Nucleic Acids Which Include Two Or Three Nucleotide Units Patents (Class 536/25.6)
  • Patent number: 9040234
    Abstract: The invention relates to design of short oligonucleotides and analogs thereof (such as, di-, and trinucleotide compounds) useful for various therapeutic applications. It is believed that the compounds of the invention can be used as antiviral agents, anticancer agents and so on. In certain embodiments, the compounds of the invention can modulate immune-stimulatory pathways and non-TLR pathways. The invention also relates to design modified oligonucleotides for therapeutic applications, by excluding nucleotide segments having off-target effects from the modified oligonucleotides. In another aspect, the invention provides pharmaceutical compositions including one or more compounds of the invention. It is believed that the compounds and compositions as described herein have therapeutic utility against a variety of diseases, including viral diseases, autoimmune diseases (such as, allergy, asthma, and inflammatory disorders) and cancer.
    Type: Grant
    Filed: August 25, 2011
    Date of Patent: May 26, 2015
    Assignee: SPRING BANK PHARMACEUTICALS, INC.
    Inventors: Radhakrishnan P. Iyer, John E. Coughlin
  • Patent number: 9035035
    Abstract: The invention describes new structures of the nucleotide conjugates (nuc-macromolecules) comprising at lease one nucleotide moiety coupled to at least one macromolecular compound via a short linker. These conjugates can be used as substrates for various kinds of polymerizing enzymes in the enzymatic synthesis of nucleic acids. In particular, these compounds can be used for labeling nucleic acids.
    Type: Grant
    Filed: March 17, 2006
    Date of Patent: May 19, 2015
    Assignee: GENOVOXX GMBH
    Inventors: Dmitry Cherkasov, Englbert Bäuml
  • Patent number: 8969545
    Abstract: Alkynyl-derivatized cap analogs, alkynyl-modified capped RNA, 1,4-disubstituted triazole-derivatized capped RNA, methods of preparation, methods of isolation, and uses thereof are provided. The “click” modification facilitates detection and isolation of capped RNAs and the 1,4-disubstituted triazole derivatives formed by the “click” reaction are useful for producing RNA transcripts and encoded protein.
    Type: Grant
    Filed: October 18, 2012
    Date of Patent: March 3, 2015
    Assignee: Life Technologies Corporation
    Inventors: Anilkumar R. Kore, Shanmugasundaram Muthian, Kyle Gee
  • Publication number: 20150056224
    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 stereosiomers thereof.
    Type: Application
    Filed: May 18, 2014
    Publication date: February 26, 2015
    Applicants: 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
  • Patent number: 8957201
    Abstract: A method for the prevention or treatment in a mammal of a disease preventable or treatable by the pharmacologically useful antisense or antigene activity of an oligonucleotide analogue or a pharmacologically acceptable salt thereof in the body of said mammal, which method comprises administering to said mammal in need of such prevention or treatment a pharmaceutically effective amount of an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of said nucleoside units is a structure of the formula (2): wherein A is methylene; and B is an unsubstituted purin-9-yl, an unsubstituted 2-oxo-pyrimidin-1-yl or a substituted purin-9-yl; or a pharmacologically acceptable salt thereof.
    Type: Grant
    Filed: July 22, 2010
    Date of Patent: February 17, 2015
    Assignee: Daiichi Sankyo Company, Limited
    Inventors: Masakatsu Kaneko, Koji Morita, Takeshi Imanishi
  • Patent number: 8957191
    Abstract: This invention provides pH-responsive zwitterionic nucleotides and nucleic acids comprising said nucleotides, wherein said zwitterions are constituted from one or more anionic internucleoside linkages and one or more cationic moieties and said zwitterionic nucleotides further comprise either one or more hydrophobic moieties or one or more TEE's with the general structure (I) Hydrophobic element-pH-responsive hydrophilic elements (I).
    Type: Grant
    Filed: July 13, 2009
    Date of Patent: February 17, 2015
    Assignee: Steffen Panzner
    Inventor: Steffen Panzner
  • Publication number: 20140349292
    Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one internucleoside 3?-NHP(O)(S?)O-5? linkage, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive thiophosphoramidate oligonucleotides were found to retain the high RNA binding affinity of the parent oligonucleotide N3??P5? phosphoramidates and to exhibit a much higher acid stability.
