Homopolymers Having Repeating Sequences Of Four Or More Identical Nucleotide Units Patents (Class 536/25.5)
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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: 9096853Abstract: A synthesized siRNA molecule having the sense strand with one or more uridine bases replaced by one or more respective nucleoside analogs, such as 5-fluoro-2?-deoxyuridine (FdU).Type: GrantFiled: September 18, 2013Date of Patent: August 4, 2015Assignees: U.S. Department of Veterans Affairs, University of Pittsburgh-Of the Commonwealth System of Higher Education, Wake Forest University Health SciencesInventors: John C. Schmitz, Sr., Edward Chu, William H. Gmeiner
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Patent number: 9035035Abstract: 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: GrantFiled: March 17, 2006Date of Patent: May 19, 2015Assignee: GENOVOXX GMBHInventors: Dmitry Cherkasov, Englbert Bäuml
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Patent number: 9012422Abstract: The present invention relates to active compounds for treating acute myelogenous leukemia (AML) in a subject in need thereof and methods of treating AML carried out by administering the subject an active compound in an amount effective to treat the leukemia. The active compound comprises a 10-mer oligonucleotide covalently linked via 3? to 5? phosphodiester linkages of 5-fluorodeoxyuridine, FdUMP[10], or a pharmaceutically acceptable salt thereof.Type: GrantFiled: August 2, 2012Date of Patent: April 21, 2015Assignee: Wake Forest University Health SciencesInventors: William H. Gmeiner, Timothy S. Pardee
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Publication number: 20140080122Abstract: Systems and methods related to optical nanosensors comprising photoluminescent nanostructures are generally described. Generally, the nanosensors comprise a photoluminescent nanostructure and a polymer that interacts with the photoluminescent nanostructure. In some cases, the interaction between the polymer and the nanostructure can be non-covalent (e.g., via van der Waals interactions). The nanosensors comprising a polymer and a photoluminescent nanostructure may be particularly useful in determining the presence and/or concentration of relatively small molecules, in some embodiments. In addition, in some instances the nanosensors may be capable of determining relatively low concentrations of analytes, in some cases determining as little as a single molecule. In some embodiments, the interaction between the analyte and the nanosensor (e.g.Type: ApplicationFiled: July 15, 2013Publication date: March 20, 2014Applicant: Massachusetts Institute of TechnologyInventors: Michael S. Strano, Jong-Ho Kim, Jinqing Zhang, Daniel A. Heller
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Patent number: 8546556Abstract: The present invention provides novel carbocyclic ?-L-bicyclic nucleosides and oligomeric compounds comprising at least one of these carbocyclic ?-L-bicyclic nucleosides. The carbocyclic ?-L-bicyclic nucleosides are useful for enhancing one or more properties of the oligomeric compounds they are incorporated into including nuclease resistance.Type: GrantFiled: November 21, 2008Date of Patent: October 1, 2013Assignee: Isis Pharmaceuticals, IncInventors: Punit P. Seth, Eric E. Swayze
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Patent number: 8536320Abstract: The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, novel tetrahydropyran nucleoside analogs are provided having at least one chiral substituent that are expected to be useful for enhancing one or more properties of oligomeric compounds such as nuclease resistance and/or binding affinity. In certain embodiments, the oligomeric compounds are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.Type: GrantFiled: February 1, 2010Date of Patent: September 17, 2013Assignee: Isis Pharmaceuticals, Inc.Inventors: Thazha P. Prakash, Eric E. Swayze
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Patent number: 8420615Abstract: 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: GrantFiled: September 23, 2009Date of Patent: April 16, 2013Assignee: Idera Pharmaceuticals, Inc.Inventors: Sudhir Agrawal, Ekambar Kandimalla, Dong Yu
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Publication number: 20130084576Abstract: The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.Type: ApplicationFiled: April 26, 2011Publication date: April 4, 2013Applicant: Isis Pharmaceuticals, Inc.Inventors: Thazha P. Prakash, Punit P. Seth, Eric E. Swayze
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Patent number: 8143233Abstract: RNA aptamers and methods for identifying the same are disclosed. The RNA aptamers selectively bind coagulation factors, E2F family members, Ang1 or Ang2, and therapeutic and other uses for the RNA aptamers are also disclosed.Type: GrantFiled: December 17, 2010Date of Patent: March 27, 2012Assignee: Duke UniversityInventors: Bruce A. Sullenger, Christopher P. Rusconi
