Method Specially Adapted For Identifying A Library Member Patents (Class 506/2)
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Patent number: 11519028Abstract: The present disclosure provides methods and compositions for sequencing nucleic acid molecules and identifying individual sample nucleic acid molecules using Molecular Index Tags (MITs). Furthermore, reaction mixtures, kits, and adapter libraries are provided.Type: GrantFiled: October 5, 2021Date of Patent: December 6, 2022Assignee: Natera, Inc.Inventors: Bernhard Zimmermann, Ryan Swenerton, Matthew Rabinowitz, Styrmir Sigurjonsson, George Gemelos, Apratim Ganguly, Himanshu Sethi
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Patent number: 11512306Abstract: Temporal variations in one or more characteristics measured from a cell-free DNA sample are used to estimate a gestational age of a fetus. Example characteristics include the methylation level measured from the cell-free DNA sample, size of DNA fragments measured from the cell-free DNA sample (e.g., proportion of fetal-derived DNA fragments longer than a specified size), and ending patterns of the DNA fragments align to a reference genome.Type: GrantFiled: October 18, 2017Date of Patent: November 29, 2022Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Patent number: 11499180Abstract: The present invention is a method and compositions for primer extension target enrichment of nucleic acids and improvements thereto including simultaneously enriching for RNA and DNA and optionally sequencing the enriched products. An embodiment of the present invention includes a method comprising the steps of: hybridizing a target-specific primer to a target DNA or RNA, wherein the primer comprises a target-binding region and a region of complementarity to an adaptor; extending the primer with a DNA polymerase or reverse transcriptase to form a primer extension product; contacting the product with an adaptor comprising a longer strand with a 5?-overhang having complementarity to said primer and a shorter strand comprising a universal priming site; hybridizing the adaptor to the product; and ligating one strand of the adaptor to the product to form a ligation product.Type: GrantFiled: August 23, 2019Date of Patent: November 15, 2022Assignee: Roche Sequencing Solutions, Inc.Inventors: Brian Christopher Godwin, Sedide Ozturk
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Patent number: 11473138Abstract: The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing. Such polynucleotide processing may be useful for a variety of applications, including polynucleotide sequencing. In some cases, this disclosure provides methods for the generation of polynucleotide barcode libraries, and for the attachment of such polynucleotides to target polynucleotides.Type: GrantFiled: November 27, 2019Date of Patent: October 18, 2022Assignee: 10X GENOMICS, INC.Inventors: Benjamin Hindson, Mirna Jarosz, Paul Hardenbol, Michael Schnall-Levin, Kevin Ness, Serge Saxonov
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Patent number: 11466319Abstract: 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: GrantFiled: August 28, 2020Date of Patent: October 11, 2022Assignee: Pacific Biosciences of California, Inc.Inventors: Lubomir Sebo, Gene Shen, Stephen Yue, Honey Osuna, Yuri Lapin, Louis Brogley, Andrei Fedorov
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Patent number: 11459609Abstract: Described herein are methods of generating a coupled sequencing read pair for a polynucleotide, and methods of analyzing the coupled sequencing read pair. The coupled sequencing read pair can be analyzed to detect polynucleotide variants, including at loci that are not directly sequenced within the coupled sequencing read pair. Other analytical methods can include using coupled sequencing read pairs to construct or validate a consensus sequence. The coupled sequencing read pair may be generated for a polynucleotide by generating sequencing data for a first region by extending a primer using labeled nucleotides; further extending the primer through a second region using nucleotides provided in a second region flow order, wherein primer extension through the second region is faster than primer extension through the first region; and generating sequencing data associated with a sequence of a third region of the polynucleotide by further extending the primer using labeled nucleotides.Type: GrantFiled: November 3, 2021Date of Patent: October 4, 2022Assignee: Ultima Genomics, Inc.Inventors: Mark Pratt, Gilad Almogy, Dumitru Brinza, Eliane Trepagnier, Omer Barad, Yoav Etzioni, Florian Oberstrass
