Synthesis Of Polynucleotides Or Oligonucleotides Patents (Class 536/25.3)
  • Patent number: 10214739
    Abstract: The subject innovation relates to a RNA binding buffer comprising (a) at least one chaotropic agent; and (b) an organic solvent selected from the group consisting of ethylene carbonate, ethylene glycol diacetate and 2-pyrrolidone or combinations thereof. The subject innovation further relates to a method of binding RNA to a solid support and to a method of isolating RNA both making use of the binding buffer of the subject innovation. The subject innovation finally relates to a kit comprising the RNA binding buffer or the organic solvent as relevant substance therein.
    Type: Grant
    Filed: October 30, 2015
    Date of Patent: February 26, 2019
    Assignee: AXAGARIUS GMBH & CO. KG
    Inventor: Christoph Kirsch
  • Patent number: 10160969
    Abstract: The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.
    Type: Grant
    Filed: January 16, 2015
    Date of Patent: December 25, 2018
    Assignee: WAVE LIFE SCIENCES LTD.
    Inventors: Meena, David Butler, Naoki Iwamoto, Nenad Svrzikapa, Gregory L. Verdine, Ivan Zlatev
  • Patent number: 10138266
    Abstract: The invention provides a cut-out method capable of suppressing production of a byproduct, wherein the object RNA oligonucleotide is not cleaved from a universal linker, which is produced in cutting out the object RNA oligonucleotide from the universal support, and capable of increasing the yield of the object RNA oligonucleotide. The RNA oligonucleotide cut-out method includes a step of bringing a universal support supporting an RNA oligonucleotide in contact with an aqueous solution containing alkylamine and a monovalent inorganic salt.
    Type: Grant
    Filed: June 17, 2016
    Date of Patent: November 27, 2018
    Assignee: Nitto Denko Corporation
    Inventors: Shohei Horie, Tatsuya Konishi, Kenjiro Mori, Eri Maeta, Tsuyoshi Mukobata, Masafumi Iwamoto
  • Patent number: 10131904
    Abstract: The invention relates to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand is/are modified by four 2?-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2?-O-methyl group at the 2nd 5?-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.
    Type: Grant
    Filed: February 11, 2009
    Date of Patent: November 20, 2018
    Assignee: RXi Pharmaceuticals Corporation
    Inventors: Pamela A. Pavco, Joanne Kamens, Tod M. Woolf, William Salomon, Anastasia Khvorova
  • Patent number: 10072261
    Abstract: Aspects of the present disclosure include methods for double coupling a nucleoside phosphoramidite during synthesis of an oligonucleotide. The method can include coupling a free hydroxyl group of a nucleoside residue with a first sample of a protected nucleoside phosphoramidite via an internucleoside P(III) linkage, followed by exposure to an oxidizing agent prior to a second coupling step with a second sample of the protected nucleoside phosphoramidite, and further exposure to an oxidizing agent. The method finds use in synthesizing an oligonucleotide on a solid phase support, such as a planar surface. The double coupling method can be utilized at one or more nucleotide positions during oligonucleotide synthesis thereby reducing single base deletion rates. Oligonucleotide containing compositions synthesized according to the disclosed methods are also provided.
    Type: Grant
    Filed: March 27, 2017
    Date of Patent: September 11, 2018
    Assignee: Agilent Technologies, Inc.
    Inventors: Joel Myerson, Siyuan Chen
  • Patent number: 10023909
    Abstract: The present invention relates to methods and kits for the detection of 5-hydroxymethylcytosine (5hmC) and/or 5-methylcytosine (5meC). In some embodiments, the present invention relates to methods and kits for detection of 5hmC and/or 5meC in nucleic acid (e.g., DNA, RNA). In some embodiments, the present invention relates to detection of 5hmC in genomic DNA, e.g., mammalian genomic DNA.
    Type: Grant
    Filed: December 13, 2012
    Date of Patent: July 17, 2018
    Assignee: OSLO UNIVERSITETSSYKEHUS HF
    Inventors: John Arne Dahl, Adam Brian Robertson, Arne Klungland, Linda Ellevog
  • Patent number: 9963735
    Abstract: The present invention provides novel compositions, kits and methods employing RNA 5? polyphosphatases, RNA 5? monophosphatases, capping enzymes, decapping enzymes, nucleic acid pyrophosphatases and RNA ligases, as well as other enzymes, for selective 5? ligation tagging of desired classes of RNA molecules that differ with respect to particular chemical moieties on their 5? ends. The 5? tagged RNA molecules can be used for synthesis of tagged first-stand cDNA, double-stranded cDNA, and sense or antisense RNA for a variety of uses.