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Publication number: 20110294869Abstract: Disclosed herein are compositions and methods for generating ribo-nucleic neutral (RNN) or deoxyribo-nucleic-neutral (DNN) polynucleotides with reduced anionic charge, for improved intracellular delivery. Also disclosed herein are methods of using RNN and DNN compositions.Type: ApplicationFiled: September 23, 2009Publication date: December 1, 2011Applicant: Traversa Therapeutics, Inc.Inventor: Scott G. Petersen
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Publication number: 20110288285Abstract: 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: ApplicationFiled: March 22, 2011Publication date: November 24, 2011Inventors: Xiaolian Gao, Peilin Yu
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Patent number: 8039611Abstract: Provided is a ribonucleoside derivative represented by General Formula (I): (wherein R1 represents a hydrogen atom or the like, R2 represents a hydrogen atom or the like, R3 represents a methyl group or the like, and B represents a nucleic acid base residue optionally having a protecting group or a modifying group). An RNA containing this ribonucleoside derivative shows excellent hybridization ability and resistance to nuclease.Type: GrantFiled: March 8, 2007Date of Patent: October 18, 2011Assignee: Tokyo Institute of TechnologyInventors: Mitsuo Sekine, Takeshi Yamada, Hisao Saneyoshi, Kohji Seio
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Publication number: 20110034541Abstract: The invention consists of oligonucleotides which inhibit the immunostimulatory activity of ISS-ODN (immunostimulatory sequence oligodeoxynucleotides) as well as methods for their identification and use. The oligonucleotides of the invention are useful in controlling therapeutically intended ISS-ODN adjuvant activity as well as undesired ISS-ODN activity exerted by recombinant expression vectors, such as those used for gene therapy and gene immunization. The oligonucleotides of the invention also have anti-inflammatory activity useful in reducing inflammation in response to infection of a host with ISS-ODN containing microbes, in controlling autoimmune disease and in boosting host Th2 type immune responses to an antigen. The invention also encompasses pharmaecutically useful conjugates of the oligonucleotides of the invention (including conjugate partners such as antigens and antibodies).Type: ApplicationFiled: February 1, 2010Publication date: February 10, 2011Inventors: Eyal Raz, Mark Roman
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Patent number: 7879811Abstract: A therapeutic and/or cosmetic formulation comprising at least one anti-sense polynucleotide to a connexin protein together with a pharmaceutically acceptable carrier or vehicle is useful in site specific down regulation of connexin protein expression, particularly in reduction of neuronal cells death, wound healing, reduction of inflammation, decrease of scar formation and skin rejuvenation and thickening.Type: GrantFiled: August 25, 2006Date of Patent: February 1, 2011Assignee: Coda Therapeutics, Inc.Inventors: Richard Colin Green, David Laurence Becker
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Publication number: 20100255547Abstract: The present invention is directed to a novel chemical compound comprising the structure [Xx-(CH2)m-phosphate-Yy]n, characterized in that 3?m?6, 30?n?60, each x and y is independently from each other 0 or 1, each X and Y is independently from each other any photometrically measurable entity; provided that the terminal X can also be an —OH group or a phosphate group, and further provided that the terminal Y can also be an —OH group. Such a compound can be used as a suitable hot start additive for PCR based amplification of nucleic acids.Type: ApplicationFiled: August 25, 2009Publication date: October 7, 2010Inventors: Waltraud Ankenbauer, Dieter Heindl, Frank Laue, Eva Walter, Renate Kolb
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Publication number: 20100029513Abstract: In some embodiments, the present disclosure provides methods of making a mixture of nucleic acid molecules, the methods comprising the steps of: synthesizing on a substrate a population of nucleic acid molecules wherein each synthesized nucleic acid molecule comprises a substrate-attached proximal nucleic acid molecule, a distal nucleic acid molecule, and a cleavable linker linking the proximal nucleic acid molecule to the distal nucleic acid molecule, and harvesting distal nucleic acid molecules from the substrate by cleaving the cleavable linker under conditions that do not release the proximal nucleic acid molecule. Related compositions and kits are also provided.Type: ApplicationFiled: February 23, 2009Publication date: February 4, 2010Inventors: Joel Myerson, Emily Marine Leproust
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Patent number: 6977245Abstract: D type CpG oligodeoxynucleotides are provided herein that include a sequence represented by the following formula: 5?X1X2X3Pu1 Py2 CpG Pu3 Py4 X4X5X6(W)M(G)N-3? wherein the central CpG motif is unmethylated, Pu is a purine nucleotide, Py is a pyrimidine nucleotide, X and W are any nucleotide, M is any integer from 0 to 10, and N is any integer from 4 to 10. Methods of using these oligodeoxynucleotides to induce an immune response are provided.Type: GrantFiled: February 6, 2002Date of Patent: December 20, 2005Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Dennis Klinman, Daniela Verthelyi, Ken Ishii, James J. Mond, Mayda Gursel
