Plural Phosphorus Atoms In N-glycoside Patents (Class 536/26.2)
  • Patent number: 9402812
    Abstract: Provided herein are methods for preparing liposomes and uses thereof. In certain embodiments, liposomes are prepared without using heat, organic solvents, proteins, and/or inorganic salts in the process. In certain embodiments, the liposomal preparation contains one or more active agents. In certain embodiments, the liposomal preparations are used in the treatment of diseases or disorders.
    Type: Grant
    Filed: September 23, 2010
    Date of Patent: August 2, 2016
    Inventors: Indu Javeri, Kaliappanadar Nellaiappan, Bharat Dixit
  • Publication number: 20150133362
    Abstract: Aspects of the invention provide methods for selecting a candidate oligonucleotide for activating expression of a target gene. Further aspects of the invention provide methods of selecting a set of oligonucleotides that is enriched in oligonucleotides that activate expression of a target gene. Further aspects provide single stranded oligonucleotides that modulate gene expression and compositions and kits comprising the same. Methods for modulating gene expression using the single stranded oligonucleotides are also provided.
    Type: Application
    Filed: May 16, 2013
    Publication date: May 14, 2015
    Applicants: RaNA Therapeutics, Inc., The General Hospital Corporation d/b/a Massachusetts General Hospital
    Inventors: Arthur M. Krieg, Romesh Subramanian, James McSwiggen, Jeannie T. Lee
  • Patent number: 8981078
    Abstract: An agent for inhibiting translesion DNA replication comprises a non-natural adenine ribose analog represented by those as set forth in FIG. 1.
    Type: Grant
    Filed: January 4, 2012
    Date of Patent: March 17, 2015
    Assignee: Case Western Reserve University
    Inventors: Anthony J. Berdis, Irene Lee, Xuemei Zhang
  • Patent number: 8969545
    Abstract: Alkynyl-derivatized cap analogs, alkynyl-modified capped RNA, 1,4-disubstituted triazole-derivatized capped RNA, methods of preparation, methods of isolation, and uses thereof are provided. The “click” modification facilitates detection and isolation of capped RNAs and the 1,4-disubstituted triazole derivatives formed by the “click” reaction are useful for producing RNA transcripts and encoded protein.
    Type: Grant
    Filed: October 18, 2012
    Date of Patent: March 3, 2015
    Assignee: Life Technologies Corporation
    Inventors: Anilkumar R. Kore, Shanmugasundaram Muthian, Kyle Gee
  • Patent number: 8957201
    Abstract: A method for the prevention or treatment in a mammal of a disease preventable or treatable by the pharmacologically useful antisense or antigene activity of an oligonucleotide analogue or a pharmacologically acceptable salt thereof in the body of said mammal, which method comprises administering to said mammal in need of such prevention or treatment a pharmaceutically effective amount of an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of said nucleoside units is a structure of the formula (2): wherein A is methylene; and B is an unsubstituted purin-9-yl, an unsubstituted 2-oxo-pyrimidin-1-yl or a substituted purin-9-yl; or a pharmacologically acceptable salt thereof.
    Type: Grant
    Filed: July 22, 2010
    Date of Patent: February 17, 2015
    Assignee: Daiichi Sankyo Company, Limited
    Inventors: Masakatsu Kaneko, Koji Morita, Takeshi Imanishi
  • Publication number: 20150031833
    Abstract: A compound has Formula I: A, B, C, D, W, X, Y, and Z are independently selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, aryl, aldehyde, protected aldehyde, CH, N, O, S, null, and bond; Q is selected from aldehyde, protected aldehyde, and null, at least one of A, B, C, D, W, X, Y, Z, or Q is an aldehyde or protected aldehyde; the bonds between each of A-B, B-C, C-D, W-X, X-Y, and Y-Z are selected from single bond, double bond, triple bond, and no bond; L is a linker selected from a C1-C12 alkyl, aralkyl, and aryl, any of which is optionally substituted; one or more methylene unit (CH2) of the C1-C12 alkyl is optionally replaced by any combination of oxygen, carbonyl(C?O), and NH; and R1 and R2 are independently selected from —NR3R4, halogen, C1-C8 alkoxy, aralkoxy, alkenyloxy, alkynyloxy, and OCH2CH2CN; R3 and R4 are independently a C1-C4, straight chain or branched alkyl group.
