Triphosphates (in Same Chain) Patents (Class 536/26.26)
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Patent number: 7371852Abstract: Alkyl-linked nucleotide non-homogeneous solid supports and nucleotide affinity media comprising an alkyl-linked nucleotide are provided. The linker is generally a hydrophobic linker that can be a 3, 4, 5, 6, 7, 8, 9, 10, or a longer carbon chain. Also included in the invention are methods for synthesis of an alkyl-linked nucleotide, nucleotide affinity media and methods of use thereof for affinity chromatography and screening methods.Type: GrantFiled: January 21, 2004Date of Patent: May 13, 2008Assignee: Serenex, Inc.Inventors: Klass P. Hardeman, Steven E. Hall, Roy W. Ware, Lindsay A. Hinkley, Matthew G. Jenks
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Patent number: 7368439Abstract: The present invention provides dinucleoside boranophosphate derivatives of the general formula I: wherein X and X? each independently is an unsubstituted or substituted purine or pyrimidine residue; Y and Y? each independently is H or OH; Z1 to Z5 each independently is O? or BH3?, but excluding the compounds wherein Z1 to Z5 are each O?; W1 to W4 each independently is O, CH2, NH or C(Halogen)2; n and n? each independently is 0 or 1; m is 3, 4 or 5; and M+ represents a pharmaceutically acceptable cation, and to pharmaceutical compositions thereof. These dinucleoside boranophosphates are useful for prevention or treatment of diseases or disorders modulated by P2Y receptors such as type 2 diabetes, cystic fibrosis and cancer.Type: GrantFiled: June 14, 2006Date of Patent: May 6, 2008Assignee: BAR - ILAN UniversityInventors: Bilha Fischer, Victoria Nahum
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Patent number: 7348315Abstract: Disclosed herein are methods of using an adenosine analog or derivative for treating heart failure, increasing cardiac muscle contractility, increasing cardiac diastolic relaxation, and increasing vasodilation.Type: GrantFiled: March 25, 2003Date of Patent: March 25, 2008Assignee: The University of ConnecticutInventors: Bruce T Liang, Kenneth A Jacobson
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Patent number: 7319093Abstract: 2-Substituted-5?-O-(1-boranotriphosphate)adenosine derivatives having at position 2 a radical R1 selected from the group consisting of H; halogen; O-hydrocarbyl; S-hydrocarbyl; NR3R4; and hydrocarbyl optionally substituted by halogen, CN, SCN, NO2, OR3, SR3 or NR3R4; wherein R3 and R4 are each independently H or hydrocarbyl or R3 and R4 together with the nitrogen atom to which they are attached form a saturated or unsaturated heterocyclic ring optionally containing 1-2 further heteroatoms selected from oxygen, nitrogen and sulfur, and pharmaceutically acceptable salts or diastereoisomers thereof or a mixture of diastereoisomers, are useful for treatment of type 2 diabetes.Type: GrantFiled: October 23, 2002Date of Patent: January 15, 2008Assignees: Bar-Ilan University, University of MontpellierInventors: Bilha Fischer, Victoria Kleiman-Nahum, Pierre Petit
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Patent number: 7285658Abstract: The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.Type: GrantFiled: February 28, 2003Date of Patent: October 23, 2007Assignee: Biota, Inc.Inventors: Phillip D. Cook, Guangyi Wang, Thomas W. Bruice, Nicholas A. Boyle, Janet M. Leeds, Jennifer L. Brooks, Marija Prhavc, Maria Eugenia Ariza, Patrick C. Fagan, Yi Jin, Vivek K. Rajwanshi, Kathleen D. Tucker
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Patent number: 7244713Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula I as follows: wherein, T, Y, W, W1 and W2 are as defined herein.Type: GrantFiled: October 21, 2004Date of Patent: July 17, 2007Assignee: Genelabs Technologies, Inc.Inventors: Christopher D. Roberts, Jesse D. Keicher, Natalia B. Dyatkina
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Patent number: 7202223Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula I as follows: wherein, each of R, Y, W, W1 and W2 are as defined herein.Type: GrantFiled: June 4, 2004Date of Patent: April 10, 2007Assignee: Genelabs Technologies, Inc.Inventors: Christopher D. Roberts, Jesse D. Keicher
