Patents Examined by Kenneth R. Horlick
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Patent number: 11795502Abstract: One or more nanoparticles, each of which is conjugated with at least one oligonucleotide, are used to multiply nucleic acids. One or more of the oligonucleotides has at least one primer sequence and an additional segment extending from the end of the primer sequence proximal to the nanoparticle in the direction of the nanoparticle, and the additional segment has at least one abasic modification. The disclosed method for multiplying nucleic acids has a multiplication step and a test step for determining the concentration of the products of the multiplication reaction. The test step begins after the multiplication step ends, and in the test step, either at least one part of the sample is supplied with substances or no substances are supplied. In a method for multiplying nucleic acids, nanoparticles transfer heat into their surroundings in a reaction volume upon being excited.Type: GrantFiled: October 11, 2019Date of Patent: October 24, 2023Assignee: HP HEALTH SOLUTIONS GERMANY GMBHInventors: Federico Buersgens, Joachim Stehr, Lars Ullerich, Cecilia Rebuffo-Scheer
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Patent number: 11788116Abstract: A method for the analysis of minimal residual disease is provided. In some embodiments, the method comprises obtaining multiple pairs of primers designed to amplify sequences that contain a plurality of sequence variations that have been previously identified in a patient's tumor. Amplicons are then obtained through a targeted multiplex amplification that amplifies those sequences from cell-free DNA isolated from a plasma sample. The amplicons are sequenced and two or more of the sequence variations are detected from sequence reads, wherein the detecting comprises comparing a quantity of sequence reads containing a sequence variation against a threshold value. A score is then calculated for the patient sample based on the combined allele frequencies of the detected two or more sequence variations, wherein the score indicates the presence of minimal residual disease.Type: GrantFiled: March 17, 2023Date of Patent: October 17, 2023Assignee: INIVATA LTD.Inventors: Vincent Plagnol, Tim Forshew, Samuel Woodhouse, Andrew Lawson, Matthew Smith
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Patent number: 11788138Abstract: The invention provides compositions and methods for sequencing nucleic acids and other applications. In sequencing by synthesis, unlabeled reversible terminators are incorporated by a polymerase in each cycle, then labeled after incorporation by binding to the reversible terminator a directly or indirectly labeled antibody or other affinity reagent.Type: GrantFiled: October 29, 2020Date of Patent: October 17, 2023Assignees: MGI Tech Co., Ltd., BGI ShenzhenInventors: Radoje Drmanac, Snezana Drmanac, Handong Li, Xun Xu, Matthew J. Callow, Leon Eckhardt, Naibo Yang
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Patent number: 11781185Abstract: Provided herein are fluorescently-labeled nucleotide conjugates for nucleic acid analysis. Also provided are reagents used for forming binding complexes between a fluorescently-labeled nucleotide conjugate and a target nucleic acid sequence in the presence of one or more reagents disclosed herein. Binding complexes can be detected in the presence of the one or more reagents. For example, the one or more reagents may contain a photobleaching reducing agent configured to reduce photobleaching resulting from use of the fluorescently-labeled nucleotide conjugate to form the binding complex in a nucleic acid analysis. Such nucleic acid analysis may be used to identify sites of nucleobase binding or incorporation between the target nucleic acid sequence and one or more nucleotide moieties of the fluorescently-labeled nucleotide conjugate in a nucleic acid sequence reaction.Type: GrantFiled: September 19, 2022Date of Patent: October 10, 2023Assignee: ELEMENT BIOSCIENCES, INC.Inventors: Sinan Arslan, Molly He, Michael Previte, Ramreddy Tippana, Hua Yu, William Light, Junhua Zhao
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Patent number: 11773453Abstract: The present disclosure provides a system and method for the detection of rare mutations and copy number variations in cell free polynucleotides. Generally, the systems and methods comprise sample preparation, or the extraction and isolation of cell free polynucleotide sequences from a bodily fluid; subsequent sequencing of cell free polynucleotides by techniques known in the art; and application of bioinformatics tools to detect rare mutations and copy number variations as compared to a reference. The systems and methods also may contain a database or collection of different rare mutations or copy number variation profiles of different diseases, to be used as additional references in aiding detection of rare mutations, copy number variation profiling or general genetic profiling of a disease.Type: GrantFiled: January 20, 2023Date of Patent: October 3, 2023Assignee: Guardant Health, Inc.Inventor: AmirAli Talasaz
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Patent number: 11773452Abstract: The disclosure provides methods and systems of analyzing single cells by simultaneously separating cells into monodisperse droplets and tagging each nucleic acid molecule from the cells with barcodes unique to each droplet. The methods and systems combine template particles with a plurality of single cells in a tube, generate in the tube monodispersed droplets encapsulating a single one of the template particles and a single one of the single cells, release nucleic acid molecules from the single cells and provide each nucleic acid molecule with a barcode unique to the respective droplet. The nucleic acid molecules can then be analyzed by any known method, for example by sequencing the nucleic acid molecules.Type: GrantFiled: August 20, 2021Date of Patent: October 3, 2023Assignee: Fluent Biosciences Inc.Inventors: Kristina Fontanez, Robert Meltzer, Yi Xue, Sepehr Kiani
