Patents Assigned to Pacific Biosciences of California, Inc.
  • Patent number: 10113197
    Abstract: Methods, Compositions, and Systems are provided for obtaining polymerase-template complex mixtures with improved levels of active polymerase. In some aspects active polymerase-template complex is separated by affinity for nucleoside phosphate moieties attached to a resin. In some aspects, a polymerase-template complex is exposed to reaction conditions in which a complementary strand to the template is produced. The extended reaction mixture is purified by reaction with a resin comprising nucleoside phosphate moieties. This purified mixture can be loaded onto substrates and can be used for further analyzes including single molecule sequencing.
    Type: Grant
    Filed: December 12, 2014
    Date of Patent: October 30, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Lei Sun, Insil Park
  • Patent number: 10081836
    Abstract: Methods, compositions, and systems are provided that allow for reliable sequencing of the initial sequence region of a sequence of interest. The methods of the invention allow for more reliable barcoding of subpopulations of nucleic acids to be sequenced.
    Type: Grant
    Filed: July 15, 2016
    Date of Patent: September 25, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Tyson A. Clark, Jonas Korlach, Cheryl Heiner, Kevin Travers, Erik Miller
  • Publication number: 20180258481
    Abstract: The present invention provides novel compositions, methods and apparatus for DNA sequencing that can be performed, e.g., in a two-electrode chamber. The present invention also provides a method for sequencing a nucleic acid comprising immobilizing a plurality of complexes comprising a target nucleic acid, a primer nucleic acid, and a polymerase onto a surface, contacting the surface with a plurality of charged particles comprising a nucleotide phosphate by applying an electric field, reversing the electric field to transport unbound charged particles away from the surface, and detecting the incorporation of a nucleotide phosphate into a single molecule of the primer nucleic acid.
    Type: Application
    Filed: May 10, 2018
    Publication date: September 13, 2018
    Applicant: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
    Inventor: John G.K. Williams
  • Patent number: 10066258
    Abstract: FRET-labeled compounds are provided for use in analytical reactions. In certain embodiments, FRET-labeled nucleotide analogs are used in place of naturally occurring nucleoside triphosphates or other analogs in analytical reactions comprising nucleic acids, for example, template-directed nucleic acid synthesis, DNA sequencing, RNA sequencing, single-base identification, hybridization, binding assays, and other analytical reactions.
    Type: Grant
    Filed: December 14, 2016
    Date of Patent: September 4, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Xiangxu Kong, Gene Shen
  • Patent number: 10030264
    Abstract: Methods for performing analytical reactions and compositions for use in such methods, where the methods have reduced signal levels deriving from non-specific adsorption of detected reagents to other components of the analytical method, e.g., other reagents, solid phase components, vessels, etc.
    Type: Grant
    Filed: January 6, 2015
    Date of Patent: July 24, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Andrei Fedorov, Stephen Yue, Lei Sun, Gene Shen, John Lyle
  • Patent number: 10023911
    Abstract: Computer implemented methods, and systems performing such methods for processing signal data from analytical operations and systems, and particularly in processing signal data from sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof.
    Type: Grant
    Filed: October 13, 2015
    Date of Patent: July 17, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Austin B. Tomaney, Kenneth Mark Maxham, David Holden, Kevin Hester, Devon Murphy, Patrick Marks
  • 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
  • Patent number: 10000798
    Abstract: The present invention provides novel compositions, methods and apparatus for DNA sequencing that can be performed, e.g., in a two-electrode chamber. The present invention also provides a method for sequencing a nucleic acid comprising immobilizing a plurality of complexes comprising a target nucleic acid, a primer nucleic acid, and a polymerase onto a surface, contacting the surface with a plurality of charged particles comprising a nucleotide phosphate by applying an electric field, reversing the electric field to transport unbound charged particles away from the surface, and detecting the incorporation of a nucleotide phosphate into a single molecule of the primer nucleic acid.
    Type: Grant
    Filed: October 7, 2014
    Date of Patent: June 19, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventor: John G. K. Williams
  • Patent number: 10000805
    Abstract: Compositions, methods and systems are provided for isolating DNA having a modified or unnatural base. Circular DNA fragments, each comprising a double stranded DNA central region and single stranded regions on the ends of the double stranded regions, are obtained. Some of the fragments have one or more modified or unnatural base. The DNA fragments are treated with a primer and a polymerase such that the polymerase extends the primer to copy at least one of the strand of the double stranded region. This results in rendering the other strand single stranded. A binding protein or antibody that is specific to the modified or unnatural base is then used to isolate strands containing the modified or unnatural bases. Methods for loading such complexes onto substrates and for single molecule sequencing of such complexes are also provided.
    Type: Grant
    Filed: September 20, 2016
    Date of Patent: June 19, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Thang Pham, Arunashree Bhamidipati, Kevin Travers, Eric Olivares, Tyson A. Clark, Jonas Korlach
  • Patent number: 9957291
    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: Grant
    Filed: August 5, 2014
    Date of Patent: May 1, 2018
    Assignee: 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
  • Patent number: 9951383
    Abstract: Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Methods are provided that include linking forward and reverse strands of a double stranded segment to form circular template molecules, and obtaining sequence data from the circular template molecule to identify modified bases, for example including the use of bisulfite treatment. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid.
