Patents by Inventor Keith Bjornson

Keith Bjornson 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: 10221436
    Abstract: This disclosure provides methods for preparing a sequencing library including the steps of providing a template nucleic acid sequence, dNTPs, dUTP, a primer, a polymerase, a dUTP excising enzyme, and a plurality of beads including oligonucleotide adapter sequence segments; amplifying the template nucleic acid with the polymerase, dNTPs, dUTP and random hexamer to provide a complementary nucleic acid sequence including occasional dUTPs; and excising the incorporated dUTPs with the dUTP excising enzyme to provide nicks in the complementary nucleic acid sequence to provide a sequencing library.
    Type: Grant
    Filed: January 7, 2016
    Date of Patent: March 5, 2019
    Assignee: 10X GENOMICS, INC.
    Inventors: Paul Hardenbol, Pranav Patel, Benjamin Hindson, Paul William Wyatt, Keith Bjornson, Indira Wu, Kamila Belhocine
  • Patent number: 10184148
    Abstract: Compositions, kits, methods and systems for single molecule nucleotide sequencing comprising producing polymerase reactions having lithium that control the median pulse width for incorporated nucleotides are disclosed. The levels of lithium are used to control pulse width while allowing other sequencing parameters to remain within a desirable range.
    Type: Grant
    Filed: April 5, 2017
    Date of Patent: January 22, 2019
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Andrei Fedorov, John Lyle, Keith Bjornson, Jeremiah Hanes
  • Publication number: 20190010183
    Abstract: 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: Application
    Filed: June 19, 2018
    Publication date: January 10, 2019
    Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
  • Patent number: 10023605
    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: Grant
    Filed: June 1, 2015
    Date of Patent: July 17, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
  • Publication number: 20180171402
    Abstract: Sequencing methods, devices, and systems are described. Arrays of nanoscale electronic elements comprising two electrodes separated by an insulating layer are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound proximate to the insulating region. A sequencing reaction mixture comprising nucleotide analogs having impedance labels is introduced to the array of nanoscale electronic elements under conditions of polymerase mediated nucleic acid synthesis. The time sequence of incorporation of nucleotide analogs is determined by identifying the types of labels of the nucleotide analogs that are incorporated into the growing strand using measured impedance.
    Type: Application
    Filed: December 8, 2017
    Publication date: June 21, 2018
    Inventors: Stephen Turner, Jeremiah Hanes, Keith Bjornson
  • Publication number: 20180023134
    Abstract: The present invention provides methods, compositions, and systems for distributing molecules and complexes into reaction sites. In particular, the methods, compositions, and systems of the present invention result in an active loading of molecules and complexes into reaction sites with improved efficiency over loading by passive diffusion methods alone.
    Type: Application
    Filed: July 21, 2017
    Publication date: January 25, 2018
    Inventors: Jeremiah Hanes, Satwik Kamtekar, Yufeng Qian, Keith Bjornson, Thang Pham, David Rank, Paul Peluso, Erik Miller, Kristin Gleitsman, Leewin Chern, Steven Lin, Stephen Turner
  • Publication number: 20170356041
    Abstract: The present invention provides methods, compositions, and systems for enriching compositions for polymerase enzyme complexes. In particular, the methods, compositions, and systems of the present invention remove free polymerases from the compositions using one or more purification steps, including protease treatment, thus enriching the compositions for polymerases complexed with a template nucleic acid.
    Type: Application
    Filed: June 9, 2017
    Publication date: December 14, 2017
    Inventors: Erik Miller, Keith Bjornson, Kristofor Nyquist, Satwik Kamtekar
  • Publication number: 20170260579
    Abstract: Compositions, kits, methods and systems for single molecule nucleotide sequencing comprising producing polymerase reactions having lithium that control the median pulse width for incorporated nucleotides are disclosed. The levels of lithium are used to control pulse width while allowing other sequencing parameters to remain within a desirable range.
    Type: Application
    Filed: April 5, 2017
    Publication date: September 14, 2017
    Inventors: Andrei Fedorov, John Lyle, Keith Bjornson, Jeremiah Hanes
  • Patent number: 9708656
    Abstract: Real time electronic sequencing methods, devices, and systems are described. Arrays of nanoscale electronic elements comprising capacitive devices with one or two electrodes, or arrays of nanoFET devices are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound proximate to the nanoscale electronic elements or to the substrate proximate to the nanoscale electronic element. A sequencing reaction mixture comprising nucleotide analogs having impedance labels, capacitive labels, or conductivity labels is introduced to the array of nanoscale electronic elements comprising capacitive devices or nanoFETs under conditions of polymerase mediated nucleic acid synthesis. The time sequence of incorporation of nucleotide analogs is determined by identifying the types of labels of the nucleotide analogs that are incorporated into the growing strand using measured impedance, conductivity, or capacitance.
    Type: Grant
    Filed: May 5, 2014
    Date of Patent: July 18, 2017
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Jeremiah Hanes, Keith Bjornson
  • Publication number: 20170184580
    Abstract: 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: Application
    Filed: January 6, 2017
    Publication date: June 29, 2017
    Inventors: Gene Shen, Natasha Popovich, Erik Miller, Satwik Kamtekar, Keith Bjornson, Jeremiah Hanes, Stephen Yue, Lubomir Sebo, Zhong Wang
  • Patent number: 9678080
    Abstract: 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: Grant
    Filed: June 12, 2014
    Date of Patent: June 13, 2017
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Erik Miller, Satwik Kamtekar, Keith Bjornson, Jeremiah Hanes
  • Patent number: 9650672
    Abstract: Provided are compositions comprising modified DNA polymerases that exhibit improved photostability compared to the parental polymerases from which they were derived. Provided are methods for generating enzymes, such as DNA polymerases, with the aforementioned phenotype. Provided are methods of using polymerases with increased resistance to photodamage to make a DNA or to sequence a DNA template.