    Type: Grant
    Filed: October 9, 2012
    Date of Patent: May 8, 2018
    Assignee: EPICENTRE TECHNOLOGIES CORPORATION
    Inventors: Jerome Jendrisak, Gary A. Dahl, Ramesh Vaidyanathan
  • Patent number: 9889423
    Abstract: De novo synthesized large libraries of nucleic acids are provided herein with low error rates. Further, devices for the manufacturing of high-quality building blocks, such as oligonucleotides, are described herein. Longer nucleic acids can be synthesized in parallel using microfluidic assemblies. Further, methods herein allow for the fast construction of large libraries of long, high-quality genes. Devices for the manufacturing of large libraries of long and high-quality nucleic acids are further described herein.
    Type: Grant
    Filed: August 23, 2016
    Date of Patent: February 13, 2018
    Assignee: TWIST BIOSCIENCE CORPORATION
    Inventors: William Banyai, Bill James Peck, Andres Fernandez, Siyuan Chen, Pierre Indermuhle
  • Patent number: 9803250
    Abstract: Disclosed herein are methods for detecting a fungal pathogen in a patient sample, involving isolating the sample, carrying out a PCR reaction on the sample to generate an amplicon that includes a region of the fungal 28S ribosomal RNA gene, and detecting the PCR amplicon. Also disclosed are sequences of primers for specifically detecting a broad range of fungal pathogens in the presence of human ribosomal DNA. In certain embodiments, the amplicon is detected by sequencing or by two-dimensional melt-curve analysis. In yet other embodiments, more than one fungal pathogen is detected in a sample using the methods disclosed herein.
    Type: Grant
    Filed: November 24, 2009
    Date of Patent: October 31, 2017
    Assignee: Fred Hutchinson Cancer Research Center
    Inventors: David N. Fredricks, Prasanna D. Khot, Daisy L. Ko
  • Patent number: 9759711
    Abstract: A method of analyzing molecules using a nanopore array including a plurality of cells included on a chip is disclosed. Nanopores are caused to be formed in at least a portion of the plurality of the cells. A first physical measurement of the nanopores is evaluated. It is determined whether to cause the molecules to interact with the nanopores. At least a portion of the nanopores is caused to interact with the molecules. A second physical measurement of the nanopores that indicates a property of the molecules is evaluated. It is determined whether to cause the nanopores to be reformed so that the cells may be reused to interact with additional molecules.
    Type: Grant
    Filed: February 5, 2013
    Date of Patent: September 12, 2017
    Assignee: Genia Technologies, Inc.
    Inventors: Roger J. A. Chen, David J. Fullagar
  • Patent number: 9688673
    Abstract: The invention provides compounds that bind to deoxycytidine kinase (dCK) and compositions including pharmaceutically acceptable compositions containing the compounds. The compounds are useful in treating diseases and disorders where dCK activity is implicated such as cancer and immune disorders. The compounds also find use in clinical methodologies including positron emission tomography (PET) imaging.
    Type: Grant
    Filed: March 8, 2012
    Date of Patent: June 27, 2017
    Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
    Inventors: Caius G. Radu, Hsiang-I Liao, Nagichettiar Satyamurthy, Johannes Czernin, Jennifer M. Murphy, David A. Nathanson
  • Patent number: 9611509
    Abstract: Assays using non-natural bases are described. In one embodiment, the method involves contacting a sample suspected of containing the target nucleic acid with a polymerase and first and second primers; amplifying the target nucleic acid by PCR using the first and second primers to generate an amplification product having a double-stranded region and a single-stranded region that comprises the non-natural base; contacting the sample with a reporter comprising a label and a non-natural base that is complementary to the non-natural base of the single-stranded region; annealing at least a portion of the reporter to the single-stranded region of the amplification product; and correlating a signal of the label with the presence of the target nucleic acid in the sample. The invention also provides corresponding kits for use in detecting target nucleic acids in a sample.