    Type: Grant
    Filed: September 21, 2016
    Date of Patent: April 24, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Jon Sorenson, Kevin Travers, Cheryl Heiner
  • Patent number: 9951321
    Abstract: Compositions that include polymerases with features for improving entry of nucleotide analogs into active site regions and for coordinating with the nucleotide analogs in the active site region are provided. Methods of making the polymerases and of using the polymerases in sequencing and DNA replication and amplification as well as kinetic models of polymerase activity and computer-implemented methods of using the models are also provided.
    Type: Grant
    Filed: December 6, 2016
    Date of Patent: April 24, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: David K. Hanzel, Geoff Otto, Paul S. Peluso, Thang Pham, David R. Rank, Fred Christians, Arekadiusz Bibillo, Insil Park, Sonya Clark, John Lyle
  • Patent number: 9945781
    Abstract: Apparatus, systems and methods for use in analyzing discrete reactions are provided. The analytical devices of the invention use an array of nanoscale regions (a chip) that has discrete patches, for example, patches of nanoscale regions. In some embodiments an analytical system is provided that has an analysis chip with an array of patches, each of the patches comprising nanoscale regions that emit fluorescent light when illuminated. The system has a two-dimensional (x, y) array of dichroic prisms, each prism comprising a dichroic element that diverts illumination light up in the z dimension of the array to a patch on the analysis chip above it. Each dichroic element transmits fluorescent light emitted by the patch that it illuminates, whereby the emitted light from each patch passes down through each dichroic prism. The analytical system also has a detector below the array of dichroic prisms that detects the transmitted fluorescent light.
    Type: Grant
    Filed: January 17, 2017
    Date of Patent: April 17, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Aaron Rulison, Mark McDonald, Paul Lundquist
  • Patent number: 9946017
    Abstract: Arrays of integrated analytical devices and their methods for production are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The integrated devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The arrays and methods of the invention make use of silicon chip fabrication and manufacturing techniques developed for the electronics industry and highly suited for miniaturization and high throughput.
    Type: Grant
    Filed: May 19, 2017
    Date of Patent: April 17, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Ravi Saxena, Michael Tzu Ru, Takashi Whitney Orimoto, Annette Grot, Mathieu Foquet, Hou-Pu Chou
  • Patent number: 9944980
    Abstract: Methods of producing substrates having selected active chemical regions by employing elements of the substrates in assisting the localization of active chemical groups in desired regions of the substrate. The methods may include optical, chemical and/or mechanical processes for the deposition, removal, activation and/or deactivation of chemical groups in selected regions of the substrate to provide selective active regions of the substrate.
    Type: Grant
    Filed: October 31, 2007
    Date of Patent: April 17, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: David R. Rank, Jonas Korlach, Yue Xu, Stephen Turner, Jeffery Wegener, Daniel Roitman, John Lyle
  • Patent number: 9920365
    Abstract: The invention provides a novel class of cyanine dyes that are functionalized with a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates.
    Type: Grant
    Filed: June 3, 2015
    Date of Patent: March 20, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventor: Gene Shen
  • Patent number: 9915612
    Abstract: Arrays of integrated analytical devices and their methods for production are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices include an integrated diffractive beam shaping element that provides for the spatial separation of light emitted from the optical reactions.
    Type: Grant
    Filed: March 6, 2017
    Date of Patent: March 13, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Annette Grot, Ravi Saxena, Paul Lundquist
  • Patent number: 9910956
    Abstract: Methods and systems for single molecule sequencing using concatemers of copies of sense and antisense strands. Concatemers are provided, for example, by carrying out rolling circle amplification on a circular molecule having sense and antisense regions to produce repeated copies of the sense and antisense regions connected by linking regions. The circular molecules can be produced by ligating hairpin adapters to each end of a double-stranded nucleic acid having a sense and antisense strand. The ligations can be carried out, for example using blunt end ligation. In some cases, a single molecule consensus sequence for a single template molecule is obtained. A single read from each template molecule can be obtained by comparing the sequence information of the sense and antisense regions.
    Type: Grant
    Filed: August 19, 2016
    Date of Patent: March 6, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Kevin Travers, Geoff Otto, Stephen Turner, Cheryl Heiner, Congcong Ma
  • Patent number: 9879319
    Abstract: Nucleic acid compositions, methods of making and using such compositions that comprise modular functional groups that can be configured to provide desired functionality to different nucleotide types through a swappable and preferably non-covalent linkage component. Such compositions are useful in a variety of applications including nucleic acid analyses.
    Type: Grant
    Filed: December 14, 2016
    Date of Patent: January 30, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Jonas Korlach, Jeffrey Wegener
  • Patent number: RE47067
    Abstract: The invention relates to devices and methods for nanopore sequencing. The invention includes arrays of nanopores having incorporated electronic circuits, for example, in CMOS. The invention includes devices having sample and reference pores connecting sample, measurement and reference chambers, wherein potential measurements in each chamber is used to provide an accurate determination of current through a sample nanopore, improving nanopore sequencing.
    Type: Grant
    Filed: July 28, 2015
    Date of Patent: October 2, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Nathaniel McCaffrey, Jeffrey Wegener, Adrian Fehr