    Type: Application
    Filed: October 10, 2014
    Publication date: January 29, 2015
    Inventors: Ryan Christopher SMITH, Randall SMITH, Xiaodong ZHAO
  • Patent number: 8674086
    Abstract: Embodiments of the invention provide non-natural bifunctional nucleotides having both nuclease resistance and nucleic acid synthesis blocking properties and methods of sequencing nucleic acids that employ non-natural bifunctional nucleic acids. Additional embodiments provide non-natural oligonucleotides and methods for sequencing nucleic acids using the non-natural oligonucleotides. Methods according to embodiments of the invention employ electronic detection and fluorescent detection of nucleic acid sequencing reactions.
    Type: Grant
    Filed: June 25, 2010
    Date of Patent: March 18, 2014
    Assignee: Intel Corporation
    Inventors: Jianquan Liu, Xing Su, Kai Wu
  • Patent number: 8603741
    Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
    Type: Grant
    Filed: February 8, 2011
    Date of Patent: December 10, 2013
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
  • Patent number: 8569259
    Abstract: Provided are adenosine analog compounds of the general formula that act as P2Y receptors, e.g., the P2Y2 receptor, including pharmaceutical compositions; and uses thereof to treat or prevent diseases associated with that receptor, e.g., disorders relating to mucus secretion, such as cystic fibrosis, chronic obstructive pulmonary disorder (COPD), asthma, constipation, chronic idiopathic constipation, dry mouth (xerostomia), gum disease, and gastrointestinal problems caused by radiation and chemotherapy for cancer.
    Type: Grant
    Filed: November 16, 2007
    Date of Patent: October 29, 2013
    Assignee: Microdose Therapeutx, Inc.
    Inventors: Efrat Ben-Zeev, Vincent Jacques, Yael Marantz, A. Sekar Reddy, Zhaoda Zhang, Oren Becker, Dilara McCauley, Pini Orbach, Sharon Shacham, Ashis K. Saha, Michael Xie
  • Patent number: 8481712
    Abstract: 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: Grant
    Filed: February 2, 2007
    Date of Patent: July 9, 2013
    Assignees: Merck Sharp & Dohme Corp., ISIS Pharmaceuticals, Inc.
    Inventors: Balkrishen Bhat, Anne B. Eldrup, Thazha P. Prakash, Phillip Dan Cook, Robert L. LaFemina, Amy L. Simcoe, Carrie A. Rutkowski, Mario A. Valenciano
  • Patent number: 8440812
    Abstract: The invention relates to analogous compounds of 6-thioguanosine triphosphate of general formula (I). A compound of the general formula (I); wherein the dashed bond in the sugar moiety can be either single or double and wherein R1, R2, R3, R4 or R5, equal or different between each other, have general formula -(Int)m-Ter, wherein m is between 0 and 12 and Int and Ter are Internal and Terminal building blocks, wherein Int is selected from the group consisting of formula (II); and Ter is selected from the group consisting of formula (III).
    Type: Grant
    Filed: December 20, 2011
    Date of Patent: May 14, 2013
    Assignee: Nogra Pharma Limited
    Inventors: Giancarlo Naccari, Sergio Baroni
  • Publication number: 20130116420
    Abstract: The present invention provides 5? modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5?-substituent and an optional 2? substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
    Type: Application
    Filed: April 26, 2011
    Publication date: May 9, 2013
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: Thazha P. Prakash, Punit P. Seth, Eric E. Swayze
  • Publication number: 20130084576
    Abstract: The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
    Type: Application
    Filed: April 26, 2011
    Publication date: April 4, 2013
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: Thazha P. Prakash, Punit P. Seth, Eric E. Swayze
  • Patent number: 8361727
    Abstract: Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3?-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group.
    Type: Grant
    Filed: May 24, 2011
    Date of Patent: January 29, 2013
    Assignee: Lasergen, Inc.
    Inventors: Weidong Wu, Vladislav A. Litosh, Brian P. Stupi, Michael L. Metzker
  • Patent number: 8349812
    Abstract: Immunostimulatory oligoribonucleotides (ORN) featuring 5?-triphosphates and various 5?-triphosphate analogs are provided. Also provided are physiologically acceptable salts of the immunostimulatory ORN and pharmaceutical compositions containing the immunostimulatory ORN of the invention. ORN of the invention are useful as adjuvants and can be combined with an antigen to promote an antigen-specific immune response. ORN of the invention are also particularly useful for promoting a Th1-type immune response. Also provided are methods of use of the compounds and pharmaceutical compositions of the invention to enhance an immune response in a subject, as well to treat a number of conditions including cancer, infection, allergy, and asthma, and to vaccinate a subject against an antigen.
