Patents Assigned to ISIS Pharmaceuticals Inc.
  • SELECTIVE REDUCTION OF ALLELIC VARIANTS
    Publication number: 20130046008
    Abstract: Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD).
    Type: Application
    Filed: February 8, 2011
    Publication date: February 21, 2013
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: C. Frank Bennett, Michael Hayden, Susan M. Freier, Sarah Greenlee, Jeffrey Carroll, Simon Warby, Eric E. Swayze
  • SELECTIVE REDUCTION OF ALLELIC VARIANTS
    Publication number: 20130046007
    Abstract: Disclosed herein are antisense compounds and methods for selectively of reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative, such as Huntington's Disease (HD).
    Type: Application
    Filed: February 8, 2011
    Publication date: February 21, 2013
    Applicant: Isis Pharmaceuticals Inc.
    Inventors: C. Frank Bennett, Susan M. Freier, Sarah Greenlee, Eric E. Swayze
  • Compositions and methods for non-parenteral delivery of oligonucleotides
    Patent number: 8377897
    Abstract: The present invention relates to compositions and methods which enhance the local and systemic uptake and delivery of oligonucleotides and nucleic acids via non-parenteral routes of administration. Pharmaceutical compositions comprising oligonucleotides disclosed herein include, for systemic delivery, emulsion and microemulsion formulations for a variety of applications and oral dosage formulations. It has also surprisingly been discovered that oligonucleotides may be locally delivered to colonic sites by rectal enemas and suppositories in simple solutions, e.g., neat or in saline. Such pharmaceutical compositions of oligonucleotides may further include one or more penetration enhancers for the transport of oligonucleotides and other nucleic acids across mucosal membranes.
    Type: Grant
    Filed: September 28, 2005
    Date of Patent: February 19, 2013
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Ching-Leou Teng, Phillip Dan Cook, Lloyd Tillman, Gregory E. Hardee, David J. Ecker, Muthiah Manoharan
  • Antibacterial 4,6-substituted 6?, 6? and 1 modified aminoglycoside analogs
    Patent number: 8377896
    Abstract: The present invention is directed to analogs of aminoglycoside compounds as well as their preparation and use as prophylactic or therapeutics against microbial infection.
    Type: Grant
    Filed: March 9, 2011
    Date of Patent: February 19, 2013
    Assignee: Isis Pharmaceuticals, Inc
    Inventors: Michael T. Migawa, Xiaojing Wang, Eric E. Swayze, Richard H. Griffey
  • BASE MODIFIED BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM
    Publication number: 20130041011
    Abstract: Provided herein are novel base modified bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, novel pyrimidine bicyclic nucleosides are provided wherein each pyrimidine base is substituted at the 5 position with an optionally substituted, aromatic or heteroaromatic ring system comprising from 5 to 7 ring atoms selected from C, N, O and S. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
    Type: Application
    Filed: January 6, 2011
    Publication date: February 14, 2013
    Applicant: ISIS PHARMACEUTICALS, INC.
    Inventors: Charles Allerson, Balkrishen Bhat, Eric E. Swayze
  • 5'-SUBSTITUTED BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM
    Publication number: 20130041144
    Abstract: Provided herein are novel 5?-(S)—CH3 substituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the furanose ring of each of the novel 5?-(S)—CH3 substituted bicyclic nucleosides includes a 2? to 4? bridging group. The 5?-(S)—CH3 substituted bicyclic nucleosides are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as for example increasing the binding affinity. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
    Type: Application
    Filed: March 10, 2011
    Publication date: February 14, 2013
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: Michael T. Migawa, Thazha P. Prakash, Charles Allerson, Balkrishen Bhat, Punit P. Seth, Eric E. Swayze
  • Compounds and methods for modulating expression of GCCR
    Patent number: 8372967
    Abstract: The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
    Type: Grant
    Filed: May 7, 2007
    Date of Patent: February 12, 2013
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Sanjay Bhanot, Richard Geary, Robert McKay, Brett P. Monia, Punit P. Seth, Andrew M. Siwkowski, Eric E. Swayze, Edward Wancewicz
  • COMPOSITIONS AND METHODS FOR MODULATION OF LMNA EXPRESSION
    Publication number: 20130035370
    Abstract: Disclosed herein are compounds, compositions and methods for modulating the expression of LMNA in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Further provided are methods of identifying cis splicing regulatory elements of a selected mRNA using the disclosed compounds.
    Type: Application
    Filed: August 3, 2012
    Publication date: February 7, 2013
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: C. Frank Bennett, Kenneth W. Dobie, Susan M. Freier, Stanley T. Crooke
  • DOUBLE STRAND COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENE MODULATION
    Publication number: 20130035369
    Abstract: The present invention provides double stranded compositions wherein the first strand is modified to have a particular motif and the second strand is modified a selected motif. More particularly, the present compositions comprise an antisense strand that is modified to have a positional/full motif and the sense strand is modified to have an alternating motif, a hemimer motif, a blockmer motif, a gapped motif, a positional motif, a positional/full motif or a fully modified motif. Each strand further comprises one or more phosphorothioate internucleoside linkage. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes.
    Type: Application
    Filed: August 3, 2012
    Publication date: February 7, 2013
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: Balkrishen Bhat, Thazha P. Prakash, Charles Allerson, Garth A. Kinberger, Eric G. Marcusson, Eric E. Swayze
  • Compositions and methods for modulation of SMN2 splicing
    Patent number: 8361977
    Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.
