Alkyl, Or Substituted Alkyl, Bonded Directly To The 5-position Of The Diazine Ring (e.g., Thymidine, 5-methyl Uridine, Etc.) Patents (Class 536/28.54)
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Patent number: 7119096Abstract: Uracil reductase inactivators, notably a 5-substituted uracil or 5,6-dihydro-5-substituted uracil, potentiate 5-flourouracil and find use particularly in the treatment of cancer. The 5-substituent is selected from bromo, ido, cyano, halo-substituted C1-4 alkyl, C2-6 alkenyl, 1-halo-C2-6 alkenyl and halo-substituted C2-6 alkynyl.Type: GrantFiled: October 1, 2001Date of Patent: October 10, 2006Assignee: SmithKlineBeecham CorporationInventors: Thomas Spector, David J. T. Porter, Saad G. Rahim
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Patent number: 7094413Abstract: The present invention relates to pharmaceutical preparations and methods for treating individuals infected with the human immunodeficiency virus (HIV). The pharmaceutical preparations comprise an immunomodulating agent and a anti-retroviral compound. The pharmaceutical preparations are used to treat HIV infected patients, particularly for gastrointestinal complications arising from viral infection. In addition, the pharmaceutical preparations of the present invention have the effect of raising the levels of CD4+ single positive and CD4+ and CD8+ double positive T cells, thus promoting restoration and normalization of the immune system following HIV infection.Type: GrantFiled: January 24, 2003Date of Patent: August 22, 2006Assignees: SangStat Medical Corporation, The Regents of the University of CaliforniaInventors: Roland Buelow, Suhasini Iyer, Satya Dandekar
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Patent number: 6987180Abstract: Uridine analogs and techniques for making and using uridine analogs are disclosed in this invention. These uridine analogs include nucleoside phosphates having a 5-aminouracil group. These nucleotides can be incorporated into a nucleic acid as an unnatural base, as a substitute for uridine or thymine. The nucleic acid can then be treated with an oxidizing agent and an alkaline solution, which causes cleavage of the nucleic acid at the position of the unnatural base. The nucleoside phosphate analogs can be used in many ways, including measuring chemical interactions between nucleic acids and other compounds, or sequencing nucleic acids. Additional compounds can also be derivitized onto the amino group, allowing other functionalities to be added to the nucleoside phosphate, or to the nucleic acid incorporating the nucleoside phosphate.Type: GrantFiled: February 7, 2002Date of Patent: January 17, 2006Assignee: President and Fellows of Harvard CollegeInventors: Gregory L. Verdine, Michael Storek
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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: 6894159Abstract: The present invention relates to a novel and improved process for preparing 2?-fluoro-5-methyl-?-L-arabinofuranosyluridine represented by formula (1) which shows anti-viral activity, especially potent anti-viral activity against hepatitis B-virus and Epstein-Barr virus:Type: GrantFiled: January 24, 2003Date of Patent: May 17, 2005Assignee: The University of Georgia Research FoundationInventors: Chung K. Chu, Jinfa Du, Yongseok Choi
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Patent number: 6891033Abstract: The application relates to compounds that are suitable as labelable precursors for synthesis of 3?-[18F]fluoro-3?-deoxythymidine and that have formula (1), in which R denotes triphenylmethyl, triphenylmethyl substituted in the phenyl group, trialkylmethyl, triphenylsilyl, triphenylsilyl substituted in the phenyl group, or trialkylsilyl, R? denotes R1—SO2, where R1 is an unsubstituted or substituted C1 to C5 alkyl or an unsubstituted or substituted phenyl, and R? denotes C2 to C10 alkyloxycarbonyl, with the exception of 3-N-Boc-1-(3-O-nosyl-5-O-trityl-2-deoxy-?-D-lyxofuranosy The application also relates to a method for preparation of these compounds and to the use of the same for synthesis of 3?-[18F]fluoro-3?-deoxythymidine.Type: GrantFiled: January 28, 2002Date of Patent: May 10, 2005Assignee: Deutsches Krebsforschungszentrum Stiftung des Offentlichen RechtsInventors: Stefan Johannes Martin, Joseph Antonius Maria Eisenbarth, Ulrike Wagner-Utermann, Michael Eisenhut, Walter Mier