    Type: Grant
    Filed: October 30, 2008
    Date of Patent: January 8, 2013
    Assignee: AdiuTide Pharmaceuticals GmbH
    Inventors: Harald Debelak, Eugen Uhlmann
  • Publication number: 20120296076
    Abstract: The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.
    Type: Application
    Filed: May 18, 2012
    Publication date: November 22, 2012
    Inventors: Richard Hung Chiu Yu, Brandon Heath Brown, Richard P. Polniaszek, Benjamin R. Graetz, Keiko Sujino, Duong Duc-Phi Tran, Alan Scott Triman, Kenneth M. Kent, Steven Pfeiffer
  • Patent number: 8304529
    Abstract: Novel cap analogs which are easily synthesized, resulting in high levels of capping efficiency and transcription and improved translation efficiencies are provided. Such caps are methylated at the N7 position of one or both guanosines of the dinucleotide cap as well as at the 3? position on the ribose ring. Substituent groups on the ribose ring also result in the cap being incorporated in the forward orientation. Also provided are methods useful for preparing capped analogs and using mRNA species containing such analogs are also contemplated herein, as well as kits containing the novel cap analogs.
    Type: Grant
    Filed: July 10, 2007
    Date of Patent: November 6, 2012
    Assignee: Life Technologies Corporation
    Inventors: Anilkumar R. Kore, Muthian Shanmugasundaram
  • Publication number: 20120245029
    Abstract: This invention provides phosphate-modified nucleosides represented by the structural formula (I): wherein W is O or S, and wherein B, R1; R3 and R2. are as defined herein. These compounds are useful as substrates for DNA/RNA polymerases, and as anti-viral agents in particular against HIV-1.
    Type: Application
    Filed: May 12, 2010
    Publication date: September 27, 2012
    Applicant: Katholieke Universiteit Leuven
    Inventors: Piet Herdewijn, Philippe Marlière
  • Patent number: 8158776
    Abstract: This invention is directed to a method of enhancing or facilitating the clearance or the lung mucus secretions in a subject. This invention is also directed to a method of facilitating the hydration of the lung mucus secretions in a subject. This invention is further directed to a method of preventing or treating diseases or conditions associated with impaired lung or airway function in a human or other mammal. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutic effective amount of P2Y6 receptor agonist compound, wherein said amount is effective to activate the P2Y6 receptors on the luminal surface of lung epithelia. The P2Y6 receptor agonist compounds useful for this invention include mononucleoside 5?-diphosphates, dinucleoside monophosphate, dinucleoside diphosphates, or dinucleoside triphosphates of general Formula I, or salts, solvates, hydrates thereof. This invention is also directed to novel P2Y6 receptor agonist compounds.
    Type: Grant
    Filed: November 4, 2010
    Date of Patent: April 17, 2012
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: José L. Boyer, Sammy R. Shaver, James G. Douglass, III, Catherine C. Redick
  • Patent number: 8034923
    Abstract: Processes are disclosed that use 3?-reversibly terminated nucleoside triphosphates to analyze DNA for purposes other than sequencing using cyclic reversible termination. These processes are based on the unexpected ability of terminal transferase to accept these triphosphates as substrates, the unexpected ability of polymerases to add reversibly and irreversibly terminated triphosphates in competition with each other, the development of cleavage conditions to remove the terminating group rapidly, in high yield, and without substantial damage to the terminated oligonucleotide product, and the ability of reversibly terminated primer extension products to capture groups. The presently preferred embodiments of the disclosed processes use a triphosphate having its 3?-OH group blocked as a 3?-ONH2 group, which can be removed in buffered NaNO2 and use variants of Taq DNA polymerase, including one that has a replacement (L616A).
    Type: Grant
    Filed: March 27, 2009
    Date of Patent: October 11, 2011
    Inventors: Steven Albert Benner, Daniel Hutter, Nicole Aurora Leal, Fei Chen
  • Publication number: 20110212437
    Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.
