Patents Examined by Lawrence E. Crane
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Patent number: 10414790Abstract: The present invention provides nucleosides an exocyclic amine-protected nucleoside of the formula: A-B where A is a 5?-protected ribose, 5?-protected-2-deoxyribose, 5?-protected-3?-phosphoramidite ribose, or 5?-protected-3?-phosphoramidite-2-deoxyribose moiety; and B is a nucleobase having an exocyclic amine group that is protected with di-tert-butylisobutylsilyl (“BIBS”) protecting group. Use of BIBS protecting group provides an exocyclic amine-protected nucleoside that is stable to a wide variety of reaction conditions associated with oligonucleotide synthesis. The present invention also provides, oligonucleotides comprising the same, and methods for producing the same.Type: GrantFiled: August 3, 2013Date of Patent: September 17, 2019Assignee: The Regents of the University of ColoradoInventors: Marvin H. Caruthers, Subhadeep Roy
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Patent number: 10385088Abstract: The present disclosure provides alternative sugar moieties and polynucleotides comprising such sugar moieties, and methods of use thereof.Type: GrantFiled: October 2, 2014Date of Patent: August 20, 2019Assignee: ModernaTX, Inc.Inventors: Andrew W. Fraley, Atanu Roy, Matthew Stanton
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Patent number: 10385090Abstract: Disclosed is a nucleoside derivative of formulae (I-1) or a salt thereof: in which R1, R2, R3, R5, A1 to A3, B, X, Y, and k are described herein. Also provided are a 5?-phosphate ester and a 3?-phosphoramidite derivative of the nucleoside derivative and substrate solutions thereof. A polynucleotide is produced using the 5?-phosphate ester or 3?-phosphoramidite derivative of the nucleoside derivative. A library of the produced polynucleotide is used in a method of selecting a nucleic acid aptamer. Further provided is a vesicular endothelial growth factor binding agent of formula (i).Type: GrantFiled: September 10, 2014Date of Patent: August 20, 2019Assignee: NATIONAL UNIVERSITY CORPORATION GUNMA UNIVERSITYInventor: Masayasu Kuwahara
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Patent number: 10376529Abstract: The present invention is related to a product comprising a pentacyclic triterpene of formula (I) and a hydroxytyrosol or derivatives thereof of formula (II), pharmaceutical compositions thereof and their uses as antioxidants, anti-inflammatories and neuron protectors.Type: GrantFiled: June 12, 2014Date of Patent: August 13, 2019Assignee: NATAC BIOTECH, S.L.Inventors: José Carlos Quintela Fernández, Esther De La Fuente García, Marco Pugliese, Pilar Mancera Aroca, Javier Bustos Santafé, Juan Francisco Espinosa Parrilla, Noemí Virgili Treserres, Blanca Wappenhans Battestini
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Patent number: 10377789Abstract: A compound represented by formula I or II below or a salt thereof: wherein B1 represents a purin-9-yl group or a 2-oxo-1,2-dihydropyrimidin-1-yl group that has any one or more substituents selected from the group consisting of a hydroxyl group, a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C1 to C6 linear alkyl group, a C1 to C6 linear alkoxy group, a mercapto group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C1 to C6 linear alkylthio group, an amino group, a C1 to C6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom.Type: GrantFiled: September 19, 2013Date of Patent: August 13, 2019Assignee: Osaka UniversityInventors: Satoshi Obika, Yutaro Kotobuki, Reiko Waki
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Patent number: 10378011Abstract: An oligonucleotide having improved affinity for AGO2 is disclosed. The oligonucleotide has a nucleotide residue or a nucleoside residue represented by formula (I) wherein X1 is an oxygen atom or the like, R1 is formula (IIA), wherein R5A is halogen or the like, and R6A is a hydrogen atom or the like, or formula (IVA) wherein Y3A is a nitrogen atom or the like, and Y4A is CH or the like, or the like, R2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R3 is a hydrogen atom or the like at the 5? end thereof, and the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3. A method for improving the knockdown activity of an oligonucleotide wherein the oligonucleotide has a knockdown activity against an mRNA encoding a protein involved in a disease.Type: GrantFiled: September 2, 2013Date of Patent: August 13, 2019Assignee: KYOWA HAKKO KIRIN CO., LTD.Inventors: Fumikazu Shinohara, Asana Makino, Junichiro Yamamoto, Taiji Oashi, Michihiko Suzuki, Jun-ichi Saito, Takahiro Nakajima, Tomoyuki Nishikawa, Masayoshi Nakoji, Yuichi Takahashi
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Patent number: 10350231Abstract: 2-Chloro-2?-deoxyadenosine, hereinafter referred to as cladribine, or a pharmaceutically acceptable salt thereof may be used in the treatment or amelioration of neuromyelitis optica, hereinafter referred to as NMO e.g. in patients known to have NMO-IgG seropositivity or in patients optic neuritis, myelitis and at least two of MRI evidence of contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis or NMO-IgG seropositivity.Type: GrantFiled: January 27, 2015Date of Patent: July 16, 2019Assignee: Chord Therapeutics S.a.r.l.Inventors: Arthur Henry Roach, Konrad Rejdak