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Patent number: 6875860Abstract: This invention provides a method for efficiently purifying 5?-protected thymidines which cannot be efficiently purified by the prior art. Impurities can be separated by obtaining crystals including a carbonyl-containing solvent to provide a highly pure 5?-protected thymidine. Thus, this invention allows 5?-protected thymidines, which cannot be purified in an industrial scale by the prior art, to be easily provided with a high purity in a large scale.Type: GrantFiled: May 15, 2002Date of Patent: April 5, 2005Assignee: Mitsui Chemicals, Inc.Inventors: Hironori Komatsu, Toshiyuki Kouno, Katsutoshi Tsuchiya, Hiroharu Tanikawa, Hiroki Ishibashi
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Patent number: 6870048Abstract: The present invention is directed to the process for the preparation of 2?-deoxy-2?-halo-?-L-arabinofuranosyl nucleosides, and in particular, 2?-deoxy-2?-fluoro-?-L-arabinofuranosyl thymine (L-FMAU), from L-arabinose, which is commercially available and less expensive than L-ribose or L-xylose, in ten steps. All of the reagents and starting materials are inexpensive and no special equipment is required to carry out the reactions.Type: GrantFiled: March 29, 2002Date of Patent: March 22, 2005Assignee: Triangle PharmaceuticalsInventor: Marcos Sznaidman
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Patent number: 6864366Abstract: Process of preparing (E)-5-(2-bromovynyl)-2?-deoxyuridine (Brivudine) characterized in that halogen-free solvent selected form esters or cyclic ethers are used in the bromination step of 5-ethyl-2?-deoxyuridine diacylate. The use of solvents is advantageous in respect of toxicity, discharge costs and environment protection.Type: GrantFiled: February 21, 2002Date of Patent: March 8, 2005Assignees: Menarini Richerche S.p.A., Berlin-Chemie AGInventors: Aldo Salimbeni, Carlo Alberto Maggi, Stefano Manzini, Damiano Turozzi
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Publication number: 20040087541Abstract: Physical forms of beta-L-2′-deoxythymidine are disclosed that can be characterized by physical appearance, purity levels, Infra-Red and Raman spectroscopy, X-ray powder diffraction patterns, thermal properties, and methods of manufacture. These forms of beta-L-2′-deoxythymidine can be used in the manufacture of other forms of beta-L-2′-deoxythymidine, or in pharmaceutical compositions. Particularly preferred uses are in the treatment of hepatitis B.Type: ApplicationFiled: August 6, 2003Publication date: May 6, 2004Inventors: David Jonaitis, Richard Storer
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Patent number: 6699978Abstract: The present invention relates to a linker nucleoside, its preparation and use for the covalent bonding of biomolecules to oligonucleotides, in particular p-RNA oligonucleotides.Type: GrantFiled: July 11, 2000Date of Patent: March 2, 2004Assignee: Nanogen Recognomics GmbHInventors: Christian Miculka, Norbert Windhab, Tilmann Brandstetter, Stefan Scherer
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Patent number: 6646118Abstract: The present invention relates to a support system for solid phase synthesis of oligomers, such as oligonucleotides, wherein the starting compound is bound to the support via a disiloxyl linkage. Furthermore, the invention relates to a method for synthesis of oligonucleotides on a solid support. The support system comprises a stable disiloxyl linkage providing high nucleoside loadings to the support and the method allows convenient non-laborious oligomer synthesis.Type: GrantFiled: March 25, 2002Date of Patent: November 11, 2003Assignee: Quiatech ABInventors: Marek Kwiatkowski, Mats Nilsson, Ulf Landegren
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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: 6635753Abstract: 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.Type: GrantFiled: September 30, 1998Date of Patent: October 21, 2003Assignee: Brantford Chemicals Inc.Inventors: Bruno K. Radatus, K. S. Keshava Murthy
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Publication number: 20030148470Abstract: Propargylethoxyamino nucleosides are disclosed having the structure 1Type: ApplicationFiled: July 9, 2002Publication date: August 7, 2003Applicant: PE Corporation (NY)Inventors: Shaheer H. Khan, Steven M. Menchen, Barnett B. Rosenblum