    Type: Application
    Filed: July 9, 2014
    Publication date: November 27, 2014
    Inventors: Sergei Gryaznov, Krisztina Pongracz, Tracy Matray
  • Publication number: 20140350234
    Abstract: The present invention is directed to n-alkylated synthetic nucleosides of high regiospecific purity and oligonucleotides that can be utilized for studies on reversal of cytotoxic and mutagenic DNA damage, and as diagnostic tools.
    Type: Application
    Filed: February 20, 2014
    Publication date: November 27, 2014
    Applicant: ChemGenes Corporation
    Inventors: Satya P. Bajpai, Sant K. Srivastav, Suresh C. Srivastava
  • Publication number: 20140341976
    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: Application
    Filed: May 19, 2014
    Publication date: November 20, 2014
    Applicant: ADURO BIOTECH, INC.
    Inventors: Thomas W. Dubensky, JR., David B. Kanne
  • Patent number: 8889843
    Abstract: To provide an excellent dimer amidite which can be subjected to purification, preferably, whose protective groups can be removed under mild conditions, and a method for synthesizing a nucleic acid using the dimer amidite, a dimer amidite having a structure represented by the following General Formula (1) and a method for synthesizing a nucleic acid including performing condensation reaction of the dimer amidite are provided: wherein in General Formula (1), R1 and R2 each independently represent any one of groups selected from General formulas (2) to (4) and Structural Formulas (12) to (15) with a compound where R1 and R2 are each represent Structural Formulas (12) being excluded: ?and wherein in the General Formulas (2) to (4), R3 represents any one group represented by the following Structural Formulas (16) to (25):
    Type: Grant
    Filed: February 26, 2010
    Date of Patent: November 18, 2014
    Assignee: Apta Biosciences Ltd.
    Inventor: Tsuyoshi Fujihara
  • Patent number: 8884000
    Abstract: Inhibitors of saporin-L1 are disclosed, as are related compositions and uses thereof, in particular in cancer therapy that employs saporin-L1-linked immunotoxins.
    Type: Grant
    Filed: February 15, 2011
    Date of Patent: November 11, 2014
    Assignees: Albert Einstein College of Medicine of Yeshiva University, Industrial Research Limited
    Inventors: Vern L. Schramm, Gary Brian Evans, Peter Charles Tyler, Jennifer Mary Mason
  • Publication number: 20140329889
    Abstract: Methods and compositions are provided for increasing the production of a type I interferon (IFN) in a cell. Aspects of the methods include increasing the level of a 2?-5? phosphodiester linkage comprising cyclic-di-nucleotide in a cell in a manner sufficient to increase production of the type I interferon (IFN) by the cell. Also provided are compositions and kits for practicing the embodiments of the methods.
    Type: Application
    Filed: May 2, 2014
    Publication date: November 6, 2014
    Inventors: Russell E. Vance, Ming C. Hammond, Dara Burdette, Ellie J. Diner, Stephen C. Wilson
  • Publication number: 20140323554
    Abstract: The present invention discloses compounds of formula (I): which exhibit antiviral properties. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject in need of anti-HBV treatment. The invention also relates to methods of treating a HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
    Type: Application
    Filed: February 21, 2014
    Publication date: October 30, 2014
    Applicant: SPRING BANK PHARMACEUTICALS, INC.
    Inventors: Radhakrishnan P. Iyer, Seetharamaiyer Padmanabhan
  • Publication number: 20140205653
    Abstract: It is an object of the present invention to provide novel and highly active cyclic-di-nucleotide (CDN) immune stimulators that activates 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 that induce STING-dependent TBK1 activation, wherein the cyclic purine dinuclotides present in the composition are substantially pure Rp,Rp or Rp,Sp stereoisomers, and particularly substantially pure Rp,Rp, or RpSp CDN thiophosphate diastereomers.
    Type: Application
    Filed: December 13, 2013
    Publication date: July 24, 2014
    Applicant: Aduro Biotech, Inc.
