Abstract: The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides induce STING-dependent type I interferon production, wherein the cyclic purine dinucleotides present in the composition are substantially pure 2?,5?,2?,5? and 2?,5?,3?,5? CDNs, and preferably Rp,Rp stereoisomers thereof.
Type:
Grant
Filed:
May 18, 2014
Date of Patent:
August 8, 2017
Assignees:
ADURO BIOTECH, INC., THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Inventors:
Thomas W. Dubensky, Jr., David B. Kanne, Meredith Lai Ling Leong, Edward Emile Lemmens, Laura H. Glickman, Russell E. Vance
Abstract: The present invention provides novel anhydrous polymorph forms of [(2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)]methyl nitrate (compound A), a selective adenosine A1 receptor agonist with a number of therapeutic uses including the treatment of elevated intra-ocular pressure. Also provided are methods for the preparation of the anhydrous polymorphic forms of compound A, pharmaceutical compositions and methods of treatment.
Abstract: The invention relates to methods of extracting DNA from seeds, said method comprising pretreating said seeds by soaking the seeds in a pretreatment solution comprising an alkali in a concentration sufficient to soften said seed; crushing said seeds; extracting said DNA from said crushed seeds. Methods also relate to the use of pretreatment solutions which further comprise an osmoticum. A method of fragmenting plant material such as seed, a method of recovering extraction medium from seed fragmentation and a process of extracting a seed component from crushed seed material are also described.
Abstract: This invention relates to antisense oligonucleotides comprising at least one N3??P5? phosphorodiamidate linkage (NPN) in the backbone, and kits and pharmaceutical compositions thereof, useful for modulating gene expression involved in the pathogenesis of a disease. Also included are compounds useful as building blocks of said antisense oligonucleotides and methods of preparing said antisense oligonucleotides and building block compounds including NPN linkages.
Abstract: The present invention relates to the use of 3?-fluoro, 4?-azido nucleoside phosphoramidate prodrug derivatives of formula I wherein the symbols are as defined in the specification, to pharmaceutically acceptable salts thereof, and to pharmaceutical compositions containing such compounds for the treatment of HCV.
Type:
Grant
Filed:
December 17, 2012
Date of Patent:
July 18, 2017
Assignee:
Riboscience, LLC
Inventors:
Mark Smith, Francisco Xavier Talamas, Jing Zhang, Zhuming Zhang
Abstract: The present invention relates to compounds according to Formula I: and salts thereof, wherein R1, R2, R3, R4, and L are as defined herein. Methods for preparing compounds of Formula I are also provided. The present invention further includes methods of treating and preventing bacterial infections, and methods of identifying pGpG-binding domains in bacteria, using the compounds of Formula I.
Type:
Grant
Filed:
June 17, 2013
Date of Patent:
June 27, 2017
Assignee:
TEMPLE UNIVERSITY—Of The Commonwealth System of Higher Education
Abstract: The present invention relates in essence to use of a compound, which decreases or inhibits the binding of mammalian T-cells to mammalian endothelial cells for use in a method of prophylaxis and/or amelioration and/or treatment of clinical adverse events caused by a therapy which comprises re-directing of T-cells against target cells in a patient. Such a therapy includes, but is not limited to, treatment with an antibody comprising a CD3 binding domain, such as a CD20×CD3 or a CD19×CD3 bispecific single chain antibody, e.g., blinatumomab (MT-103). Methods of treatment of patients having or being at risk of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells are also contemplated, as are methods of identifying a compound for administration in the methods of prophylaxis, amelioration and/or treatment.
Type:
Grant
Filed:
February 8, 2014
Date of Patent:
June 27, 2017
Assignee:
AMGEN RESEARCH (MUNICH) GMBH
Inventors:
Peter Kufer, Dirk Nagorsen, Juergen Scheele, Gerhard Zugmaier, Matthias Klinger, Patrick Hoffmann, Virginie Naegele, Elaine-Pashupati Dopfer
Abstract: The present invention relates to matrix materials suitable for use in purifying and/or isolating nucleic acids from a biological sample, which matrix comprises a surface comprising at least one element selected from the group consisting of Germanium, Tin and/or Lead, or at least one salt thereof, and methods related therewith.
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, comprising reacting a compound represented by formula (II) with a compound represented by formula (III) in the presence of a condensation agent to obtain a compound represented by formula (I).
Abstract: The present description discloses a novel biologically active ingredient of manuka honey. Specially, the present description discloses a compound represented by the following formula. In this formula, each of R1, R2 and R3 independently represents a hydrogen atom or optionally substituted C1-4 alkyl group, m represents an integer from 1 to 3, each of R4-m, R5-m and R6-m independently represents a hydrogen atom or optionally substituted C1-4 alkyl group, and each of R7, R8, R9 and R10 independently represents a hydrogen atom or optionally substituted C1-4 alkyl group.
