Biochemical Method (e.g., Using An Enzyme Or Whole Viable Micro-organism, Etc.) Patents (Class 506/26)
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Patent number: 10988761Abstract: Presented herein is a high-throughput (HTP) genomic engineering platform for improving the production of therapeutic proteins in Chinese hamster ovary (CHO) cells. The disclosed HTP genomic engineering platform is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. The platform utilizes a unique suite of HTP genetic engineering tools to explore the genomic landscape associated with therapeutic protein production pathways, in order to unravel the biological drivers and disentangle the uncharacterized genetic architecture responsible for optimizing therapeutic protein production in CHO cells.Type: GrantFiled: July 20, 2020Date of Patent: April 27, 2021Assignee: Zymergen Inc.Inventors: Kate Caves, Amarjeet Singh
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Patent number: 10968447Abstract: High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduces sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are methods and compositions for sequencing nucleic acids. Further provided are methods of identifying an error in a nucleic acid sequence.Type: GrantFiled: January 17, 2018Date of Patent: April 6, 2021Assignee: MYRIAD WOMEN'S HEALTH, INC.Inventors: Henry H. Lai, Clement S. Chu
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Patent number: 10865410Abstract: Provided herein is technology relating to next-generation sequencing and particularly, but not exclusively, to methods and compositions for preparing a next-generation sequencing library comprising short overlapping DNA fragments and using the library to sequence one or more target nucleic acids.Type: GrantFiled: June 29, 2018Date of Patent: December 15, 2020Assignee: ABBOTT MOLECULAR INC.Inventor: Dae Hyun Kim
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Patent number: 10814299Abstract: Methods, compositions, and systems for distributing nucleic acids into array regions are provided. The methods, compositions, and systems utilize nucleic acid condensing agents to increase efficiency of distribution of the nucleic acids into the array regions. Various methods for facilitating distribution of the nucleic acids to the array regions are provided.Type: GrantFiled: November 17, 2016Date of Patent: October 27, 2020Assignee: Pacific Biosciences of California, Inc.Inventors: Lei Sun, Jaime Juan Benitez-Marzan, Natasha Popovich, Sassan Sheikholeslami, Steven Lin, Aparna Vedula
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Patent number: 10808277Abstract: An example method includes reacting a first solution and a different, second solution on a flow cell by flowing the first solution over amplification sites on the flow cell and subsequently flowing the second solution over the amplification sites. The first solution includes target nucleic acids and a first reagent mixture that comprises nucleoside triphosphates and replication enzymes. The target nucleic acids in the first solution transport to and bind to the amplification sites at a transport rate. The first reagent mixture amplifies the target nucleic acids that are bound to the amplification sites to produce clonal populations of amplicons originating from corresponding target nucleic acids. The amplicons are produced at an amplification rate that exceeds the transport rate. The second solution includes a second reagent mixture and lacks the target nucleic acids. The second solution is to increase a number of the amplicons at the amplification sites.Type: GrantFiled: December 15, 2017Date of Patent: October 20, 2020Assignees: ILLUMINA, INC., ILLUMINA CAMBRIDGE LIMITEDInventors: Shaun Hunter, Peter McInerney, Jonathan Boutell, Claire Bevis-Mott
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Patent number: 10774374Abstract: A method for spatially tagging nucleic acids of a biological specimen, including steps of (a) providing a solid support comprising different nucleic acid probes that are randomly located on the solid support, wherein the different nucleic acid probes each includes a barcode sequence that differs from the barcode sequence of other randomly located probes on the solid support; (b) performing a nucleic acid detection reaction on the solid support to locate the barcode sequences on the solid support; (c) contacting a biological specimen with the solid support that has the randomly located probes; (d) hybridizing the randomly located probes to target nucleic acids from portions of the biological specimen; and (e) modifying the randomly located probes that are hybridized to the target nucleic acids, thereby producing modified probes that include the barcode sequences and a target specific modification, thereby spatially tagging the nucleic acids of the biological specimen.Type: GrantFiled: April 4, 2016Date of Patent: September 15, 2020Assignee: Spatial Transcriptomics AB and Illumina, Inc.Inventors: Jonas Frisén, Patrik Ståhl, Joakim Lundeberg, Gordon M. Cann, Leila Bazargan, Alex Aravanis
