Patents Assigned to Pacific Biosciences of California, Inc.
  • Publication number: 20250146054
    Abstract: A method for identifying a nucleic acid template that include (a) providing a plurality of primer-template hybrids, wherein a first hybrid of the plurality includes a first template hybridized to a first primer, and wherein a second hybrid of the plurality includes a second template hybridized to a second primer, the second primer having a ternary complex inhibitor moiety at the 3? end; (b) delivering polymerases and nucleotides to the plurality, whereby the first hybrid binds a polymerase and nucleotide to form a stabilized ternary complex and whereby the second hybrid does not bind a polymerase and nucleotide to form a stabilized ternary complex; and (c) detecting the stabilized ternary complex to identify the first template.
    Type: Application
    Filed: November 13, 2024
    Publication date: May 8, 2025
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Hari K.K. SUBRAMANIAN, Chad FLEISCHER, Denis MALYSHEV
  • Patent number: 12259564
    Abstract: Disclosed herein is a high throughput optical scanning device and methods of use. The optical scanning device and methods of use provided herein can allow high throughput scanning of a continuously moving object with a high resolution despite fluctuations in stage velocity. This can aid in high throughput scanning of a substrate, such as a biological chip comprising fluorophores. Also provided herein are improved optical relay systems and scanning optics.
    Type: Grant
    Filed: June 9, 2023
    Date of Patent: March 25, 2025
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Windsor Owens, Bryan P. Staker, Robert Hartlage, Edvinas Zizminskas, David Stern, Paul Heilman
  • Patent number: 12234511
    Abstract: Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. These have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy of polynucleotide sequencing applications.
    Type: Grant
    Filed: December 21, 2021
    Date of Patent: February 25, 2025
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Bryan P. Staker, Niandong Liu, Michael David McLaughlin, Bart Lee Staker
  • Publication number: 20250002960
    Abstract: The present disclosure relates to a deblocking agent and compositions thereof for cleaving an NO bond in an amineoxy group at the 3? position of a non-extendable polynucleotide, the deblocking agent being a carbonyl phosphonate and/or sulfonate, or salt thereof. The present disclosure further relates to methods of activating and/or extending a non-extendable polynucleotide using the deblocking agent of the present disclosure. The present disclosure also relates to methods of sequencing a target nucleic acid comprising the methods of activating a non-extendable polynucleotide of the present disclosure.
    Type: Application
    Filed: June 25, 2024
    Publication date: January 2, 2025
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Sima YAZDANI, Chih-Yuan CHEN, Richard LECOULTRE, Lubomir SEBO, Joshua GARRETSON
  • Publication number: 20250002989
    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: May 28, 2024
    Publication date: January 2, 2025
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Lubomir SEBO, Gene SHEN, Stephen YUE, Honey OSUNA, Yuri LAPIN, Louis BROGLEY, Andrei FEDOROV
  • Patent number: 12179196
    Abstract: Provided herein is a method of performing a nucleic acid sequencing reaction using a sequencing system comprising a reagent cartridge coupled to a detection apparatus, and a pump coupled to the reagent cartridge. The reagent cartridge includes a plurality of reagent reservoirs and a main channel. The detection apparatus includes a flow cell that is coupled to the reagent cartridge when the reagent cartridge interacts transiently with the detection apparatus.
    Type: Grant
    Filed: November 10, 2022
    Date of Patent: December 31, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Christopher Kilcoin, Kristin Dills, Rebecca McGinley
  • Patent number: 12180545
    Abstract: A method of determining a nucleic acid sequence that includes steps of: (a) contacting a primed template nucleic acid with a series of mixtures for forming ternary complexes, wherein each of the mixtures includes a polymerase and nucleotide cognates for at least two different base types suspected of being present at the next template position of the template nucleic acid; (b) monitoring the next template position for ternary complexes formed by the series of mixtures, wherein a signal state indicates presence or absence of ternary complex formed at the next template position by each individual mixture, thereby determining a series of signal states that encodes a base call for the next template position; and (c) decoding the series of signal states to distinguish a correct base call for the next template position from an error in the base call.