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Patent number: 11447829Abstract: Provided herein are methods and systems for identifying chimeric nucleic acid fragments, e.g., organism-pathogen chimeric nucleic acid fragments and chromosomal rearrangement chimeric nucleic acid fragments. Also provided herein are methods and systems relating to determining a pathogen integration profile or a chromosomal rearrangement in a biological sample and determining a classification of pathology based at least in part on a pathogen integration profile or a chromosomal rearrangement in a biological sample. In certain aspects of the present disclosure, cell-free nucleic acid molecules from a biological sample are analyzed.Type: GrantFiled: June 28, 2019Date of Patent: September 20, 2022Assignee: GRAIL, LLCInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Wai Kei Lam, Haiqiang Zhang
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Patent number: 11441240Abstract: Provided herein are methods that enable parallel evaluation of multiple functional nucleic acids in individual cells or subpopulations of cells, in the context of incubation with other types of single cells. The key insight is concurrent measurement of polynucleic acids derived from small populations of at least two different cell types, such that function in one cell type is linked to the clonal identity of another cell. These methods simultaneously process thousands, millions, or more single cells or small populations of cells. The method integrates molecular, algorithmic, and engineering approaches. This invention has broad and useful application in a number of biological and medical fields, including immunology and drug discovery.Type: GrantFiled: May 16, 2019Date of Patent: September 13, 2022Assignee: GigaGen, Inc.Inventors: David Scott Johnson, Adam Shultz Adler, Matthew James Spindler, Rena Aviva Mizrahi
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Patent number: 11427870Abstract: A method for estimating a risk for a subject suffering from encapsulating peritoneal sclerosis is provided, including measuring an expression level of at least one microRNA from a sample of the subject, and the microRNA is selected from miR-17, miR-100, miR-155, miR-202, miR-422a, and miR-483; comparing the expression level of the microRNA in the sample to that of a same miRNA of a control, when the expression level of miRNA in the sample is lower than that of the control, the subject is estimated having the risk of encapsulating peritoneal sclerosis. A kit for estimating a risk for a subject suffering from encapsulating peritoneal sclerosis is also provided, including at least one agent for identifying the at least one microRNA as above mentioned from the sample of the subject.Type: GrantFiled: July 9, 2020Date of Patent: August 30, 2022Assignee: National Central UniversityInventors: Nian-Han Ma, Chiu-Chin Huang, Jin-Bor Chen, Chin-Chung Tseng, I-Kuan Wang, Chien-Lung Chen, An-Lun Li
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Patent number: 11427933Abstract: Provided herein are methods that enable parallel evaluation of multiple functional nucleic acids in individual cells or subpopulations of cells, in the context of incubation with other types of single cells. The key insight is concurrent measurement of polynucleic acids derived from small populations of at least two different cell types, such that function in one cell type is linked to the clonal identity of another cell. These methods simultaneously process thousands, millions, or more single cells or small populations of cells. The method integrates molecular, algorithmic, and engineering approaches. This invention has broad and useful application in a number of biological and medical fields, including immunology and drug discovery.Type: GrantFiled: August 3, 2021Date of Patent: August 30, 2022Assignee: GigaGen, Inc.Inventors: David Scott Johnson, Adam Shultz Adler, Matthew James Spindler, Rena Aviva Mizrahi
