Patents Assigned to Pacific Biosciences of California, Inc.
  • Patent number: 11359235
    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: Grant
    Filed: June 13, 2019
    Date of Patent: June 14, 2022
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Gene Shen, Stephen Yue, Lubomir Sebo, Louis Brogley
  • Patent number: 11339428
    Abstract: A method for identifying a nucleotide in a template nucleic acid by (a) providing a plurality of primer-template nucleic acid hybrids, wherein the primers have an extendable 3? end; (b) contacting the plurality with: (i) blocked nucleotides to produce a first subset of the primer-template nucleic acid hybrids that include a blocked nucleotide at the 3? end, and (ii) a ternary complex inhibitor to produce a second subset of the primer-template nucleic acid hybrids that include a ternary complex inhibitor; (c) forming ternary complexes that each include a polymerase, a primer-template nucleic acid hybrid of the first subset, and a cognate nucleotide; and (d) detecting the ternary complexes, thereby identifying a nucleotide in the template nucleic acid.
    Type: Grant
    Filed: April 12, 2019
    Date of Patent: May 24, 2022
    Assignee: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
    Inventors: Chad Fleischer, Denis Malyshev
  • Patent number: 11332787
    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 loading of polymerase enzyme complexes into a predetermined number of reaction sites, including nanoscale wells.
    Type: Grant
    Filed: June 28, 2019
    Date of Patent: May 17, 2022
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Jaime Juan Benitez-Marzan, Natasha Popovich, Lei Sun
  • Patent number: 11326206
    Abstract: The present disclosure provides compositions, methods and systems for quantifying target sequences and identifying target sequence variants.
    Type: Grant
    Filed: April 6, 2017
    Date of Patent: May 10, 2022
    Assignee: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
    Inventors: Yi Zhang, Steven Brentano, Eugene Tu, Kandaswamy Vijayan
  • Patent number: 11299720
    Abstract: Compositions that include polymerases with features for improving entry of nucleotide analogues into active site regions and for coordinating with the nucleotide analogues 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: July 14, 2020
    Date of Patent: April 12, 2022
    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: 11272132
    Abstract: Provided are pixels, devices, systems, and methods relating to active pixel sensor in which each active pixel puts out a signal that represents a temporal differential. The output of the active pixel represents a comparison or difference between successive frames. The differential can represent the state of the sensor element in the pixel at the end of one frame compared to the state of the sensor element of the frame, at the end of the prior frame.
    Type: Grant
    Filed: June 5, 2020
    Date of Patent: March 8, 2022
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Annette Grot, Stephen Turner, Steven Benjamin Warren
  • Patent number: 11269199
    Abstract: We describe methods of producing gratings such as Bragg gratings with optical waveguides. Described are the writing and erasing of gratings within SiON waveguides by forming standing waves. Methods, systems, instruments, and devices are described that provide improved transmission of light through such waveguides.
    Type: Grant
    Filed: April 11, 2019
    Date of Patent: March 8, 2022
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Mark McDonald, Aaron Rulison, Paul Lundquist, Tsuei-Lian Wang, Deborah Pao-Tung Kwo, Shang Wang
  • Patent number: 11214830
    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: October 21, 2019
    Date of Patent: January 4, 2022
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Jon Sorenson, Kenneth Mark Maxham, John Eid
  • Patent number: 11203689
    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: Grant
    Filed: January 31, 2020
    Date of Patent: December 21, 2021
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Lubomir Sebo, Honey Osuna, Stephen Yue, Yuri Lapin
  • Patent number: 11198906
    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: March 9, 2020
    Date of Patent: December 14, 2021
    Assignee: Pacific Biosciences of California, inc.