    Type: Grant
    Filed: August 5, 2015
    Date of Patent: May 16, 2017
    Assignee: Pacific Biosciences of California, Inc.
    Inventor: Keith Bjornson
  • Patent number: 9650671
    Abstract: Compositions, kits, methods and systems for single molecule nucleotide sequencing comprising producing polymerase reactions having lithium that control the median pulse width for incorporated nucleotides are disclosed. The levels of lithium are used to control pulse width while allowing other sequencing parameters to remain within a desirable range.
    Type: Grant
    Filed: March 9, 2015
    Date of Patent: May 16, 2017
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Andrei Fedorov, John Lyle, Keith Bjornson, Jeremiah Hanes
  • Patent number: 9551028
    Abstract: Provided are methods for sequencing a nucleic acid with a sequencing enzyme, e.g., a polymerase or exonuclease. The sequencing enzyme can optionally be exchanged with a second sequencing enzyme, which continues the sequencing of the nucleic acid. In certain embodiments, a template is fixed to a surface through a template localizing moiety. The template localizing moiety can optionally anneal with the nucleic acid and/or associate with the sequencing enzyme. Also provided are compositions comprising a nucleic acid and a first sequencing enzyme, which can sequence the nucleic acid and optionally exchange with a second sequencing enzyme present in the composition. Compositions in which a template localizing moiety is immobilized on a surface are provided. Also provided are methods for using data from analytical reactions wherein two different enzymes are employed, e.g., at a same or different reaction regions.
    Type: Grant
    Filed: November 25, 2014
    Date of Patent: January 24, 2017
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Keith Bjornson, Arek Bibillo, Fred Christians, Kevin Travers, Robin Emig, Stephen Turner
  • Publication number: 20160257984
    Abstract: This disclosure provides methods for preparing a sequencing library including the steps of providing a template nucleic acid sequence, dNTPs, dUTP, a primer, a polymerase, a dUTP excising enzyme, and a plurality of beads including oligonucleotide adapter sequence segments; amplifying the template nucleic acid with the polymerase, dNTPs, dUTP and random hexamer to provide a complementary nucleic acid sequence including occasional dUTPs; and excising the incorporated dUTPs with the dUTP excising enzyme to provide nicks in the complementary nucleic acid sequence to provide a sequencing library.
    Type: Application
    Filed: January 7, 2016
    Publication date: September 8, 2016
    Inventors: Paul Hardenbol, Pranav Patel, Benjamin Hindson, Paul William Wyatt, Keith Bjornson, Indira Wu, Kamila Belhocine
  • Publication number: 20160177384
    Abstract: Systems for nucleotide sequencing comprising producing polymerase reactions that exhibit two kinetically observable steps within an observable phase of the polymerase reaction. Two slow step systems can be produced, for example, by selecting the appropriate polymerase enzyme, polymerase reaction conditions including cofactors, and polymerase reaction substrates including the primed template and nucleotides.
    Type: Application
    Filed: January 26, 2016
    Publication date: June 23, 2016
    Inventors: Keith Bjornson, Harold Lee, Jonas Korlach
  • Publication number: 20160083789
    Abstract: Sequencing methods, devices, and systems are described. Arrays of nanoscale electronic elements comprising two electrodes separated by an insulating layer are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound proximate to the insulating region. A sequencing reaction mixture comprising nucleotide analogs having impedance labels is introduced to the array of nanoscale electronic elements under conditions of polymerase mediated nucleic acid synthesis. The time sequence of incorporation of nucleotide analogs is determined by identifying the types of labels of the nucleotide analogs that are incorporated into the growing strand using measured impedance.
    Type: Application
    Filed: October 21, 2015
    Publication date: March 24, 2016
    Inventors: Stephen Turner, Jeremiah Hanes, Keith Bjornson
  • Patent number: 9279155
    Abstract: The Application relates to methods, and systems for nucleotide sequencing comprising producing polymerase reactions that comprise both catalytic and non-catalytic divalent metal ions. Polymerase/template/primer complexes are immobilized on a substrate. The complexes are exposed to a solution comprising a non-catalytic metal and nucleotides labeled with a detectable label on a portion of the nucleotide that is released upon incorporation. The cognate nucleotide is sequestered in the active site of the polymerase, unable to proceed to incorporation. After observing the sequestered cognate nucleotide, the complex is exposed to a catalytic metal, resulting in the incorporation of the bound cognate nucleotide and consequent release of the label resulting in a single-base extended primer.
    Type: Grant
    Filed: February 20, 2014
    Date of Patent: March 8, 2016
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Keith Bjornson, Harold Lee, Jonas Korlach
  • Publication number: 20160024558
    Abstract: Compositions, systems and methods employing nucleic acid binding proteins for use in the regulation and/or modulation of nucleic acid based reactions, including transcription, translation, modification, digestion, and hybridization reactions. Such compositions are employed in controlling a variety of different reaction types involving nucleic acids.
    Type: Application
    Filed: July 22, 2015
    Publication date: January 28, 2016
    Inventors: Paul Hardenbol, Keith Bjornson
  • Patent number: RE47177
    Abstract: Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties include increased resistance to photodamage, and can also include enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased thermostability, increased accuracy, increased speed, increased readlength, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.
    Type: Grant
    Filed: January 24, 2018
    Date of Patent: December 25, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Satwik Kamtekar, Arek Bibillo, Keith Bjornson, Fred Christians, Colleen Cutcliffe, Jeremiah Hanes, Lei Jia, Walter Lee, Erik Miller, Pranav Patel