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Patent number: 11430543Abstract: Embodiments of a method and/or system can include generating a set of target-associated molecules (e.g., spike-in molecules) associated with one or more biological targets; generating one or more spike-in mixtures based on processing the set of target-associated molecules with one or more samples including the one or more biological targets; performing one or more Sanger sequencing operations on the one or more spike-in mixtures; determining one or more abundance metrics based on chromatogram-related outputs from the one or more Sanger sequencing operations; and/or facilitating characterization of one or more medical conditions based on the one or more abundance metrics.Type: GrantFiled: August 6, 2018Date of Patent: August 30, 2022Assignee: BillionToOne, Inc.Inventors: David Tsao, Oguzhan Atay
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Patent number: 11419949Abstract: Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.Type: GrantFiled: January 29, 2021Date of Patent: August 23, 2022Assignee: 4D Molecular Therapeutics Inc.Inventors: David H. Kirn, Melissa Kotterman, David Schaffer
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Patent number: 11414710Abstract: The present technology provides polynucleotide compositions and methods of using the same to detect circulating tumor DNA (ctDNA) in a patient. Kits for use in practicing the methods are also provided.Type: GrantFiled: December 27, 2017Date of Patent: August 16, 2022Assignee: Quest Diagnostics Investments LLCInventors: Suzzette Arnal, Taraneh Angeloni
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Patent number: 11414700Abstract: Disclosed herein are systems, methods, and compositions useful for profiling T cell receptor (TCR) and B cell receptor (BCR) repertoire using next-generation sequencing (NGS) methods. In certain embodiments, the methods include enriching a sample for TCR/BCR RNA sequences, and determining the TCR/BCR profile of a subject using five different oligonucleotide pools. Also disclosed herein are systems and methods for diagnosing, treating, or predicting infection, disease, medical conditions, therapeutic outcome, or therapeutic efficacy based on the TCR/BCR profile data from a subject in need thereof.Type: GrantFiled: April 21, 2021Date of Patent: August 16, 2022Assignee: Tempus Labs, Inc.Inventors: Jason Perera, Taylor Harding, Brittany Mineo, Aly A. Khan, Richard Blidner, Jenna L. Malinauskas
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Patent number: 11408033Abstract: This disclosure provides systems and methods for sample processing and data analysis. Sample processing may include nucleic acid sample processing and subsequent sequencing. Some or all of a nucleic acid sample may be sequenced to provide sequence information, which may be stored or otherwise maintained in an electronic storage location. The sequence information may be analyzed with the aid of a computer processor, and the analyzed sequence information may be stored in an electronic storage location that may include a pool or collection of sequence information and analyzed sequence information generated from the nucleic acid sample. Methods and systems of the present disclosure can be used, for example, for the analysis of a nucleic acid sample, for producing one or more libraries, and for producing biomedical reports. Methods and systems of the disclosure can aid in the diagnosis, monitoring, treatment, and prevention of one or more diseases and conditions.Type: GrantFiled: October 23, 2020Date of Patent: August 9, 2022Assignee: Personalis, Inc.Inventors: Gabor T. Bartha, Gemma Chandratillake, Richard Chen, Sarah Garcia, Hugo Yu Kor Lam, Shujun Luo, Mark R. Pratt, John West
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Patent number: 11408037Abstract: The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.Type: GrantFiled: February 28, 2019Date of Patent: August 9, 2022Assignee: Natera, Inc.Inventors: Joshua Babiarz, Tudor Pompiliu Constantin, Lane A. Eubank, George Gemelos, Matthew Micah Hill, Huseyin Eser Kirkizlar, Matthew Rabinowitz, Onur Sakarya, Styrmir Sigurjonsson, Bernhard Zimmermann
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Patent number: 11401316Abstract: The present invention pertains to novel high avidity antigen recognizing constructs against Human Papilloma Virus antigens. The invention provides novel T cell receptor (TCR) based molecules which are selective and specific for HPV 16/18 proteins E5, E6 and E7. The TCR of the invention, and HPV antigen-binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of HPV infection, as well as for the diagnosis, treatment and prevention of HPV infection mediated secondary diseases as HPV infection caused cancers, such as cervical, nasopharyngeal or head and neck cancer. Further provided are nucleic acids encoding the proteins of the invention, and recombinant cells expressing the same.Type: GrantFiled: October 13, 2016Date of Patent: August 2, 2022Assignee: MAX-DELBRUECK-CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFTInventors: Thomas Blankenstein, Gerald Willimsky