    Inventors: Thomas W. Dubensky, JR., David B. Kanne, Meredith Lai Ling Leong, Edward Emile Lemmens, Laura Hix Glickman
  • Publication number: 20140194610
    Abstract: Described herein are methods for the synthesis of derivatives of thiosulfonate reagents. Said reagents have utility for the synthesis of phosphorothiotriesters from H-phosphonates in a stereospecific fashion.
    Type: Application
    Filed: July 13, 2012
    Publication date: July 10, 2014
    Inventors: Gregory L. Verdine, Meena Meena, Naoki Iwamoto, David Charles Donnell Butler
  • Publication number: 20140163213
    Abstract: The invention relates to oligonucleotides including at least one lipophilic substituted nucleotide analog and a pyrimidine-purine dinucleotide. The invention also relates to pharmaceutical compositions and methods of use thereof.
    Type: Application
    Filed: October 4, 2013
    Publication date: June 12, 2014
    Applicant: COLEY PHARMACEUTICAL GMBH
    Inventors: Harald Debelak, Eugen Uhlmann, Marion Jurk
  • Patent number: 8741869
    Abstract: A substantially pure or isolated oligodeoxynucleotide of at least 10 nucleotides is disclosed, wherein the oligodeoxynucleotide comprised a sequence represented by either formula: 5? N1N2N3T-CpG-WN4N5N6 3? wherein the CpG motif is unmethylated, W is A or T, and N1, N2, N3, N4, N5, and N6 are nucleotides, or the formula: 5? RY-CpG-RY 3? wherein the central CpG motif is unmethylated, R is A or G, and Y is C or T, as well as an oligodeoxynucleotide delivery complex and a pharmacological composition comprising the present inventive oligodeoxynucleotide, and a method of inducing an immune response by administering the present inventive oligodeoxynucleotide to a host. In some embodiments, the oligodeoxynucleotide includes the nucleic acid sequences set forth as SEQ ID NO: 137.
    Type: Grant
    Filed: February 5, 2013
    Date of Patent: June 3, 2014
    Assignees: The United States of America as represented by the Secretary of the Department of Health and Human Services, Uniformed Services University of the Health Sciences, an institution of higher learning within the Department of Defense
    Inventors: Dennis M. Klinman, Ken J. Ishii, Daniela Verthelyi, James J. Mond
  • Patent number: 8728465
    Abstract: Compositions comprising dendritic cells pulsed with tumor lysate and at least one toll-like receptor (TLR) ligand which may be used for eliciting a specific immune response in a mammal in need thereof for treating diseases including a tumor are disclosed. Also disclose are methods of activating dendritic cells, comprising providing at least one toll-like receptor (TLR) ligand; and pulsing a dendentic cell with the at least one TLR ligand. A method further comprises pulsing the dendritic cell with a tumor lysate.
    Type: Grant
    Filed: June 17, 2009
    Date of Patent: May 20, 2014
    Assignee: Cedars-Sinai Medical Center
    Inventors: Keith L. Black, Dwain Morris-Irvin, Moshe Arditi
  • Patent number: 8669055
    Abstract: The invention further relates to conjugated polymers, and methods, articles and compositions employing them as described herein. In some aspects, the invention relates to methods, articles and compositions for the detection and analysis of biomolecules in a sample. Provided assays include those determining the presence of a target biomolecule in a sample or its relative amount, or the assays may be quantitative or semi-quantitative. The methods can be performed on a substrate. The methods can be performed in an array format on a substrate, which can be a sensor. In some embodiments, detection assays are provided employing sensor biomolecules that do not comprise a fluorophore that can exchange energy with the cationic multichromophore. In some aspects biological assays are provided in which energy is transferred between one or more of the multichromophore, a label on the target biomolecule, a label on the sensor biomolecule, and/or a fluorescent dye specific for a polynucleotide, in all permutations.
    Type: Grant
    Filed: October 12, 2010
    Date of Patent: March 11, 2014
    Assignee: The Regents of the University of California
    Inventors: Guillermo C. Bazan, Bin Liu
  • Patent number: 8580944
    Abstract: The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for preventing or treating an immune-mediated disorder, such as, but not limited to, an autoimmune disease, by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide. Also disclosed are methods of suppressing an immune response in a subject by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.