    Type: Grant
    Filed: July 24, 2013
    Date of Patent: April 4, 2017
    Assignee: LUMINEX CORPORATION
    Inventors: David J. Marshall, James R. Prudent, Christopher B. Sherrill, Gideon Shapiro, Jennifer K. Grenier, Craig S. Richmond, Simona Jurczyk, Jerod L. Ptacin
  • Patent number: 9567364
    Abstract: Nucleotide and/or oligonucleotide represented by formula (1) and the liquid phase synthesis process thereof. The present invention provides a liquid phase synthesis process for preparing a nucleotide and/or an oligonucleotide, comprising a process for combining the nucleotide and/or oligonucleotide protective groups, in which, under the condition that the 2?-hydroxyl group is protected by a group with a sterically hindered silane structure, the 3? phosphate group(s) of the nucleotide and/or oligonucleotide is/are directly protected by (a)?-cyanoethyl group(s), and after the ?-cyanoethyl group(s) is/are removed, the resulting product can directly participate in the next cycle of synthesis, wherein the synthesis reaction is carried out in a reaction flask or reaction kettle, without being limited by a solid carrier or synthesizer, so that the large scale preparation of oligonucleotides can be achieved.
    Type: Grant
    Filed: July 20, 2011
    Date of Patent: February 14, 2017
    Assignee: Suzhou Ribo Life Sciene Co., Ltd.
    Inventors: Zhen Xi, Zicai Liang, Jinyu Huang
  • Patent number: 9404147
    Abstract: The invention provides compositions and methods for making closed nucleic acid structures in which one or both strands are continuous. The closed nucleic acid structures can be used as sequencing templates among other applications.
    Type: Grant
    Filed: December 19, 2012
    Date of Patent: August 2, 2016
    Assignee: GEN-PROBE INCORPORATED
    Inventors: Norman C. Nelson, Jijumon Chelliserry
  • Patent number: 9334534
    Abstract: This invention concerns non-standard nucleotides that can form non-standard Watson-Crick nucleobase pairs having geometries similar to the geometries of standard nucleotide pairs, but that are joined by a non-standard hydrogen bonding schemes. Disclosed are processes that yield oligonucleotides that are semi-complementary to a standard oligonucleotide, where the region of semi-complementarity pairs one or more standard nucleotides with a non-standard nucleotide, or vice versa. Duplexes formed from two semi-complementary oligonucleotides are also inventions disclosed.
    Type: Grant
    Filed: December 16, 2009
    Date of Patent: May 10, 2016
    Inventor: Steven Albert Benner
  • Patent number: 9181592
    Abstract: A method is provided for detecting a bacterial pathogen in a sample. One step of the method includes obtaining a sample and then subjecting the sample to nested PCR. The nested PCR is conducted in the presence of at least two outer oligonucleotide primers complementary to a target nucleotide sequence of the bacterial pathogen so that a first amplified product is produced. The target nucleotide sequence includes at least a portion of a 16S-23S ribosomal RNA sequence. The first amplified product is subjected to the nested PCR in the presence of at least two inner oligonucleotide primers complementary to the nucleotide sequence of the first amplified product so that a second amplified product is obtained. Detection of the second amplified product indicates the presence of the bacterial pathogen in the sample.
    Type: Grant
    Filed: March 27, 2008
    Date of Patent: November 10, 2015
    Assignee: Case Western Reserve University
    Inventors: Yiping W. Han, Akihiko Ikegami
  • Patent number: 9169286
    Abstract: A method and compositions for sulfurizing at least one phosphite or thiophosphite linkage in an oligonucleotide. The addition of N-alkyl imidazole to the acetyldisulfide sulfurization solution enables the use of industrially preferred solvents or solvents that are derived from renewable resources.
    Type: Grant
    Filed: October 9, 2012
    Date of Patent: October 27, 2015
    Assignee: Agilent Technologies, Inc.