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Patent number: 11390916Abstract: The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.Type: GrantFiled: January 24, 2020Date of Patent: July 19, 2022Assignee: Natera, Inc.Inventors: Bernhard Zimmermann, Matthew Hill, Philippe Lacroute, Michael Dodd, Alexander Wong
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Patent number: 11384377Abstract: The invention provides improved methods for synthesizing polynucleotides, such as DNA and RNA, using renewable initiators coupled to a solid support. Using the methods of the invention, specific sequences of polynucleotides can be synthesized de novo, base by base, in an aqueous environment, without the use of a nucleic acid template.Type: GrantFiled: April 6, 2020Date of Patent: July 12, 2022Assignee: Molecular Assemblies, Inc.Inventors: J. William Efcavitch, Kim Albizati, Natasha Paul, Sanjay Agarwalla
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Patent number: 11377699Abstract: The present disclosure provides a method for diagnosing a head and neck cancer in a subject. The method comprises the steps of: a) measuring an expression level of miR-125b or miR-342 and miR-125b in a sample from the subject; b) measuring an expression level of a normalizing miR in the sample and normalizing the measured expression level of miR-125b or miR-342 and miR-125b using the measured expression level of the normalizing miR; and c) diagnosing a head and neck cancer in a subject having a normalized measured expression level of miR-125b elevated relative to a reference expression level of miR-125b or having a ratio of normalized measured expression level of miR-342 to normalized measured expression level of miR-125b reduced relative to a reference ratio of expression level of miR-342 to expression level of miR-125b. Uses and kits associated with the herein disclosed methods are also disclosed.Type: GrantFiled: November 30, 2018Date of Patent: July 5, 2022Assignee: PROVINCIAL HEALTH SERVICES AUTHORITYInventors: Catherine Garnis, Martial Guillaud
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Patent number: 11374124Abstract: Described examples include integrated circuits, drain extended transistors and fabrication methods in which a silicide block material or other protection layer is formed on a field oxide structure above a drift region to protect the field oxide structure from damage during deglaze processing. Further described examples include a shallow trench isolation (STI) structure that laterally surrounds an active region of a semiconductor substrate, where the STI structure is laterally spaced from the oxide structure, and is formed under gate contacts of the transistor.Type: GrantFiled: June 28, 2018Date of Patent: June 28, 2022Assignee: Texas Instruments IncorporatedInventors: James Robert Todd, Xiaoju Wu, Henry Litzmann Edwards, Binghua Hu
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Patent number: 11371100Abstract: The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.Type: GrantFiled: February 28, 2019Date of Patent: June 28, 2022Assignee: Natera, Inc.Inventors: Joshua Babiarz, Tudor Pompiliu Constantin, Lane A. Eubank, George Gemelos, Matthew Micah Hill, Huseyin Eser Kirkizlar, Matthew Rabinowitz, Onur Sakarya, Styrmir Sigurjonsson, Bernhard Zimmermann
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Patent number: 11371084Abstract: Methods and systems described herein involve using long cell-free DNA fragments to analyze a biological sample from a pregnant subject. The status of methylated CpG sites and single nucleotide polymorphisms (SNPs) is often used to analyze DNA fragments of a biological sample. A CpG site and a SNP are typically separated from the nearest CpG site or SNP by hundreds or thousands of base pairs. Finding two or more consecutive CpG sites or SNPs on most cell-free DNA fragments is improbable or impossible. Cell-free DNA fragments longer than 600 bp may include multiple CpG sites and/or SNPs. The presence of multiple CpG sites and/or SNPs on long cell-free DNA fragments may allow for analysis than with short cell-free DNA fragments alone. The long cell-free DNA fragments can be used to identify a tissue of origin and/or to provide information on a fetus in a pregnant female.Type: GrantFiled: March 9, 2021Date of Patent: June 28, 2022Assignee: The Chinese University of Hong KongInventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Suk Hang Cheng, Cheuk Yin Yu, Yee Ting Cheung, Wenlei Peng
