Patents Assigned to Pacific Biosciences of California, Inc.
  • Patent number: 10662461
    Abstract: The present disclosure provides improved methods for generating asymmetrically-tagged nucleic acid constructs, compositions comprising such constructs, and kits and systems for generating such constructs.
    Type: Grant
    Filed: May 9, 2019
    Date of Patent: May 26, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventor: Joan Wilson
  • Patent number: 10655168
    Abstract: 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: Grant
    Filed: December 21, 2018
    Date of Patent: May 19, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Satwik Kamtekar, Lubomir Sebo, Leewin Chern, Thomas Linsky, Jeremiah Hanes, Erik Miller, Ying Yang, Stephen Yue
  • Patent number: 10655172
    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: June 27, 2014
    Date of Patent: May 19, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: David R. Rank, Jeffrey Wegener, Jonas Korlach, Daniel Roitman, Yue Xu, John Lyle, Stephen Turner, Paul Peluso, Geoff Otto, Ronald L. Cicero
  • Publication number: 20200142127
    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: Application
    Filed: June 3, 2019
    Publication date: May 7, 2020
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Ravi SAXENA, Michael Tzu RU, Takashi Whitney ORIMOTO, Annette GROT, Mathieu FOQUET, Hou-Pu CHOU
  • Patent number: 10640825
    Abstract: An analytical assembly within a unified device structure for integration into an analytical system. The analytical assembly is scalable and includes a plurality of analytical devices, each of which includes a reaction cell, an optical sensor, and at least one optical element positioned in optical communication with both the reaction cell and the sensor and which delivers optical signals from the cell to the sensor. Additional elements are optionally integrated into the analytical assembly. Methods for forming and operating the analytical system are also disclosed.
    Type: Grant
    Filed: October 17, 2017
    Date of Patent: May 5, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Nathaniel Joseph McCaffrey, Stephen Turner, Ravi Saxena, Scott Edward Helgesen
  • Patent number: 10640818
    Abstract: Methods are provided for reducing the complexity of a population of nucleic acids prior to performing an analysis of the nucleic acids, e.g., sequence analysis. The methods result in a subset of the initial population enriched for a target region, which is typically located within one or more target fragments. The methods are particularly useful for analyzing populations having a high degree of complexity, e.g., chromosomal-derived DNA, whole genomic DNA, or mRNA populations.
    Type: Grant
    Filed: November 16, 2016
    Date of Patent: May 5, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Thang Tat Pham, Yu-Chih Tsai, Jonas Korlach, Tyson A. Clark, Stephen Turner
  • Patent number: 10626457
    Abstract: Arrays of integrated optical devices and their methods for production are provided. The devices include an integrated bandpass filter layer that comprises at least two multi-cavity filter elements with different central bandpass wavelengths. The device 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 provide for the efficient and reliable coupling of optical excitation energy from an optical source to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination. The device arrays are well suited for miniaturization and high throughput.
    Type: Grant
    Filed: October 28, 2016
    Date of Patent: April 21, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Ravi Saxena, Annette Grot, Nicolaas Tack, Pilar Gonzalez, Bert Du Bois, Simone Severi
  • Patent number: 10626456
    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 or nucleic acid amplification. Such properties include enhanced performance with large nucleotide analogs, increased stability, increased readlength, and improved detection of modified bases, and can also include resistance to photodamage, 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 accuracy, altered speed, increased cosolvent resistance, 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: December 14, 2017
    Date of Patent: April 21, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Satwik Kamtekar, Erik Miller
  • Patent number: 10612087
    Abstract: Compositions, kits, methods and systems for single molecule nucleotide sequencing comprising producing polymerase reactions having monovalent cations that control the median pulse width for incorporated nucleotides are disclosed. The levels of monovalent cations are used to control pulse width while allowing other sequencing parameters to remain within a desirable range.