    Inventors: Satwik Kamtekar, Erik Miller
  • Patent number: 11198135
    Abstract: Disclosed herein is a novel method to fabricate magnetic silica nanomembranes using thin polymer cores based on silica deposition and self-wrinkling induced by thermal shrinkage. These micro- and nano-scale structures have vastly enlarged the specific area of silica, thus the magnetic silica nanomembranes can be used for solid phase extraction of nucleic acids. The magnetic silica nanomembranes are suitable for nucleic acid purification and isolation and demonstrated better performance than commercial particles in terms of nucleic acid recovery yield and integrity. In addition, the magnetic silica nanomembranes may have high nucleic acid capacity due to significantly enlarged specific surface area of silica. Methods of use and devices comprising the magnetic silica nanomembranes are also provided herein.
    Type: Grant
    Filed: June 30, 2020
    Date of Patent: December 14, 2021
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Kelvin Jeng-Fang Liu, Jeffrey Michael Burke
  • Patent number: 11186871
    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: April 14, 2020
    Date of Patent: November 30, 2021
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: David R. Rank, Jeffery Wegener, Jonas Korlach, Daniel Roitman, Yue Xu, John Lyle, Stephen Turner, Paul Peluso, Geoff Otto, Ron L. Cicero
  • Patent number: 11186870
    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: January 27, 2020
    Date of Patent: November 30, 2021
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Xiangxu Kong, Gene Shen
  • Patent number: 11162138
    Abstract: Sets of compounds bearing detectably different groups of labels are provided. Typically, different compounds bear different numbers of a single type of label and are thus distinguishable by the amplitude of signal produced by the label. The compounds are assembled from label components and protein cores to facilitate modular production of the compounds. In compounds containing two or more proteins, the proteins are typically covalently linked. Useful sets of compounds include sets of labeled nucleotide analogs, particularly dye-label nucleotide analogs that include tetravalent biotin-binding protein cores.
    Type: Grant
    Filed: October 24, 2018
    Date of Patent: November 2, 2021
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Erik Miller, Satwik Kamtekar
  • Publication number: 20210325306
    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: Application
    Filed: December 7, 2020
    Publication date: October 21, 2021
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Annette GROT, Ravi SAXENA, Paul LUNDQUIST
  • Publication number: 20210317511
    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: Application
    Filed: June 25, 2021
    Publication date: October 14, 2021
    Applicant: Pacific Biosciences of California, Inc.
    Inventor: Joan Wilson
  • Patent number: 11142793
    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: Grant
    Filed: October 30, 2019
    Date of Patent: October 12, 2021
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Jeremiah Hanes, Keith Bjornson
  • Patent number: 11142792
    Abstract: Real time electronic sequencing devices, chips, and systems are described. Arrays of nanoFET devices are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound to the nanoFET. The nanoFET devices typically have a source, a drain and a gate comprising a nanowire. A single polymerase enzyme complex comprising a polymerase enzyme complexed with the template nucleic acid is bound to the gate. The polymerase is bound to the gate non-covalently through a polymeric binding agent that has two strands, each strand interacting with the nanowire such that the polymerase is in a central location between the strands with the polymeric binding agent extending away from the polymerase complex along the nanowire in both directions.
    Type: Grant
    Filed: September 20, 2018
    Date of Patent: October 12, 2021
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Jonas Korlach, Satwik Kamtekar, Jeremiah Hanes
  • Publication number: 20210311254
    Abstract: Provided herein are systems, devices, and methods for improved optical waveguide transmission and alignment in an analytical system. Waveguides in optical analytical systems can exhibit variable and increasing back reflection of single-wavelength illumination over time, thus limiting their effectiveness and reliability. The systems are also subject to optical interference under conditions that have been used to overcome the back reflection. Novel systems and approaches using broadband illumination light with multiple longitudinal modes have been developed to improve optical transmission and analysis in these systems. Novel systems and approaches for the alignment of a target waveguide device and an optical source are also disclosed.
    Type: Application
    Filed: March 15, 2021
    Publication date: October 7, 2021
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Alexey KURITSYN, Mark MCDONALD, Aaron RULISON, Russell BERMAN
  • Patent number: 11137532
    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. 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: March 1, 2020
    Date of Patent: October 5, 2021
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Annette Grot, Shang Wang, Hans Callebaut, Paul Lundquist, Stephen Turner