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Patent number: 6596859Abstract: A process for the production of a compound of the formula: wherein R1 is hydrogen, alkyl, C1-C16 substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyls, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cyano, carboxy, carboxy esters, carboxamido, N-mono substituted and N,N-disubstituted carboxamido with alkyl, aralkyl and aryl groups; R2 is hydrogen, alkyl C1-C16 substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyls, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl; R3 is alkyl C2-C6, branched alkyl, aryl C2-C, substituted aryl and R4 is halogen or H.Type: GrantFiled: July 18, 2000Date of Patent: July 22, 2003Assignee: The Board of Govenors for Higher Education, State of Rhode Island and Providence PlantationsInventors: Elie Abushanab, Palle V. P. Pragnacharyulu
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Patent number: 6579976Abstract: 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.Type: GrantFiled: October 26, 1999Date of Patent: June 17, 2003Assignee: Ajinomoto Co., Inc.Inventors: Satoshi Takamatsu, Satoshi Katayama, Naoko Hirose, Kunisuke Izawa
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Patent number: 6566344Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-&bgr;-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-&bgr;-L-erythro-pentoftiranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted.Type: GrantFiled: December 14, 2001Date of Patent: May 20, 2003Assignee: Idenix Pharmaceuticals, Inc.Inventors: Gilles Gosselin, Jean-Louis Imbach, Martin L. Bryant
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Publication number: 20030078416Abstract: The invention relates to 1,10 phenanthroline derivatives substituted at the 3-,8-positions.Type: ApplicationFiled: May 15, 1996Publication date: April 24, 2003Inventors: YITZHAK TOR, DIMITRIOS TZALIS
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Patent number: 6548486Abstract: New compounds of the general formula (I): Nu-O-Fa, wherein O represents an oxygen, Nu is a nucleoside or nucleoside analogue, and Fa is an acyl group of a mono-unsaturated C18 or 20 fatty acid. The invention also concerns anti viral pharmaceutical and veterinary compositions comprising a compound of formula (I) alone in a combination with a pharmaceutically acceptable carrier.Type: GrantFiled: September 21, 1994Date of Patent: April 15, 2003Assignee: Norsk Hydro a.s.Inventors: Are Dalen, Finn Myhren, Bernt Børretzen, Kjell Torgeir Stokke
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Patent number: 6512107Abstract: 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: GrantFiled: July 23, 1998Date of Patent: January 28, 2003Assignee: The University of Georgia Research FoundationInventors: Chung K. Chu, Jinfa Du, Yongseok Choi
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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: 6498149Abstract: The present invention provides substances having an efficacy against tumors and viruses on which the conventional anti-tumor agents and anti-virus agents exhibit only insufficient effects, and having carcinostatic effect and anti-virus effect on various resistant tumors as well as a reduced side effect such that normal human cells will not be impaired. The present invention relates to an anti-tumor or anti-viral substance represented by the formula (1) wherein R1 represents a nucleic acid base represented by a specific formula, and R2 represents a hydrogen atom, a hydroxy group or a methoxy group, or a pharmaceutically acceptable salt thereof.Type: GrantFiled: December 3, 1999Date of Patent: December 24, 2002Assignees: Techno Seven Co., Ltd.Inventors: Tsuneatsu Mori, Maowu Guo, Etsuko Mori
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Patent number: 6482805Abstract: Contraceptive activity as well as anti-viral protection can be provided by contraceptive compositions containing a pyrimidine-based nucleoside or nucleotide exhibiting spermicidal or sperm-immobilizing activity. In one example, the active ingredient contains a thymine ring (e.g. AZT) that has 5-halo, 6-alkoxy substitution. Additional improvements in anti-HIV activity for certain AZT derivatives are seen by providing the pentose ring of AZT with aryl phosphate substitution.Type: GrantFiled: December 1, 2000Date of Patent: November 19, 2002Assignee: Parker Hughes InstituteInventors: Fatih M. Uckun, Osmond D'Cruz, Taracad Venkatachalam