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Patent number: 6812341Abstract: The present invention provides methods and compositions, including kits, for the isolation and purification of mRNA, particularly poly(A) RNA. It concerns the use of isostabilizing salts such as TMAC and TEAC to reduce rRNA carryover during the purification process, thus facilitating the isolation of poly(A) RNA.Type: GrantFiled: May 11, 2001Date of Patent: November 2, 2004Assignee: Ambion, Inc.Inventor: Richard C. Conrad
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Patent number: 6743584Abstract: The invention relates to plasmids derived from pBluescript KS(+), which contains more than 1, preferably 2, 7, 14, 21 and 27, respective SK primer elements, and their use in analytical electron microscopy.Type: GrantFiled: March 1, 2002Date of Patent: June 1, 2004Assignee: Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen RechtsInventors: Sabine Bub, Helmut Troester, Karsten Richter, Ansgar Haking, Stefan Raddatz, Manfred Wiessler, Eberhard Spiess, Michael Trendelenburg
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Patent number: 6730475Abstract: The invention features methods of diagnosing and treating Meniere disease. The invention also features kits and probes for diagnosing Meniere disease.Type: GrantFiled: May 25, 2000Date of Patent: May 4, 2004Assignees: Brigham and Women's Hospital, University of AntwerpInventors: Nahid Robertson, Cynthia Morton, Guy Van Camp, Erik Fransen, Paul Van de Heyning
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Publication number: 20030225261Abstract: Methods, compositions, and kits for separating heteroduplex and homoduplex DNA molecules in a test mixture by temperature-compression denaturing high performance liquid chromatography (tcDHPLC). The method includes use of nitrogen-containing additives in the mobile phase that allow detection of diverse heteroduplex molecules to be performed at the same pre-selected temperature. An example of a preferred additive is betaine. Standard mixtures of DNA fragments, such as mutation standards containing known heteroduplex and homoduplex molecules, can be used to select the concentration of additive and temperature. Compositions and kits including the mobile phase, mutation standards, PCR primers, separation media, and DNA polymerase are also provided.Type: ApplicationFiled: October 7, 2002Publication date: December 4, 2003Applicant: Transgenomic, Inc.Inventors: Paul D. Taylor, Liem T. Nguyen
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Patent number: 6610841Abstract: This invention relates to nucleotide-based prodrugs and their drug-delivery applications. The nucleotide-based prodrugs of the present invention comprise a drug component covalently attached via junctional ester bond(s) to one or more nucleotide components. Release and activation of the drug component of a nucleotide-based prodrug arises from hydrolysis of the junctional ester bond joining the nucleotide component to the drug component. The active drug component may be a nucleoside analog, a nucleic acid ligand, or a non-nucleoside drug. The nucleotide component provides a means of targeting and/or anchoring the nucleotide-based prodrug to the desired tissue compartment and/or a mechanism of sustained release of the active drug, thereby providing for a more effective drug delivery system with reduced toxicity.Type: GrantFiled: December 18, 1997Date of Patent: August 26, 2003Assignee: Gilead Sciences, Inc.Inventor: Stephen Warren
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Patent number: 6545138Abstract: A method for producing a composition including a nucleic-acid-containing complex is characterized in that two single strand nucleic acid polymers which can at least partly form double strands are separately mixed, in a single strand form, with a cationic carrier or with source materials for the cationic carrier before the cationic carrier is formed. The resulting mixture is then dispersed in water during the production process of the nucleic-acid-containing complex.Type: GrantFiled: November 20, 2000Date of Patent: April 8, 2003Assignee: Nippon Shinyaku Co., Ltd.Inventors: Katsuhiro Sugihara, Junzo Seki, Kazuko Hirabayashi
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Patent number: 6538129Abstract: Luminescent compounds, reactive intermediates used to synthesize luminescent compounds, and methods of synthesizing and using luminescent compounds. These compounds may be based on squaric, croconic, and rhodizonic acid, and their analogs, among others, and relate generally to the structure: where Z is a four, five, or six-member aromatic ring, and A, B, C, D, E, and F are substituents of Z, in any order, that may include O, S, Se, Te, C(Ra)(Rb), N—Rc, N(Rd)(Re), W1, and W2. Generally, each compound includes at least one of W1 or W2, where W1 and W2 have the structures: respectively. The compounds may include a reactive group and/or a carrier. The luminescent compounds may be useful in both free and conjugated forms as probes, labels, and/or indicators.Type: GrantFiled: October 6, 2000Date of Patent: March 25, 2003Inventors: Ewald A. Terpetschnig, Leonid D. Patsenker, Bernhard Oswald