    Type: Grant
    Filed: June 21, 2012
    Date of Patent: November 12, 2013
    Assignee: The United States of America as represented by the Secretary of the Department of Health and Human Services
    Inventors: Dennis M. Klinman, Rainald Zeuner, Mayda Gursel, Ihsan Gursel, Daniela Verthelyi
  • Publication number: 20130264207
    Abstract: This disclosure is related to a method of sequencing a single-stranded DNA using deoxynucleotide polyphosphate analogues and translocation of tags from incorporated deoxynucleotide polyphosphate analogues through a nanopore.
    Type: Application
    Filed: December 16, 2011
    Publication date: October 10, 2013
    Inventors: Jingyue Ju, Shiv Kumar, Zengmin Li, Chuanjuan Tao, Minchen Chien, James J. Russo, Sergey Kalachikov, Ken Shepard, Jacob Karl Rosenstein
  • Publication number: 20130267697
    Abstract: The present invention provides a protected nucleotide for elongation, which can be purified efficiently and in a high yield by a liquid-liquid extraction operation, and can achieve an oligonucleotide production method by a phosphoramidite method. It has been found that the above-mentioned problem can be solved by a particular oligonucleotide comprising a protected base and/or particular oligonucleotide protected by a branched chain-containing aromatic group at 3?-position.
    Type: Application
    Filed: February 15, 2013
    Publication date: October 10, 2013
    Inventors: Kunihiro Hirai, Satoshi Katayama, Takayoshi Torii, Ryotaro Nakaya, Daisuke Takahashi
  • Patent number: 8481711
    Abstract: An object of the present invention is to provide a non-peptidic nerve axon and/or neurite outgrowth agent for allowing a nerve axon and a neurite to elongate. 3-(Aminocarbonyl)-1-[5-O-[[1-(6-amino-9H-purin-9-yl)-1-deoxy-?-D-ribofuranos-5-O-yl]phosphonyloxy(oxylato)phosphinyl]-?-L-ribofuranosyl]pyridinium that is an analogue of nicotinamide adenine dinucleotide (NAD) comprising ?-L-ribose as the sugar component is used as a nerve axon and/or neurite outgrowth agent or composition, a cancer cell growth suppressing and/or apoptosis inducing agent, or a cancer cell growth suppressing and/or apoptosis inducing composition.
    Type: Grant
    Filed: April 20, 2011
    Date of Patent: July 9, 2013
    Assignee: Hidenori Kamanishi
    Inventors: Hidenori Kaminishi, Junei Kinjo, Ryota Tsuchihashi, Tsuyoshi Ikeda, Akihiro Sakamoto
  • Publication number: 20130102034
    Abstract: The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using thereof.
    Type: Application
    Filed: May 25, 2012
    Publication date: April 25, 2013
    Inventor: Jason P. Schrum
  • Patent number: 8420615
    Abstract: The invention provides an immunostimulatory nucleic acid. In certain embodiments according to this aspect of the invention, the sequence of the immunostimulatory oligonucleotide and/or immunomer is at least partially self-complementary.
    Type: Grant
    Filed: September 23, 2009
    Date of Patent: April 16, 2013
    Assignee: Idera Pharmaceuticals, Inc.
    Inventors: Sudhir Agrawal, Ekambar Kandimalla, Dong Yu
  • Patent number: 8389495
    Abstract: A substantially pure or isolated oligodeoxynucleotide of at least 10 nucleotides is disclosed, wherein the oligodeoxynucleotide comprised a sequence represented by either formula: 5?N1N2N3T-CpG-WN4N5N63? wherein the CpG motif is unmethylated, W is A or T, and N1, N2, N3, N4, N5, and N6 are nucleotides, or the formula: 5?RY-CpG-RY3? wherein the central CpG motif is unmethylated, R is A or G, and Y is C or T, as well as an oligodeoxynucleotide delivery complex and a pharmacological composition comprising the present inventive oligodeoxynucleotide, and a method of inducing an immune response by administering the present inventive oligodeoxynucleotide to a host. In some embodiments, the oligodeoxynucleotide includes the nucleic acid sequences set forth as SEQ ID NO: 137.