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Patent number: 6458772Abstract: Compounds of the formula I or corresponding monohydroxynucleoside derivatives wherein: R1 is hydroxy, amino or carboxy: optionally having esterified/amide bonded thereon; a C4-C22 saturated or unsaturated, optionally substituted fatty acid or alcohol, or an aliphatic L-amino acid; R2 is the residue of an aliphatic L-amino acid; L1 is a trifunctional linker group; L2 is absent or a difunctional linker group; and pharmaceutically acceptable salts thereof have favorable pharmacological properties and are antivirally active.Type: GrantFiled: February 12, 1999Date of Patent: October 1, 2002Assignee: Medivir ABInventors: Xiao-Xiong Zhou, Nils Gunnar Johansson, Horst Wahling, Christian Sund, Hans Wallberg, Lourdes Salvador, Stefan Lindstrom, Christer Sahlberg
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Patent number: 6429309Abstract: The present invention relates to a support system for the solid phase synthesis of oligomers, such as oligonucleotide, wherein the starting compound is bound to the support via a disiloxyl linkage. Furthermore, the invention relates to a method for synthesis of oligonucleotides on a solid support. The support system comprises a stable disiloxyl linkage providing high nucleoside loadings to the support and the method allows convenient non-laborious oligomer synthesis.Type: GrantFiled: August 2, 2001Date of Patent: August 6, 2002Assignee: Quiatech ABInventors: Marek Kwiatkowski, Mats Nilsson, Ulf Landegren
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Patent number: 6414137Abstract: A process for the purification of nucleosides, and more particularly to a selective solvent extraction method for purifying protected nucleosides. In the purification process, solid particles of protected nucleosides are selectively washed to remove undesirable polar and/or non-polar impurities, while leaving the solid particles substantially undissolved.Type: GrantFiled: November 15, 1999Date of Patent: July 2, 2002Assignee: AlliedSignal Inc.Inventors: Raymond J. Swedo, Mathias P. Koljack, Romulus Gaita, Stephen Frederick Yates, Charles Wu
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Patent number: 6407078Abstract: Contraceptive activity as well as anti-viral protection can be provided by contraceptive compositions containing a pyrimidine-based nucleoside or nucleotide exhibiting spermicidal or sperm-immobilizing activity. In one example, the active ingredient contains a thymine ring (e.g. AZT) that has 5-halo, 6-alkoxy substitution. Additional improvements in anti-HIV activity for certain AZT derivatives are seen by providing the pentose ring of AZT with aryl phosphate substitution.Type: GrantFiled: February 3, 2000Date of Patent: June 18, 2002Assignee: Parker Hughes InstituteInventors: Osmond D'Cruz, Faith M. Uckun, Taracad Venkatachalam
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Patent number: 6392032Abstract: Heavily fluorinated sugar analogs of formula wherein R1 is selected from alkyl, alkenyl, aryl, —CH2—O-alkyl, —CH2—O-aryl, —CH2OPO3H, —CH2—O-carbohydrate, —CH2—NH-peptide, or —CH2—O-peptide; wherein R2 is selected from hydroxy, —O-carbohydrate, —NH-peptide, wherein R3 is selected from H, halogen, lower alkyl, lower alkenyl, lower haloalkyl, lower haloalkenyl, amino, mono- or di-lower alkylamino; wherein R4 is selected from amino, hydroxy, alkoxy, or halogen; and wherein R5 is H or amino. The compounds of formula (I) are useful as antiviral and antineoplastic agents and the compounds of formula (II) are useful as plant growth inhibitors and herbicides.Type: GrantFiled: September 2, 1999Date of Patent: May 21, 2002Assignee: Board of Regents University of Nebraska-LincolnInventor: Stephen G. Dimagno
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Patent number: 6362329Abstract: A process for the production of a compound of the formula: wherein R1 is hydrogen, alkyl, C1-C16 substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyls, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cyano, carboxy, carboxy esters, carboxamido, N-mono substituted and N,N-disubstituted carboxamido with alkyl, aralkyl and aryl groups; R2 is hydrogen, alkyl C1-C16 substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyls, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl; R3 is alkyl C2-C6, branched alkyl, aryl C2-C6, substituted aryl and R4 is halogen or H.Type: GrantFiled: July 18, 2000Date of Patent: March 26, 2002Assignee: The Board of Govenors for Higher Education, State of Rhode Island and Providence PlantationsInventors: Elie Abushanab, Palle V. P. Pragnacharyulu