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Patent number: 7173125Abstract: Hydrazino, oxyamino and carbonyl-based monomers and methods for incorporation into oligonucleotides during enzymatic synthesis are provided. Modified oligonucleotides are provided that incorporate the monomers provided herein. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.Type: GrantFiled: November 24, 2003Date of Patent: February 6, 2007Inventors: David A. Schwartz, Richard I. Hogrefe
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Patent number: 7157434Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula I as follows: wherein, Y, W, W1 and W2 are as defined herein.Type: GrantFiled: October 20, 2004Date of Patent: January 2, 2007Assignee: Genelabs Technologies, Inc.Inventors: Jesse D. Keicher, Christopher D. Roberts, Natalia B. Dyatkina
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Patent number: 7151089Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula I as follows: wherein, R, Y, W, W1 and W2 are as defined herein.Type: GrantFiled: June 4, 2004Date of Patent: December 19, 2006Assignee: Genelabs Technologies, Inc.Inventors: Christopher D. Roberts, Jesse D. Keicher
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Patent number: 7144868Abstract: Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula I as follows: wherein, each of R, Y, W, W1 and W2 is as defined herein.Type: GrantFiled: June 4, 2004Date of Patent: December 5, 2006Assignee: Genelabs Technologies, Inc.Inventors: Christopher D. Roberts, Jesse D. Keicher
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Patent number: 7115585Abstract: The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides.Type: GrantFiled: February 27, 2002Date of Patent: October 3, 2006Assignee: Inspire Pharmaceuticals, Inc.Inventors: Benjamin R. Yerxa, James G. Douglass, III, Sammy Ray Shaver, Ward M. Peterson, Edward G. Brown, Christopher S. Crean
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Patent number: 7094768Abstract: Disclosed are 6-hydroxyamino- or a 6-alkoxyamino-7-deazapurine-ribofuranose derivatives, salts, pharmaceutical compositions, and methods of use thereof for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus.Type: GrantFiled: April 8, 2004Date of Patent: August 22, 2006Assignee: Genelabs Technologies, Inc.Inventors: Christopher D. Roberts, Jesse Keicher, Natalia B. Dyatkina
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Patent number: 7045617Abstract: Protein kinase inhibitors have applications as anti-cancer therapeutic agents and biological tools in cell signalling. Potent and selective bisubstrate inhibitors for the insulin receptor tyrosine kinase are based on a phosphoryl transfer mechanism involving a dissociative transition state. One such inhibitor is synthesized by linking ATP?S to a peptide substrate analog via a two-carbon spacer. The compound is a high-affinity competitive inhibitor against both nucleotide and peptide substrate and shows a slow off-rate. A crystal structure of this inhibitor bound to the tyrosine kinase domain of the insulin receptor confirms the key design features inspired by a dissociative transition state, and reveal that the linker takes part in the octahedral coordination of an active site Mg2+ ion.Type: GrantFiled: March 21, 2001Date of Patent: May 16, 2006Assignees: Mount Sinai School of Medicine, Johns Hopkins UniversityInventors: Philip A. Cole, Keykavous Parang, Ararat Abloogu, Ronald A. Kohanski, Aliya Courtney
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Patent number: 7018985Abstract: The present invention provides novel compounds of dinucleotide polyphosphates and the method of preventing or treating diseases or conditions associated with platelet aggregation. The method comprises administering systemically to a patient a pharmaceutical comprising a purinergic P2? receptor antagonist, in an amount effective to elevate its extracellular concentration to bind to P2? receptors and inhibit P2? receptor-mediated platelet aggregation. Methods of systemic administration include injection by intravenous, intramuscular, intrasternal and intravitreal routes, infusion, transdermal administration, oral administration, rectal administration and intra-operative instillation.Type: GrantFiled: August 21, 2000Date of Patent: March 28, 2006Assignees: Inspire Pharmaceuticals, Inc., University of North Carolina at Chapel HillInventors: José L. Boyer, Gillian M. Olins, Benjamin R. Yerxa, James G. Douglass, III