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Patent number: 11365408Abstract: The disclosure provides DNA library preparation methods that do not require a purification between adapter ligation and PCR amplification. Adaptors are added to DNA fragments to form oligonucleotide extension products and the oligonucleotide extension products are amplified without stopping or interruption for a cleanup step. Excess materials, such as enzymes, adaptors, or co-factors, from the adaptor addition step do not interfere with the amplification step and the amplification step proceeds without regards to the presence of reagents from the ligation step. In preferred embodiments, the ligation and amplification step make use of a common priming sequence e.g., in the form of one of the adaptor oligos.Type: GrantFiled: February 6, 2019Date of Patent: June 21, 2022Assignee: NUGEN TECHNOLOGIES, INC.Inventors: Bin Li, Benjamin G. Schroeder, Manqing Hong, Maureen Peterson
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Patent number: 11359239Abstract: The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing. Such polynucleotide processing may be useful for a variety of applications, including polynucleotide sequencing.Type: GrantFiled: May 7, 2021Date of Patent: June 14, 2022Assignee: 10X GENOMICS, INC.Inventors: Benjamin Hindson, Kevin Ness, Serge Saxonov, Paul Hardenbol
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Patent number: 11359248Abstract: Disclosed herein are methods for use in detection of single nucleotide variants (SNVs) or indels. The methods may comprise enriching cell-free DNA molecules for a panel of genomic regions and deep sequencing the enriched cfDNA to detect the SNVs or indels.Type: GrantFiled: October 21, 2021Date of Patent: June 14, 2022Assignee: GUARDANT HEALTH, INC.Inventors: Stefanie Ann Ward Mortimer, Amirali Talasaz, Darya Chudova, Helmy Eltoukhy
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Patent number: 11345968Abstract: Disclosed herein are methods for use in detection of molecular residual disease. The methods may comprise deep sequencing a panel of genomic regions in cell-free DNA molecules and computer processing sequence reads to detect variants that are indicative of molecular residual disease.Type: GrantFiled: July 2, 2021Date of Patent: May 31, 2022Assignee: GUARDANT HEALTH, INC.Inventors: Stefanie Ann Ward Mortimer, AmirAli Talasaz, Darya Chudova, Helmy Eltoukhy
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Patent number: 11332787Abstract: 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: GrantFiled: June 28, 2019Date of Patent: May 17, 2022Assignee: Pacific Biosciences of California, Inc.Inventors: Jaime Juan Benitez-Marzan, Natasha Popovich, Lei Sun
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Patent number: 11326160Abstract: This disclosure provides, among other things, a method for making a cDNA library. In some embodiments the method may comprise reverse transcribing mRNA to produce DNA:mRNA hybrids, treating the DNA:mRNA hybrids with RNAseH to produce mRNA fragments, and reverse transcribing the mRNA fragments.Type: GrantFiled: June 3, 2020Date of Patent: May 10, 2022Assignee: BIOO SCIENTIFIC CORPORATIONInventors: Kevin Allen, Adam Morris
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Patent number: 11319591Abstract: Disclosed are methods for identifying the core regulatory circuitry or cell identity program of a cell or tissue, and related methods of diagnoses, screening, and treatment involving the core regulatory circuitry and/or cell identity programs identified using the methods.Type: GrantFiled: December 23, 2016Date of Patent: May 3, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Violaine Saint-Andre, Brian J. Abraham, Zi Peng Fan, Tong Ihn Lee, Richard A. Young
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Patent number: 11319596Abstract: The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.Type: GrantFiled: February 28, 2019Date of Patent: May 3, 2022Assignee: Natera, Inc.Inventors: Joshua Babiarz, Tudor Pompiliu Constantin, Lane A. Eubank, George Gemelos, Matthew Micah Hill, Huseyin Eser Kirkizlar, Matthew Rabinowitz, Onur Sakarya, Styrmir Sigurjonsson, Bernhard Zimmermann