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Patent number: 6348451Abstract: 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: GrantFiled: June 7, 1995Date of Patent: February 19, 2002Assignee: Pro-Neuron, Inc.Inventors: Reid Warren von Borstel, Michael Kevin Bamat
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Patent number: 6339151Abstract: This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.Type: GrantFiled: January 22, 1999Date of Patent: January 15, 2002Assignee: NewBiotics, Inc.Inventors: H. Michael Shepard, Michael P. Groziak
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Patent number: 6326491Abstract: A process for the production of a compound of the formula: wherein R1 is hydrogen, alkyl, C1-C16 substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyls, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cyano, carboxy, carboxy esters, carboxamido, N-mono substituted and N,N-disubstituted carboxamido with alkyl, aralkyl and aryl groups; R2 is hydrogen, alkyl C1-C16 substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyls, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl; R3 is alkyl C2-C6, branched alkyl, aryl C2-C6, substituted aryl and R4 is halogen or H.Type: GrantFiled: July 18, 2000Date of Patent: December 4, 2001Assignee: The Board of Governors for Higher Education, State of Rhode Island and Providence PlantationsInventors: Elie Abushanab, Palle V. P. Pragnacharyulu
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Patent number: 6320040Abstract: 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.Type: GrantFiled: October 7, 1999Date of Patent: November 20, 2001Assignee: ISIS Pharmaceuticals, Inc.Inventors: Phillip Dan Cook, Kelly Teng
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Patent number: 6297223Abstract: Uracil reductase inactivators, notably a 5-substituted uracil or 5,6-dihydro-5-substituted uracil, potentiate 5-fluorouracil and find use particularly in the treatment of cancer. The 5-substituent is selected from bromo, iodo, cyano, halo-substituted C1-4 alkyl, C2-6 alkenyl, 1-halo-C2-6 alkenyl and halo-substituted C2-6 aklynyl.Type: GrantFiled: June 30, 2000Date of Patent: October 2, 2001Assignee: Glaxo Wellcome Inc.Inventors: Thomas Spector, David J. T. Porter, Saad G. Rahim
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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: 6268374Abstract: The present invention relates to a group of 5-substituted uracil derivatives which are inactivators of uracil reductase and which are particularly useful in cancer chemotherapy, especially in combination with antimetabolite antineoplastic agents such as 5-fluorouracil.Type: GrantFiled: July 23, 1993Date of Patent: July 31, 2001Assignee: Glaxo Wellcome Inc.Inventors: Thomas Spector, David J. T. Porter, Saad G. Rahim
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Patent number: 6268183Abstract: The invention discloses a two-step process for recovery of thuringiensin, comprising adsorbing the thuringiensin from fermentation broth by calcium silicate, and dissociating the thuringiensin by dibasic sodium phosphate. The resulting thuringiensin can be further purified by using semi-preparative HPLC and electrodialysis to remove the excess salts from the recovered thuringiensin solution.Type: GrantFiled: June 2, 2000Date of Patent: July 31, 2001Assignee: National Science CouncilInventors: Yew-Min Tzeng, Bing-Lan Liu, Shyuan-Shuenn Huang, Cheng-Ming Liu, Hung-Yieng Tsun
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Patent number: 6245750Abstract: This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.Type: GrantFiled: January 22, 1999Date of Patent: June 12, 2001Assignee: NewBiotics, Inc.Inventor: H. Michael Shepard