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Patent number: 6960568Abstract: The invention provides novel nucleosides and related processes, pharmaceutical compositions, and methods. The novel nucleosides are useful in a wide variety of antiviral, antineoplastic, and antibacterial applications. Preferred embodiments of the instant invention include novel 2 halogen-substituted, 3 halogen-substituted, and 2?,3?dihalogen-substituted analogues of 3-deazaadenosine, and novel 3 halogen-substituted analogues of 3-deazaguanosine. Compounds of the instant invention, including 4-Amino-6-fluoro-1-(?-D-ribofuranosyl)imidazo[4,5-c]pyridine and 6-Amino-7-bromo-1,5-dihydro-1-?-D-ribofuranosylimidazo[4,5-c]pyridin-4-one, have exhibited potent antiviral and anticancer activity in vitro. The compounds are also useful in the concomitant treatment of bacterial infections associated with viral infections such as AIDS.Type: GrantFiled: December 17, 2002Date of Patent: November 1, 2005Assignee: Yale UniversityInventors: Alan C. Sartorelli, Yung-Chi Cheng, Mao-Chin Liu
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Patent number: 6924271Abstract: The invention is directed to 3-?-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.Type: GrantFiled: November 27, 2002Date of Patent: August 2, 2005Assignee: Anadys Pharmaceuticals, Inc.Inventors: Devron R. Averett, Stephen E. Webber, Joseph R. Lennox, Erik J. Rueden
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Patent number: 6911540Abstract: 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.Type: GrantFiled: June 27, 2002Date of Patent: June 28, 2005Assignee: ISIS Pharmaceuticals, Inc.Inventors: Chris A. Buhr, Mark Matteucci
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Patent number: 6897201Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a nucleoside 5?-pyrophosphate pyranoside or analogue, which is defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as found in glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with another therapeutic agent or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure. The present invention also provides a novel composition comprising a nucleoside 5?-pyrophosphate pyranoside or analogues.Type: GrantFiled: February 27, 2002Date of Patent: May 24, 2005Assignee: Inspire Pharmaceuticals, Inc.Inventors: Jose L. Boyer, Benjamin R. Yerxa, Robert Plourde, Jr., Edward G. Brown
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Patent number: 6875859Abstract: 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.Type: GrantFiled: March 11, 2002Date of Patent: April 5, 2005Assignee: Roche Diagnostics GmbHInventors: Klaus Mühlegger, Herbert Von Der Eltz
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Patent number: 6783957Abstract: The method of polypeptide synthesis in eukaryotic or porkaryotic cell-free systems based on a modified verion of synthesis in the continuous flow or continuous exchange modes when, in addition to input into the reaction mixture of components maintaining the synthesis and removal from the reaction mixture of low molecular weight components inhibiting the synthesis, the concentration of at least one of the components selected from the group consisting of Mg2+, K+, NTP, polyamines or their combinations determining the productivity of the synthesis is continuously changed within the given range of concentrations, while the concentrations of the other components are maintained constant.Type: GrantFiled: January 21, 2003Date of Patent: August 31, 2004Assignees: Roche Diagnostics GmbH, Institute of Protein ResearchInventors: Sergey Vladimirovich Biryukov, Peter Nikolaevich Simonenko, Vladimir Anatolievich Shirokov, Alexander Sergeyevich Spirin
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Patent number: 6777395Abstract: The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.Type: GrantFiled: January 18, 2002Date of Patent: August 17, 2004Assignees: Merck & Co., Inc., Isis Pharmaceuticals, Inc.Inventors: Balkrishen Bhat, Neelima Bhat, Anne B. Eldrup, Thazha P. Prakash, Marija Prhavc, Quanlai Song, Phillip Dan Cook, Steven S. Carroll, Malcolm Maccoss, David B. Olsen