    Type: Application
    Filed: February 8, 2011
    Publication date: September 1, 2011
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Robin Emig, Lei Jia, Jeremiah Hanes, Lubomir Sebo
  • Patent number: 7964352
    Abstract: Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3?-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group.
    Type: Grant
    Filed: November 11, 2008
    Date of Patent: June 21, 2011
    Assignee: LaserGen, Inc.
    Inventors: Weidong Wu, Vladislav A. Litosh, Brian P. Stupi, Michael L. Metzker
  • Publication number: 20110086813
    Abstract: The present invention relates to a novel class of guanine nucleotide analogs which inhibit RelA and Relseq synthetic activity and which possess anti-bacterial activity. The present invention also relates to pharmaceutical compositions that include such compounds, and to methods of use of such compounds or compositions for combating bacteria and treating bacterial infections.
    Type: Application
    Filed: March 18, 2009
    Publication date: April 14, 2011
    Inventors: Gad Glaser, Jehoshua Katzhendler, Rolf Hilgenfeld, Roee Vidavski, Ezequiel Wexselblatt, Tamar Prez-Menahemov, Ilana Kaspy
  • Patent number: 7897737
    Abstract: Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3?-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group.
    Type: Grant
    Filed: December 5, 2006
    Date of Patent: March 1, 2011
    Assignee: LaserGen, Inc.
    Inventors: Weidong Wu, Vladislav A. Litosh, Brian P. Stupi, Michael L. Metzker
  • Patent number: 7893227
    Abstract: Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3?-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a non-cleavable terminating group. The non-cleavable-fluorescent group is designed to terminate DNA synthesis so that DNA oligomers can be sequenced efficiently in a parallel format. These reagents and methods will lead to more accurate identification of polymorphisms and other valuable genetic information.
    Type: Grant
    Filed: December 5, 2006
    Date of Patent: February 22, 2011
    Assignee: LaserGen, Inc.
    Inventors: Weidong Wu, Vladislav A. Litosh, Brian P. Stupi, Michael L. Metzker
  • Publication number: 20100290990
    Abstract: The present invention relates to a method for preparing a 2-fluoropurine marked with the radioisotope 18F comprising a fluorination step for a 2-nitropurine derivative. The present invention comprises a 2-fluoropurine derivative marked with the radioisotope 18F which can be obtained by or during a method according to the invention and its various uses.
    Type: Application
    Filed: December 23, 2008
    Publication date: November 18, 2010
    Inventors: Louisa Barre, Patrice Marchand
  • Patent number: 7816333
    Abstract: A method for the prevention or treatment in a mammal of a disease preventable or treatable by the pharmacologically useful antisense or antigene activity of an oligonucleotide analogue or a pharmacologically acceptable salt thereof in the body of said mammal, which method comprises administering to said mammal in need of such prevention or treatment a pharmaceutically effective amount of an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of said nucleoside units is a structure of the formula (2): wherein A is methylene; and B is an unsubstituted purin-9-yl, an unsubstituted 2-oxo-pyrimidin-1-yl or a substituted purin-9-yl; or a pharmacologically acceptable salt thereof.
    Type: Grant
    Filed: July 27, 2007
    Date of Patent: October 19, 2010
    Assignees: Daiichi Sankyo Company, Limited, Mitsubishi-Kagaku Foods Corporation
    Inventors: Masakatsu Kaneko, Koji Morita, Takeshi Imanishi
  • Publication number: 20100227327
    Abstract: Disclosed herein are methods and compositions for continuous single-molecule nucleic acid sequencing by synthesis with fluorogenic nucleotides.
    Type: Application
    Filed: March 5, 2010
    Publication date: September 9, 2010
    Inventors: Xiaoliang Sunney Xie, Peter A. Sims, William J. Greenleaf
  • Publication number: 20100152424
    Abstract: Nucleic acid compositions, methods of making and using such compositions that comprise modular functional groups that can be configured to provide desired functionality to different nucleotide types through a swappable and preferably non-covalent linkage component. Such compositions are useful in a variety of applications including nucleic acid analyses.
    Type: Application
    Filed: November 18, 2009
    Publication date: June 17, 2010
    Applicant: Pacific Biosciences of California, Inc.