    Inventors: Agnieszka B. Sierzchala, Douglas J. Dellinger, Paul A. Metz, Victor R. Mokler
  • Patent number: 9156778
    Abstract: Disclosed is a method for lowering the detection limit in a method of detecting a nucleic acid comprising (i) contacting a solution comprising a first PNA with a substrate having a second PNA affixed thereto, the second PNA comprising at least one trans-cyclopentane residue, wherein the first PNA has two linker-attached biotins attached thereto and the first and second PNAs being complementary to different portions of a target DNA; (ii) contacting a sample suspected of containing the nucleic acid with the first and second PNAs; and (iii) determining the presence of the reporter molecule on the substrate. Also disclosed are a detection assay and a kit for detecting a target nucleic acid.
    Type: Grant
    Filed: August 23, 2012
    Date of Patent: October 13, 2015
    Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
    Inventors: Daniel H. Appella, Christopher Micklitsch
  • Patent number: 9085802
    Abstract: The invention relates to methods of generating templates for a nucleic acid sequencing reaction which comprise: providing at least one double-stranded nucleic acid molecule, wherein both strands of the double-stranded nucleic acid molecule are attached to a solid support at the 5? end, cleaving one or both strands of the double-stranded nucleic acid molecule, and subjecting the cleaved strand(s) to denaturing conditions to remove the portion of the cleaved strand(s) not attached to the solid support, thereby generating a partially or substantially single-stranded template for a nucleic acid sequencing reaction.
    Type: Grant
    Filed: January 28, 2014
    Date of Patent: July 21, 2015
    Assignee: Illumina Cambridge Limited
    Inventors: Xiaohai Liu, John Milton, Geoffrey Paul Smith, Colin Lloyd Barnes, Isabelle Marie Julia Rasolonjatovo, Roberto Rigatti, Xiaolin Wu, Tobias William Barr Ost, Graham John Worsley, David James Earnshaw, Gerardo Turcatti, Anthony Romieu
  • Patent number: 9074210
    Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Brain derived neurotrophic factor (BDNF), in particular, by targeting natural antisense polynucleotides of Brain derived neurotrophic factor (BDNF). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of BDNF.
    Type: Grant
    Filed: February 12, 2010
    Date of Patent: July 7, 2015
    Assignee: CuRNA, Inc.
    Inventors: Joseph Collard, Olga Khorkova Sherman, Carlos Coito
  • Patent number: 9040677
    Abstract: Described herein are techniques for assembling a polynucleotide encoding a transcription activator-like effector nucleases (TALEN). The techniques ligate and digest necessary modules for a TALEN assembly in one reactor or system. Methods and Kits for generating a TALEN are also described.
    Type: Grant
    Filed: August 13, 2013
    Date of Patent: May 26, 2015
    Assignee: SIDANSAI Biotechnology CO., LTD
    Inventors: Jinlong Zhao, Zhao Wu
  • Publication number: 20150140568
    Abstract: DNA oligomers comprising sequences that are absent from the genome of one or more organisms of interest are used as reference markers (RMs). The RMs are added to biological samples to “tag” and subsequently identify the samples as authentic and to distinguish tagged samples from samples obtained without said markers, for example, in forensic, medical, legal and other applications.
    Type: Application
    Filed: November 26, 2014
    Publication date: May 21, 2015
    Inventor: Greg Hampikian
  • Publication number: 20150140567
    Abstract: Methods and compositions for the amplification of nucleic acids and generation of concatemers are disclosed. Amplification methods provided herein may be performed under isothermal conditions. Methods and compositions may include reagents such as nucleic acid polymerases and primers.
    Type: Application
    Filed: November 18, 2014
    Publication date: May 21, 2015
    Inventors: Kamila Belhocine, Josephine Lee, Pranav Patel, Aaron Richardson, Scott Tabakman
  • Publication number: 20150133648
    Abstract: A method for preparing a crosslinked polymer coated controlled porosity glass (CPG) particle is provided. The method involves mixing CPG particles in a solution comprising polyvinylbenzylchloride and a first solvent at a temperature below 10° C. A second solvent is added and a crosslinking agent is added to the mixture. The first solvent is removed rapidly within hours of addition of the crosslinking agent. The crosslinking reaction is permitted to proceed and the mixture is then cooled and treated to remove any remaining solvent. The resulting coated CPG particles are washed and dried. Also provided a polymer coated CPG particles using for loading ligand thereon.
