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).
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Publication number: 20170145495Abstract: 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: ApplicationFiled: November 21, 2016Publication date: May 25, 2017Inventors: Lubomir SEBO, Honey OSUNA, Stephen YUE, Yuri LAPIN
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Publication number: 20170145502Abstract: 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: ApplicationFiled: November 21, 2016Publication date: May 25, 2017Inventors: Gene SHEN, Stephen YUE, Lubomir SEBO, Louis BROGLEY
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Patent number: 9587275Abstract: 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: GrantFiled: September 8, 2015Date of Patent: March 7, 2017Assignee: Pacific Biosciences of California, Inc.Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
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Patent number: 9447464Abstract: 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: GrantFiled: November 5, 2013Date of Patent: September 20, 2016Assignee: Pacific Biosciences of California, Inc.Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
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Publication number: 20160237279Abstract: 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: ApplicationFiled: February 4, 2016Publication date: August 18, 2016Applicant: 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
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Publication number: 20160010150Abstract: 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: ApplicationFiled: September 8, 2015Publication date: January 14, 2016Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
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Publication number: 20150330987Abstract: 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: ApplicationFiled: June 1, 2015Publication date: November 19, 2015Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
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Publication number: 20150307933Abstract: 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: ApplicationFiled: November 3, 2014Publication date: October 29, 2015Inventors: Gene Shen, Lubomir Sebo, Stephen Yue, Wei-Chuan Sun, Louis Brogley, Anderi Fedorov
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Patent number: 9062091Abstract: 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: GrantFiled: February 14, 2013Date of Patent: June 23, 2015Assignee: Pacific Biosciences of California, Inc.Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
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Publication number: 20150050659Abstract: 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: ApplicationFiled: August 5, 2014Publication date: February 19, 2015Inventors: Lubomir SEBO, Jeremiah HANES, Gene SHEN, Louis BROGLEY, Stephen YUE, Frank ZHENG, Yuri LAPIN, John LYLE, Honey OSUNA, Andrei FEDOROV
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Patent number: 8906612Abstract: 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: GrantFiled: August 25, 2011Date of Patent: December 9, 2014Assignee: Pacific Biosciences of California, Inc.Inventors: Gene Shen, Lubomir Sebo, Stephen Yue, Wei-Chuan Sun, Louis Brogley, Andrei Fedorov
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Publication number: 20140127680Abstract: 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: ApplicationFiled: November 5, 2013Publication date: May 8, 2014Applicant: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.Inventors: Robin Emig, LEI JIA, JEREMIAH HANES, LUBOMIR SEBO
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Patent number: 8603741Abstract: 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: GrantFiled: February 8, 2011Date of Patent: December 10, 2013Assignee: Pacific Biosciences of California, Inc.Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
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Publication number: 20130316912Abstract: 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: ApplicationFiled: February 14, 2013Publication date: November 28, 2013Applicant: Pacific Biosciences of California, Inc.Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
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Patent number: 8388982Abstract: 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: GrantFiled: November 19, 2009Date of Patent: March 5, 2013Assignee: Pacific Biosciences of California, Inc.Inventors: Xiangxu Kong, Gene Shen, Andrei Fedorov, John Lyle, Grace Lee, Lubomir Sebo, Duc Do, Robert Weber, Stephen Dudek
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Patent number: 8252911Abstract: 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: GrantFiled: February 12, 2009Date of Patent: August 28, 2012Assignee: Pacific Biosciences of California, Inc.Inventors: Keith Bjornson, Arek Bibillo, Lubomir Sebo
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Publication number: 20120077189Abstract: 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: ApplicationFiled: August 25, 2011Publication date: March 29, 2012Applicant: Pacific Biosciences of California, Inc.Inventors: Gene Shen, Lubomir Sebo, Stephen Yue, Wei-Chuan Sun, Louis Brogley, Andrei Fedorov
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Publication number: 20120058473Abstract: 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: ApplicationFiled: August 25, 2011Publication date: March 8, 2012Applicant: Pacific Biosciences of California, Inc.Inventors: Stephen Yue, Gene Shen, Louis Brogley, Lubomir Sebo, Jeffrey Wegener
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Publication number: 20110212437Abstract: 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: ApplicationFiled: February 8, 2011Publication date: September 1, 2011Applicant: Pacific Biosciences of California, Inc.Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
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Publication number: 20100136592Abstract: 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: ApplicationFiled: November 19, 2009Publication date: June 3, 2010Applicant: Pacific Biosciences of California, Inc.Inventors: Xiangxu Kong, Gene Shen, Andrei Fedorov, John Lyle, Grace Lee, Lubomir Sebo, Duc Do, Robert Weber, Stephen Dudek