Abstract: The invention relates to a 3′-deoxypentopyranosylnucleic acid consisting essentially of 3′-deoxypentopyranosylnucleosides of the formulae (I) or of the formulae (II)
their preparation and use for the production of a therapeutic, diagnostic and/or electronic component.
Type:
Grant
Filed:
April 19, 2001
Date of Patent:
February 24, 2004
Assignee:
Nanogen Recognomics GmbH
Inventors:
Christian Miculka, Thomas Wagner, Norbert Windhab
Abstract: Disclosed are oligonucleotides and oligonucleosides that include one or more modified nucleoside units. The oligonucleotides and oligonucleosides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.
Type:
Application
Filed:
May 23, 2003
Publication date:
January 22, 2004
Inventors:
Anne Eldrup, Phillip Dan Cook, B. Lynne Parshall
Abstract: The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as &agr;-L-oxy-LNA, amino-LNA, &agr;-L-amino-LNA, thio-LNA, &agr;-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues.
Type:
Application
Filed:
May 8, 2003
Publication date:
January 22, 2004
Inventors:
Mads Detlef Sorensen, Jesper Wengel, Troels Koch, Signe M. Christensen, Christoph Rosenbohm, Daniel Sejer Pedersen
Abstract: The present invention provides for the preparation &bgr;-adenine nucleosides by coupling an adenine derivative containing an unprotected exocyclic amino group at the C-6 position and a blocked arabinofuranosyl derivative, in the presence of a base and solvent. The present invention also provides for the stereoselective preparation of 2-deoxy-&bgr;-D-adenine nucleosides wherein a blocked 2-deoxy-&agr;-D-arabinofuranosyl halide is coupled with the salt of an adenine derivative. The forgoing aspects of the present invention are utilized in the preparation of a clofarabine composition wherein the ratio of &bgr; to &agr;-anomer is at least 99:1.
Type:
Grant
Filed:
August 1, 2002
Date of Patent:
January 20, 2004
Assignee:
Ilex Products, Inc.
Inventors:
William E. Bauta, Brian D. Burke, Brian E. Schulmeier, William R. Cantrell, Jr., Dennis P. Lovett, Jose Puente
Abstract: The present invention provides a process for the removal of protecting groups, i.e. deprotection, from chemically synthesized oligonucleotides. In one embodiment, the invention provides reagents suitable for use in such a process, and kits incorporating such reagents in a convenient, ready-to-use format. By use of the process and reagents of the invention, side-reactions leading to certain impurities that contaminate the synthesized oligonucleotides can be minimized.
Methods and reagents are provided for deprotection of an oligonucleotide by reacting a protected oligonucleotide with a deprotection reagent wherein the deprotection reagent comprises an active methylene compound and an amine reagent. The active methylene compound has the structure:
where substituent EWG is an electron-withdrawing group and R is hydrogen, C1-C12 alkyl, C6-C20 aryl, heterocycle or an electron-withdrawing group.
Abstract: The present invention comprises nucleoside derivatives for use in the treatment or prophylaxis of hepatitis C virus infections. In particular, the present invention discloses the novel use of known 2′-deoxy-2′-fluoro nucleoside derivatives as inhibitors of hepatitis C virus (HCV) RNA replication and pharmaceutical compositions of such compounds. The compounds of this invention have potential use as therapeutic agents for the treatment of HCV infections.
Type:
Grant
Filed:
March 26, 2002
Date of Patent:
December 9, 2003
Assignee:
Hoffmann-la Roche Inc.
Inventors:
Rene Robert Devos, Christopher John Hobbs, Wen-Rong Jiang, Joseph Armstrong Martin, John Herbert Merrett, Isabel Najera
Abstract: Silylating reagents having a group other than a divalent oxygen separating two silyl groups provide regioselective protection of reactive groups under robust conditions, such as basic conditions used in alkylation, acylation and deoxygenation. In particular, silylating reagents having a group other than oxygen separating two silyl groups are useful for protecting two hydroxy groups of a ribonucleic or deoxyribonucleic acid. Alkylation of a 2′-hydroxy group of a ribonucleoside protected with the inventive silylating agents in the presence of an excess of a mild hindered base such as sodium HMDS may be carried out without protecting the exocyclic amine and oxo functionalities of nucleobases.