    Type: Application
    Filed: January 19, 2015
    Publication date: May 14, 2015
    Inventors: Marc L. Rothstein, Dianne M. Rothstein, Dan P. Lee
  • Publication number: 20150133631
    Abstract: An oligonucleotide derivative having the structure of formula (A) and methods for preparing the oligonucleotide derivative are disclosed. wherein R3 is a first oligonucleotide; R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, a polyethylene glycol, a peptide, a protein, a polysaccharide, and a second oligonucleotide; R2 is a linker or a direct bond; Z1 is NR4, S, or O, and Z2 is NR4 or S, wherein R4 is selected from H, alkyl, aryl, heterocyclyl, or heteroaryl. A method includes: synthesizing an oligonucleotide derivative comprising an amino or thiol group; and reacting a 3,4-dialkoxycyclobutene-1,2-dione with the oligonucleotide derivative to produce an oligonucleotide-squarate mono-conjugate.
    Type: Application
    Filed: April 29, 2013
    Publication date: May 14, 2015
    Inventors: Kenneth W. Hill, Victor R Mokler
  • Publication number: 20150133317
    Abstract: Disclosed herein are compositions and methods for sequencing, analyzing, and utilizing samples such as single samples. Also disclosed herein are compositions and methods for matching together two or more sequences from a sample. Also disclosed herein are compositions and methods for expressing and screening molecules of interest.
    Type: Application
    Filed: April 27, 2012
    Publication date: May 14, 2015
    Applicants: Department of Veterans Affairs, The Board of Trustees of the Leland Stanford Junior University
    Inventors: William H. Robinson, Yann Chong Tan, Jeremy Sokolove
  • Patent number: 9029103
    Abstract: Provided herein is a method for sequencing a polynucleotide molecules. The method includes the steps of providing a plurality of polynucleotide molecules attached to a surface, wherein a first portion of each polynucleotide molecule is attached to a first location of the surface and a second portion of each polynucleotide molecule is attached to a second location of the surface, the relative proximity of the first and second locations being correlated with the probability that the first and second portions are paired, separating the first and second portions of the polynucleotide molecules on the surface, determining the sequences of the first and second portions of the polynucleotide molecules and comparing the relative proximities and the sequences to determine which first and second portions are paired and to determine the sequence of the target polynucleotide molecules.
    Type: Grant
    Filed: August 26, 2011
    Date of Patent: May 12, 2015
    Assignee: Illumina Cambridge Limited
    Inventors: Roberto Rigatti, Niall Anthony Gormley, Jonathan Mark Boutell
  • Patent number: 9017971
    Abstract: The invention provides improved methods for investigating nucleic acid sequences, wherein at least one additional probe is used which is specific for a (pseudo)gene variant of a target nucleic acid.
    Type: Grant
    Filed: November 5, 2009
    Date of Patent: April 28, 2015
    Assignee: Stichting Sanquin Bloedvoorziening
    Inventors: Taco Willem Kuijpers, Martin de Boer
  • Patent number: 9012225
    Abstract: Disclosed are lipophilic polynucleotide conjugates including polynucleotide-cholesterol conjugates and methods of delivering therapeutic polynucleotides to a mammalian cell or patient in need of treatment using said conjugates. The disclosure further provides methods of synthesizing the lipophilic polynucleotide conjugates. The conjugates are designed to mimic or target cellular miRNAs. The lipophilic moiety, such as cholesterol or cholesterol derivative, is spaced from the polynucleotide by a substantially linear hydrocarbon group. Due to an absence of significantly polar groups and/or exchangeable protons in the vicinity of the lipophilic moiety, the interaction between the lipophilic moiety and cell membranes is enhanced to provide for efficient entry into cells.
    Type: Grant
    Filed: May 5, 2010
    Date of Patent: April 21, 2015
    Assignee: miRagen Therapeutics
    Inventors: Kurt Vagle, William S. Marshall
  • Patent number: 9005892
    Abstract: The present invention relates to methods and reagents for detecting analytes, e.g. nucleic acids. The new methods and reagents allow a simple and sensitive detection even in complex biological samples.