Abstract: The present invention relates to novel phosphoramidites, A-n-bz, C-n-bz, C-n-ac, G-n-ac and U are produced with an HPLC purity of greater than 98% and 31P NMR purity greater than 99%. A novel process of reverse 5??3? directed synthesis of RNA oligomers has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.
Type:
Grant
Filed:
December 11, 2014
Date of Patent:
March 28, 2017
Assignee:
ChemGenes Corporation
Inventors:
Suresh C Srivastava, Divya Pandey, Satya P Bajpai, Naveen P Srivastava
Abstract: The present application, among other things, provides technologies, e.g., reagents, methods, etc. for preparing oligonucleotides comprising phosphorothiotriesters linkages, e.g., oligonucleotides having the structure of IIIa, IIIb or IIIc. 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.
Type:
Grant
Filed:
July 13, 2012
Date of Patent:
March 28, 2017
Assignee:
WAVE LIFE SCIENCES LTD.
Inventors:
Gregory L. Verdine, Meena, Naoki Iwamoto, David Charles Donnell Butler
Abstract: Disclosed herein are phosphorothioate nucleotide analogs, methods of synthesizing phosphorothioate nucleotide analogs and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with the phosphorothioate nucleotide analogs.
Abstract: The invention is directed to processes for synthesizing bicyclic nucleoside antiviral compounds and for synthesizing the intermediates used in the process. The invention is also directed to novel intermediate compounds useful in the process. The antiviral compounds are useful in the treatment of herpes zoster (i.e., varicella zoster virus, VZV, shingles) and for the prevention of post herpetic neuralgia (PHN) resulting from this viral infection.
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.
Abstract: The invention features compounds of formula V or XII: In one embodiment, the invention relates compounds and processes for conjugating ligand to oligonucleotide. The invention further relates to methods for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, cancers, allergies, autoimmune diseases, immunodeficiencies and immunosuppression.
Type:
Grant
Filed:
October 20, 2015
Date of Patent:
February 14, 2017
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
Muthiah Manoharan, Jayaprakash K. Nair, Kallanthottahil G. Rajeev, Michael E. Jung
Abstract: Methods for removing 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from a N-methylimidazole and methods for making oligonucleotides using N-methylimidazole are provided. In one embodiment, a method for removing 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from a feedstock containing N-methylimidazole includes contacting the feedstock with small or medium pore molecular sieves. The small or medium pore molecular sieves adsorb 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from the feedstock. The method further includes separating the small or medium pore molecular sieves from the feedstock.
Type:
Grant
Filed:
August 28, 2014
Date of Patent:
January 31, 2017
Assignee:
HONEYWELL INTERNATIONAL INC.
Inventors:
Venkatraman Mohan, Sandra M. Lorenz, Gregory Gajda
Abstract: An amino acid conjugate of a cyclic or acyclic nucleoside phosphonate is provided. In some cases, the amino acid conjugate is a tyrosine alkyl amide phosphonate ester conjugate of a cyclic or acyclic nucleoside phosphonate, and is useful as an antiviral compound. In certain cases, the tyrosine conjugate includes a long chain alkyl group on the carboxamide group of the tyrosine residue. In a method of preparing an acyclic tyrosine conjugate, a tert-butyloxycarbonyl (Boc) protected tyrosine residue containing a long chain alkyl group is reacted with an acyclic nucleoside phosphonate mono-ethyl ester in the presence of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate to produce a Boc-protected nucleoside phosphonate di-ester, and the di-ester is deethylated and deprotected to produce the tyrosine conjugate. Methods of inhibiting viral replication and methods of treating a viral infection using the amino acid conjugate are also provided.
Type:
Grant
Filed:
May 7, 2012
Date of Patent:
January 24, 2017
Assignee:
University of Southern California
Inventors:
Charles E. McKenna, Boris A Kashemirov, Ivan S Krylov, Valeria M. Zakharova
Abstract: The present invention provides cyclic-di-nucleotide (CDN) compounds that inhibit signaling at a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides which inhibit STING-dependent TBK1 activation and the resulting production of type I interferon.
Type:
Grant
Filed:
May 19, 2014
Date of Patent:
January 24, 2017
Assignee:
ADURO BIOTECH, INC.
Inventors:
Thomas W. Dubensky, Jr., David B. Kanne
Abstract: The present invention relates to pharmaceutical compositions and combination therapies for treating patients having a neoplasm or a proliferative disorder, the combination comprises an inhibitor of the e1F4E gene product, such as ribavirin, and a chemotherapeutic agent, such as cytarabine, wherein said combination therapy overcomes resistance developed in patients during anti-neoplastic treatment. The present invention also provides for the use of a combination therapy for treating patients having a neoplasm, a proliferative disorder, pre-neoplasm or a precancerous lesion, comprising an inhibitor of the e1F4E gene product, a chemotherapeutic agent, and a therapeutically effective amount of a hedgehog pathway inhibitor, such as GDC-0449; and the method of using said combination therapy.