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Publication number: 20040122223Abstract: Nucleotide derivatives of formula (1) are described: wherein: G is a hydrogen atom or an optionally substituted aliphatic, heteroaliphatic, cycloaliphatic, polycycloaliphatic, aromatic or heteroaromatic group or a non-natural nucleoside as defined herein; G′ is a non-natural necleoside as defined herein; n is zero, or the integer 1 or 2; m is zero or the integer 1 or 2; and the salts, solvates, hydrates and N-oxides thereof. The compounds are P2Y receptor agonists and are of use in the prophylaxis and treatment of diseases and disorders involving abnormal secretory mechanisms such as inadequate functioning of mucociliary clearance mechanisms or abnormal tear secretion or in the treatment of diseases involving inappropriate cellular glucose uptake.Type: ApplicationFiled: January 15, 2004Publication date: June 24, 2004Inventors: Jeremy Martin Davis, Stephen Robert Mack, Verity Margaret Sabin, Richard John Davenport
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Patent number: 6723737Abstract: The invention discloses methods for the chronic administration of adenosine, which contrary to the acute delivery of the drug by injection or infusion, acts in desensitizing adenosine receptors towards the action of adenosine. The methods and oral compositions of adenosine triphosphate (ATP), which is degraded to adenosine in vivo, can be used in the treatment of disorders and diseases that are therapeutically targeted by agonists or antagonists of adenosine receptors. One example is the stimulation of lipolysis in achieving weight loss in humans and in the treatment of obesity.Type: GrantFiled: April 22, 2002Date of Patent: April 20, 2004Inventor: Eliezer Rapaport
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Patent number: 6686461Abstract: Hydrazino, oxyamino and carbonyl-based monomers and methods for incorporation into oligonucleotides during enzymatic synthesis are provided. Modified oligonucleotides are provided that incorporate the monomers provided herein. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.Type: GrantFiled: August 1, 2000Date of Patent: February 3, 2004Assignee: Solulink Bioscience, Inc.Inventors: David A. Schwartz, Richard I. Hogrefe
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Patent number: 6680303Abstract: A method and composition for the treatment of HIV and HBV infections in humans and other host animals is disclosed that includes the administration of an effective amount of a [5-carboxamido or 5-fluoro]-2′,3′-dideoxy-2′,3′-didehydro-pyrimidine nucleoside or a [5-carboxamido or 5-fluoro]-3′-modified-pyrimidine nucleoside, or a mixture or a pharmaceutically acceptable derivative thereof, including a 5′ or N4 alkylated or acrylated derivative, or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.Type: GrantFiled: May 15, 2002Date of Patent: January 20, 2004Assignee: Emory UniversityInventors: Raymond F. Schinazi, Dennis C. Liotta
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Patent number: 6677310Abstract: The present invention relates to compositions comprising analogues of purine nucleosides containing a ring-expanded (“fat”) heterocyclic ring, in place of purine, and an unmodified or modified sugar residue, pharmaceutically acceptable derivatives of such compositions, as well as methods of use thereof. In particular, these compositions may be utilized in the treatment of certain cancers, bacterial, fungal, parasitic, and viral infections, including, but not limited to, Acquired Immunodeficiency Syndrome (AIDS), hepatitis, Epstein-Barr and cytomegalovirus.Type: GrantFiled: April 21, 1999Date of Patent: January 13, 2004Assignees: Nabi, University of Maryland Baltimore CountyInventors: Ramachandra S. Hosmane, Ramesh K. Sood
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Patent number: 6642373Abstract: The present invention relates to improved methods for the preparation of nucleoside phosphoramidites and oligonucleotides. In one aspect, the methods of the invention are used to prepare phosphitylating reagents using pyridinium salts as activators. In a further aspect, the methods of the invention are used to prepare internucleoside linkages using activators which include at least one pyridinium salt and at least one substituted imidazole. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having 2′-substituents using imidazolium or benzimidazolium salts as an activator. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having bioreversible protecting group that confers enhanced chemical and biophysical properties, without exocyclic amine protection, using imidazolium or benzimidazolium salts as an activator.Type: GrantFiled: December 12, 2002Date of Patent: November 4, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthia Manoharan, Vasulinga T. Ravikumar