Type:
Application
Filed:
April 11, 2002
Publication date:
December 4, 2003
Inventors:
Yogesh S. Sanghvi, Emmanuel A. Theodorakis, Ke Wen
Abstract: There can be provided an excellent industrial process for producing compounds having sugar-moiety hydroxyl groups or halogen atoms reduced in nucleic acids or in derivatives thereof by allowing O-thiocarbonyl derivatives of sugar-moiety hydroxyl groups or allowing halogenated derivatives in the sugar-moiety, in the nucleic acids or in derivatives thereof to react with any one of hypophosphorous acids (including salts thereof) and phosphites (esters) which are inexpensive, non-toxic and safely usable as radical reducing agents in industrial scale, in the presence of a radical reaction initiator.
Abstract: There are disclosed novel Stavudine solvates as follows: Stavudine NN-dimethyllacetamide solvates; Stavudine NN-dimethylacrylamide solvates and Stavudine NN-dimethylpropionamide solvates and processes for producing Stavudine NN-dimethylacetamide solvates, Stavudine NN dimethylacrylamide solvates and Stavudine NN dimethylpropionamide solvates which results in pure Stavudine.
Abstract: Modified dimers having a ribose sugar moiety in the 5′ nucleoside and a 2′ modified sugar in the 3′ nucleoside are provided. The modified dimers are useful in the preparation of oligonucleotide analogs having enhanced properties compared to native oligonucleotides, including increased nuclease resistance, enhanced binding affinity and improved protein binding.
Type:
Application
Filed:
July 15, 2002
Publication date:
September 25, 2003
Inventors:
Phillip Dan Cook, Muthiah Manoharan, Balkrishen Bhat
Abstract: Methods for the regioselective alkylation at the 2′-hydroxy position over the 3′-hydroxy position of nucleosides and nucleoside analogs, forming 2′-O-ester modified compounds, are disclosed. Reduction and derivatization of the 2′-O-ester provides 2′-O-modified nucleosides and nucleoside analogs useful for the synthesis of oligomeric compounds having improved hybridization affinity and nuclease resistance.
Type:
Grant
Filed:
April 16, 2002
Date of Patent:
September 23, 2003
Assignee:
ISIS Pharmaceuticals, Inc.
Inventors:
Andrew M. Kawasaki, Allister S. Fraser, Muthiah Manoharan, P. Dan Cook, Thazha P. Prakash
Abstract: L-nucleosides are conformationally constrained by at least one additional ring formed by a bridge connecting at least two atoms within a sugar moiety of the nucleoside. While a single additional ring is formed by bridging C1-C4 atoms, two additional rings are formed by bridging both C1-C2, and C3-C4 atoms, or C1-C3 and C2-C4 atoms by bridges having the general structure A—B—Z. The conformationally constrained nucleosides may be incorporated into oligonucleotides and dinucleotides, and it is contemplated that compositions including the conformationally constrained nucleosides may have superior viral inhibitory or antineoplastic properties.
Abstract: The present invention relates to the use of self-assembled monolayers with mixtures of conductive oligomers and insulators to detect target analytes.
Abstract: The present invention relates to a method for identification of enzymes that are preferentially expressed in certain tumor tissue as compared with rapidly growing normal cells or tissue, use of said enzymes for the compound design to generate an active anti-cancer substance selectively in tumor tissue, compounds designed based on said enzymes, their pharmaceutically acceptable salts as well as pharmaceutical composition thereof.
Abstract: A process for the preparation of 5′-deoxy-5-fluorouridine, which comprises the transformation of 2′,3′-O-isopropylidene-5-fluorouridine in the corresponding 5′-O-sulfonyl derivative, subsequent reaction with alkaline or earth-alkaline iodides and, after hydrolysis of the isopropylidene group, reduction of the 5′-deoxy-5′-iodo-5-fluorouridine thus obtained, is described.
Type:
Grant
Filed:
April 19, 2002
Date of Patent:
July 15, 2003
Assignee:
Clariant Finance (BVI) Limited
Inventors:
Giovanni Cotticelli, Giuseppe De Meglio, Simone Monciardini, Giancarlo Ordanini
Abstract: There can be provided an excellent industrial process for producing compounds having sugar-moiety hydroxyl groups or halogen atoms reduced in nucleic acids or in derivatives thereof by allowing O-thiocarbonyl derivatives of sugar-moiety hydroxyl groups or allowing halogenated derivatives in the sugar-moiety, in the nucleic acids or in derivatives thereof to react with any one of hypophosphorous acids (including salts thereof) and phosphites (esters) which are inexpensive, non-toxic and safely usable as radical reducing agents in industrial scale, in the presence of a radical reaction initiator.
The process of the present invention is an industrially useful and highly safe process for reducing sugar-moiety hydroxyl groups and halogen atoms in nucleic acids or derivatives thereof (including nucleic acid-related compounds) at low costs.