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Patent number: 10767171Abstract: This invention relates to, in part, compositions of beta-lactamases and methods of using these enzymes in, for example, gastrointestinal tract (GI tract) disorders such as C. difficile infection (CDI).Type: GrantFiled: January 24, 2020Date of Patent: September 8, 2020Assignee: Synthetic Biologics, Inc.Inventors: Michael Kaleko, Sheila Connelly
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Patent number: 10760121Abstract: Methods, devices and systems for analyzing precious samples of cells, including single cells are provided. The methods, devices, and systems in various embodiments of the invention are used to assess genomic heterogeneity, which has been recognized as a central feature of many cancers and plays a critical role in disease initiation, progression, and response to treatment. The methods devices and systems are also used to analyze embryonic biopsies for preimplantation genetic diagnosis (PGD). In one embodiment, the devices, systems and methods provided herein allow for the construction of genomic and RNA-seq libraries without a pre-amplification step.Type: GrantFiled: February 4, 2016Date of Patent: September 1, 2020Assignee: The University of British ColumbiaInventors: Carl Lars Genghis Hansen, Hans Zahn, Jens Huft, Marinus Theodorus Johannes Van Loenhout, Kaston Leung, Bill Kengli Lin, Anders Klaus, Samuel Alves Jana Rodrigues Aparicio, Sohrab Prakash Shah, Adi Steif
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Patent number: 10752949Abstract: 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: December 6, 2018Date of Patent: August 25, 2020Assignee: 10X GENOMICS, INC.Inventors: Benjamin Hindson, Christopher Hindson, Michael Schnall-Levin, Kevin Ness, Mirna Jarosz, Serge Saxonov, Paul Hardenbol
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Patent number: 10731211Abstract: The present disclosure provides methods, compositions, and systems for distributing polymerase compositions into array regions. In particular, the described methods, compositions, and systems utilize density differentials and/or additives to increase efficiency in the distribution of polymerase compositions to a surface as compared to methods utilizing only diffusion control.Type: GrantFiled: November 17, 2016Date of Patent: August 4, 2020Assignee: Pacific Biosciences of California, Inc.Inventors: Sassan Sheikholeslami, Michael Hunkapiller, Natasha Popovich, Lei Sun, Erik Miller, Satwik Kamtekar
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Patent number: 10725027Abstract: The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing and analyte characterization from a single cell. Such polynucleotide processing may be useful for a variety of applications. The compositions, methods, systems, and devices disclosed herein generally describe barcoded oligonucleotides, which can be bound to a bead, such as a gel bead, useful for characterizing one or more analytes including, for example, protein (e.g., cell surface or intracellular proteins) and chromatin (e.g., accessible chromatin).Type: GrantFiled: April 4, 2019Date of Patent: July 28, 2020Assignee: 10X GENOMICS, INC.Inventors: Jason Bell, Geoffrey McDermott, Francesca Meschi, Michael Schnall-Levin, Xinying Zheng
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Patent number: 10711296Abstract: Processes, oligonucleotides, and kits for amplifying RNA. In particular, the processes generate and amplify cDNA libraries in which the orientation of the input RNA molecule is preserved in the products. Among the various aspects of the present disclosure is the provision of process for directionally amplifying RNA. The process comprises reverse transcribing at least one RNA molecule in the presence of a plurality of first synthesis primers to generate a plurality of first strands of complementary DNA (cDNA), wherein each of the first synthesis primers comprises a 3? sequence having complementarity to a portion of the RNA molecule, a non-complementary 5? sequence corresponding to one or more amplification primers, and optionally an internal tag sequence comprising a first tag sequence.Type: GrantFiled: March 24, 2016Date of Patent: July 14, 2020Assignee: Sigma-Aldrich Co. LLCInventors: Kenneth B Heuermann, Carol A Kreader, Jaime K Robert, Brian W Ward