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Patent number: 6613926Abstract: Novel compounds are provided in the form of nucleoside pyrophosphate and triphosphate analogs. In these analogs, the pyrophosphate or triphosphate group is replaced with a moiety that is isosterically and electronically identical thereto, but is hydrolytically and enzymatically more stable. The compounds are useful as therapeutic agents, e.g., as antiviral agents, anticancer agents, metabolic moderators and the like. The invention also provides pharmaceutical compositions containing a compound of the invention as an active agent, and in addition provides methods of treating disease, including viral infections, cancer, bacterial infections, inflammatory and/or autoimmune diseases, and the like, by administering a compound of the invention to a patient in need of such treatment.Type: GrantFiled: November 1, 2000Date of Patent: September 2, 2003Assignee: SRI InternationalInventors: Jeffrey C. Bottaro, Robert J. Schmitt, Mark A. Petrie, Paul E. Penwell
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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: 6600028Abstract: Nucleoside analogues have structure (2) wherein Q is H or a sugar moiety or sugar analogue or a modified sugar or a nucleic backbone or backbone analogue, W is an alkylene or alkenylene chain of 0-5 carbon atoms, any of which may carry a substituent R8, X is O or N or NR12 or CR10, X′ is O or S or N, provided that when X′ is O or S, then X is C, Y is CH or N, R6 is NH2 or SMe or SO2Me or NHNH2, each of R7 and R8 is independently H or F or alkyl or alkenyl or aryl or acyl or a reporter moiety, R12 is independently H or alkyl or alkenyl or aryl or acyl or a reporter moiety, and R10 is H or ═O or F or alkyl or aryl or a reporter moiety.Type: GrantFiled: February 1, 2000Date of Patent: July 29, 2003Assignee: Amersham Pharmacia Biotech UK LimitedInventors: Daniel Brown, David Loakes, David Williams, Fergal Hill, Shiv Kumar, Satyam Nampalli, Mark McDougall, Alan Hamilton, Clifford Smith, Adrian Christopher Simmonds, William Jonathan Cummins, Patrick Finn
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Patent number: 6600026Abstract: The present invention relates to the use of self-assembled monolayers with mixtures of conductive oligomers and insulators to detect target analytes.Type: GrantFiled: May 6, 1999Date of Patent: July 29, 2003Assignee: Clinical Micro Sensors, Inc.Inventor: Changjun Yu
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Patent number: 6573374Abstract: Nucleoside-5′-triphosphates and phosphoramidites which carry a residue absorbing in the long wavelength region, preferably a carbocyanine group of the general formula (I), on the base portion or on the phosphorus atom in which R1 and R2 each denote hydrogen or together form a phenyl residue; R3 denotes hydrogen if linkage with the nucleotide is via the R4 position or it denotes a —NHCS— group if linkage with the nucleotide is via the R3 position; both R4 and R5, or R5, alone denote an alkylsulfonyl group with n being a number from 3 to 5 or R4 represents a —NHCS— group with n being a number from 3 to 8, as well as the use of the compounds to label, detect and sequence nucleic acids.Type: GrantFiled: March 28, 1995Date of Patent: June 3, 2003Assignee: Boehringer Mannheim GmbHInventors: Klaus Muehlegger, Hans-Joachim Hoeltke, Christian Birkner, Herbert Von Der Eltz
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Publication number: 20030050454Abstract: oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at the 2′ and 5′ positions. Monomeric sub-units having these modifications may be further modified at the 2′ position. Improved processes for the synthesis of 2′-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2′-anhydropyrimidine nucleoside or a 2S,2′-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.Type: ApplicationFiled: December 22, 2000Publication date: March 13, 2003Applicant: ISIS Pharmaceuticals, Inc.Inventors: Phillip Dan Cook, Yogesh S. Sanghvi, Kelly G. Sprankle, Bruce S. Ross, Rich H. Griffey, Robert H. Springer
