Patents Assigned to ISIS Pharmaceuticals Inc.
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Publication number: 20160046939Abstract: 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: ApplicationFiled: July 28, 2015Publication date: February 18, 2016Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Thazha P. Prakash, Punit P. Seth, Eric E. Swayze
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Publication number: 20160032285Abstract: Disclosed are methods for modulating splicing of Tau mRNA in an animal with Tau antisense compounds. Also disclosed herein are methods for reducing expression of Tau mRNA and protein in an animal with Tau antisense compounds. Such compounds and methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Examples of neurodegenerative diseases that can be treated, prevented, and ameliorated with the administration Tau antisense oligonucleotides include Alzheimer's Disease, Fronto-temporal Dementia (FTD), FTDP-17, Progressive Supranuclear Palsy, Chronic Traumatic Encephalopathy, Epilepsy, and Dravet's Syndrome.Type: ApplicationFiled: March 14, 2014Publication date: February 4, 2016Applicant: Isis Pharmaceuticals, Inc.Inventors: Frank Rigo, C. Frank Bennett
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Publication number: 20160024496Abstract: Disclosed herein are methods for monitoring expression of C9ORF72 mRNA and protein in an animal with C9ORF72 specific inhibitors. Such C9ORF72 specific inhibitors include antisense compounds.Type: ApplicationFiled: October 15, 2013Publication date: January 28, 2016Applicants: The Johns Hopkins University, Isis Pharmaceuticals, Inc.Inventors: C. Frank Bennett, Susan M. Freier, Jeffrey D. Rothstein, Christopher Donnelly, Rita G. Sattler
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Patent number: 9243291Abstract: Described herein are compounds useful for the treatment and investigation of diseases, methods for the prediction of in vivo toxicity of compounds useful for the treatment and investigation of diseases, and methods of discovering and identifying compounds useful for the treatment and investigation of diseases that have reduced in vivo toxicity.Type: GrantFiled: December 3, 2012Date of Patent: January 26, 2016Assignee: Isis Pharmaceuticals, Inc.Inventor: Sebastien Burel
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Publication number: 20160017323Abstract: Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.Type: ApplicationFiled: June 19, 2015Publication date: January 21, 2016Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Thazha P. Prakash, Punit P. Seth, Eric E. Swayze
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Publication number: 20160017328Abstract: The present invention provides double stranded compositions wherein each strand is modified to have a motif defined by positioning of ?-D-ribonucleosides and sugar modified nucleosides. More particularly, the present compositions comprise one strand having an alternating motif and another strand having a hemimer motif, a blockmer motif, a fully modified motif or a positionally modified motif. At least one of the strands has complementarity to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.Type: ApplicationFiled: July 21, 2015Publication date: January 21, 2016Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Balkrishen Bhat, Thaza P. Prakash, Charles Allerson, Richard H. Griffey, Eric E. Swayze
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Publication number: 20160017324Abstract: Oligomer 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 at least one nucleotide comprising a chimeric organic composition. 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 comprising a chimeric organic composition.Type: ApplicationFiled: June 22, 2015Publication date: January 21, 2016Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Brenda F. Baker, Anne B. Eldrup, Muthiah Manoharan, Balkrishen Bhat, Richard H. Griffey, Eric E. Swayze, Stanley T. Crooke
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Publication number: 20160010086Abstract: The present invention provides method of optimizing the efficacy and potency of antisense compounds. In certain embodiments, the invention provides assays useful for determining favorable oligonucleotide characteristics and excipients for improved cellular uptake.Type: ApplicationFiled: December 2, 2014Publication date: January 14, 2016Applicant: ISIS PHARMACEUTICALS, INC.Inventors: C. FRANK BENNETT, RICHARD S. GEARY, ERIC E. SWAYZE, ANDREW M. SIWKOWSKI
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Publication number: 20160002625Abstract: In certain embodiments, methods, compounds, and compositions for treating B-cell lymphoma or hepatocellular carcinoma by inhibiting expression of ST AT3 mRNA or protein in an animal are provided herein. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate B-cell lymphoma or hepatocellular carcinoma. The STAT (signal transducers and activators of transcription) family of proteins are DNA-binding proteins that play a dual role in signal transduction and activation of transcription.Type: ApplicationFiled: October 30, 2013Publication date: January 7, 2016Applicant: ISIS PHARMACEUTICALS INC.Inventors: Stanley T. CROOKE, Mason YAMASHITA
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Publication number: 20160002624Abstract: The present disclosure provides compositions comprising an antisense oligonucleotide and one or more excipients that modulates viscosity, turbidity or both viscosity and turbidity. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity are provided. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low turbidity are provided. In certain embodiments, pharmaceutical compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity and turbidity are provided.Type: ApplicationFiled: May 17, 2013Publication date: January 7, 2016Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Andrew Dibble, Lloyd Tillman, Bret Coldren, Marc Lim
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Publication number: 20160002627Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. 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: ApplicationFiled: January 9, 2014Publication date: January 7, 2016Applicant: Isis Pharmaceuticals. Inc.Inventors: C. Frank Bennett, Gene Hung, Frank Rigo
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Publication number: 20150376625Abstract: The present disclosure provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. In certain embodiments, certain oligomeric compounds selectively reduce the expression of a target nucleic acid transcript relative to a non-target nucleic acid transcript.Type: ApplicationFiled: February 4, 2014Publication date: December 31, 2015Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Michael Oestergaard, Punit P. Seth, Eric E. Swayze
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Publication number: 20150376623Abstract: This invention provides compounds which comprise modified oligonucleotides capable of inhibitory expression of connective tissue factor and composition containing same as well as methods of treating hyperprolific disorders and fibrotic diseases, and of reducing scarring resulting from wound healing using such compounds.Type: ApplicationFiled: June 29, 2015Publication date: December 31, 2015Applicants: EXCALIARD PHARMACEUTICALS, INC., ISIS PHARMACEUTICALS, INC.Inventors: Nicholas M. Dean, J. Gordon Foulkes, Niall O'Donnell, C. Frank Bennett, Susan M. Freier
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Publication number: 20150376614Abstract: Provided are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein for treating, preventing, delaying, or ameliorating Fredrickson Type I dyslipidemia/FCS/LPLD, in a patient. Such methods, compounds, and compositions increase HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in the patient, and are useful to treat, prevent, delay, or ameliorate any one or more of pancreatitis, cardiovascular disease, metabolic disorder, and associated symptoms.Type: ApplicationFiled: February 14, 2014Publication date: December 31, 2015Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Veronica J. Alexander, Nicholas J. Viney, Joseph L. Witztum
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Patent number: 9221864Abstract: The present disclosure provides tricyclic nucleosides and oligomeric compounds prepared therefrom. The tricyclic nucleosides each have a tricyclic ribosyl sugar moiety wherein a bridge between the 2? and 4? ribosyl ring carbon atoms further comprises a fused carbocyclic or heterocyclic ring. The tricyclic nucleosides are expected to be useful for enhancing properties of oligomeric compounds including for example binding affinity and nuclease resistance.Type: GrantFiled: March 20, 2013Date of Patent: December 29, 2015Assignee: Isis Pharmaceuticals, Inc.Inventors: Punit P. Seth, Eric E. Swayze, Stephen Hanessian, Benjamin R. Schroeder, Robert D. Giacometti, