Patents Represented by Attorney Isis Patent Department
  • Patent number: 8338185
    Abstract: Provided herein are methods for determining potency of RNAi agents. Such methods include, but are not limited to, cell-based and cell-free assays that measure binding of an RNAi agent with Ago2 or that measure Ago2 activity in the presence of such RNAi agents. Also provided are assays that determine potency of RNAi agents by assessing their ability to compete with other RNAi agents, including control RNAi agents, for binding and/or activation of Ago2.
    Type: Grant
    Filed: December 5, 2011
    Date of Patent: December 25, 2012
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Walter F. Lima, Timothy Vickers, Stanley T. Crooke
  • Patent number: 7919612
    Abstract: Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2? substituent group on a sugar moiety that is not H or OH. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide of the oligomer has a modified sugar and/or backbone modification.
    Type: Grant
    Filed: November 4, 2003
    Date of Patent: April 5, 2011
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Brenda F. Baker, Anne B. Eldrup, Muthiah Manoharan, Balkrishen Bhat, Richard Griffey, Eric E. Swayze, Stanley T. Crooke, Thazha P. Prakash
  • Patent number: 7884086
    Abstract: The present invention provides methods of identifying oligomeric compounds, such as siRNA and double-stranded RNA compounds, having bioactivity in vivo, and kits.
    Type: Grant
    Filed: September 7, 2005
    Date of Patent: February 8, 2011
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: C. Frank Bennett, Robert McKay, Brett P. Monia, Brenda F. Baker, Namir Sioufi
  • Patent number: 7825215
    Abstract: Compositions and methods are provided for the nucleic acid mimic determination of nucleic acids. The compositions and methods may be used in the diagnosis and treatment of diseases amenable through modulation of nucleic acids which encode proteins that are implicated in disease states. In accordance with preferred embodiments, mimics are comprised of non-naturally occurring backbones to which are appended modified heterocyclic bases. Such bases preferably have sterically bulky substituents 1, 2, or 3 atoms removed from the sites of attachment to the backbone.
    Type: Grant
    Filed: March 8, 1996
    Date of Patent: November 2, 2010
    Inventors: Leif Christensen, Henrik Frydenlund Hansen, Peter E. Nielsen
  • Patent number: 7812149
    Abstract: Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2?-F substituent group on a sugar moiety. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleoside of the oligomer has a modified sugar and/or backbone modification.
    Type: Grant
    Filed: November 4, 2003
    Date of Patent: October 12, 2010
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Thazha P. Prakash, Brenda F. Baker, Anne B. Eldrup, Muthiah Manoharan, Balkrishen Bhat, Richard Griffey, Eric E. Swayze, Stanley T. Crooke
  • Patent number: 7790691
    Abstract: The present invention provides double stranded compositions that have a region that is complementary to a target nucleic acid. One of the targeting strand or the second strand comprises linked ribofuranosyl nucleosides and the other strand comprises linked modified nucleosides that have 3?-endo conformational geometry. The strands can be linked together or separate and may contain additional groups. The present invention also provides methods of using the compositions for modulating gene expression.
    Type: Grant
    Filed: June 3, 2004
    Date of Patent: September 7, 2010
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Bryan A. Kraynack, Brenda F. Baker, Balkrishen Bhat, Eric E. Swayze, Richard H. Griffey
  • Patent number: 7759480
    Abstract: A process of manufacturing oligonucleotides includes a 5?-deblocking step in which the 5-blocking group is removed with dichloroacetic acid that is essentially free of chloral. The process is useful for making oligonucleotides that are substantially free of chloral adducts.
    Type: Grant
    Filed: January 29, 2007
    Date of Patent: July 20, 2010
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Achim Krotz, Daniel C. Capaldi, Hans-Joachim Josef Gaus, Brett Turney
  • Patent number: 7723511
    Abstract: Methods for the formation of sulfurized oligonucleotides are provided. The methods allow for the formation of phosphorothioate linkages in the oligonucleotides or derivatives, without the need for complex solvent mixtures and repeated washing or solvent changes. Oligonucleotides having from about 8, and up to about 50, nucleotides can be sulfurized according to the methods of the invention with higher yields than have been previously reported.
    Type: Grant
    Filed: April 21, 2008
    Date of Patent: May 25, 2010
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Douglas L. Cole, Vasulinga Ravikumar, Zacharia S. Cheruvallath
  • Patent number: 7718810
    Abstract: Universal linkers, their facile processes of manufacture and methods of using the same are provided.
    Type: Grant
    Filed: July 17, 2008
    Date of Patent: May 18, 2010
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Vasulinga Ravikumar, Muthiah Manoharan, Andrei P. Guzaev, Zhiwei Wang, Raju K. Kumar
  • Patent number: 7576119
    Abstract: Universal linkers, their facile processes of manufacture and methods of using the same are provided.
    Type: Grant
    Filed: January 11, 2007
    Date of Patent: August 18, 2009
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Vasulinga Ravikumar, Muthiah Manoharan, Andrei P. Guzaev, Zhiwei Wang, Raju K. Kumar
  • Patent number: 7569659
    Abstract: The invention concerns compositions comprising a nucleic acid mimic. The compositions may be used in the diagnosis and treatment of diseases amenable through modulation of nucleic acids which encode proteins that are implicated in disease states. In accordance with preferred embodiments, mimics are comprised of non-naturally occurring backbones to which are appended modified heterocyclic bases. Such bases preferably have sterically bulky substituents 1, 2, or 3 atoms removed from the sites of attachment to the backbone.
    Type: Grant
    Filed: March 7, 1997
    Date of Patent: August 4, 2009
    Inventors: Leif Christensen, Henrik Frydenlund Hansen, Peter E. Nielsen
  • Patent number: 7511125
    Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.
    Type: Grant
    Filed: August 19, 2004
    Date of Patent: March 31, 2009
    Assignee: Carlsbad
    Inventors: Kuei-Ying Lin, Mark D. Matteucci
  • Patent number: 7491524
    Abstract: The present invention provides polynucleotides encoding human RNase III and polypeptides encoded thereby. Methods of using said polynucleotides and polypeptides are also provided.
    Type: Grant
    Filed: December 2, 2004
    Date of Patent: February 17, 2009
    Assignee: Isis Pharmaceuticals, Inc.
    Inventor: Stanley T. Crooke
  • Patent number: 7446193
    Abstract: Methods for detecting chloral hydrate in dichloroacetic acid are described.
    Type: Grant
    Filed: February 1, 2007
    Date of Patent: November 4, 2008
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Patrick Wheeler, Daniel C. Capaldi
  • Patent number: 7427675
    Abstract: The present invention relates to oligonucleotide synthesis. In particular, the present invention provides methods for characterizing samples useful for making oligonucleotides.
    Type: Grant
    Filed: August 22, 2005
    Date of Patent: September 23, 2008
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Daniel C. Capaldi, Hans-Joachim Josef Gaus, Claus Andre Frank Rentel, Philip Dmitri Olsen, Christine C. Kurata, Quanlai Song
  • Patent number: 7378485
    Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.
    Type: Grant
    Filed: May 23, 2002
    Date of Patent: May 27, 2008
    Inventors: Ole Buchardt, Michael Egholm, Peter Eigil Nielsen, Rolf Henrik Berg
  • Patent number: 7348391
    Abstract: The present invention provides solid support media for use in oligomer synthesis, methods of producing the media, and methods of using the media. In some embodiments, the processes of the invention comprise (a) providing an organic phase comprising an olefin monomer, a cross-linker, a functionalizing reagent and an initiator; and (b) contacting the organic phase with an aqueous phase under conditions of time and temperature effective to form the polymeric bead.
    Type: Grant
    Filed: September 2, 2005
    Date of Patent: March 25, 2008
    Assignees: Isis Pharmaceuticals, Inc., Nitto Denko Corporation
    Inventors: Vasulinga Ravikumar, Raju K. Kumar, Kenjirou Mori, Tatsuya Konishi, Ayako Matsunawa, Takeo Matsumura, Cheiko Kitaura, Gang Zhao
  • Patent number: 7285537
    Abstract: For use in controlling biologic functions in an organism, a stabilized oligonucleotide, preferably in a phosphotriester form, having a base sequence substantially complementary to a portion of messenger ribonucleic acid coding for a biological component, such as a protein, of the organism. The oligonucleotide has about fourteen bases or more, such as twenty-three bases, and can be a deoxyribo-nucleotide. The oligonucleotide sequence can be derived from the organism's ribonucleic or deoxyribonucleic acid that codes for a vital protein, and can be synthesized in bulk either chemically or by insertion into a plasmid.
    Type: Grant
    Filed: June 16, 1993
    Date of Patent: October 23, 2007
    Assignee: ISIS Pharmaceuticals, Inc.
    Inventor: Richard H. Tullis
  • Patent number: 7235650
    Abstract: Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2?-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2?-deoxy-2?-fluoro, 2?-O-methoxy, 2?-O-ethoxy, 2?-O-propoxy, 2?-O-aminoalkoxy or 2?-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3? or the 5? positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.
    Type: Grant
    Filed: October 31, 2002
    Date of Patent: June 26, 2007
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Muthiah Manoharan, Phillip Dan Cook, Clarence Frank Bennett
  • Patent number: 7227016
    Abstract: Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, phosphorodithioate, or other covalent linkages. The oligomers have substantially reduced exocyclic adducts deriving from acrylonitrile or related contaminants.
    Type: Grant
    Filed: December 28, 2004
    Date of Patent: June 5, 2007
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Vasulinga T. Ravikumar, Muthiah Manoharan, Daniel C. Capaldi, Achim Krotz, Douglas L. Cole, Andrei Guzaev