Abstract: Compounds of formula RS—P(═O)(QR)—Nu where: R is a radical —(CH2)n—W—X; X is a radical —C(═Z)(Y) or —S—U; Z is O or S; W is O or S; Q is O or S; Y and U are an alkyl, aryl or saccharide radical which is optionally substituted with, for example, an OH, SH or NH group; n is equal to 1 to 4, preferably 1 or 2; and Nu is a radical consisting of a residue of a biologically active compound or the dephosphorylated residue of a compound which is biologically active when it bears a phosphate or phosphonate group.
Type:
Grant
Filed:
September 21, 2001
Date of Patent:
April 29, 2003
Assignee:
Centre National de la Recherche Scientifique
Inventors:
Gilles Gosselin, Jean-Louis Imbach, Christian Perigaud
Abstract: Methods for the regioselective alkylation at the 2′-hydroxy position over the 3′-hydroxy position of nucleosides and nucleoside analogs, forming 2′-O-ester modified compounds, are disclosed. Reduction and derivatization of the 2′-O-ester provides 2′-O-modified nucleosides and nucleoside analogs useful for the synthesis of oligomeric compounds having improved hybridization affinity and nuclease resistance.
Type:
Application
Filed:
April 16, 2002
Publication date:
April 24, 2003
Inventors:
Andrew M. Kawasaki, Allister S. Fraser, Muthiah Manoharan, P. Dan Cook, Thazha P. Prakash
Abstract: Sugar-modified SIN-1 compositions are provided. The compositions are useful for generating NO in response to hydrolytic activity of a glycosidase specific for the O-glycosidic bond between the sugar and SIN-1 moieties. Pharmaceutical compositions containing the sugar-modified SIN-1 compositions and methods of using the compositions are also provided.
Type:
Application
Filed:
August 9, 2001
Publication date:
March 13, 2003
Inventors:
Peng George Wang, Xuejun Wu, Xiaoping Tang
Abstract: Oligomers which have substituents on the 2′ position are resistant to oligonucleases and furthermore can be derivatized to deliver reagents or drugs, to carry label, or to provide other properties.
Abstract: Novel agents acting as co-factors for replacement of NAD(P)+/NAD(P)H co-enzyme systems in enzymatic oxido-reductive reactions. Agents mimicking the action of NAD(P)+/NAD(P)H system in enzymatic oxidation/reduction of substrates into reduced or oxidized products. A method for selection and preparation of the mimicking agents for replacement of NAD(P)+/NAD(P)H system and a device comprising co-factors for replacement of NAD(P)+/NAD(P)H system.
Type:
Application
Filed:
March 12, 2001
Publication date:
January 30, 2003
Inventors:
Richard H. Fish, John B. Kerr, Christine H. Lo
Abstract: The present invention relates to a novel and improved process for preparing 2′-fluoro-5-methyl-&bgr;-L-arabinofuranosyluridine represented by formula (I) which shows anti-viral activity, especially potent anti-viral activity against hepatitis B-virus and Epstein-Barr virus:
Type:
Grant
Filed:
July 23, 1998
Date of Patent:
January 28, 2003
Assignee:
The University of Georgia Research Foundation
Abstract: Certain known and novel pyruvate derivatives are particularly active in restoring or preserving metabolic integrity in oxidatively competent cells that have been subjected to oxygen deprivation. These pyruvate-derived compounds include, but are not limited to oximes, amides, pyruvate analogues, modified pyruvate analogues, esters of pyruvate (e.g., polyol-pyruvate esters, pyruvate thioesters, glycerol-pyruvate esters and dihydroxyacetone-pyruvate esters). Such pyruvate derivatives (including single tautomers, single stereoisomers and mixtures of tautomers and/or stereoisomers, and the pharmaceutically acceptable salts thereof) are useful in the manufacture of pharmaceutical compositions for treating a number of conditions characterized by oxidative stress.
Type:
Application
Filed:
May 3, 2002
Publication date:
January 16, 2003
Inventors:
Bing Wang, Guy Miller, Satyanarayana Janagani, Wei Zhang
Abstract: Propargylethoxyamino nucleosides are disclosed having the structure
wherein R1 and R2 are —H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is —H or —OH; W2 is —OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3′-position; and W3 is
—PO4, —P2O7, —P3O10, phosphate analog, or —OH. Additionally, a primer extension method is provided employing the above propargylethoxyamino nucleosides.