    Type: Grant
    Filed: March 2, 2012
    Date of Patent: April 14, 2015
    Assignee: Baseclick GmbH
    Inventors: Thomas Carell, Anja Schwögler, Glenn A. Burley, Johannes Gierlich, Mohammad Reza Mofid
  • Patent number: 9005985
    Abstract: This invention provides compositions that have a light emitting reporter linked to biomolecules, preferably, nucleotide oligomers. The light reporter particles are silylated and functionalized to produce a coated light reporter particle, prior to covalently linking the biomolecules to the light reporter particle. The light reporter particles of the invention can be excited by a light excitation source such as UV or IR light, and when the biomolecule is DNA, the attached DNA molecule(s) are detectable by amplification techniques such as PCR.
    Type: Grant
    Filed: February 7, 2013
    Date of Patent: April 14, 2015
    Assignee: APDN (B.V.I.) Inc.
    Inventors: Thomas Kwok, Benjamin MingHwa Liang, Stephane Shu Kin So
  • Patent number: 8993271
    Abstract: A nucleic acid molecule can be annealed to an appropriate immobilized primer. The primer can then be extended and the molecule and the primer can be separated from one another. The extended primer can then be annealed to another immobilized primer and the other primer can be extended. Both extended primers can then be separated from one another and can be used to provide further extended primers. The process can be repeated to provide amplified, immobilized nucleic acid molecules. These can be used for many different purposes, including sequencing, screening, diagnosis, in situ nucleic acid synthesis, monitoring gene expression, nucleic acid fingerprinting, etc.
    Type: Grant
    Filed: March 14, 2013
    Date of Patent: March 31, 2015
    Assignee: Illumina, Inc.
    Inventors: Eric H. Kawashima, Laurent Farinelli, Pascal Mayer
  • Publication number: 20150087070
    Abstract: Synthetic, derivative promoters for expression of chimeric genes in Zymomonas, Zymobacter, and related bacteria were created. The promoters have a C to T change in the nucleotide at position 90 of the Z. mobilis glyceraldehyde-3-phosphate dehydrogenase gene promoter. Promoters with this change have higher expression as compared to the native promoter from which they are derived and are useful for genetic engineering for expressing coding regions or regulatory RNA to obtain high levels of expressed proteins or regulatory RNAs.
    Type: Application
    Filed: September 26, 2013
    Publication date: March 26, 2015
    Applicant: E I DU PONT DE NEMOURS AND COMPANY
    Inventor: JIANJUN YANG
  • Publication number: 20150087820
    Abstract: The present disclosure generally pertains to systems and methods for the chemical synthesis of micro-quantities of oligonucleotides or other chemical molecules. The system includes a reusable glass micro-reactor containing a paramagnetic solid support, a magnet, an electronic drive controller and an optical spectroscopy system capable of driving a plurality individual reactors. The system utilizes the electroosmotic movement of reactants through microfluidic channels. Spectrophotometric monitoring of the reaction products allows for the real-time determination of synthesis yield.
    Type: Application
    Filed: July 17, 2014
    Publication date: March 26, 2015
    Inventors: Lance Amate Larka, John D. Williams, Randy Gaillard
  • Patent number: 8987437
    Abstract: The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.
    Type: Grant
    Filed: May 18, 2012
    Date of Patent: March 24, 2015
    Assignee: Gilead Sciences, Inc.
    Inventors: Richard Hung Chiu Yu, Brandon Heath Brown, Richard P. Polniaszek, Benjamin R. Graetz, Keiko Sujino, Duong Duc-Phi Tran, Alan Scott Triman, Kenneth M. Kent, Steven Pfeiffer
  • Patent number: 8980584
    Abstract: This invention relates to improved methods for sequencing and genotyping nucleic acid in a single molecule configuration. The method involves single molecule detection of fluorescent labeled PPi moieties released from NTPs as a polymerase extension product is created.
    Type: Grant
    Filed: October 24, 2007
    Date of Patent: March 17, 2015
    Assignee: Pacific Biosciences of California, Inc.
    Inventor: John G. K. Williams
  • Patent number: 8981076
    Abstract: This invention relates to synthesis of novel -N-FMOC protected nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-FMOC as nucleoside base protecting group, which is highly base labile protecting group is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of FMOC protecting groups of the natural deoxy and ribonucleosides occurs under very mild deprotection conditions such as mild bases, secondary and tertiary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application.
