Patents Examined by Lawrence E. Crane
  • Patent number: 10344047
    Abstract: Embodiments are directed to methods for joining oligonucleotides. The methods include joining together one or more oligonucleotides by reacting an alkyne group linked to an oligonucleotide with an azide group linked to an oligonucleotide to form a triazole linkage. The alkyne group is a strained alkyne group. The methods can include ligating together ends of one or more oligonucleotides or cross-linking strands of an oligonucleotide duplex to form the triazole linkage. The methods described allow oligonucleotide strands to be ligated together without the need for a ligase enzyme. The methods can be useful for joining together single strands of DNA, cross-linking complementary strands, cyclizing single and double strands, labeling oligonucleotides with reporter groups, attaching DNA to surfaces, producing analogs of DNA with modified nucleobases and backbones, synthesizing large chemically modified RNA constructs, and creating biochemically active PCR templates.
    Type: Grant
    Filed: March 1, 2012
    Date of Patent: July 9, 2019
    Assignee: ATDBIO LTD.
    Inventors: Tom Brown, Afaf Helmy El-Sagheer
  • Patent number: 10336690
    Abstract: Methods for purifying an acetonitrile waste stream are provided. An exemplary method for purifying an acetonitrile waste stream includes generating an acetonitrile waste stream during oligonucleotide synthesis and fractionating the acetonitrile waste stream to produce a single overhead fraction. The method includes condensing the single overhead fraction to produce a condensed single overhead fraction and contacting the condensed single overhead fraction with an adsorbent material to produce an acetonitrile stream that comprises an amount of an impurity that is reduced relative to the acetonitrile waste stream.
    Type: Grant
    Filed: January 29, 2015
    Date of Patent: July 2, 2019
    Assignee: HONEYWELL INTERNATIONAL INC.
    Inventors: Gregory J. Gajda, Mark G. Riley, Venkatraman Mohan, Sandra M. Lorenz, Alan P. Cohen
  • Patent number: 10323241
    Abstract: A method of recovering short-chain nucleic acids having a length of 1000 bases or less from a whole blood sample, which includes bringing a first mixture including a whole blood sample into contact with a first nucleic acid adsorbent to adsorb nucleic acids derived from the whole blood sample, removing the first nucleic acid adsorbent from being in contact with the first mixture to recover liquid components of the first mixture, bringing a second mixture including the recovered liquid components into contact with a second nucleic acid adsorbent to adsorb short-chain nucleic acids having a length of 1000 bases or less from the whole blood sample, separating the second nucleic acid adsorbent from being in contact with the second mixture, and eluting the short-chain nucleic acids absorbed in the second nucleic acid adsorbent and recovering the short-chain nucleic acids from the second nucleic acid adsorbent.
    Type: Grant
    Filed: October 13, 2016
    Date of Patent: June 18, 2019
    Assignee: TOPPAN PRINTING CO., LTD.
    Inventor: Kei Tsukamoto
  • Patent number: 10301345
    Abstract: Phosphoramidate esters and related nucleotide analogs useful in polynucleotide sequencing techniques, and synthetic methods for preparing those compounds, are disclosed, including compounds having the following structure: wherein R1, R2, R3 and R4 are as defined herein.
    Type: Grant
    Filed: November 20, 2015
    Date of Patent: May 28, 2019
    Assignee: STRATOS GENOMICS, INC.
    Inventors: Mark Stamatios Kokoris, John Tabone, Melud Nabavi, Aaron Jacobs
  • Patent number: 10292996
    Abstract: The present invention provides a pharmacological therapy using deoxyribonucleoside monophosphate compounds, or mixtures thereof, for the treatment of human genetic diseases. The compounds of the present invention can be used to treat mitochondrial DNA depletion syndromes or other disorders of unbalanced nucleotide pools, such as thymidine kinase 2 (TK2) deficiency.
    Type: Grant
    Filed: March 28, 2016
    Date of Patent: May 21, 2019
    Assignee: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
    Inventors: Michio Hirano, Caterina Garone
  • Patent number: 10294260
    Abstract: Disclosed are a compound represented by formula (I) and a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, W, n are defined as in the present application. Also disclosed is a method for treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of the compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The compound and a salt thereof according to the present application possess good anticancer and/or antitumor activity, and good water solubility and stability, as well as good tolerance in animal bodies. Also disclosed is a process for preparing a compound represented by formula (I) of the present application.
    Type: Grant
    Filed: May 5, 2017
    Date of Patent: May 21, 2019
    Assignee: TIANJIN HEMAY ONCOLOGY PHARMACEUTICAL CO., LTD.
    Inventors: Hesheng Zhang, Aihong Huo, Zhenzhong Li
  • Patent number: 10294261
    Abstract: The present invention provides a compound represented by the following chemical formula (I); a tautomer or stereoisomer of the compound; or a salt of the compound, the tautomer, or the stereoisomer. In the chemical formula (I), R1 and R2 are each a Group 1 element or a protecting group of an amino group and may be identical to or different from each other, or alternatively, R1 and R2 together may form a protecting group of an amino group. R3 is a Group 1 element or a protecting group of a hydroxy group. R4 is a Group 1 element or —PR5R6R7R8 (R5, R6, R7, and R8 are each a Group 1 element, a lone electron pair, a Group 16 element, a Group 17 element, or a protecting group of a phosphorus atom, and may be identical to or different from each other). J is a hydrogen atom or an arbitrary atomic group, A is a hydrogen atom, a hydroxy group, an alkyl group, an aralkyl group, an alkoxy group, an electron-withdrawing group, a silylene group, or a sulfide group, or alternatively, J and A together may form a linker.