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Patent number: 6518052Abstract: The present invention provides a nucleic acid and amino acid sequence of a human Pif-1 type helicase. The invention also provides methods of screening for compounds that modulate the activity of human Pif-1 type helicase, as well as methods for affecting viability of a cell by contacting the cell with a human Pif-1 helicase modulator. Such contacting specifically increases or decreases the specific activity of the human helicase in the cell, and may affect its viability, by affecting telomere length regulatory processes.Type: GrantFiled: October 22, 1999Date of Patent: February 11, 2003Assignee: Bristol-Myers Squibb CompanyInventor: Roberto Weinmann
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Patent number: 6458941Abstract: This invention presents novel methods for recovery of phophoramidites from the waste products of oligonucleotide synthesis. The methods include reacting a tribromophenoxydichlorophosphorane with an H-phosphonate in the presence of an amine.Type: GrantFiled: August 27, 2001Date of Patent: October 1, 2002Assignee: ISIS Pharmaceuticals, Inc.Inventors: Richard H. Griffey, Douglas L. Cole, Vasulinga Ravikumar
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Patent number: 6453244Abstract: The present invention provides a method for detecting polymorphisms in a nucleic acid by preconditioning a sample of nucleic acids to completely denature the nucleic acids, e.g., via heating and/or chemical treatment, and performing high-performance liquid chromatography (HPLC) on the nucleic acid under denaturing conditions to identify any polymorphisms. The nucleic acids to be analyzed are completely denatured prior to application of the sample to a stationary reverse-phase support and throughout the HPLC process. Sample elution is also carried out under completely denaturing conditions, and the sample mixture is eluted with a mobile phase containing an ion-pairing reagent and an organic solvent.Type: GrantFiled: February 10, 2000Date of Patent: September 17, 2002Assignee: Stanford UniversityInventor: Peter J. Oefner
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Publication number: 20020058250Abstract: The invention presented is a novel method for the extraction of VNTR alleles and for the concomitant detection of polymorphic markers for inherited traits at multiple loci by simultaneous comparison of complex genomes from multiple individuals. The product is designated a Total Representation of Alleles that are Informative for a Trait (TRAIT). These alleles may be used directly as genetic markers or may be used as vehicles to facilitate precise localisation of sequence variations responsible.Type: ApplicationFiled: January 18, 2000Publication date: May 16, 2002Applicant: Marshall, Gerstein & BorunInventor: GREG FIRTH
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Patent number: 6316608Abstract: Methods are provide for determining the relative amounts of individual polynucleotides in a complex mixture. The polynucleotides, after fluorescent labeling, are contacted under hybridization conditions with an array having element disposed at discrete locations on a substrate. The elements comprise two or more distinct polynucleotides that are combined prior to arraying. The level of fluorescence associated with each element provides a measure of its relative amount in the mixture.Type: GrantFiled: March 20, 2000Date of Patent: November 13, 2001Assignee: Incyte Genomics, Inc.Inventors: Mark A. Reynolds, Michael Ruvolo, Lyle J. Arnold, Jr.
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Patent number: 6245513Abstract: Methods for detecting the presence or absence of an analyte in a sample are disclosed. Kits for performing the analysis methods of the invention are also disclosed.Type: GrantFiled: April 16, 1999Date of Patent: June 12, 2001Assignee: Tm Technologies, Inc.Inventors: Michael J. Lane, Albert S. Benight, Brian D. Faldasz
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Patent number: 6184369Abstract: The oligonucleotides have sufficient guanosine to form a guanosine tetrad and can be composed of at least about 40% guanosine nucleotides, the nucleotide sequence containing at least two runs of at least two guanosines. Some of the new oligonucleotides also contain phosphorothioate backbones and 3′ end modifications. Representative guanosine-rich oligonucleotides of the present invention demonstrate anti-viral activity in tissue culture against HSV-2, HIV-1, HCMV and FMLV, and show specific inhibition of bacterial RNA polymerase enzymes T7 and T3, the FMLV and HIV-1 reverse transcriptase enzyme and eukaryotic RNA polymerase.Type: GrantFiled: October 23, 1995Date of Patent: February 6, 2001Assignee: Aronex Pharmaceuticals, Inc.Inventors: Robert F. Rando, Susan Fennewald, Joseph G. Zendegui, Joshua O. Oiwana, Michael E. Hogan