    Inventors: Jonas Korlach, Jeffrey Wegener
  • Patent number: 7666851
    Abstract: This invention relates to the field of nucleic acid chemistry, more specifically to the field of compositions and processes that are nucleic acid analogs. More specifically, it relates to purine analogs that contain three rings, where the third ring bridges the exocyclic substituent at position 6 to position 7, using the purine numbering system. Still more specifically it relates to analogs having this structure that are able to form nucleobase pairs having the Watson-Crick geometry with a pyrimidine or pyrimidine analog, where the nucleobase pair is joined by hydrogen bonding patterns that either present a standard hydrogen bonding pattern, or a non-standard hydrogen bonding pattern. Most specifically, it to nucleoside analogs that are analogs of isoguanosine, but where the 5-6 ring system of the purine ring in isoguanosine is fused to another five- or six-membered ring, where the fused ring joins the exocyclic amino group with an atom that is, by analogy, at position 7 of the isoguanine ring system.
    Type: Grant
    Filed: May 18, 2006
    Date of Patent: February 23, 2010
    Inventor: Steven Albert Benner
  • Publication number: 20100041041
    Abstract: The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.
    Type: Application
    Filed: June 11, 2009
    Publication date: February 18, 2010
    Inventors: Vladislav A. LITOSH, Megan N. HERSH, Brian P. STUPI, Weidong WU, Michael L. METZKER
  • Publication number: 20100016250
    Abstract: The present invention provides TLR9 agonists comprising, as an active ingredient, a compound represented by formula (I): (wherein a represents 0 or 1; n represents an integer of 0 to 2; m represents an integer of 0 to 5; X1 and X2 each independently represent a hydrogen atom or hydroxy; Y represents an oxygen atom or a sulfur atom; -Q1-represents —O— or the like; -Q2- represents —O— or the like; -Z- represents —O— or the like; R1, R3 and R4 each independently represent hydroxy or the like; R2 and R5 each independently represent a hydrogen atom, hydroxy or the like; and A represents 6-aminopurin-9-yl or the like) or a pharmaceutically acceptable salt thereof, and the like.
    Type: Application
    Filed: April 13, 2007
    Publication date: January 21, 2010
    Applicant: KYOWA HAKKO KIRIN CO., LTD.
    Inventors: Hiroyuki Nagata, Michio Ichimura, Rieko Nakatsu, Shun-Ichi Ikeda, Ayako Kawabata, Toshio Ota, Masayuki Abe, Michio Takashima, Makoto Suzuki
  • Patent number: 7612047
    Abstract: 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. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.
    Type: Grant
    Filed: September 10, 2008
    Date of Patent: November 3, 2009
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: James G. Douglass, III, Benjamin R. Yerxa, Sammy R. Shaver, Ward M. Peterson, Edward G. Brown, Christopher S. Crean, José L. Boyer
  • Patent number: 7598230
    Abstract: 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: Grant
    Filed: June 14, 2007
    Date of Patent: October 6, 2009
    Assignee: Biota Scientific Management Pty Ltd
    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
  • Publication number: 20090215635
    Abstract: The present invention relates to methods and reagents for detecting analytes, e.g. nucleic acids. The new methods and reagents allow a simple and sensitive detection even in complex biological samples.
    Type: Application
    Filed: April 28, 2006
    Publication date: August 27, 2009
    Applicant: BASF SE
    Inventors: Thomas Carell, Anja Schwögler, Glenn A. Burley, Johannes Gierlich, Mohammad Reza Mofid
  • Publication number: 20090093623
    Abstract: A set of 4,7-dichlororhodamine compounds useful as fluorescent dyes are disclosed having the structures wherein R1-R6 are hydrogen, fluorine, chlorine, lower alkyl, lower alkene, lower alkyne, sulfonate, sulfone, amino, amido, nitrile, lower alkoxy, linking group, or, when taken together, R1 and R6 is benzo, or, when taken together, R4 and R5 is benzo; R7-R10, R12-R16 and R18 may be hydrogen, fluorine, chlorine, lower alkyl lower alkene, lower alkyne, sulfonate, sulfone, amino, amido, nitrile, lower alkoxy, linking group; R11 and R17 may be hydrogen, lower alkyl lower alkene, lower alkyne, phenyl, aryl, linking group; Y1-Y4 are hydrogen, lower alkyl or cycloalkyl, or, when taken together, Y1 and R2, Y2 and R1 Y3 and R3, and/or Y4 and R4 is propano, ethano, or substituted forms thereof, and X1-X3 taken separately are hydrogen, chlorine, fluorine, lower alkyl, carboxylate, sulfonate, hydroxymethyl, and linking group, or any combinations thereof.