    Type: Grant
    Filed: August 29, 2011
    Date of Patent: March 5, 2013
    Assignee: The United States of America as represented by the Secretary of the Department of Health and Human Services
    Inventors: Dennis Klinman, Ken Ishii, Daniela Verthelyi, James J. Mond
  • Publication number: 20130041144
    Abstract: Provided herein are novel 5?-(S)—CH3 substituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the furanose ring of each of the novel 5?-(S)—CH3 substituted bicyclic nucleosides includes a 2? to 4? bridging group. The 5?-(S)—CH3 substituted bicyclic nucleosides are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as for example increasing the binding affinity. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
    Type: Application
    Filed: March 10, 2011
    Publication date: February 14, 2013
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: Michael T. Migawa, Thazha P. Prakash, Charles Allerson, Balkrishen Bhat, Punit P. Seth, Eric E. Swayze
  • Publication number: 20130030164
    Abstract: Water-forming NADH oxidase derived from Streptococcus mutans should be further improved in terms of stability for practical use in industrial production. An object of the present invention is to provide an enzyme that is obtained through modification of a water-forming NADH oxidase, which is useful as an NAD+ regeneration system for stereoselective oxidation catalyzed by an oxidoreductase, by protein engineering techniques so that the enzyme can withstand long-term use without exhibiting a reduction of its activity for the regeneration of NAD+, that is, an enzyme having improved stability, and to provide a method for efficiently producing a useful substance such as an optically active alcohol or amino acid. The present invention relates to an enzyme modification method that can improve the stability of water-forming NADH oxidase derived from Streptococcus mutans by appropriately introducing mutation.
    Type: Application
    Filed: January 19, 2011
    Publication date: January 31, 2013
    Applicant: Kaneka Corporation
    Inventors: Shinichi Yoshida, Akira Iwasaki, Motohisa Washida, Tozo Nishiyama, Daisuke Moriyama, Naoaki Taoka
  • Patent number: 8361478
    Abstract: Described are vaccines against malarial infections, which are based on recombinant viral vectors, such as alpha viruses, adenoviruses, or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against different Plasmodium infections, such as infections by P. falciparum or P. yoelii. Codon-optimized circumsporozoite genes are disclosed. Replication-defective adenoviruses may be used, derived from serotypes that encounter low titers of neutralizing antibodies. Also described is the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.
    Type: Grant
    Filed: November 8, 2011
    Date of Patent: January 29, 2013
    Assignee: Crucell Holland B.V.
    Inventors: Maria G. Pau, Lennart Holterman, Jorn Kaspers, Antonius J. H. Stegmann
  • Publication number: 20120321550
    Abstract: The present invention provides: a mononuclear metal complex that has high catalytic activity and can be used as a hydrogenation reduction catalyst that allows efficient hydrogenation reduction of a substance to be reduced; a tautomer or stereoisomer thereof; or a salt thereof. Provided is the mononuclear metal complex represented by the following formula (1), a tautomer or stereoisomer thereof; or a salt thereof. In the formula (1), Ar1 is an aromatic anionic ligand or an aromatic ligand, or is not present, Ar2 is a ligand having aromaticity and may or may not be substituted, and when Ar2 is substituted, the number of substituents may be one or more, M is an atom or ion of a transition metal, A1 and A2 are both carbon atoms, or one of A1 and A2 is a carbon atom and the other is a nitrogen atom, Y is an anionic group or a cationic group, or is not present, L is any ligand or is not present, and m is a positive integer, 0, or a negative integer.
    Type: Application
    Filed: March 4, 2011
    Publication date: December 20, 2012
    Applicant: OSAKA UNIVERSITY
    Inventors: Shunichi Fukuzumi, Tomoyoshi Suenobu, Yuta Maenaka
  • Publication number: 20120316224
    Abstract: Described herein are nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties. Also described herein are methods of making and using nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties.
    Type: Application
    Filed: July 6, 2010
    Publication date: December 13, 2012
    Applicant: ONTORII, INC
    Inventors: Gregory L. Verdine, Meena Meena, Naoki Iwamoto
  • Publication number: 20120296074
    Abstract: The problem of the present invention is provision of a method of producing an n+p-mer oligonucleotide efficiently in a high yield, which includes use of, as a starting material, an n-mer oligonucleotide wherein the 3?-terminal hydroxyl group is protected, and the 5?-terminal hydroxyl group is protected by a temporary protecting group, and continuously performing, in a solution, (1) a deprotection step of the 5?-terminal hydroxyl group, (2) a 5?-terminal elongation step by the addition of a p-mer oligonucleotide wherein the 3?-position is phosphoramidited, and (3) an oxidation step or a sulfurization step of a phosphite triester moiety. It has been found that the above-mentioned problem can be solved by adding a particular cation scavenger during the deprotection step, applying a neutralization treatment after completion of the deprotection reaction, and using a particular oxidizing agent or sulfurizing agent in the oxidation step or sulfurization step.