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Patent number: 6225450Abstract: The invention describes a new method to sequence DNA. The improvements over the existing DNA sequencing technologies are high speed, high throughput, no electrophoresis and gel reading artifacts due to the complete absence of an electrophoretic step, and no costly reagents involving various substitutions with stable isotopes. The invention utilizes the Sanger sequencing strategy and assembles the sequence information by analysis of the nested fragments obtained by base-specific chain termination via their different molecular masses using mass spectrometry, as for example, MALDI or ES mass spectrometry. A flirter increase in throughput can be obtained by introducing mass-modifications in the oligonucleotide primer, chain-terminating nucleoside triphosphates and/or in the chain-elongating nucleoside triphosphates, as well as using integrated tag sequences which allow multiplexing by hybridization tag specific probes with mass differentiated molecular weights.Type: GrantFiled: June 7, 1995Date of Patent: May 1, 2001Assignee: Sequenom, Inc.Inventor: Hubert Köster
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Patent number: 6211166Abstract: Novel 5′-deoxy-cytidine derivatives represented by the general formula (I) wherein R1 is a hydrogen atom or a group easily hydrolyzable under physiological conditions; R2 is a hydrogen atom, or —CO—OR4 group [wherein R4 is a saturated or unsaturated, straight or branched hydrocarbon group consisting of one to fifteen carbon atoms, or a group of the formula —(CH2)n—Y (in which Y is cyclohexyl or phenyl; n is an integer from 0 to 4)]; R3 is a hydrogen atom, bromo, iodo, cyano, a C1-4 alkyl group [which may be substituted with halogen atom(s)], a vinyl or ethynyl group [which may be substituted with halogen atom(s), C1-4 alkyl, cycloalkyl, aralkyl, or aromatic ring which may have one or more hetero atom(s)], or an aralkyl group which may be substituted for use in medical therapy, especially tumor therapy.Type: GrantFiled: March 24, 2000Date of Patent: April 3, 2001Assignee: Hoffman-La Roche Inc.Inventors: Kazuo Hattori, Tohru Ishikawa, Hideo Ishitsuka, Yasunori Kohchi, Nobuhiro Oikawa, Nobuo Shimma, Hitomi Suda
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Patent number: 6207650Abstract: Provided are very highly water soluble, stable, crystalline salts of 2′,3′-dideoxy-2′,3′-didehydrothymidine (“d4T”), 2′,3′-dideoxyinosine (“ddI”), and 2′,3′-dideoxy-2′-fluoroinosine (“F-ddI”). Such salts are useful as intermediates or as antiviral agents.Type: GrantFiled: December 6, 1991Date of Patent: March 27, 2001Assignee: Bristol-Myers Squibb CompanyInventors: Joseph B. Bogardus, Murray A. Kaplan, Robert K. Perrone
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Patent number: 6191120Abstract: Contraceptive activity as well as anti-viral protection can be provided by contraceptive compositions containing a pyrimidine-based nucleoside or nucleotide exhibiting spermicidal or sperm-immobilizing activity. In one example, the active ingredient contains a thymine ring (e.g. AZT) that has 5-halo, 6-alkoxy substitution. Additional improvements in anti-HIV activity for certain AZT derivatives are seen by providing the pentose ring of AZT with aryl phosphate substitution.Type: GrantFiled: March 25, 1998Date of Patent: February 20, 2001Assignee: Wayne Hughes InstituteInventors: Osmond D'Cruz, Fatih M. Uckun, Taracad Venkatachalam
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Patent number: 6187914Abstract: The invention relates to nucleoside derivatives bearing electrolabile protector groupings and their use in an oligonucleotide synthesis method comprising at least one step of electronic deprotection.Type: GrantFiled: December 3, 1998Date of Patent: February 13, 2001Assignee: Cis Bio InternationalInventors: Robert Teoule, André Roget, Thierry Livache
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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
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Patent number: RE38416Abstract: This invention is directed to novel substituted nucleotide bases with a crosslinking arm which accomplish crosslinking between specific sites on adjoining strands of oligonucleotides a oligodeoxynucleotides. The invention is also directed to oligonucleotides comprising at least one of these crosslinking agents and to the use of the resulting novel oligonucleotides for diagnostic and therapeutic purposes.Type: GrantFiled: October 19, 2000Date of Patent: February 3, 2004Assignee: Epoch Biosciences, Inc.Inventors: Charles R. Petrie, Rich B. Meyer, John C. Tabone, Gerald D. Hurst