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Patent number: 10683495Abstract: The present invention relates to improved yeast transformation of yeast cells and yeast cell libraries transformed thereby. More specifically, the present invention relates to the transformation of yeast by electroporation.Type: GrantFiled: November 15, 2017Date of Patent: June 16, 2020Assignee: IMMATICS BIOTECHNOLOGIES GMBHInventors: Sebastian Bunk, Dominik Maurer, Felix Unverdorben
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Patent number: 10647775Abstract: Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.Type: GrantFiled: April 4, 2016Date of Patent: May 12, 2020Assignees: Subdomain LLC, Arcellx, Inc.Inventors: David William Lafleur, David M. Hilbert
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Patent number: 10633651Abstract: The present invention relates to nucleic acid samples for massively parallel sequencing. More particularly, the present invention relates to assay methods, compositions and kits for detecting contamination of nucleic acid identifiers such as sample barcodes.Type: GrantFiled: July 10, 2017Date of Patent: April 28, 2020Assignee: AGILENT TECHNOLOGIES, INC.Inventors: Katie Leigh Zobeck, Paige Anderson, Javelin Chi, Henrik Johansson
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Patent number: 10625234Abstract: The present disclosure provides a fabrication process that results in creating large arrays of living cells, such as stem cells, which are subsequently exposed to nanoliter quantities of compounds to test the efficacy on cellular metabolism.Type: GrantFiled: August 28, 2015Date of Patent: April 21, 2020Assignee: StemoniX Inc.Inventor: Robert John Petcavich
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Patent number: 10619207Abstract: Provided herein is a method for analyzing polynucleotides such as genomic DNA. In certain embodiments, the method comprises: (a) treating chromatin isolated from a population of cells with an insertional enzyme complex to produce tagged fragments of genomic DNA; (b) sequencing a portion of the tagged fragments to produce a plurality of sequence reads; and (c) making an epigenetic map of a region of the genome of the cells by mapping information obtained from the sequence reads to the region. A kit for performing the method is also provided.Type: GrantFiled: May 21, 2019Date of Patent: April 14, 2020Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Paul Giresi, Jason D. Buenrostro, Howard Y. Chang, William J. Greenleaf
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Patent number: 10619199Abstract: Processes and kits for preparing a plurality of amplification products with reduced non-specific amplification artifacts.Type: GrantFiled: March 4, 2016Date of Patent: April 14, 2020Assignee: Sigma-Aldrich Co. LLCInventors: Timothy Seebeck, Fuqiang Chen, Brian W Ward
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Patent number: 10604804Abstract: Next Generation DNA sequencing promises to revolutionize clinical medicine and basic research. However, while this technology has the capacity to generate hundreds of billions of nucleotides of DNA sequence in a single experiment, the error rate of approximately 1% results in hundreds of millions of sequencing mistakes. These scattered errors can be tolerated in some applications but become extremely problematic when “deep sequencing” genetically heterogeneous mixtures, such as tumors or mixed microbial populations. To overcome limitations in sequencing accuracy, a method Duplex Consensus Sequencing (DCS) is provided. This approach greatly reduces errors by independently tagging and sequencing each of the two strands of a DNA duplex. As the two strands are complementary, true mutations are found at the same position in both strands. In contrast, PCR or sequencing errors will result in errors in only one strand.Type: GrantFiled: May 13, 2019Date of Patent: March 31, 2020Assignee: UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATIONInventors: Jesse Salk, Lawrence A. Loeb, Michael Schmitt