Type:
Grant
Filed:
June 14, 2001
Date of Patent:
January 7, 2003
Assignee:
PE Corporation (NY)
Inventors:
Shaheer H. Khan, Steven M. Menchen, Barnett B. Rosenblum
Abstract: Oligomers which have substituents on the 2′ position are resistant to oligonucleases and furthermore can be derivatized to deliver reagents or drugs, to carry label, or to provide other properties.
Abstract: The present invention relates to isotopically enriched nucleic acids and methods for their production and purification. The invention further relates to methods for the use of said nucleic acids in analysis with mass spectrometry. Use of isotopically enriched nucleic acids in creating second generation products is also provided.
Abstract: The present invention provides 2-aminopyridine and 2-pyridone C-nucleosides and oligonucleotides containing the subject nucleosides. The nucleosides are useful in the preparation of the subject oligonucleotides. The oligonucleotides are useful in oligonucleotide-based diagnosis and separation through triplex binding.
Type:
Grant
Filed:
August 5, 1997
Date of Patent:
September 10, 2002
Assignee:
Isis Pharmaceuticals, Inc.
Inventors:
Brian C. Froehler, Arnold J. Gutierrez, Mark D. Matteucci
Abstract: Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule.
Abstract: The invention concerns compounds of the general formula (I) in which the residues R1 to R7 have the meanings given in the application as well as methods for their preparation. The compounds are in particular suitable as substrates for RNA or DNA polymerases and can thus be incorporated into RNA or DNA oligonucleotides and are especially suitable for labelling and detecting nucleic acids or for DNA sequencing.
Abstract: Methods for the regioselective alkylation at the 2′-hydroxy position over the 3′-hydroxy position of nucleosides and nucleoside analogs, forming 2′-O-ester modified compounds, are disclosed. Reduction and derivatization of the 2′-O-ester provides 2′-O-modified nucleosides and nucleoside analogs useful for the synthesis of oligomeric compounds having improved hybridization affinity and nuclease resistance.
Type:
Grant
Filed:
January 8, 1999
Date of Patent:
June 11, 2002
Assignee:
ISIS Pharmaceuticals, Inc.
Inventors:
Andrew M. Kawasaki, Allister S. Fraser, Muthiah Manoharan, P. Dan Cook, Thazha P. Prakash
Abstract: The present invention is directed to polymeric-prodrug transport forms of the formula:
wherein:
G is a linear or branched, terminally functionalized polymer residue;
Y1 is O, S, or NR1;
M is X or Q;
wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(═Y1);
R1-5 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls;
R6 is OR7 or N3, NH2, NO2 or CN, where R7 is selected from the same group which defines R1-5;
R8-9 are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, iodo, or R6; and
a and n are each independently zero or a positive integer.
Abstract: The subject invention concerns materials and methods usefull in the control of non-mammalian pests and, particularly, plant pests. In a specific embodiment, the subject invention provides new Bacillus thuringiensis toxins usefull for the control of lepidopterans. The subject invention further provides nucleotide sequences which encode the toxins of the subject invention. The nucleotide sequences of the subject invention can be used to transform hosts, such as plants, to express the pesticidal toxins of the subject invention. The subject invention further concerns novel nucleotide primers for the identification of genes encoding toxins active against pests. The primers are useful in PCR techniques to produce gene fragments which are characteristic of genes encoding these toxins. The primers are also usefull as nucleotide probes to detect the toxin-encoding genes.
Type:
Grant
Filed:
December 31, 1997
Date of Patent:
April 9, 2002
Assignee:
Mycogen Corporation
Inventors:
H. Ernest Schnepf, Carol Wicker, Kenneth E. Narva, Michele Walz, Brian A. Stockhoff, Judy Muller-Cohn
Abstract: The present invention pertains to novel inhibitors of DNA glycosylases. The invention is based at least in part on the observation that specific substituted pyrrolidines, and analogs thereof, are capable of specifically inhibiting DNA glycosylases, e.g., as transition state analogs, and consequently are useful for modulation of DNA repair. Such compounds can, for example, be used for treating subjects having a disorder associated with excessive cell proliferation, such as in the treatment of various cancers. Furthermore, these glycosylase inhibitors can be used as anti-bacterial, anti-viral and anti-fungal agents.
Type:
Grant
Filed:
March 7, 1997
Date of Patent:
April 9, 2002
Assignee:
President and Fellows of Harvard College
Abstract: A method of increasing efficiency and/or decreasing the cytotoxic effect of a human immunodeficiency virus (HIV) reproduction-suppressing drug such as Azidothimidin (AZT) involves administering the drug to an HIV-positive patient and subjecting the patient to hyperbaric oxygenation (HBO).