    Type: Application
    Filed: August 27, 2008
    Publication date: April 9, 2009
    Applicant: Applied Biosystems Inc.
    Inventors: Linda G. Lee, Scott C. Benson, Barnett B. Rosenblum, Sandra L. Spurgeon, Ronald J. Graham
  • Patent number: 7476734
    Abstract: The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.
    Type: Grant
    Filed: December 6, 2005
    Date of Patent: January 13, 2009
    Assignee: Helicos Biosciences Corporation
    Inventor: David R. Liu
  • Publication number: 20090005550
    Abstract: The present invention concerns modified oligonucleotides and processes for their production wherein these oligonucleotides contain at least once the structure P?N-Acc where Acc is an electron acceptor or an electron acceptor substituted with a residue R and R is any organic substituent.
    Type: Application
    Filed: May 16, 2008
    Publication date: January 1, 2009
    Inventors: Dieter Heindl, Dirk Kessler
  • Publication number: 20090004101
    Abstract: The present invention provides a method of enhancing the absorption of molecules across the airway epithelium, thereby enhancing the delivery of desired therapeutic or diagnostic agents across the airway epithelium via the systemic circulation to the target site of action. The method comprises administration of a formulation comprising a pharmaceutical composition comprising a synthetic or natural nucleoside diphosphate, nucleoside triphosphate, or dinucleoside polyphosphate, together with a pharmaceutically acceptable carrier. Preferably the nucleotide is a P2Y receptor agonist which is administered at any time during treatment with a therapeutic or diagnostic agent. A preferred embodiment is a method of administering a pharmaceutical composition comprising a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds.
    Type: Application
    Filed: August 1, 2005
    Publication date: January 1, 2009
    Applicant: UNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITED
    Inventors: Glyn Taylor, Navdeep Thoofer, Richard Evans, Carole Evans, Benjamin Yerxa, Gregory Mossinghoff
  • Patent number: 7462733
    Abstract: Novel phosphonate compounds are provided including a phosphonoglyoxylamide ester, an ?-keto phosphonophosphinate ester, a carbonylbisphosphonate analog of a nucleotide, and a diazomethylenebisphosphonate analog of a nucleotide, as well as methods of making synthetically and medically useful ?-keto phosphonate compounds.
    Type: Grant
    Filed: July 30, 2002
    Date of Patent: December 9, 2008
    Assignee: University of Southern California
    Inventors: Charles E. McKenna, Boris A. Kashemirov, Patricia I. Bonaz-Krause
  • Publication number: 20080153774
    Abstract: The present invention provides a 4?-C-substituted-2-haloadenosine derivative represented by the following formula [I], [II], or [III]: (wherein X represents a halogen atom, R1 represents an ethynyl group or a cyano group, and R2 represents hydrogen, a phosphate residue, or a phosphate derivative residue). The present invention also provides a pharmaceutical composition containing the derivative and a pharmaceutically acceptable carrier therefor.
    Type: Application
    Filed: November 19, 2007
    Publication date: June 26, 2008
    Inventors: Satoru Kohgo, Hiroshi Ohrui, Eiichi Kodama, Masao Matsuoka, Hiroaki Mitsuya
  • Patent number: 7335765
    Abstract: A compound of the formula (1): wherein R1 and R2 are the same or different and represent a hydrogen atom, a hydroxyl protecting group, a phosphate group, or —P(R3)R4, wherein R3 and R4 are the same or different and represent a hydroxyl group, an amino group, an alkoxy group having from 1 to 4 carbon atoms, a cyanoalkoxy group having from 1 to 5 carbon atoms or an amino group substituted by an alkyl group having from 1 to 4 carbon atoms; A represents an alkylene group having from 1 to 4 carbon atoms and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group or a substituted 2-oxo-pyrimidin-1-yl group having a substituent ? selected from the group consisting of a hydroxyl group which may be protected, an alkoxy group having from 1 to 4 carbon atoms, a mercapto group which may be protected, an alkylthio group having from 1 to 4 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms, an amino group which may be protected, a mono- or di-alkylamino group which may b
    Type: Grant
    Filed: August 9, 2001
    Date of Patent: February 26, 2008
    Assignees: Daiichi Sankyo Company, Limited, Mitsubishi-Kagaku Foods Corporation
    Inventors: Masakatsu Kaneko, Koji Morita, Takeshi Imanishi
  • Patent number: 7314923
    Abstract: A probe for a gene or a primer for starting amplification comprising an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of the nucleoside units is a structure of the formula (2): wherein A represents a C1-C4 alkylene group, and B is an unsubstituted purin-9-yl group, an unsubstituted 2-oxo-pyrimidin-1-yl-group, a substituted purin-9-yl-group or a substituted 2-oxo-pyrimidin-1-yl group. Also a method for preventing or treating a disease preventable or treatable by the antisense or antigene activity of an oligonucleotide by administering the oligonucleotide analogue.