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Patent number: 11767554Abstract: Provided herein are synthetic size standards that allow one to detect size bias in a sample that includes a plurality of polynucleotides. The size standards can provide an internal control to detect and correct for size bias in data obtained after manipulating and/or processing of sample polynucleotide. Also provided herein are methods for detecting size bias in a sample or in a sequencing run.Type: GrantFiled: February 14, 2019Date of Patent: September 26, 2023Assignee: REGENTS OF THE UNIVERSITY OF MINNESOTAInventors: Daryl M. Gohl, Kenneth B. Beckman
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Patent number: 11767561Abstract: The present invention encompasses methods and kits employing pattern recognition receptor expression as a measure of systemic health in a subject afflicted with an oral health condition. In particular, the present invention is directed to methods involving measurement of the expression levels of one or more Pattern Recognition Receptors including but not limited to Toll-Like Receptors, myeloid differentiation primary response gene 88 (MyD88), and Nucleotide Binding oligomerization domain containing protein 1 (NOD1), in a companion animal, e.g., a dog or a cat, afflicted with an oral health condition. The described methods enable evaluation of the systemic health of the animal afflicted with an oral health condition by measuring expression levels of the indicated genes as compared to suitable controls.Type: GrantFiled: November 20, 2020Date of Patent: September 26, 2023Assignee: Hill's Pet Nutrition, Inc.Inventors: Samer Al-Murrani, Dale S. Scherl
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Patent number: 11767555Abstract: Disclosed herein in are methods and systems for determining genetic variants (e.g., copy number variation) in a polynucleotide sample. A method for determining copy number variations includes tagging double-stranded polynucleotides with duplex tags, sequencing polynucleotides from the sample and estimating total number of polynucleotides mapping to selected genetic loci. The estimate of total number of polynucleotides can involve estimating the number of double-stranded polynucleotides in the original sample for which no sequence reads are generated. This number can be generated using the number of polynucleotides for which reads for both complementary strands are detected and reads for which only one of the two complementary strands is detected.Type: GrantFiled: October 27, 2021Date of Patent: September 26, 2023Assignee: Guardant Health, Inc.Inventors: Amirali Talasaz, Helmy Eltoukhy
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Patent number: 11767556Abstract: Disclosed herein in are methods and systems for determining genetic variants (e.g., copy number variation) in a polynucleotide sample. A method for determining copy number variations includes tagging double-stranded polynucleotides with duplex tags, sequencing polynucleotides from the sample and estimating total number of polynucleotides mapping to selected genetic loci. The estimate of total number of polynucleotides can involve estimating the number of double-stranded polynucleotides in the original sample for which no sequence reads are generated. This number can be generated using the number of polynucleotides for which reads for both complementary strands are detected and reads for which only one of the two complementary strands is detected.Type: GrantFiled: October 27, 2021Date of Patent: September 26, 2023Assignee: Guardant Health, Inc.Inventors: AmirAli Talasaz, Helmy Eltoukhy, Stefanie Ann Ward Mortimer
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Patent number: 11761038Abstract: Provided herein are methods of identifying a location of an RNA in a sample that include: (a) contacting the sample with an array comprising capture probes, where a capture probe comprises a capture domain and a spatial barcode; (b) releasing the RNA from the sample; (c) extending a 3? end of the capture probe using the capture domain-bound RNA as a template; (d) generating nick(s) in the extended capture probe-hybridized RNA and performing random-primed DNA synthesis; (e) performing end repair on the second strand DNA molecule; (f) adding a single adenosine nucleotide to the 3? end of the extended capture probe; (g) ligating a double-stranded sequencing adaptor to the double-stranded DNA product; and (h) determining all or a part of the sequence of the RNA, and the sequence of the spatial barcode, or complements thereof, and using the determined sequences to identify the location of the RNA in the sample.Type: GrantFiled: July 6, 2021Date of Patent: September 19, 2023Assignee: 10x Genomics, Inc.Inventor: Marlon Stoeckius
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Patent number: 11761025Abstract: A method for preserving and processing cell-free nucleic acids located within a blood sample is disclosed, wherein a blood sample containing cell-free nucleic acids is treated to reduce both blood cell lysis and nuclease activity within the blood sample. The treatment of the sample aids in increasing the amount of cell-free nucleic acids that can be identified and tested while maintaining the structure and integrity of the nucleic acids.Type: GrantFiled: June 22, 2020Date of Patent: September 19, 2023Assignee: STRECK LLCInventor: M. Rohan Fernando