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Patent number: 11306356Abstract: Methods and compositions are described herein for primer extension target enrichment of immune receptor (BCR or TCR) sequences.Type: GrantFiled: June 1, 2017Date of Patent: April 19, 2022Assignee: Roche Sequencing Solutions, Inc.Inventors: Jan Berka, Brian Godwin, Carolina Dallett, Sedide Ozturk, Joseph Platzer, Seoyoung Kim
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Patent number: 11306358Abstract: Provided is a method for determining a genetic condition of a fetus, the method including: an objective region selection step of selecting an objective region for determining the genetic condition, from regions on a human genome; a step of isolating a single cell from a maternal blood sample; a step of extracting genomic DNA from the single cell; a step of performing PCR amplification on the objective region using a primer set designed so as to perform the PCR amplification on the objective region using genomic DNA extracted from the single cell as a template; and a DNA sequencing step of decoding a DNA base sequence of a PCR amplification product of the objective region, in which the primer set designed so as to perform the PCR amplification on the objective region is designed through a method for designing a primer set used for the polymerase chain reaction, the method for designing a primer set including a first stage selection step based on a local alignment score and a second stage selection step based oType: GrantFiled: September 22, 2017Date of Patent: April 19, 2022Assignee: FUJIFILM CorporationInventors: Aya Ouchi, Takayuki Tsujimoto, Masaya Nagase, Yasuyuki Ishii
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Patent number: 11306348Abstract: The present disclosure relates to methods, compositions, and kits for generating a library of tagged nucleic acid fragments without using PCR amplification, including methods and compositions for fragmenting and tagging nucleic acids (e.g., DNA) using transposome complexes immobilized on solid support.Type: GrantFiled: May 3, 2021Date of Patent: April 19, 2022Assignee: Illumina Cambridge LimitedInventors: Andrew Slatter, Esther Musgrave-Brown, Susan C. Verity, Niall Anthony Gormley
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Patent number: 11282610Abstract: The present disclosure provides methods for determining a probability that after any of a number of therapeutic interventions, an initial state of a subject, such as somatic cell mutational status of a subject with cancer, will develop a subsequent state. Such probabilities can be used to inform a health care provider as to particular courses of treatment to maximize probability of a desired outcome for the subject.Type: GrantFiled: September 3, 2020Date of Patent: March 22, 2022Assignee: GUARDANT HEALTH, INC.Inventors: Helmy Eltoukhy, AmirAli Talasaz
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Patent number: 11268075Abstract: Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising modifying the aptamer by uracil-DNA glycosylase enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamers are circular and comprise one or more deoxyuridine nucleotides providing for aptamer-specific recognition and modification of the circular aptamer by the uracil-DNA glycosylase enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing uracil-DNA glycosylase enzymatic activity are provided.Type: GrantFiled: June 26, 2020Date of Patent: March 8, 2022Assignee: CepheidInventors: Igor V. Kutyavin, Sergey G. Lokhov
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Patent number: 11268131Abstract: Reagents and methods for the analysis of nucleic acids (e.g. genomic DNA) of circulating microparticles (i.e. microparticles originating from blood) are provided. The methods comprise linking at least two fragments of a target nucleic acid of a circulating microparticle to produce a set of at least two linked fragments of the target nucleic acid. In the methods, fragments of a target nucleic acid may be linked by techniques such as barcoding, partitioning, ligation and/or separate sequencing. The sequencing of a set of linked fragments provides a set of informatically linked sequence reads corresponding to the sequences of fragments from a single microparticle.Type: GrantFiled: May 4, 2020Date of Patent: March 8, 2022Assignee: CS Genetics LimitedInventor: Lucas Brandon Edelman