    Type: Grant
    Filed: June 23, 2006
    Date of Patent: January 29, 2013
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Brenda F. Baker, Adrian R. Krainer, Yimin Hua
  • Compounds and methods for modulating expression of SGLT2
    Patent number: 8362232
    Abstract: The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
    Type: Grant
    Filed: September 15, 2010
    Date of Patent: January 29, 2013
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Sanjay Bhanot, Richard S. Geary, Robert McKay, Brett P. Monia, Punit P. Seth, Andrew M. Siwkowski, Eric E. Swayze, Edward Wancewicz
  • MODULATION OF ANGIOPOIETIN-LIKE 3 EXPRESSION
    Publication number: 20130023579
    Abstract: Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing plasma lipids, plasma glucose and atherosclerotic plaques in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disease, or a symptom thereof.
    Type: Application
    Filed: January 7, 2011
    Publication date: January 24, 2013
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: Rosanne M. Crooke, Mark J. Graham, Richard Lee, Kenneth W. Dobie
  • ANTIBACTERIAL 4,5-SUBSTITUTED AMINOGLYCOSIDE ANALOGS HAVING MULTIPLE SUBSTITUENTS
    Publication number: 20130005674
    Abstract: The present invention is directed to analogs of aminoglycoside compounds as well as their preparation and use as prophylactic or therapeutics against microbial infection.
    Type: Application
    Filed: January 5, 2012
    Publication date: January 3, 2013
    Applicant: ISIS Pharmaceuticals, Inc.
    Inventors: Eric E. Swayze, Stephen Hanessian, Janek Szychowski, Susanta Sekhar Adhikari, Kandasamy Pachamuthu, Xiaojing Wang, Michael T. Migawa, Richard H. Griffey
  • Methods of determining potency of chemically-synthesized oligonucleotides
    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
  • Modulation of factor 11 expression
    Patent number: 8334372
    Abstract: Disclosed herein are antisense compounds and methods for decreasing Factor 11 and treating or preventing thromboembolic complications in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 11 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Antisense compounds targeting Factor 11 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism.
    Type: Grant
    Filed: October 15, 2009
    Date of Patent: December 18, 2012
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Susan M. Freier, Brett P. Monia, Hong Zhang, Chenguang Zhao, Jeffrey R. Crosby, Andrew M. Siwkowski
  • COMPOSITIONS AND THEIR USES DIRECTED TO IL-4R ALPHA
    Publication number: 20120316221
    Abstract: Disclosed herein are compounds, compositions and methods for modulating the expression of IL-4R alpha in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders related to expression of IL 4R-?, airway hyperresponsiveness, and/or pulmonary inflammation.
    Type: Application
    Filed: February 29, 2012
    Publication date: December 13, 2012
    Applicant: ISIS PHARMACEUTICALS, INC.
    Inventors: JAMES G. KARRAS, SUSAN GREGORY, JEFFREY R. CROSBY, MAUSUMEE GUHA, DAVID TUNG, SUSAN M. FREIER, KENNETH W. DOBIE
  • MODULATION OF APOLIPOPROTEIN(A) EXPRESSION
    Publication number: 20120316219
    Abstract: Compounds, compositions and methods are provided for modulating the expression of apolipoprotein(a). The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein(a). Methods of using these compounds for modulation of apolipoprotein(a) expression and for diagnosis and treatment of disease associated with expression of apolipoprotein(a) are provided.
    Type: Application
    Filed: January 18, 2012
    Publication date: December 13, 2012
    Applicant: Isis Pharmaceuticals, Inc.
    Inventors: Rosanne M. Crooke, Mark J. Graham
  • COMPOSITIONS AND METHODS FOR TOPICAL DELIVERY OF OLIGONUCLEOTIDES
    Publication number: 20120309815
    Abstract: The present invention relates to compositions and methods which enhance the delivery of nucleic acids and other nucleosidic moieties via topical routes of administration. The invention relates to the use of an aqueous solution to preferentially deliver nucleic acids preferentially to hair follicles. The invention relates to a method of inhibiting hair growth comprising administration of a nucleic acid preferentially to a hair follicle.
    Type: Application
    Filed: April 4, 2012
    Publication date: December 6, 2012
    Applicant: ISIS PHARMACEUTICALS, INC.
    Inventors: Sujatha Dokka, Scott Cooper, Susan Kelly, Greg Hardee, James G. Karras
  • Compounds and methods for improving cellular uptake of oligomeric compounds
    Patent number: 8318496
    Abstract: The present invention provides method of optimizing the efficacy and potency of antisense drugs. In certain embodiments, the invention provides assays useful for determining favorable oligonucleotide characteristics and excipeints for improved cellular uptake.
    Type: Grant
    Filed: October 6, 2008
    Date of Patent: November 27, 2012
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Erich Koller, C. Frank Bennett
  • PROINFLAMMATORY NUCLEIC ACIDS
    Publication number: 20120295272
    Abstract: The present invention provides compositions and methods for identifying and utilizing proinflammatory nucleic acids. In particular, this invention relates to compounds, particularly oligonucleotides, which exert their effect through triggering receptors expressed by myeloid cells (TREMs), specifically TREM 2.
    Type: Application
    Filed: December 12, 2011
    Publication date: November 22, 2012
    Applicant: Isis Pharmaceuticals, Inc.
    Inventor: Joseph Senn