    Type: Grant
    Filed: December 12, 2018
    Date of Patent: April 7, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Andrei Fedorov, John Lyle, Keith Bjornson, Jeremiah Hanes
  • Publication number: 20200087722
    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: June 13, 2019
    Publication date: March 19, 2020
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Gene SHEN, Stephen YUE, Lubomir SEBO, Louis BROGLEY
  • Patent number: 10590484
    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. 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: January 19, 2018
    Date of Patent: March 17, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Jonas Korlach, Stephen Turner, Tyson A. Clark
  • Patent number: 10577651
    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: May 10, 2018
    Date of Patent: March 3, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventor: John G. K. Williams
  • Patent number: 10578788
    Abstract: Optical analytical devices and their methods of use are provided. The devices 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 include optical waveguides for illumination of the optical reactions. In some embodiments, the devices comprise an optical waveguide comprising a plurality of optical cores and a cladding, a plurality of nanometer-scale apertures disposed on a surface of the device above the optical waveguide, such that optical energy passing through the plurality of optical cores of the optical waveguide illuminates the plurality of nanometer-scale apertures by an evanescent field that emanates from the waveguide, and a plurality of detectors optically coupled to the plurality of nanometer-scale apertures. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions.
    Type: Grant
    Filed: July 9, 2018
    Date of Patent: March 3, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Annette Grot, Shang Wang, Hans Callebaut, Paul Lundquist, Stephen Turner
  • Patent number: 10570450
    Abstract: Optical analytical devices and their methods of use are provided. The devices 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 include integrated illumination elements and optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput.
    Type: Grant
    Filed: December 3, 2018
    Date of Patent: February 25, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Paul Lundquist, Stephen Turner
  • Patent number: 10570445
    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: July 30, 2018
    Date of Patent: February 25, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Xiangxu Kong, Gene Shen
  • Patent number: 10563255
    Abstract: Methods, devices, and systems for performing intermittent detection during analytical reactions are provided. Such methods facilitate collection of reaction data from disparate reaction times. Further, such methods are useful for reducing photo-induced damage of one or more reactants in an illuminated analytical reaction at a given reaction time. In preferred embodiments, the reaction mixture is subjected to at least one illuminated and non-illuminated period and allowed to proceed such that the time in which the reaction mixture is illuminated is less than a photo-induced damage threshold period.
    Type: Grant
    Filed: June 23, 2017
    Date of Patent: February 18, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Jon Sorenson, Kenneth Mark Maxham, John Eid
  • Patent number: 10562766
    Abstract: Methods, compositions and arrays for non-random loading of single analyte molecules into array structures are provided. Arrays of confined regions are produced wherein each confined region comprises a single island within the confined region. The island can be selectively functionalized with a coupling agent to couple a single molecule of interest within the confined region.
    Type: Grant
    Filed: March 24, 2017
    Date of Patent: February 18, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Ron Kuse, Gregory Kearns, Pezhman Monadgemi, Mathieu Foquet, Drew Martinez
  • Publication number: 20200049882
    Abstract: Integrated target waveguide devices and optical analytical systems comprising such devices are provided. The target devices include an optical coupler that is optically coupled to an integrated waveguide and that is configured to receive optical input from an optical source through free space, particularly through a low numerical aperture interface. The devices and systems 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 provide for the efficient and reliable coupling of optical excitation energy from an optical source to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination. The devices and systems are well suited for miniaturization and high throughput.
    Type: Application
    Filed: July 18, 2019
    Publication date: February 13, 2020
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Shang WANG, Mathieu FOQUET, Paul LUNDQUIST, Aaron RULISON, Mark MCDONALD, Ariel HERRMANN
  • Patent number: 10544449
    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: January 6, 2017
    Date of Patent: January 28, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Gene Shen, Natasha Popovich, Erik Miller, Satwik Kamtekar, Keith Bjornson, Jeremiah Hanes, Stephen Yue, Lubomir Sebo, Zhong Wang
  • Patent number: 10544457
    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: Grant
    Filed: June 9, 2017
    Date of Patent: January 28, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Erik Miller, Keith Bjornson, Kristofor Nyquist, Satwik Kamtekar