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Patent number: 10590465Abstract: Assays can be used to detect mutations found in neoplasms of the pancreas, as well as for other neoplasms and other uses. Nucleic acids can be captured from body fluids such as cyst fluids. Thousands of oligonucleotides can be synthesized in parallel, amplified and ligated together. The ligated products can be further amplified. The amplified, ligated products are used to capture complementary DNA sequences, which can be analyzed, for example by massively parallel sequencing.Type: GrantFiled: May 30, 2017Date of Patent: March 17, 2020Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Jian Wu
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Patent number: 10584326Abstract: This invention relates to, in part, compositions of beta-lactamases and methods of using these enzymes in, for example, gastrointestinal tract (GI tract) disorders such as C. difficile infection (CDI).Type: GrantFiled: May 16, 2019Date of Patent: March 10, 2020Assignee: Synthetic Biologics, Inc.Inventors: Michael Kaleko, Sheila Connelly
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Patent number: 10562004Abstract: The present disclosure provides a fabrication process that results in creating large arrays of living cells, such as stem cells, which are subsequently exposed to nanoliter quantities of compounds to test the efficacy on cellular metabolism.Type: GrantFiled: August 28, 2015Date of Patent: February 18, 2020Assignee: StemoniX Inc.Inventor: Robert John Petcavich
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Patent number: 10563257Abstract: The invention provides in situ nucleic acid sequencing to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ sequencing of nucleic acids as well as new methods for fluorescent in situ sequencing (FISSEQ) in a new process referred to herein as “expansion sequencing” (ExSEQ).Type: GrantFiled: August 23, 2018Date of Patent: February 18, 2020Assignees: Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Edward Stuart Boyden, Fei Chen, Shahar Alon, George Church, Paul Warren Tillberg, Adam Henry Marblestone, Evan R. Daugharthy
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Patent number: 10545494Abstract: A method for determining performance characteristics of a fermenter batch in a biofuel production plant based on stoichiometry of fermentation reactions, comprising determining a cell mass of a sample of the fermenter batch; a glucose equivalent total (GET) based at least on the cell mass of the sample of the fermenter batch, and a starch to glucose conversion factor (SGCF) based at least on the GET; a total amount of glucose based at least on the SGCF, a volume of ethanol based at least on the total amount of glucose and the GET; at least one of a fermenter yield based at least on the volume of ethanol, and a fermenter efficiency based on the fermenter yield or the volume of ethanol; and generating an output based on the fermenter yield and/or the fermenter efficiency.Type: GrantFiled: June 18, 2010Date of Patent: January 28, 2020Assignee: Rockwell Automation Technologies, Inc.Inventors: Srinivas Budaraju, James F. Bartee
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Patent number: 10538812Abstract: The present invention provides a means for efficiently amplifying the exons of PKD1 and PKD2 genes, and a primer set that can amplify all the exons of PKD1 and PKD2 genes under a single set of PCR conditions.Type: GrantFiled: November 13, 2015Date of Patent: January 21, 2020Assignee: OTSUKA PHARMACEUTICAL CO., LTD.Inventors: Kiyonori Katsuragi, Moritoshi Kinoshita, Daisuke Koga, Ryo Higashiyama
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Patent number: 10538594Abstract: Provided herein are methods and compositions for analyzing epigenetic modifications of genomes. The methods and compositions are suited for complete epigenome sequencing of any modification for which an antibody or an affinity binding agent has been developed. In one aspect, provided herein is a method for analyzing epigenetic modification of a genome. In some embodiments of aspects provided herein, the method further comprises sequencing a sequencing library to generate sequence reads, and assembling the sequence reads with aid of a positional barcode sequence information. In some embodiments of aspects provided herein, the method further comprises determining a location of at least two different epigenetic modifications of the nucleic acid. Another aspect of the present disclosure provides a kit for analyzing an epigenetic modification of a nucleic acid.Type: GrantFiled: April 6, 2016Date of Patent: January 21, 2020Assignee: Centrillion Technology Holdings CorporationInventors: Wei Zhou, Jeremy Edwards, Justin Costa