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Patent number: 10351586Abstract: The present disclosure provides cytidine derivative dimers, salts and compositions of the cytidine derivative dimers, and methods of making and using the cytidine derivative dimers. The disclosed compounds are useful for treating a neoplasm in mammalian subjects. The cytidine derivative dimer has the following general formula (I). where R1 is C1-C10 alkyl, C1-C10 substituted alkyl, —(CH2)n-Ph, or substituted —(CH2)n-Ph; R2 is C1-C10alkyl, C1-C10 substituted alkyl, —(CH2)n-Ph, or substituted —(CH2)n-Ph; R3 is hydrogen, alkoxycarbonyl or substituted alkoxycarbonyl; R4 is hydrogen, alkoxycarbonyl or substituted alkoxycarbonyl; and R5 is —(CH2)n—, substituted —(CH2)n—, or —(CH2)n1—O—(CH2)n2-Ph-, where n, n1, and n2 are an integer from 0 to 3. The disclosed cytidine derivative dimers/salts provide high anti-tumor activity with low toxicity and are useful for treating cancers.Type: GrantFiled: December 14, 2017Date of Patent: July 16, 2019Assignees: CHANGZHOU FANGYUAN PHARMACEUTICAL CO., LTD, INNER MONGOLIA PUYIN PHARMACEUTICAL CO., LTDInventors: Daria Yang, Haidong Wang, Hui-Juan Wang
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Patent number: 10342817Abstract: The present invention relates to pharmaceutical compositions and combination therapies for treating patients having a neoplasm or a proliferative disorder, the combination comprises ribavirin, GDC-0449 and a chemotherapeutic agent, wherein said combination therapy overcomes resistance developed in patients during anti-neoplastic treatment. The present invention also provides a combination therapy for treating patients having leukemia.Type: GrantFiled: January 16, 2017Date of Patent: July 9, 2019Assignee: Universite de MontrealInventors: Katherine Borden, Hiba Zahreddine, Biljana Culjkovic Kraljacic
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Patent number: 10344047Abstract: 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: GrantFiled: March 1, 2012Date of Patent: July 9, 2019Assignee: ATDBIO LTD.Inventors: Tom Brown, Afaf Helmy El-Sagheer
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Patent number: 10336690Abstract: 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: GrantFiled: January 29, 2015Date of Patent: July 2, 2019Assignee: HONEYWELL INTERNATIONAL INC.Inventors: Gregory J. Gajda, Mark G. Riley, Venkatraman Mohan, Sandra M. Lorenz, Alan P. Cohen
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Patent number: 10323241Abstract: 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: GrantFiled: October 13, 2016Date of Patent: June 18, 2019Assignee: TOPPAN PRINTING CO., LTD.Inventor: Kei Tsukamoto
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Patent number: 10301345Abstract: 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: GrantFiled: November 20, 2015Date of Patent: May 28, 2019Assignee: STRATOS GENOMICS, INC.Inventors: Mark Stamatios Kokoris, John Tabone, Melud Nabavi, Aaron Jacobs
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Patent number: 10292996Abstract: 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: GrantFiled: March 28, 2016Date of Patent: May 21, 2019Assignee: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORKInventors: Michio Hirano, Caterina Garone
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Patent number: 10294260Abstract: 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: GrantFiled: May 5, 2017Date of Patent: May 21, 2019Assignee: TIANJIN HEMAY ONCOLOGY PHARMACEUTICAL CO., LTD.Inventors: Hesheng Zhang, Aihong Huo, Zhenzhong Li
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Patent number: 10294261Abstract: 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: GrantFiled: September 3, 2013Date of Patent: May 21, 2019Assignee: KABUSHIKI KAISHA DNAFORMInventors: Yoshihide Hayashizaki, Takahiro Soma, Takeshi Hanami, Hajime Kanamori, Masaru Baba
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Patent number: 10280191Abstract: 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: GrantFiled: September 16, 2014Date of Patent: May 7, 2019Assignees: The Regents of the University of California, Sorbonne UniversiteInventors: David W. Deamer, Marie-Christine Maurel, Laura Da Silva
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Patent number: 10280192Abstract: 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: GrantFiled: March 30, 2018Date of Patent: May 7, 2019Assignee: WAVE LIFE SCIENCES LTD.Inventors: Gregory L. Verdine, Meena, Naoki Iwamoto, David Charles Donnell Butler
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Patent number: 10239910Abstract: 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: GrantFiled: May 8, 2017Date of Patent: March 26, 2019Assignee: OPTIMUS DRUGS (P) LIMITEDInventors: Srinivas Reddy Desi Reddy, Srinivas Rao Velivela
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Patent number: 10240151Abstract: 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: GrantFiled: October 17, 2016Date of Patent: March 26, 2019Assignee: Regulus Therapeutics Inc.Inventor: Balkrishen Bhat