    Type: Application
    Filed: May 17, 2012
    Publication date: November 22, 2012
    Applicant: AJINOMOTO CO., INC.
    Inventors: Kunihiro HIRAI, Satoshi KATAYAMA
  • Patent number: 8288359
    Abstract: The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for preventing or treating inflammatory arthropathies by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.
    Type: Grant
    Filed: April 25, 2011
    Date of Patent: October 16, 2012
    Assignee: The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services
    Inventors: Dennis Klinman, Rainald Zeuner, Daniela Verthelyi, Ihsan Gursel, Mayda Gursel
  • Publication number: 20120252030
    Abstract: 5-bromo-2?-deoxy-uridine (BrdU) labeled nucleotide triphosphates and nucleic acid probes are described herein. The BrdU labeled nucleotide triphosphates include a linker between the nucleotide triphosphate and the BrdU moiety. The linker can be cleavable or non-cleavable. The nucleotide triphosphates can be a ribonucleotide triphosphates, 2?-deoxyribonucleotide triphosphates or 2?,3?-dideoxyribonucleotide triphosphates. The nucleic acid probes can be used for in situ hybridization.
    Type: Application
    Filed: April 3, 2012
    Publication date: October 4, 2012
    Applicant: LIFE TECHNOLOGIES CORPORATION
    Inventors: Anilkumar R. KORE, Zhongting Hu
  • Patent number: 8263091
    Abstract: A method is disclosed herein for increasing an immune response to an opportunistic infection in an immunocompromised subject. In one embodiment, the subject is infected with a lentivirus. The method includes increasing an immune response to a pathogen using D oligodeoxynucleotides including a CpG motif.
    Type: Grant
    Filed: September 17, 2003
    Date of Patent: September 11, 2012
    Assignee: The United States of America as represented by the Secretary of the Department of Health and Human Services
    Inventors: Dennis M. Klinman, Daniela Verthelyi
  • Patent number: 8227438
    Abstract: The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for preventing or treating an immune-mediated disorder, such as, but not limited to, an autoimmune disease, by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide. Also disclosed are methods of suppressing an immune response in a subject by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.
    Type: Grant
    Filed: February 27, 2009
    Date of Patent: July 24, 2012
    Assignee: The United States of America as represented by the Secretary of the Department of Health and Human Services
    Inventors: Dennis M. Klinman, Rainald Zeuner, Mayda Gursel, Ihsan Gursel, Daniela Verthelyi
  • Patent number: 8227243
    Abstract: Described are new uses of recombinant adenoviral vectors in vaccination regimens, such as prime/boost set-ups and subsequent vaccinations and applications for gene therapy. Moreover, also described are new assays to determine the best regimen for applying the most suitable recombinant viral vector in a vaccination or gene therapy setting.
    Type: Grant
    Filed: August 23, 2011
    Date of Patent: July 24, 2012
    Assignee: Crucell Holland B.V.
    Inventors: Ronald Vogels, Maria Grazia Pau, Lennart Holterman, Stefan Kostense, Menzo Jans Emco Havenga, Mieke Caroline Sprangers
  • Patent number: 8222398
    Abstract: The invention provides immunomodulatory compounds and methods for immunomodulation of individuals using the immunomodulatory compounds.