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Patent number: 10457982Abstract: It is an object of the present invention to provide a method for amplifying a nucleic acid, using RNA as a template, which can realize elimination of the risk of non-specific amplification caused by DNA mixed from reagents and/or working environment, an increase in the detection sensitivity of trace RNA, and a reduction in amplification bias. According to the present invention, there is provided a method for amplifying a nucleic acid, which comprises a step of incubating a mixture comprising template RNA, a primer, a degrading enzyme specific to DNA in RNA-DNA hybrid, an RNase H minus reverse transcriptase, and a substrate.Type: GrantFiled: September 30, 2015Date of Patent: October 29, 2019Assignee: RIKENInventors: Tetsutaro Hayashi, Yohei Sasagawa, Itoshi Nikaido
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Patent number: 10300452Abstract: The present invention provides methods, compositions, and systems for distributing single polymerase molecules into array regions. In particular, the methods, compositions, and systems of the present invention result in a distribution of single polymerase molecules into array regions at a percentage that is larger than the percentage expected to be occupied under a Poisson distribution.Type: GrantFiled: March 23, 2016Date of Patent: May 28, 2019Assignee: Pacific Biosciences of California, Inc.Inventors: Lei Sun, Natasha Popovich, Gene Shen, Thang Pham, Stephen Turner
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Patent number: 10294511Abstract: Embodiments provided herein relate to methods and compositions for preparing nucleic acid libraries. Some embodiments include preparing libraries from nucleic acids obtained from degraded samples, such as ancient samples and fixed samples.Type: GrantFiled: October 16, 2014Date of Patent: May 21, 2019Assignee: ILLUMINA, INC.Inventors: Raquel Maria Sanches-Kuiper, Vincent Peter Smith, Sean Humphray
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Patent number: 10240196Abstract: Provided herein, among other things, are a variety of methods for transposase-mediated tagging and amplification of short DNA fragments, e.g., between about 150 bp and 1.5 Kb in length. In some aspects, the method includes tagging the DNA fragments with a first primer sequence using barcoded transposases followed by a primer extension reaction to introduce a second primer sequence, e.g., using random or gene-specific primers. Kits for performing this method are also provided.Type: GrantFiled: May 27, 2016Date of Patent: March 26, 2019Assignee: AGILENT TECHNOLOGIES, INC.Inventors: Bahram Arezi, Michael Borns, Holly Hogrefe, Connie Hansen
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Patent number: 10208338Abstract: The present disclosure describes a method of adapter ligation to the ends of fragmented double-stranded DNA molecules.Type: GrantFiled: March 3, 2015Date of Patent: February 19, 2019Assignee: SWIFT BIOSCIENCES, INC.Inventors: Vladimir Makarov, Julie Laliberte
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Patent number: 10150991Abstract: Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.Type: GrantFiled: June 6, 2016Date of Patent: December 11, 2018Assignee: The Johns Hopkins UniversityInventors: Bert Vogelstein, Frank Diehl, Kenneth W. Kinzler, Meng Li
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Patent number: 10108147Abstract: An image photography play method which is suited to playing a stereoscopic video. The image photography method includes: a step of forming a hologram pattern from a reference light and a subject light; a step of digitally processing the obtained hologram pattern; a step of writing the digitized hologram pattern as a magnetized vector pattern to a spatial lighting modulator which is formed from a magneto-optical material; and a step of inputting linearly polarized light into the spatial lighting modulator and playing an image according to the digitized hologram pattern.Type: GrantFiled: May 31, 2012Date of Patent: October 23, 2018Assignee: NATIONAL UNIVERSITY CORPORATION TOYOHASHI UNIVERSITY OF TECHNOLOGYInventors: Mitsuteru Inoue, Hiroyuki Takagi
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Patent number: 10100347Abstract: The invention provides materials and methods to identify and analyze in a genome-wide manner the structural determinants of this organization. Next generation sequencing methods, combined with a novel assay and integrated data analysis, are used to map the long-range interactions in chromatin that are involved in the regulation of transcription.Type: GrantFiled: April 26, 2016Date of Patent: October 16, 2018Assignee: Board of Regents, The University of Texas SystemInventors: Zbyszek Otwinowski, Dominika Borek