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Patent number: 11268907Abstract: Methods of detecting compromise of at least one analyte reagent upon reaction with a test sample are disclosed. Also disclosed are reflectance spectroscopic diagnostic instruments that perform the method, and systems that contain same.Type: GrantFiled: December 12, 2017Date of Patent: March 8, 2022Assignee: Siemens Healthcare Diagnostics Inc.Inventors: Lloyd Schulman, Christopher Zimmerle, Julie Chaney
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Patent number: 11261492Abstract: The present invention relates to methods for detecting, enriching, and analyzing rare cells that are present in the blood, e.g. fetal cells. The invention further features methods of analyzing rare cell(s) to determine the presence of an abnormality, disease or condition in a subject, e.g. a fetus by analyzing a cellular sample from the subject.Type: GrantFiled: October 7, 2019Date of Patent: March 1, 2022Assignees: The General Hospital Corporation, Verinata Health, Inc., GPB Scientific, LLCInventors: Ravi Kapur, Mehmet Toner, Zihua Wang, Martin Fuchs
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Patent number: 11254976Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.Type: GrantFiled: August 19, 2019Date of Patent: February 22, 2022Assignee: Illumina, Inc.Inventors: Min-Jui Richard Shen, Jonathan Mark Boutell, Kathryn M. Stephens, Mostafa Ronaghi, Kevin L. Gunderson, Bala Murali Venkatesan, M. Shane Bowen, Kandaswamy Vijayan
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Patent number: 11254975Abstract: A method of amplifying a target nucleic acid (polynucleotide) contained in a particle including an enclosing lipid bilayer membrane according to the present invention includes the steps of: lysing the particle which is stored in a compartment constituted by a liquid in an amount of 100 ?l or less; and amplifying the target nucleic acid in the compartment.Type: GrantFiled: May 23, 2019Date of Patent: February 22, 2022Inventors: Toru Uchiyama, Masafumi Onodera
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Patent number: 11248253Abstract: Methods are provided for correction of amplification bias and quantitation of adaptive immune cells in a sample using synthetic templates that include random oligonucleotide sequences.Type: GrantFiled: May 1, 2020Date of Patent: February 15, 2022Assignee: Adaptive Biotechnologies CorporationInventors: Anna M. Sherwood, Ryan O. Emerson, Harlan S. Robins, Mark J. Rieder, Joe Parsons
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Patent number: 11242542Abstract: This invention pertains to mutant Cas9 nucleic acids and proteins for use in CRISPR/Cas endonuclease systems, and their methods of use. In particular, the invention pertains to an isolated mutant Cas9 protein, wherein the isolated mutant Cas9 protein is active in a CRISPR/Cas endonuclease system, wherein the CRISPR/Cas endonuclease system displays reduced off-target editing activity and maintained on-target editing activity relative to a wild-type CRISPR/Cas endonuclease system. The invention also includes isolated nucleic acids encoding mutant Cas9 proteins, ribonucleoprotein complexes and CRISPR/Cas endonuclease systems having mutant Cas9 proteins that display reduced off-target editing activity and maintained on-target editing activity relative to a wild-type CRISPR/Cas endonuclease system.Type: GrantFiled: April 26, 2018Date of Patent: February 8, 2022Assignee: Integrated DNA Technologies, Inc.Inventors: Christopher Anthony Vakulskas, Nicole Mary Bode, Michael Allen Collingwood, Garrett Richard Rettig, Mark Aaron Behlke
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Patent number: 11214798Abstract: Rapid nucleic acid libraries, methods of generation, kits, and compositions relating to library synthesis, including reagents, intermediaries and final products are disclosed herein. The disclosure enables rapid synthesis of libraries that allow independent verification of sequence information and rapid identification of sequence information with template of origin.Type: GrantFiled: September 6, 2019Date of Patent: January 4, 2022Assignee: iGenomX International Genomics CorporationInventor: Keith Brown