    Type: Grant
    Filed: May 5, 2003
    Date of Patent: January 1, 2008
    Assignees: Daiichi Sankyo Company, Limited, Mitsubishi-Kagaku Foods Corporation
    Inventors: Masakatsu Kaneko, Koji Morita, Takeshi Imanishi
  • Patent number: 7285658
    Abstract: 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: Grant
    Filed: February 28, 2003
    Date of Patent: October 23, 2007
    Assignee: 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
  • Patent number: 7268119
    Abstract: Nucleosides and nucleotides containing a tricyclic base portion thereof are useful for treating infectious diseases and proliferative disorders, such as viral infections or cancer respectively.
    Type: Grant
    Filed: February 14, 2007
    Date of Patent: September 11, 2007
    Assignee: Biota Scientific Management Pty Ltd
    Inventors: Phillip Dan Cook, Deborah K. Ewing, legal representative, Yi Jin, John Lambert, Marija Prhavc, Vasanthankumar Rajappan, Vivek K. Rajwanshi, Kandasamy Sakthivel, Gregory Ewing, deceased
  • Patent number: 7115585
    Abstract: 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: Grant
    Filed: February 27, 2002
    Date of Patent: October 3, 2006
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, James G. Douglass, III, Sammy Ray Shaver, Ward M. Peterson, Edward G. Brown, Christopher S. Crean
  • Patent number: 7091334
    Abstract: The present invention provides new methods for the synthesis of the therapeutic dinucleotide, P1,P4-di(uridine 5?)-tetraphosphate, and demonstrates applicability to the production of large quantities. The methods of the present invention substantially reduce the time period required to synthesize diuridine tetraphosphate, preferably to three days or less. The novel tetrammonium and tetrasodium salts of P1,P4-di(uridine 5?)-tetraphosphate (Formula I) prepared by these methods are stable, soluble, nontoxic, and easy to handle during manufacture. wherein: X is Na, NH4 or H, provided that all X groups are not H.
    Type: Grant
    Filed: July 20, 2004
    Date of Patent: August 15, 2006
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, William Pendergast
  • Patent number: 7056894
    Abstract: The present invention provides compounds having the formula: wherein A is chosen from a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group; both B and C are hydrogen, or either B or C is a halogen, amino, or thiol group and the other of B or C is hydrogen; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.
    Type: Grant
    Filed: January 4, 2002
    Date of Patent: June 6, 2006
    Assignee: Albert Einstein College of Medicine of Yeshiva University
    Inventors: Anthony A. Sauve, Vern L. Schramm
  • Patent number: 7026469
    Abstract: The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds, which comprise a phosphocholine moiety covalently conjugated with one or more therapeutic agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus.
    Type: Grant
    Filed: April 27, 2001
    Date of Patent: April 11, 2006
    Assignees: Wake Forest University School of Medicine, University of North Carolina at Chapel
    Inventors: Louis S. Kucera, Ronald A. Fleming, Khalid S. Ishaq, Gregory L. Kucera, Susan L. Morris-Natschke
  • Patent number: 7022680
    Abstract: The present invention provides compounds having the formula: wherein A is a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group, the group being further substituted with an electron contributing moiety; B is hydrogen, or a halogen, amino, or thiol group; C is hydrogen, or a halogen, amino, or thiol group; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.
    Type: Grant
    Filed: May 30, 2002
    Date of Patent: April 4, 2006
    Assignee: Albert Einstein College of Medicine of Yeshiva University
    Inventors: Anthony A. Sauvé, Vern L. Schramm