE, Yuri LAPIN, John LYLE, Honey OSUNA, Andrei FEDOROV, Lubomir SEBO
  • Publication number: 20160010150
    Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
    Type: Application
    Filed: September 8, 2015
    Publication date: January 14, 2016
    Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
  • Publication number: 20150330987
    Abstract: Compositions, methods, and systems are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The nucleotide analogs have two avidin proteins connected by a central dye component, and each avidin protein is further connected to a nucleotide component. The protein can prevent the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties.
    Type: Application
    Filed: June 1, 2015
    Publication date: November 19, 2015
    Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
  • Publication number: 20150307933
    Abstract: The invention provides a novel class of scaffold-based labeled polymerase enzyme substrates. The polymerase enzyme substrates have a multivalent core or scaffold to which is attached fluorescent dye moieties and nucleoside phosphate moities. The polymerase enzyme substrates have multiple fluorescent dye moities and/or multiple nucleoside phosphate moieties. Preferred multivalent cores comprise trifunctional six membered aromatic moities. The invention also provides for sequencing methods and kits with scaffold-based labeled polymerase enzyme substrates.
    Type: Application
    Filed: November 3, 2014
    Publication date: October 29, 2015
    Inventors: Gene Shen, Lubomir Sebo, Stephen Yue, Wei-Chuan Sun, Louis Brogley, Anderi Fedorov
  • Patent number: 9062091
    Abstract: Compositions and methods are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The protein prevents the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties.
    Type: Grant
    Filed: February 14, 2013
    Date of Patent: June 23, 2015
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
  • Publication number: 20150050659
    Abstract: Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.
    Type: Application
    Filed: August 5, 2014
    Publication date: February 19, 2015
    Inventors: Lubomir SEBO, Jeremiah HANES, Gene SHEN, Louis BROGLEY, Stephen YUE, Frank ZHENG, Yuri LAPIN, John LYLE, Honey OSUNA, Andrei FEDOROV
  • Patent number: 8906612
    Abstract: The invention provides a novel class of scaffold-based labeled polymerase enzyme substrates. The polymerase enzyme substrates have a multivalent core or scaffold to which is attached fluorescent dye moieties and nucleoside phosphate moities. The polymerase enzyme substrates have multiple fluorescent dye moities and/or multiple nucleoside phosphate moieties. Preferred multivalent cores comprise trifunctional six membered aromatic moities. The invention also provides for sequencing methods and kits with scaffold-based labeled polymerase enzyme substrates.
    Type: Grant
    Filed: August 25, 2011
    Date of Patent: December 9, 2014
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Gene Shen, Lubomir Sebo, Stephen Yue, Wei-Chuan Sun, Louis Brogley, Andrei Fedorov
  • Publication number: 20140127680
    Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
    Type: Application
    Filed: November 5, 2013
    Publication date: May 8, 2014
    Applicant: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
    Inventors: Robin Emig, LEI JIA, JEREMIAH HANES, LUBOMIR SEBO
  • Patent number: 8603741
    Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
    Type: Grant
    Filed: February 8, 2011
    Date of Patent: December 10, 2013
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
  • Publication number: 20130316912
    Abstract: Compositions and methods are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The protein prevents the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties.
    Type: Application
    Filed: February 14, 2013
    Publication date: November 28, 2013
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
  • Patent number: 8388982
    Abstract: Compositions, devices, systems and methods for reducing and/or preventing photo-induced damage of one or more reactants in an illuminated analytical reaction by addition of one or more photo-induced damage mitigating agents to the reaction mixture and allowing the reaction to proceed for a period that is less than a photo-induced damage threshold period.
    Type: Grant
    Filed: November 19, 2009
    Date of Patent: March 5, 2013
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Xiangxu Kong, Gene Shen, Andrei Fedorov, John Lyle, Grace Lee, Lubomir Sebo, Duc Do, Robert Weber, Stephen Dudek
  • Patent number: 8252911
    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.
    Type: Grant
    Filed: February 12, 2009
    Date of Patent: August 28, 2012
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Keith Bjornson, Arek Bibillo, Lubomir Sebo
  • Publication number: 20120077189
    Abstract: The invention provides a novel class of scaffold-based labeled polymerase enzyme substrates. The polymerase enzyme substrates have a multivalent core or scaffold to which is attached fluorescent dye moieties and nucleoside phosphate moities. The polymerase enzyme substrates have multiple fluorescent dye moities and/or multiple nucleoside phosphate moieties. Preferred multivalent cores comprise trifunctional six membered aromatic moities. The invention also provides for sequencing methods and kits with scaffold-based labeled polymerase enzyme substrates.
    Type: Application
    Filed: August 25, 2011
    Publication date: March 29, 2012
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Gene Shen, Lubomir Sebo, Stephen Yue, Wei-Chuan Sun, Louis Brogley, Andrei Fedorov
  • Publication number: 20120058473
    Abstract: In various embodiments, the present invention provides fluorescent dyes that are linked to another species through an adaptor moiety. In an exemplary embodiment, the dye is linked to a polyphosphate nucleic acid through an adaptor. An adaptor can be a component of a linker. These conjugates find use in single molecule DNA sequencing and other applications. In various embodiments, the dye moiety is a cyanine dye. Cyanine dyes that are highly charged, such as those including multiple sulfonate, alkylsulfonate, carboxylate and/or alkylcarboxylate moieties are examples of cyanine dyes of use in the compounds of the invention.
    Type: Application
    Filed: August 25, 2011
    Publication date: March 8, 2012
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Stephen Yue, Gene Shen, Louis Brogley, Lubomir Sebo, Jeffrey Wegener
  • Publication number: 20110212437
    Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
    Type: Application
    Filed: February 8, 2011
    Publication date: September 1, 2011
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
  • Publication number: 20100136592
    Abstract: Compositions, devices, systems and methods for reducing and/or preventing photo-induced damage of one or more reactants in an illuminated analytical reaction by addition of one or more photo-induced damage mitigating agents to the reaction mixture and allowing the reaction to proceed for a period that is less than a photo-induced damage threshold period.
    Type: Application
    Filed: November 19, 2009
    Publication date: June 3, 2010
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Xiangxu Kong, Gene Shen, Andrei Fedorov, John Lyle, Grace Lee, Lubomir Sebo, Duc Do, Robert Weber, Stephen Dudek