    Type: Grant
    Filed: October 1, 2008
    Date of Patent: July 17, 2012
    Assignee: Dynavax Technologies Corporation
    Inventors: Karen L. Fearon, Dino Dina, Stephen F. Tuck
  • Patent number: 8193338
    Abstract: A di(pyrimidine nucleoside 5?-)polyphosphate is synthesized by converting a pyrimidine nucleoside 5?-triphosphate into a pyrimidine nucleoside 5?-cyclic triphosphate by use of a condensing agent, and subsequently reacting the pyrimidine nucleoside 5?-cyclic triphosphate with a pyrimidine nucleotide in the presence of a salt of a metal selected from among magnesium, manganese, and iron. Through the method of the invention, a di(pyrimidine nucleoside 5?-)polyphosphate can be synthesized from an unprotected pyrimidine nucleoside 5?-phosphate serving as a starting material at a synthesis yield of 50% or higher. Therefore, the method of the invention is suitable for large-scale synthesis of a di(pyrimidine nucleoside 5?-)polyphosphate.
    Type: Grant
    Filed: July 25, 2007
    Date of Patent: June 5, 2012
    Assignee: Yamasa Corporation
    Inventors: Satoru Kogo, Kohei Yamada, Yuko Iwai, Kazuomi Osawa, Hiroyuki Hayakawa
  • Publication number: 20120071640
    Abstract: An oligonucleotide which comprises at least one internucleotide linkage comprising a P—S—R bond and at least two nucleosides, wherein R corresponds to the formula (I) wherein A is a geminally substituted alkylene group, preferably CH2, X and Y are independently selected from S and O, and R0 is selected from the group consisting of optionally substituted carbon bonded organic residue, such as in particular optionally substituted alkyl or aryl, SRx, ORx and NRxRy wherein Rx and/or Ry are selected from H and organic residues and at least Rx is a substituent other than H. Another object of the invention is a sulfurizing agent useful for oligonucleotide manufacture and the manufacture thereof.
    Type: Application
    Filed: June 22, 2011
    Publication date: March 22, 2012
    Applicant: GIRINDUS AMERICA, INC.
    Inventors: Wieslaw Adam MAZUR, Yigang HE, Victor D. SOROKIN
  • Publication number: 20120053226
    Abstract: The invention relates to design of short oligonucleotides and analogs thereof (such as, di-, and trinucleotide compounds) useful for various therapeutic applications. It is believed that the compounds of the invention can be used as antiviral agents, anticancer agents and so on. In certain embodiments, the compounds of the invention can modulate immune-stimulatory pathways and non-TLR pathways. The invention also relates to design modified oligonucleotides for therapeutic applications, by excluding nucleotide segments having off-target effects from the modified oligonucleotides. In another aspect, the invention provides pharmaceutical compositions including one or more compounds of the invention. It is believed that the compounds and compositions as described herein have therapeutic utility against a variety of diseases, including viral diseases, autoimmune diseases (such as, allergy, asthma, and inflammatory disorders) and cancer.
    Type: Application
    Filed: August 25, 2011
    Publication date: March 1, 2012
    Applicant: Spring Bank Pharmaceuticals, Inc.
    Inventors: Radhakrishnan P. Iyer, John E. Coughlin
  • Publication number: 20120041057
    Abstract: The invention provides analogs cyclic diguanosine monophosphate (c-di-GMP) having different substituents at the guanine C8 position.
    Type: Application
    Filed: August 10, 2011
    Publication date: February 16, 2012
    Inventors: Roger A. Jones, Elizabeth Veliath
  • Patent number: 8097453
    Abstract: Described are vaccines against malarial infections, which are based on recombinant viral vectors, such as alpha viruses, adenoviruses, or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against different Plasmodium infections, such as infections by P. falciparum or P. yoelii. Codon-optimized circumsporozoite genes are disclosed. Replication-defective adenoviruses may be used, derived from serotypes that encounter low titers of neutralizing antibodies. Also described is the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.
    Type: Grant
    Filed: December 1, 2010
    Date of Patent: January 17, 2012
    Assignee: Crucell Holland B.V.
    Inventors: Maria G. Pau, Lennart Holterman, Jorn Kaspers, Antonius J. H. Stegmann
  • Publication number: 20110306138
    Abstract: The use of at least one nucleic acid based nuclear localization signal including a natural or synthetic m3G-CAP is shown to increase transmembrane transport of a molecular cargo, in particular large molecules, into the nucleus. The use of natural and synthetic m3G-CAP is disclosed and the effect shown with a natural RNA 5? end nuclear localization signal composed of a 2,2,7-trimethylguanosine CAP (m3G-CAP) coupled to fluorescent Streptavidin in one example, and an antisense oligonucleotide in another. A methylenephosphonate modified m3G-CAP is shown to have improved stability in human serum and in cytosolic extract.