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Patent number: 6509460Abstract: Novel nucleoside triphosphates, methods of synthesis and process of incorporating these nucleoside triphosphates into oligonucleotides are disclosed.Type: GrantFiled: August 23, 2000Date of Patent: January 21, 2003Assignee: Ribozyme Pharmaceuticals, Inc.Inventors: Leonid Beigelman, Alex Burgin, Amber Beaudry, Alexander Karpeisky, Jasenka Matulic-Adamic, David Sweedler
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Publication number: 20030013089Abstract: The invention provides novel dye-labeled ribonucleotide analogs and methods for synthesizing those analogs. The compounds of the invention are especially useful for DNA sequencing by the polymerase chain reaction.Type: ApplicationFiled: June 22, 2001Publication date: January 16, 2003Inventors: Peter Virgil Fisher, Paolo Vatta, Shaheer H. Khan
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Patent number: 6506888Abstract: Novel nucleoside or nucleotide analogs comprising 2′-O-amino residues, processes for their synthesis and incorporation into polynucleotides.Type: GrantFiled: September 19, 2000Date of Patent: January 14, 2003Assignee: Ribozyme Pharmaceuticals, Inc.Inventors: Alexander Karpeisky, Leonid Beigelman
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Patent number: 6504024Abstract: 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: GrantFiled: June 14, 2001Date of Patent: January 7, 2003Assignee: PE Corporation (NY)Inventors: Shaheer H. Khan, Steven M. Menchen, Barnett B. Rosenblum
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Patent number: 6479463Abstract: Novel purine L-nucleoside compounds are disclosed, in which both the purine rings and the sugar are either modified, functionalized or both. The novel compounds or pharmaceutically acceptable esters or salts thereof may be used in pharmaceutical compositions, and such compositions may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. The novel compounds may also be used to modulate aspects of the immune system, including modulation of Th1 and Th2.Type: GrantFiled: June 16, 2000Date of Patent: November 12, 2002Assignee: ICN Pharmaceuticals, Inc.Inventors: Guangyi Wang, Robert Tam, Devron Averett
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Patent number: 6476205Abstract: 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.Type: GrantFiled: August 10, 1998Date of Patent: November 5, 2002Assignee: ISIS Pharmaceuticals, Inc.Inventors: Chris A. Buhr, Mark Matteucci
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Publication number: 20020082417Abstract: The present invention relates to certain novel dinucleotides and formulations thereof which are highly selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. They are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, PCD, cystic fibrosis, as well as prevention of pneumonia due to immobility. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis, otitis media and nasolacrimal duct obstruction. They are also useful for treatment of dry eye disease and retinal detachment as well as facilitating sputum induction and expectoration.Type: ApplicationFiled: November 6, 2001Publication date: June 27, 2002Inventors: William Pendergast, Benjamin R. Yerxa, Janet L. Rideout, Suhaib M. Siddiqi
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Patent number: 6407223Abstract: The process of the instant invention is drawn to the synthesis of modified P-chiral nucleotide analogues in the form of pure diastereomers possessing preselected configuration at the P-atom. Oligonucleotides prepared by the method of the invention containing P-chiral compounds have enhanced hybridization and transporting properties.Type: GrantFiled: October 14, 1999Date of Patent: June 18, 2002Assignee: Polska Akademia Nauk Cenirum Badan Molekularnych i MakromlekularnychInventors: Wojciech J. Stec, Lucyna A. Woźniak, Arkadiusz Chworoś, Jaroslaw Pyzowski
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Patent number: 6320035Abstract: 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.Type: GrantFiled: October 25, 2000Date of Patent: November 20, 2001Assignee: Roche Diagnostics GmbHInventors: Klaus Mühlegger, Herbert Von Der Eltz, Frank Seela, Helmet Rosemeyer