    Type: Grant
    Filed: November 30, 2009
    Date of Patent: March 17, 2015
    Assignee: ChemGenes Corporation
    Inventors: Suresh C. Srivastava, Naveen P. Srivastava
  • Patent number: 8981070
    Abstract: An oligonucleotide-solid phase conjugate, wherein the solid phase is thiophilic and the oligonucleotide comprises at least one thiooxonucleobase according to Formula I, wherein X is CH or N, R1 is H or NH2, --- indicates a covalent bond, and said oligonucleotide is bound to said solid phase via the sulfur atom of said thiooxonucleotide. Also disclosed are methods for producing such conjugate as well as various uses for such oligonucleotide metal conjugate.
    Type: Grant
    Filed: April 19, 2013
    Date of Patent: March 17, 2015
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Simone Budow, Ping Ding, Dieter Heindl, Alfons Nichtl, Frank Seela
  • Patent number: 8969047
    Abstract: Solid support assays using non-standard bases are described. A capture oligonucleotide comprising a molecular recognition sequence is attached to a solid support and hybridized with a target. In some instances, the molecular recognition sequence includes one or more non-standard bases and hybridizes to a complementary tagging sequence of the target oligonucleotide. In other instances, incorporation of a non-standard base (e.g., via PCR or ligation) is used in the assay.
    Type: Grant
    Filed: July 24, 2013
    Date of Patent: March 3, 2015
    Assignee: Luminex Corporation
    Inventors: Jennifer K. Grenier, David J. Marshall, James R. Prudent, Craig S. Richmond, Eric B. Roesch, Christopher W. Scherrer, Christopher B. Sherrill, Jerod L. Ptacin
  • Patent number: 8951728
    Abstract: The invention combines the advantages of split and mix synthesis with the advantages of template directed synthesis. The method comprises the steps of: a) adding a linker molecule L to one or more reaction wells; b) adding a molecule fragment to each of said reaction wells; c) adding an oligonucleotide identifier to each of said reaction wells; d) subjecting said wells to conditions sufficient to allow said molecule fragments and said oligonucleotide identifiers to become attached to said linker molecule, or conditions sufficient for said molecule fragments to bind to other molecule fragments and sufficient for said oligonucleotide identifiers to bind to other oligonucleotide identifiers; e) combining the contents of said one or more reaction wells; and f) contacting the resulting bifunctional molecule(s) of step e) with one or more (oligonucleotide) templates each capable of hybridizing to at least one of the oligonucleotide identifiers added in step c).
    Type: Grant
    Filed: October 30, 2013
    Date of Patent: February 10, 2015
    Assignee: ChemGene Holding ApS
    Inventor: Peter Birk Rasmussen
  • Publication number: 20150037787
    Abstract: A mixed polynucleotide includes a first double stranded (ds) portion, a second portion including at least one single stranded (ss) portion, and a third ds portion. The second portion connects the first ds portion and the third ds portion to provide a modified polynucleotide.
    Type: Application
    Filed: July 31, 2013
    Publication date: February 5, 2015
    Applicant: INTERNATIONAL BUSINESS MACHINES CORPORATION
    Inventors: Binquan Luan, Ajay K. Royyuru, Gustavo A. Stolovitzky, Chao Wang, Deqiang Wang
  • Publication number: 20150038691
    Abstract: A mixed polynucleotide includes a first double stranded (ds) portion, a second portion including at least one single stranded (ss) portion, and a third ds portion. The second portion connects the first ds portion and the third ds portion to provide a modified polynucleotide.
    Type: Application
    Filed: August 28, 2013
    Publication date: February 5, 2015
    Applicant: INTERNATIONAL BUSINESS MACHINES CORPORATION
    Inventors: Binquan Luan, Ajay K. Royyuru, Gustavo A. Stolovitzky, Chao Wang, Deqiang Wang
  • Publication number: 20150038555
    Abstract: The invention provides compositions and methods for reducing expression of a target gene in a cell, involving contacting a cell with an isolated double stranded nucleic acid (dsNA) in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a single stranded extension (in most embodiments, the single stranded extension comprises at least one modified nucleotide and/or phosphate back bone modification). Such single stranded extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.
    Type: Application
    Filed: October 20, 2014
    Publication date: February 5, 2015
    Inventor: Bob Dale Brown
  • Publication number: 20150038558
    Abstract: This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.