Type:
Application
Filed:
May 3, 1999
Publication date:
February 14, 2002
Inventors:
VLADIMIR ILICH PAKHOMOV, EDUARD VLADIMIROVICH KARAMOV, ALEXANDR EVGENEVICH SOKOLOV, GALINA VLADIMIROVNA KORNILAEVA, MIKHAIL YUREVICH SHTSHELKANOV, VLADIMIR NIKOLAEVICH KOSTYUNIN
Abstract: Tetrahydrofuranyl compounds are provided that are functionalized to include pendant conjugate groups, and which are useful in diagnosis assays and as research reagents. Novel intermediates for the synthesis of the compounds are also provided.
Abstract: The invention relates to compositions comprising acyl derivatives of 2′-deoxyribonucleosides. The invention also relates to methods of treating or preventing radiation, mutagen and sunlight-induced biological damage, and methods for improving wound healing and tissue repair, comprising administering the compositions of the present invention to an animal.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
October 2, 2001
Assignee:
Pro-Neuron, Inc.
Inventors:
Reid Warren von Borstel, Michael Kevin Bamat
Abstract: Disclosed are 3′-deoxyribonucleotide derivatives represented by the following general formula [I]:
Q—V—(CH2)n—NH—R [I]
wherein Q represents a 3′-deoxyribonucleotide residue, n represents an integer not less than 4, V represents —C≡C— or —CH═CH—, and R represents a fluorescent group.
The above 3′-deoxyribonucleotide derivatives are derivatives with improved rates for incorporation using RNA polymerases, which are useful as terminators in the DNA sequence determination methods utilizing RNA polymerases.
Type:
Grant
Filed:
March 5, 1999
Date of Patent:
July 24, 2001
Assignee:
The Institute of Physical and Chemical Research
Abstract: Novel nucleoside analogs, such as 3-(&bgr;-D-Ribofuranosyl)-2-fluoropyridine, 3-(&bgr;-D-Ribofuranosyl)-pyridin-2-one, 3-(&bgr;-D-Ribofuranosyl)-pyridin-2-(4-nitrophenylethyl)-one, 3-(&agr;-D-Ribofuranosyl)-2-fluoropyridine, 5-(&bgr;-D-Ribofuranosyl)-2-bromopyridine, 5-(&agr;-D-Ribofuranosyl)-2-bromopyridine, 5-(&bgr;-D-Ribofuranosyl)-pyridin-2-one, 5-(&agr;-D-Ribofuranosyl)-pyridin-2-one, 5-(&bgr;-D-Ribofuranosyl)-2-aminopyridine, 5-(&bgr;-D-Ribofuranosyl)-pyridin-2-(4-nitrophenylethyl)-one, and 5-(&agr;-D-Ribofuranosyl)-2-aminopyridine; process for their synthesis and incorporation into polynucleotides.
Type:
Grant
Filed:
November 21, 1997
Date of Patent:
June 19, 2001
Assignee:
Ribozyme Pharmaceuticals, Inc.
Inventors:
Jasenka Matulic-Adamic, Leonid Beigelman, Alexander Karpeisky
Abstract: Nucleic acid ligands containing modified nucleotides are described as are methods for producing such oligonucleotides. Such ligands enrich the chemical diversity of the candidate mixture for the SELEX process. Specific examples are provided of nucleic acids containing nucleotides modified at the 2′- and 5-position. Specific 2-OH and 2′-NH2 modified RNA ligands to thrombin are described.
Type:
Grant
Filed:
September 27, 1999
Date of Patent:
February 6, 2001
Assignee:
NeXstar Pharmaceuticals, Inc.
Inventors:
Wolfgang Pieken, Diane Tasset, Nebojsa Janjic, Larry Gold, Gary P Kirschenheuter
Abstract: The invention concerns pyrrolo-[3,2-d]pyrimidine, pyrazolo-[4,3-d]pyrimidine and pyrimidine-furanosides i.e. so-called C-nucleosides of the general formulae I-V
or appropriate derivatives as well as processes for their production. The compounds are in particular suitable as substrates for RNA or DNA polymerases and can thus be incorporated into RNA or DNA oligonucleotides. Therefore the compounds are especially suitable for labelling and for detecting nucleic acids and for DNA sequencing.
Type:
Grant
Filed:
September 15, 1997
Date of Patent:
January 16, 2001
Assignee:
Roche Diagnostics GmbH
Inventors:
Klaus M{umlaut over (u)}hlegger, Herbert Von der Eltz, Frank Seela, Helmet Rosemeyer