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Patent number: 6303774Abstract: Novel compounds are provided in the form of nucleoside pyrophosphate and triphosphate analogs. In these analogs, the pyrophosphate or triphosphate group is replaced with a moiety that is isosterically and electronically identical thereto, but is hydrolytically and enzymatically more stable. The compounds are useful as therapeutic agents, e.g., as antiviral agents, anticancer agents, metabolic moderators and the like. The invention also provides pharmaceutical compositions containing a compound of the invention as an active agent, and in addition provides methods of treating disease, including viral infections, cancer, bacterial infections, inflammatory and/or autoimmune diseases, and the like, by administering a compound of the invention to a patient in need of such treatment.Type: GrantFiled: August 20, 1999Date of Patent: October 16, 2001Assignee: SRI InternationalInventors: Jeffrey C. Bottaro, Robert J. Schmitt, Mark A. Petrie, Paul E. Penwell
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Patent number: 6281201Abstract: Antiviral compounds have the formula wherein m is zero, 1, 2 or 3; n is from 1 to 8, preferably 1, 2 or 3; most preferably 1 or 2; R is independently selected from the group consisting of provided that all R may not be R1 is independently selected from the group consisting of hydroxyl and hydrogen; R2 is independently selected from the group consisting of oxygen and sulfur; or water soluble salts thereof.Type: GrantFiled: December 8, 1999Date of Patent: August 28, 2001Assignee: Temple University- of the Commonwealth System of Higher EducationInventors: Robert J. Suhadolnik, Wolfgang Pfleiderer
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Patent number: 6274725Abstract: The present invention relates to improved methods for the preparation of nucleoside phosphoramidites and oligonucleotides. In one aspect, the methods of the invention are used to prepare phosphitylating reagents using pyridinium salts as activators. In a further aspect, the methods of the invention are used to prepare internucleoside linkages using activators which include at least one pyridinium salt and at least one substituted imidazole. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having 2′-substituents using imidazolium or benzimidazolium salts as an activator. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having bioreversible protecting group that confers enhanced chemical and biophysical properties, without exocyclic amine protection, using imidazolium or benzimidazolium salts as an activator.Type: GrantFiled: October 23, 1998Date of Patent: August 14, 2001Assignee: Isis Pharmaceuticals, Inc.Inventors: Yogesh Sanghvi, Muthiah Manoharan
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Patent number: 6271212Abstract: Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.Type: GrantFiled: March 3, 1998Date of Patent: August 7, 2001Assignees: University of Georgia Research Foundation Inc., Emory UniversityInventors: Chung K. Chu, Lakshimi Kotra, Kostantine K. Manouilov, Jinfa Du, Raymond Schinazi
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Patent number: 6271358Abstract: 2′-O-modified ribosyl nucleosides and modified oligonucleotides containing such nucleotides are disclosed. Oligonucleotides are disclosed that have increased binding affinity as shown by molecular modeling experiments. The 2′-O-modified nucleosides of the invention include ring structures that position the sugar moiety of the nucleosides preferentially in 3′ endo geometries.Type: GrantFiled: July 27, 1998Date of Patent: August 7, 2001Assignee: Isis Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Venkatraman Mohan, Herb Boswell
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Patent number: 6265569Abstract: 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: GrantFiled: March 5, 1999Date of Patent: July 24, 2001Assignee: The Institute of Physical and Chemical ResearchInventors: Yoshihide Hayashizaki, Kaori Ozawa, Kazunari Fujio, Takumi Tanaka
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Patent number: RE38090Abstract: The invention relates to a 3′-substituted nucleoside derivative represented by the following general formula (1): wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: in which Ra, Rb and Rc are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R1 and R2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3′-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.Type: GrantFiled: May 26, 2000Date of Patent: April 22, 2003Assignees: Taiho Pharmaceutical Co., Ltd.Inventors: Akira Matsuda, Takuma Sasaki