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Patent number: 11761040Abstract: Methods and compositions for protecting DNA from light-induced damage and other modifications that occur during DNA sequencing using fluorescent dyes are disclosed.Type: GrantFiled: April 19, 2021Date of Patent: September 19, 2023Assignee: MGI Tech Co., Ltd.Inventors: Snezana Drmanac, Matthew J. Callow, Radoje T. Drmanac
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Patent number: 11753673Abstract: Provided are methods for determining a location of a target nucleic acid in a biological sample including: disposing the biological sample onto an array including a plurality of capture probes, where a first capture probe includes a first spatial barcode and a capture domain and a second capture probe includes a second spatial barcode and the capture domain. The second capture probe is not covered by the biological sample on the array and is contacted with a solution comprising TdT and one or more dideoxynucleotides, such that a dideoxynucleotide is incorporated into the second capture domain. Target nucleic acids are captured by the first capture probe, and the sequence of the first spatial barcode or a complement thereof and all or a portion of a sequence of the target nucleic acid, or a complement thereof, are used to determine the location of the target nucleic acid in the biological sample.Type: GrantFiled: March 9, 2023Date of Patent: September 12, 2023Assignee: 10x Genomics, Inc.Inventors: Jennifer Chew, David Michael Patterson
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Patent number: 11739369Abstract: The present disclosure provides methods, systems, devices, kits, and reagents for performing single cell sequencing (e.g., single cell RNA sequencing) from a low volume, capillary blood (or any low volume blood sample which is not obtained from a vein or by venipuncture).Type: GrantFiled: March 23, 2021Date of Patent: August 29, 2023Assignee: California Institute of TechnologyInventors: Matthew W. Thomson, Tatyana Dobreva, David Brown, Jong Hwee Park
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Patent number: 11732257Abstract: The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and/or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.Type: GrantFiled: October 23, 2018Date of Patent: August 22, 2023Assignees: Massachusetts Institute of Technology, The General Hospital CorporationInventors: Peter van Galen, Volker Hovestadt, Travis Hughes, Marc H. Wadsworth, II, Bradley Bernstein, Alexander K. Shalek, Todd M. Gierahn, J. Christopher Love, Ang A. Tu
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Patent number: 11713480Abstract: The present disclosure relates to materials and methods for spatial detection of nucleic acid in a tissue sample or a portion thereof. In particular, provided herein are materials and methods for detecting RNA so as to obtain spatial information about the localization, distribution or expression of genes in a tissue sample. In some embodiments, the materials and methods provided herein enable detection of gene expression in a single cell.Type: GrantFiled: March 30, 2022Date of Patent: August 1, 2023Assignee: The Regents of the University of MichiganInventor: Jun Hee Lee
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Patent number: 11708602Abstract: The present invention relates to, among other things, probes, compositions, methods, and kits for simultaneous, multiplexed detection and quantification of protein and/or nucleic acid expression in a user-defined region of a tissue, user-defined cell, and/or user-defined subcellular structure within a cell.Type: GrantFiled: October 8, 2019Date of Patent: July 25, 2023Assignees: NanoString Technologies, Inc., Board of Regents, The University of Texas SystemInventors: Joseph M. Beechem, Charles Warren, Chris Merritt, Jaemyeong Jung, Dwayne L. Dunaway, Scott Crowder, Kristina Sorg, Gordon B. Mills
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Patent number: 11702685Abstract: Methods for the high-throughput analysis of transgenic events are herein disclosed. The methods use libraries of sheared genomic DNA ligated to specialized adapters and pooled for sequence analysis and comparison to known genomic and insert sequence. The method finds use in detecting characterizing insertion site, transgene integrity, and transgene copy number.Type: GrantFiled: February 8, 2021Date of Patent: July 18, 2023Inventors: Mary Beatty, Kevin Hayes, Jenna Hoffman, Haining Lin, Gina Marie Zastrow-Hayes
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Patent number: 11697845Abstract: The majority of glioblastomas can be classified into molecular subgroups based on mutations in the TERT promoter (TERTp) and isocitrate dehydrogenase 1 or 2 (IDH). These molecular subgroups utilize distinct genetic mechanisms of telomere maintenance, either TERTp mutation leading to telomerase activation or ATRX-mutation leading to an alternative lengthening of telomeres phenotype (ALT). However, about 20% of glioblastomas lack alterations in TERTp and IDH. These tumors, designated TERTpWT-IDHWT glioblastomas, did not have well-established genetic biomarkers or defined mechanisms of telomere maintenance. The genetic landscape of TERTpWT-IDHWT glioblastoma includes tumors that have chromosomal rearrangements upstream of TERT. These rearrangements define a novel molecular subgroup of glioblastoma, that is a telomerase-positive subgroup driven by TERT-structural rearrangements (IDHWT-TERTSV).Type: GrantFiled: March 8, 2019Date of Patent: July 11, 2023Assignee: Duke UniversityInventors: Hai Yan, Bill H. Diplas