    Type: Application
    Filed: December 17, 2009
    Publication date: December 15, 2011
    Inventors: Edvard Smith, Pedro Moreno, Roger Strömberg, Malgorzata Wenska
  • Publication number: 20110300534
    Abstract: Embodiments relate to methods of sequencing nucleic acids. Embodiments encompass the use of nucleotide analogs and a nucleic acid polymerase enzyme or enzyme complex comprising proofreading activity. The nucleotide analogs may become incorporated into a replicating strand and induce the proofreading activity of the polymerizing enzyme, thereby prolonging the duration of a signal associated with nucleotide incorporation, resulting in more observable sequencing events and increasing the accuracy of nucleic acid sequencing.
    Type: Application
    Filed: May 27, 2011
    Publication date: December 8, 2011
    Applicant: Industrial Technology Research Institute
    Inventors: Chung-Fan Chiou, Chao-Chi Pan, Jenn-Yeh Fann, Shang-Chia Chang, Tsu-Ju Fu
  • Publication number: 20110288285
    Abstract: The present invention describes novel compounds and methods for capping reactive groups on support and during multistep synthesis. These new capping reagents are also useful for high quality synthesis on solid supports and surfaces used as microarrays, biosensors, or in general as biochips. The compounds are also useful for controlling surface density of reactive groups on a support. The compounds may also be used to modify the hydrophilic/hydrophobic characteristics of a surface or a molecule. The compounds have functional utility in various applications in the fields of genomics, proteomics, diagnostics and medicine.
    Type: Application
    Filed: March 22, 2011
    Publication date: November 24, 2011
    Inventors: Xiaolian Gao, Peilin Yu
  • Publication number: 20110257252
    Abstract: The invention features compounds of formula I and methods of their use as antiplatelet and antithrombotic compounds: H/N=Q?2OOOO?Q2-N, HR6/NIf)(?XMO-M??OM°?X1MQ?)r(?rfHOOHHOOQHiN?iR2 Formula (I).
    Type: Application
    Filed: November 20, 2009
    Publication date: October 20, 2011
    Applicant: GLSynthesis Inc.
    Inventors: Ivan Borisso Yanachkov, George Edward Wright
  • Patent number: 8034923
    Abstract: Processes are disclosed that use 3?-reversibly terminated nucleoside triphosphates to analyze DNA for purposes other than sequencing using cyclic reversible termination. These processes are based on the unexpected ability of terminal transferase to accept these triphosphates as substrates, the unexpected ability of polymerases to add reversibly and irreversibly terminated triphosphates in competition with each other, the development of cleavage conditions to remove the terminating group rapidly, in high yield, and without substantial damage to the terminated oligonucleotide product, and the ability of reversibly terminated primer extension products to capture groups. The presently preferred embodiments of the disclosed processes use a triphosphate having its 3?-OH group blocked as a 3?-ONH2 group, which can be removed in buffered NaNO2 and use variants of Taq DNA polymerase, including one that has a replacement (L616A).
    Type: Grant
    Filed: March 27, 2009
    Date of Patent: October 11, 2011
    Inventors: Steven Albert Benner, Daniel Hutter, Nicole Aurora Leal, Fei Chen
  • Publication number: 20110201674
    Abstract: Inhibitors of saporin-L1 are disclosed, as are related compositions and uses thereof, in particular in cancer therapy that employs saporin-L1-linked immunotoxins.
    Type: Application
    Filed: February 15, 2011
    Publication date: August 18, 2011
    Inventors: Vern L. Schramm, Gary Brian Evans, Peter Charles Tyler, Jennifer Mary Mason
  • Publication number: 20110190485
    Abstract: The present invention provides for compounds of Formulas I-III, and salts thereof, wherein n, m, R1, R2, R3, and R4 have any of the values defined there for in the specification. The compounds of formula I may be used in the synthesis of oligonucleotides such as compounds of formula II (bearing a 3?-thiol) or formula III (bearing a 3?-disulfide).
    Type: Application
    Filed: February 2, 2010
    Publication date: August 4, 2011
    Applicant: Berry and Associates, Inc.
    Inventor: David Allen Berry