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Patent number: 10072260Abstract: Provided herein are various methods for enriching a target fragment that is present in randomly sheared genomic DNA. In some embodiments, the method may involve hybridizing randomly sheared genomic DNA to a halo probe to produce a first circular complex, and then enzymatically digesting the overhanging ends of the genomic fragment. Other embodiments may include hybridizing randomly sheared genomic DNA to an RNA oligonucleotide that comprises a region that hybridizes to a fragment of the randomly sheared genomic DNA to produce an RNA/DNA duplex. The overhanging ends of the genomic fragment in the RNA/DNA duplex can then be enzymatically digested.Type: GrantFiled: October 3, 2013Date of Patent: September 11, 2018Assignee: AGILENT TECHNOLOGIES, INC.Inventors: Scott Robert Happe, Emily Marine Leproust, Julia Barboza, Joseph Hoang Hai Ong
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Patent number: 10059938Abstract: The present invention is directed to methods and kits for gene analysis. The methods of the invention comprise the steps of providing nucleic acid; synthesis of a single-stranded DNA that is complementary to said nucleic acid molecule by contacting the nucleic acid with a DNA polymerase, a primer and a mixture of dNTPs under conditions that allow the generation of the DNA, wherein the primer comprises a target-complementary region and wherein the dNTP mixture comprises dATP, dGTP, dCTP, dTTP and dUTP; cleaving the DNA 5? to dU sites by (i) contacting the DNA with an uracil deglycosylase to generate a basic sites at positions of dUTP incorporation in the DNA; and (ii) contacting the DNA with an apurinic/apyrimidinic (AP) endonuclease; contacting the DNA comprising at its 5?-end the nucleotide sequence of the primer with a ssDNA ligase to circularize the DNA; and sequencing the circularized cDNA. The kits comprise the components necessary to perform the methods of the invention.Type: GrantFiled: October 30, 2015Date of Patent: August 28, 2018Assignee: RHEINISCHE FRIEDRICH-WILHELMS-UNIVERSITAT BONNInventors: Veit Hornung, Jonathan Schmid-Burgk
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Patent number: 10036013Abstract: Provided herein is technology relating to next-generation sequencing and particularly, but not exclusively, to methods and compositions for preparing a next-generation sequencing library comprising short overlapping DNA fragments and using the library to sequence one or more target nucleic acids.Type: GrantFiled: August 19, 2014Date of Patent: July 31, 2018Assignee: Abbott Molecular Inc.Inventor: Dae Hyun Kim
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Patent number: 9920367Abstract: The present invention provides methods and systems for analyzing mammalian transcriptomes, particularly, for low abundant transcripts, and with the use of high throughput technologies. Heptamer primers and sequence tags generated by the iterative randomized algorithm, as well as the sequencing-library generation system for amplifying and synthesis-based sequencing low abundant transcripts using the heptamer primers are also provided. The present invention further provides the use of the invention system and method for identifying key embryological lineage specific transcripts that anticipate differentiation of specific cell types.Type: GrantFiled: December 13, 2013Date of Patent: March 20, 2018Assignee: The Regents of the University of CaliforniaInventors: Vipul Bhargava, Pang Ko, Shankar Subramaniam
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Patent number: 9914965Abstract: The present invention provides compositions and methods for rapidly amplifying target nucleic acid (e.g., using whole genome amplification) that allows small amounts of starting nucleic acid to be employed. In certain embodiments, the methods employ compositions that comprise: phi29 polymerase, exo? Klenow polymerase and/or Klenow polymerase, dNTPs, primers, and a buffering agent. In some embodiments, the target nucleic acid is amplified at a rate that would result in at least 1000-fold amplification in thirty minutes.Type: GrantFiled: August 29, 2016Date of Patent: March 13, 2018Assignee: IBIS BIOSCIENCES, INC.Inventors: Mark Eshoo, Stanley Motley, John Picuri
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Micro-liquid phase reaction method based on substrate with hydrophilic-hydrophobic patterned surface