    Type: Grant
    Filed: September 3, 2013
    Date of Patent: May 21, 2019
    Assignee: KABUSHIKI KAISHA DNAFORM
    Inventors: Yoshihide Hayashizaki, Takahiro Soma, Takeshi Hanami, Hajime Kanamori, Masaru Baba
  • Patent number: 10280191
    Abstract: Provided herein is a method for synthesizing polynucleic acids, comprising the steps of (a) providing an acidic solution substantially free of nucleic acid polymerase and lipids, but containing mononucleotides and a monovalent salt; (b) drying and resolubilizing the mixture of step (a) a plurality of times; and (c) recovering polynucleic acids from a resolubilized mixture of step (b). In certain aspects, the method further uses a low pH, e.g. about 3; it can utilize monophosphates, such as AMP rather than ATP; and it can be used with a polynucleotide template to form a sequence at least partially complementary to said template. Thus, both single-stranded and double-stranded polynucleic acids are provided. Ammonia salts have been used to obtain RNA lengths from 10 to 300 nucleotides after 16 half hour cycles and an effective temperature includes between 80° C. and 100° C.
    Type: Grant
    Filed: September 16, 2014
    Date of Patent: May 7, 2019
    Assignees: The Regents of the University of California, Sorbonne Universite
    Inventors: David W. Deamer, Marie-Christine Maurel, Laura Da Silva
  • Patent number: 10280192
    Abstract: The present application, among other things, provides technologies, e.g., reagents, methods, etc. for preparing oligonucleotides comprising phosphorothiotriesters linkages. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ia or Ib with a silylating reagent to provide a silyloxyphosphonate, and reacting the silyloxyphosphonate with a thiosulfonate reagent of structure IIa or IIb to provide an oligonucleotide of structure IIIa or IIIb. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ic with a silylating reagent to provide a silyloxyphosphonate, reacting the silyloxyphosphonate with a bis(thiosulfonate) reagent of structure IVc to provide a phosphorothiotriester comprising a thiosulfonate group of structure Vc, and then reacting the phosphorothiotriester comprising a thiosulfonate group of structure Vc with a nucleophile of structure VIc to provide an oligonucleotide of structure IIIc.
    Type: Grant
    Filed: March 30, 2018
    Date of Patent: May 7, 2019
    Assignee: WAVE LIFE SCIENCES LTD.
    Inventors: Gregory L. Verdine, Meena, Naoki Iwamoto, David Charles Donnell Butler
  • Patent number: 10240151
    Abstract: Described herein are conjugated modified oligonucleotides that are complementary to a target RNA. The conjugate facilitates cellular uptake of the modified oligonucleotide, resulting improved potency.
    Type: Grant
    Filed: October 17, 2016
    Date of Patent: March 26, 2019
    Assignee: Regulus Therapeutics Inc.
    Inventor: Balkrishen Bhat
  • Patent number: 10239910
    Abstract: The present invention relates to an improved, commercially viable and industrially advantageous process for the preparation of sofosbuvir, which uses reagents that are less expensive and easier to handle.
    Type: Grant
    Filed: May 8, 2017
    Date of Patent: March 26, 2019
    Assignee: OPTIMUS DRUGS (P) LIMITED
    Inventors: Srinivas Reddy Desi Reddy, Srinivas Rao Velivela
  • Patent number: 10231987
    Abstract: A method for reducing or maintaining platelet inhibition in a patient by administering cangrelor prior to an invasive procedure is described. The method of this invention can be used for patients in need of antiplatelet therapy or at risk of thrombosis. The method can further be used in patients who were previously treated with long-acting platelet inhibitors without increasing the risk of excessive bleeding.
    Type: Grant
    Filed: March 3, 2014
    Date of Patent: March 19, 2019
    Assignee: Chiesi Farmaceutici S.p.A.
    Inventors: Lisa Ruderman Chen, Simona Skerjanec, Dawn Bell, Jayne Prats, Meredith Todd
  • Patent number: 10220050
    Abstract: The present disclosure provides isotopologues of 5-azacytidine.
    Type: Grant
    Filed: December 7, 2017
    Date of Patent: March 5, 2019
    Assignee: Celgene Corporation
    Inventors: John F. Traverse, William W. Leong, Jeffrey B. Etter, Mei Lai, Jay Thomas Backstrom
  • Patent number: 10214765
    Abstract: Provided herein are compounds for use as sialidase inhibitors, including alkynyl-3-fluorosialyl fluoride. The compounds, which include the compound DFSA, function by trapping a 3-fluorosialylenzyme intermediate (reporter-inhibitor-enzyme conjugate). These compounds can be conjugated with a detectable tagging moiety for isolation and identification of sialidases.