    Type: Grant
    Filed: July 29, 2022
    Date of Patent: December 31, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Sean Stromberg, John Vieceli, Kandaswamy Vijayan, Arnold Oliphant
  • Patent number: 12105310
    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: May 1, 2023
    Date of Patent: October 1, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Annette Grot, Shang Wang, Hans Callebaut, Paul Lundquist, Stephen Turner
  • Patent number: 12083534
    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: November 3, 2021
    Date of Patent: September 10, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Kelvin Jeng-Fang Liu, Jeffrey Michael Burke
  • Patent number: 12078843
    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: Grant
    Filed: August 15, 2022
    Date of Patent: September 3, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Alexey Kuritsyn, Mark McDonald, Aaron Rulison, Russell Berman
  • Publication number: 20240271203
    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: Application
    Filed: December 18, 2023
    Publication date: August 15, 2024
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Satwik Kamtekar, Erik Miller
  • Patent number: 12060608
    Abstract: Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. There have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy or polynucleotide sequencing applications.
    Type: Grant
    Filed: March 9, 2023
    Date of Patent: August 13, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Bryan P. Staker, Niandong Liu, Manohar R. Furtado, Rixun Fang, Norman Burns, Windsor Owens
  • Patent number: 12060383
    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: February 10, 2023
    Date of Patent: August 13, 2024
    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
  • Publication number: 20240247305
    Abstract: Provided are methods and systems for detecting formation of nucleotide-specific ternary complexes comprising a DNA polymerase, a nucleic acid, and a nucleotide complementary to the templated base of the primed template nucleic acid. The methods and systems facilitate determination of the next correct nucleotide without requiring chemical incorporation of the nucleotide into the primer. This advantageously improves signal-to-noise ratios and increases the quality of results obtainable in a sequencing-by-binding protocol, and enables extended read lengths. These results can even be achieved in procedures employing unlabeled, native nucleotides.
    Type: Application
    Filed: July 28, 2023
    Publication date: July 25, 2024
    Applicant: Pacific Biosciences of California, Inc.
    Inventor: Corey M. DAMBACHER
  • Patent number: 12043868
    Abstract: This invention provides devices for use in various analytical applications including single-molecule analytical reactions. Methods for detecting analytes optically by propagating optical energy by waveguides within a substrate are provided. Analytical devices are provided which have both shallow and deep waveguides in which illumination light is transported through the deep waveguides and coupled into the shallow waveguides. The shallow waveguides provide evanescent field illumination to analytes, such as single-molecule analytes, within nanometer scale wells. Integrated devices including integrated detectors such as CMOS detectors are included.
    Type: Grant
    Filed: December 21, 2022
    Date of Patent: July 23, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Cheng Frank Zhong, Paul Lundquist, Mathieu Foquet, Jonas Korlach, Hovig Bayandorian
  • Publication number: 20240240162
    Abstract: Provided herein are engineered DNA polymerases comprising modifications improving accuracy and processivity of the polymerase including modifications in the Motif A region, optionally, along with additional modifications in the palm and/or exonuclease domains of the polymerase. Also provided are nucleic acids encoding the engineered DNA polymerases comprising modifications in motif A of the polymerase, optionally, with additional modifications. Methods, vectors, kits, and compositions comprising the nucleic acids and compositions, methods and kits comprising the engineered polymerases are also provided.
    Type: Application
    Filed: November 21, 2023
    Publication date: July 18, 2024
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Pinar IYIDOGAN, Mariam IFTIKHAR, Bridget KIDD, Lewis CHURCHFIELD
  • Patent number: 12037641
    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, 2022
    Date of Patent: July 16, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Gene Shen, Stephen Yue, Lubomir Sebo, Louis Brogley
  • Patent number: 12018296
    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: June 1, 2022
    Date of Patent: June 25, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Satwik Kamtekar, Erik Miller, Pranav Patel
  • Patent number: 12012631
    Abstract: The present disclosure provides improved methods for isolating asymmetrically-primed and/or asymmetrically-tagged nucleic acid complexes that find use in downstream analytical analyses, including sequence analysis. Compositions comprising such complexes and kits and systems for generating such complexes are also provided.
    Type: Grant
    Filed: January 15, 2021
    Date of Patent: June 18, 2024
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Lei Sun, Sassan Sheikholeslami, Natasha Popovich, David Christopher Scherer
  • Patent number: D1071248
    Type: Grant
    Filed: October 14, 2022
    Date of Patent: April 15, 2025
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Matias Negatu, Eugene Pogrebinsky, Eric Vennemeyer