Patent number: 9797007Abstract: A micro-liquid phase reaction method based on a substrate with a hydrophilic-hydrophobic patterned surface, including the following: applying a liquid phase system containing a hydrotropic substance and/or an amphipathic substance to a hydrophobic smooth plane in a sample-spotting manner to form an array of tiny droplets, subsequently removing the solvent in each droplet to bond the hydrotropic substance and/or amphipathic substance in each droplet to the hydrophobic smooth plane so as to form an array of hydrophilic bonding points, then moving an aqueous phase system or hydrophilic liquid phase system containing more than one reactants over the hydrophobic smooth plane, thereby forming island-like tiny reaction droplets at each hydrophilic bonding point, and finally under the set reaction conditions, reacting the reactants in each tiny reaction droplet.Type: GrantFiled: November 30, 2012Date of Patent: October 24, 2017Assignee: Suzhou Institute of Nano-Tech and Nano-Bionics of Chinese Academy of ScienceInventors: Jiong Li, Kexiao Zheng -
Patent number: 9631227Abstract: Provided herein are methods for ligation of polynucleotides containing modified ligation components, particularly modified ligase cofactors, modified acceptors and modified donors. The methods readily applied to ligation-based assays for detection of a nucleic acid sequence where the use of the modified cofactor improves discrimination between matched and mismatched templates. Furthermore, the use of the modified ligation components reduces or eliminates the ligation in the absence of nucleic acid template. In addition, methods are applied to the preparation of nucleic acid libraries using modified acceptor probes and modified donor probes that reduce or eliminate probe dimerization during the ligation process.Type: GrantFiled: March 15, 2013Date of Patent: April 25, 2017Assignee: TRILINK BIOTECHNOLOGIES, INC.Inventors: Natasha Paul, Sabrina Shore, Jonathan Shum, Alexandre Lebedev, Gerald Zon
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Patent number: 9528148Abstract: Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5? or 3? flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are hybridized to dU probes so that 5? and 3? flaps are generated. The flaps are cleaved using 5? or 3? flap endonucleases or 3? to 5? exonucleases. The target sequences are then ligated to common primers, the dU probes digested and the ligated targets amplified.Type: GrantFiled: March 23, 2015Date of Patent: December 27, 2016Assignee: Affymetrix, Inc.Inventors: Jianbiao Zheng, Li Weng, Malek Faham
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Patent number: 9506055Abstract: Provided herein is a method of reducing adapter dimer formation comprising contacting a sample comprising target nucleic acid sequences with 5? and 3? adapters in the presence of one or more hairpin oligonucleotides. Also provided is a method of preparing a library of nucleic acid sequences comprising contacting first adapter oligonucleotides with a sample comprising target nucleic acid sequences under conditions to form first ligation products, contacting the sample with one or more hairpin oligonucleotides that binds to the first adapter oligonucleotides, and contacting the sample with second adapter oligonucleotides under conditions to bind to the first ligation products and form second ligation products, wherein the second ligation products form the library of nucleic acid sequences.Type: GrantFiled: September 22, 2013Date of Patent: November 29, 2016Assignee: Illumina, Inc.Inventors: Patrick Lau, Danny Lee
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Patent number: 9506915Abstract: The present invention encompasses methods of identifying proteins and protein modifications of proteins specifically associated with a chromatin.Type: GrantFiled: June 19, 2015Date of Patent: November 29, 2016Assignee: BOARD OF TRUSTEES OF THE UNIVERSITY OF ARKANSASInventors: Alan J. Tackett, Stephanie Byrum, Sean Taverna, Kevin Raney, Zachary Waldrip
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Patent number: 9469864Abstract: The present invention relates to methods of use of glycosyltransferases and related novel compounds. The invention exploits the reversibility of glycosyltransferases to generate new sugars, unnatural biomolecules and numerous one-pot reactions for generation of new biomolecules having varied backbones such as enediynes, vancomycins, bleomycins, anthracyclines, macrolides, pluramycins, aureolic acids, indolocarbazoles, aminglycosides, glycopeptides, polyenes, coumarins, benzoisochromanequinones, calicheamicins, erythromycin, avermectins, ivermectins, angucyclines, cardiac glycosides, steroids or flavinoids. In preferred embodiments, the invention specifically relates to biosynthesis of anticancer (the enediyne calicheamicin, CLM), anthelmintic agents (the macrolides avermectin, ivermectin and erythromycin) and antibiotic (the glycopeptide vancomycin, VCM) natural product-based drugs developed by reversible, bidirectional glycosyltransferase-catalyzed reactions.Type: GrantFiled: July 18, 2014Date of Patent: October 18, 2016Assignee: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Jon S. Thorson, Changsheng Zhang, Byron R. Griffith