    Type: Grant
    Filed: January 26, 2018
    Date of Patent: February 26, 2019
    Assignee: Academia Sinica
    Inventors: Chi-Huey Wong, Jim-Min Fang, Yih-Shyun E. Cheng, Chamg-Sheng Tsai
  • Patent number: 10214556
    Abstract: A method for purifying a salt of reduced form of ?-nicotinamide adenine dinucleotide (NADH) includes: sequentially microfiltrating and nanofiltrating a reaction solution obtained after an enzymatic reaction, collecting a concentrate for use; adding an ion pair reagent to the concentrate, and purifying by gradient elution to obtain a purified filtrate using a reverse-phase chromatographic column as a stationary phase, a buffer solution as a phase A, and ethanol as a phase B; changing the cations in the purified filtrate into sodium ions to obtain a filtrate by using a cation exchange resin; and nanofiltrating the filtrate, and freeze drying in a vacuum freeze drier. The method results in an excellent purity and yield of a salt of NADH that meets requirements in industry.
    Type: Grant
    Filed: December 4, 2015
    Date of Patent: February 26, 2019
    Assignee: BONTAC BIO-ENGINEERING (SHENZHEN) CO., LTD
    Inventors: Rongzhao Fu, Zhu Dai, Qi Zhang
  • Patent number: 10214555
    Abstract: In this method, an oligonucleotide is prepared by using, as a synthesis unit, a novel nucleoside monomer compound represented by formula (I) [wherein X, R1, Y, Base, Z, Ar, R2, R3 and n are each as defined in Claim 1]. The novel nucleoside monomer compound is a nucleoside, the base moiety of which is substituted with an aromatic-hydrocarbon-ring-carbonyl or -thiocarbonyl group having at least one hydrophobic group. The method cars dispense with column-chromatographic purification in every reaction, and enables base elongation not only in the 3?-direction but also in the 5?-direction, thus attaining efficient liquid-phase mass synthesis of an oligonucleotide.
    Type: Grant
    Filed: November 13, 2013
    Date of Patent: February 26, 2019
    Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITJED
    Inventors: Mitsuru Nonogawa, Toshiaki Nagata, Hideki Saito, Tsuneo Yasuma
  • Patent number: 10214552
    Abstract: A method for purifying ?-nicotinamide mononucleotide (NMN) includes: sequentially microfiltrating and nanofiltrating a crude product solution containing NMN using membrane concentration devices to obtain a concentrated crude product solution; adjusting the concentrated crude product solution to pH 3-7 to obtain a loading solution, loading the loading solution onto a preparative reverse phase high performance liquid chromatographic column, and purifying by gradient elution using an octadecylsilane-bonded silica gel as a stationary phase, a hydrochloric acid solution at pH 3-7 as a mobile phase A, and 100% ethanol as a mobile phase B, to obtain a purified sample solution; concentrating the purified sample solution by nanofiltration and freeze drying in a vacuum freeze drier to obtain a purified NMN.
    Type: Grant
    Filed: December 2, 2015
    Date of Patent: February 26, 2019
    Assignee: BONTAC BIO-ENGINEERING (SHENZHEN) CO., LTD.
    Inventors: Rongzhao Fu, Zhu Dai, Qi Zhang
  • Patent number: 10201558
    Abstract: The present application relates to compositions comprising selenium compounds, such as 5?-Methylselenoadenosine, a compound of Formula (I), and combinations thereof, and methods of using the same for inhibiting ? amyloid aggregation, ApoE4 expression, p38 or Tau protein phosphorylation, or increasing Neprilysin and Insulin Degrading Enzyme expression.
    Type: Grant
    Filed: September 15, 2015
    Date of Patent: February 12, 2019
    Assignee: Alltech, Inc.
    Inventors: Ronan Power, Zi-Jian Lan
  • Patent number: 10189873
    Abstract: The invention provides compounds of the purine cyclic dinucleotide (CDN) class, useful as inhibitors of the STING (Stimulator of Interferon Genes) pathway, and methods of their administration to individuals in need thereof.
    Type: Grant
    Filed: January 20, 2017
    Date of Patent: January 29, 2019
    Assignee: ADURO BIOTECH, INC.
    Inventors: Thomas W. Dubensky, Jr., David B. Kanne
  • Patent number: 10130653
    Abstract: An absorbable periodontal tissue and bone regeneration material uses bacterial cellulose that has been exposed to radiation. The bacterial cellulose was confirmed to block the invasion of soft tissue in a calvarial defect in rat and rabbit models and to display excellent absorptiveness enough to contribute bone formation. Therefore, the bacterial cellulose can be developed as an absorbable periodontal tissue and bone regeneration material useful in the field of medical engineering by regulating biodegradability without using chemicals that are toxic to human and environment.
    Type: Grant
    Filed: April 13, 2016
    Date of Patent: November 20, 2018
    Assignee: KOREA ATOMIC ENERGY RESEARCH INSTITUTE
    Inventors: Youn-Mook Lim, Sung In Jeong, Hui-Jeong Gwon, Jong Seok Park, Jung-Bo Huh