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Patent number: 11209368Abstract: A method and test kit are useful for detecting specific nucleic acid sequences. The process includes (1) matrix-dependent new synthesis of the target nucleic acid; (2) target-specific probe hybridization; and (3) detection of the hybridization event. In the first step, an oligonucleotide 1, which is marked by a marker 1 and is entirely or partially complementary to the target sequence, acts as a primer in the matrix-dependent new synthesis of the target nucleic acid and, in the second step, an oligonucleotide 2, which is marked by a marker 2 and, owing to its melting temperature being lower than that of the oligonucleotide 1, is not involved in the first step, partially or completely hybridizes with the DNA new synthesis product of oligonucleotide 1.Type: GrantFiled: July 23, 2018Date of Patent: December 28, 2021Assignee: IST Innuscreen GmbHInventors: Elmara Graser, Timo Hillebrand
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Patent number: 11208678Abstract: Disclosed are methods and kits for improving global gene expression analysis for a population of RNA molecules derived from a human urine sample. In an embodiment, the method comprises the step of selectively depleting miR-10a-5p fragments from the population of RNA molecules or selectively blocking miR-10a-5p fragments within the RNA population. The miR-10a-5p depleted or miR-10a-5p blocked population of RNA can be used in a variety of global gene expression analysis protocols, including next generation sequencing. In a further embodiment, the method comprises selectively depleting or blocking miR-10b-5p fragments within the RNA population. The miR-10a-5p and/or miR-10b-5p depleted or blocked populations of RNA can also be used in global gene expression analysis protocols, including next generation sequencing.Type: GrantFiled: July 23, 2018Date of Patent: December 28, 2021Assignee: Norgen Biotek Corp.Inventor: Yousef Haj-Ahmad
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Patent number: 11192105Abstract: An analysis system may perform operations on an analyte that may be combined with multiple regents prior to being introduced into a flow cell. The instrument may include a volume into which the reagents to be combined with the analyte are aspirated one-by-one. The volume may be formed as a serpentine channel in a valve manifold associated with sippers for aspirating the reagents. The reagents may then be mixed by cycling a pump to move the reagents within the mixing volume or channel. For this, the reagents may be aspirated from a recipient into the volume or channel, ejected back into the recipient, and this process may be performed repeatedly to enhance mixing.Type: GrantFiled: March 23, 2020Date of Patent: December 7, 2021Assignee: Illumina, Inc.Inventors: Bradley Kent Drews, Michael Dai Wang, Umberto Ulmanella, Stephen Wayne Clark, Johanna Lynn Whitacre, Steven Scott Phelps, Michelle L. Alvarez, Michael Adalbert Niziolek, Debra Sue Bryan, Joshua Augustin Darland
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Patent number: 11193164Abstract: Provided herein are, inter alia, methods and compositions to detect, monitor and treat cancer, wherein the cancer includes amplified extrachromosomal oncogenes. The methods are useful for personalized treatment and exploit differential expression of amplified extrachromosomal oncogenes in cancer cells versus healthy cells.Type: GrantFiled: May 24, 2018Date of Patent: December 7, 2021Assignees: The Regents of the University of California, Ludwig Institute for Cancer Research LtdInventors: Paul Mischel, Prashant Mali, Vineet Bafna, Kristen Turner, Viraj Deshpande, Doruk Beyter
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Patent number: 11180800Abstract: The disclosure provides methods, compositions, systems, and kits for the concurrent detection and analysis of different structural and chemical forms of nucleic acids in a sample.Type: GrantFiled: May 13, 2020Date of Patent: November 23, 2021Assignee: Karius, Inc.Inventors: Timothy A. Blauwkamp, Rene Sit, Igor D. Vilfan
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Patent number: 11180804Abstract: The present invention provides methods for analyzing polynucleotides such as genomic DNA. In some embodiments, the disclosure provides a method for preparing and amplifying a genomic DNA library in situ in a fixed biological sample. The method comprises treating a fixed biological sample with an insertional enzyme complex to produce tagged fragments of genomic DNA. The method further comprises circularizing the tagged fragments of genomic DNA. The method further comprises amplifying the tagged fragments of genomic DNA.Type: GrantFiled: July 24, 2018Date of Patent: November 23, 2021Assignees: Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Fei Chen, Andrew C. Payne, Jason D. Buenrostro, Paul Reginato, Edward Stuart Boyden, Shahar Alon