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Patent number: 9340826Abstract: Provided is a method of preparing nucleic acid molecules comprising: (a) a step of providing nucleic acid fragments constituting at least a portion of the complete sequence of a target nucleic acid; (b) tagging the nucleic acid fragments with barcode sequences; (c) identifying the sequence of the nucleic acid fragments tagged by the barcode sequences; and (d) recovering desired nucleic acid fragments among the sequence-identified nucleic acid fragments using the barcode sequences.Type: GrantFiled: August 1, 2012Date of Patent: May 17, 2016Assignee: CELEMICS, INC.Inventors: Duhee Bang, Hwangbeom Kim, Hyojun Han
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Patent number: 9238809Abstract: The present disclosure relates to methods for isolating, amplifying, and/or analyzing nucleic acids in the presence of an anion exchange material by performing the isolation, amplification and/or analysis step in the presence of at least one anionic compound.Type: GrantFiled: August 5, 2010Date of Patent: January 19, 2016Assignees: QIAGEN GAITHERSBURG, INC., QIAGEN GMBHInventors: Yuri Khripin, Dirk Loeffert, Roland Fabis, Nadine Krueger
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Publication number: 20150148246Abstract: The present invention provides, in part, an antibody display system that simultaneously uses a secretion and a display mode. Embodiments of the invention provide a system in which a bait complexed with a monovalent antibody fragment can be captured prior to secretion in a host cell by virtue of surface displaying an antibody light chain and utilizing the covalent interaction of this light chain with the heavy chain of an antibody molecule that is co-expressed in the same host. Polypeptides, polynucleotides and host cells useful for making the antibody display system are also provided along with methods of using the system for identifying antibodies that bind specifically to an antigen of interest.Type: ApplicationFiled: May 6, 2013Publication date: May 28, 2015Inventors: Hussam Hisham Shaheen, Donxing Zha
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Publication number: 20150148238Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of splitting a droplet is provided, the method including providing a droplet microactuator including a droplet including one or more beads and immobilizing at least one of the one or more beads. The method further includes conducting one or more droplet operations to divide the droplet to yield a set of droplets including a droplet including the one or more immobilized beads and a droplet substantially lacking the one or more immobilized beads.Type: ApplicationFiled: January 30, 2015Publication date: May 28, 2015Applicants: ADVANCED LIQUID LOGIC, INC., Duke UniversityInventors: Vamsee Pamula, Vijay Srinivasan, Michael G. Pollack, Richard B. Fair
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Publication number: 20150148263Abstract: The invention provides methods for controlling the density of different molecular species on the surface of a solid support. A first mixture of different molecular species is attached to a solid support under conditions to attach each species at a desired density, thereby producing a derivatized support having attached capture molecules. The derivatized support is treated with a second mixture of different molecular species, wherein different molecular species in the second mixture bind specifically to the different capture molecules attached to the solid support. One or more of the capture molecules can be reversibly modified such that the capture molecules have a different activity before and after the second mixture of molecular species are attached. In particular embodiments, the different molecular species are nucleic acids that are reversibly modified to have different activity in an amplification reaction.Type: ApplicationFiled: February 2, 2015Publication date: May 28, 2015Applicant: ILLUMINA, INC.Inventors: Andrea Sabot, Roberto Rigatti, Min-Jui Richard Shen