    Type: Application
    Filed: August 11, 2014
    Publication date: February 5, 2015
    Inventors: Katalin Kariko, Drew Weissman
  • Patent number: 8932992
    Abstract: The present invention relates to a method for synthesizing templated molecules. In one aspect of the invention, the templated molecules are linked to the template which templated the synthesis thereof. The intion allows the generation of libraries which can be screened for e.g. therapeutic activity.
    Type: Grant
    Filed: December 9, 2008
    Date of Patent: January 13, 2015
    Assignee: Nuevolution A/S
    Inventors: Henrik Pedersen, Alex Haahr Gouilaev, Thomas Franch, Christian Klarner Sams, Eva Kampmann Olsen, Frank Abilgaard Sløk, Gitte Nystrup Husemoen, Jakob Felding, Lene Hyldtoft, Mads Nørregaard-Madsen, Michael Anders Godskesen, Sanne Schrøder Glad, Thomas Thisted, Per-Ola Freskgård, Anette Holtmann
  • Publication number: 20150011746
    Abstract: The invention features protected linker compounds which comprise at one terminus a protected amino group and at another other terminus a phosphorous activating group, such as a phosphoramidite group. These protected linker compounds are introduced chemically at the 5?-end of oligonucleotides for the purpose of preparing 5?-amino modified oligonucleotides. After deprotection, the thereby introduced amino group then allows further modification (e.g. attachment of dyes) or immobilization (on surfaces or beads) of the oligonucleotide. Specifically, the presented amino protecting group is designed to provide such protected linker compounds in a solid form, which facilitates efficient purification by precipitation or crystallization and aliquoting for distribution and storage.
    Type: Application
    Filed: December 19, 2012
    Publication date: January 8, 2015
    Inventors: Stefan Pitsch, Stefan Berger
  • Patent number: 8916694
    Abstract: Compounds, compositions and methods are provided for modulating the expression of apolipoprotein B. The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein B. Methods of using these compounds for modulation of apolipoprotein B expression and for diagnosis and treatment of diseases and conditions associated with expression of apolipoprotein B are provided.
    Type: Grant
    Filed: January 28, 2011
    Date of Patent: December 23, 2014
    Assignee: Genzyme Corporation
    Inventors: Rosanne M. Crooke, Mark J. Graham, Steven Mah
  • Patent number: 8912317
    Abstract: Sequences of ribonucleic acid interference molecules are provided. For example, in one aspect, at least one nucleic acid molecule comprising at least one of one or more precursor sequences having SEQ_ID NO: 1 through SEQ_ID NO: 3,197 and one or more corresponding mature sequences having SEQ_ID NO: 3,198 through SEQ_ID NO: 6,565 is provided. Techniques are also provided for regulating gene expression.
    Type: Grant
    Filed: July 31, 2008
    Date of Patent: December 16, 2014
    Assignee: International Business Machines Corporation
    Inventors: Tien Huynh, Isidore Rigoutsos
  • Patent number: 8906615
    Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(?O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-aribino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.
    Type: Grant
    Filed: February 15, 2013
    Date of Patent: December 9, 2014
    Assignee: Geron Corporation
    Inventors: Sergei M. Gryaznov, Ronald G. Schultz
  • Publication number: 20140357700
    Abstract: The invention is directed to compositions and methods for selectively reducing the expression of a gene product from a desired target gene in a cell, as well as for treating diseases caused by the expression of the gene. More particularly, the invention is directed to compositions that contain double stranded RNA (“dsRNA”), and methods for preparing them, that are capable of reducing the expression of target genes in eukaryotic cells. The dsRNA has a first oligonucleotide sequence that is between 25 and about 30 nucleotides in length and a second oligonucleotide sequence that anneals to the first sequence under biological conditions. In addition, a region of one of the sequences of the dsRNA having a sequence length of at least 19 nucleotides is sufficiently complementary to a nucleotide sequence of the RNA produced from the target gene to trigger the destruction of the target RNA by the RNAi machinery.
    Type: Application
    Filed: August 19, 2014
    Publication date: December 4, 2014
    Applicants: CITY OF HOPE, INTEGRATED DNA TECHNOLOGIES, INC.
    Inventors: John J. ROSSI, Mark A. BEHLKE, Dongho KIM