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: 20200299319Abstract: 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: January 31, 2020Publication date: September 24, 2020Applicant: Pacific Biosciences of California, Inc.Inventors: Lubomir SEBO, Honey OSUNA, Stephen YUE, Yuri LAPIN
-
Patent number: 10781483Abstract: 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: GrantFiled: November 21, 2016Date of Patent: September 22, 2020Assignee: Pacific Biosciences of California, Inc.Inventors: Lubomir Sebo, Gene Shen, Stephen Yue, Honey Osuna, Yuri Lapin, Louis Brogley, Andrei Fedorov
-
Publication number: 20200224258Abstract: Multi-biotinylated reactants are provided which can be used in divalent complexes for various applications such as colocalization, labeling, immobilization, and purification. Methods for constructing, purifying, and using the bis-biotinylated reactants are also provided. In certain embodiments, two bis-biotinylated reactants are bound to a single streptavidin tetramer to provide a complex having a 1:1 stoichiometry with respect to the bis-biotinylated reactants.Type: ApplicationFiled: December 9, 2019Publication date: July 16, 2020Inventors: Gene Shen, Natasha Popovich, Erik Miller, Satwik Kamtekar, Keith Bjornson, Jeremiah Hanes, Stephen Yue, Lubomir Sebo, Zhong Wang
-
Patent number: 10676788Abstract: 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: GrantFiled: May 19, 2017Date of Patent: June 9, 2020Assignee: Pacific Biosciences of California, Inc.Inventors: Gene Shen, Stephen Yue, Lubomir Sebo, Louis Brogley
-
Patent number: 10669299Abstract: 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: GrantFiled: November 21, 2016Date of Patent: June 2, 2020Assignee: Pacific Biosciences of California, Inc.Inventors: Lubomir Sebo, Honey Osuna, Stephen Yue, Yuri Lapin
-
Patent number: 10655168Abstract: Compositions comprising covalently modified and mutated biotin-binding proteins, particularly biotin-binding proteins having a negative charge at physiological pH, are provided. Methods of producing such proteins are also provided, as are methods of immobilizing, sequencing, and making nucleic acids employing such proteins.Type: GrantFiled: December 21, 2018Date of Patent: May 19, 2020Assignee: Pacific Biosciences of California, Inc.Inventors: Satwik Kamtekar, Lubomir Sebo, Leewin Chern, Thomas Linsky, Jeremiah Hanes, Erik Miller, Ying Yang, Stephen Yue
-
Publication number: 20200087722Abstract: 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: June 13, 2019Publication date: March 19, 2020Applicant: Pacific Biosciences of California, Inc.Inventors: Gene SHEN, Stephen YUE, Lubomir SEBO, Louis BROGLEY
-
Patent number: 10544449Abstract: Multi-biotinylated reactants are provided which can be used in divalent complexes for various applications such as colocalization, labeling, immobilization, and purification. Methods for constructing, purifying, and using the bis-biotinylated reactants are also provided. In certain embodiments, two bis-biotinylated reactants are bound to a single streptavidin tetramer to provide a complex having a 1:1 stoichiometry with respect to the bis-biotinylated reactants.Type: GrantFiled: January 6, 2017Date of Patent: January 28, 2020Assignee: Pacific Biosciences of California, Inc.Inventors: Gene Shen, Natasha Popovich, Erik Miller, Satwik Kamtekar, Keith Bjornson, Jeremiah Hanes, Stephen Yue, Lubomir Sebo, Zhong Wang
-
Publication number: 20190309171Abstract: 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: December 4, 2018Publication date: October 10, 2019Applicant: 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: 20190249237Abstract: Compositions comprising covalently modified and mutated biotin-binding proteins, particularly biotin-binding proteins having a negative charge at physiological pH, are provided. Methods of producing such proteins are also provided, as are methods of immobilizing, sequencing, and making nucleic acids employing such proteins.Type: ApplicationFiled: December 21, 2018Publication date: August 15, 2019Inventors: Satwik Kamtekar, Lubomir Sebo, Leewin Chern, Thomas Linsky, Jeremiah Hanes, Erik Miller, Ying Yang, Stephen Yue
-
Publication number: 20190010183Abstract: Compositions, methods, and systems are provided for fluorescent polymerase enzyme substrates comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Fluorescent polymerase enzyme substrates of the invention have a protein shield between the fluorescent dye moieties and nucleotide moieties of the polymerase enzyme substrate. The polymerase enzyme substrates have a nucleotide component and a dye component, each attached to a protein. The attachments can be covalent. The protein can, for example, prevent the direct interaction of the fluorescent dye moiety with the enzyme when carrying out nucleotide synthesis, preventing photodamage to the enzyme. The polymerase enzyme substrates of the invention can have multiple dyes and multiple nucleotide moieties.Type: ApplicationFiled: June 19, 2018Publication date: January 10, 2019Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
-
Patent number: 10150872Abstract: 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: GrantFiled: February 4, 2016Date of Patent: December 11, 2018Assignee: 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: 20180346507Abstract: 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: April 30, 2018Publication date: December 6, 2018Inventors: Lubomir SEBO, Jeremiah HANES, Gene SHEN, Louis BROGLEY, Stephen YUE, Frank ZHENG, Yuri LAPIN, John LYLE, Honey OSUNA, Andrei FEDOROV
-
Patent number: 10023605Abstract: 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: GrantFiled: June 1, 2015Date of Patent: July 17, 2018Assignee: Pacific Biosciences of California, Inc.Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
-
Patent number: 9957291Abstract: 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: GrantFiled: August 5, 2014Date of Patent: May 1, 2018Assignee: Pacific Biosciences of California, Inc.Inventors: Lubomir Sebo, Jeremiah Hanes, Gene Shen, Louis Brogley, Stephen Yue, Frank Zheng, Yuri Lapin, John Lyle, Honey Osuna, Andrei Fedorov
-
Publication number: 20170321268Abstract: 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: May 19, 2017Publication date: November 9, 2017Inventors: Gene SHEN, Stephen YUE, Lubomir SEBO, Louis BROGLEY
-
Patent number: 9777320Abstract: 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: GrantFiled: August 25, 2011Date of Patent: October 3, 2017Assignee: Pacific Biosciences of California, Inc.Inventors: Stephen Yue, Gene Shen, Louis Brogley, Lubomir Sebo, Jeffrey Wegener
-
Patent number: 9702001Abstract: 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: November 3, 2014Date of Patent: July 11, 2017Assignee: Pacific Biosciences of California, Inc.Inventors: Gene Shen, Lubomir Sebo, Stephen Yue, Wei-Chuan Sun, Louis Brogley, Andrei Fedorov
-
Publication number: 20170184580Abstract: Multi-biotinylated reactants are provided which can be used in divalent complexes for various applications such as colocalization, labeling, immobilization, and purification. Methods for constructing, purifying, and using the bis-biotinylated reactants are also provided. In certain embodiments, two bis-biotinylated reactants are bound to a single streptavidin tetramer to provide a complex having a 1:1 stoichiometry with respect to the bis-biotinylated reactants.Type: ApplicationFiled: January 6, 2017Publication date: June 29, 2017Inventors: Gene Shen, Natasha Popovich, Erik Miller, Satwik Kamtekar, Keith Bjornson, Jeremiah Hanes, Stephen Yue, Lubomir Sebo, Zhong Wang
-
Publication number: 20170145496Abstract: 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, Gene SHEN, Stephen YUE, Honey OSUNA, Yuri LAPIN, Louis BROGLEY, Andrei FEDOROV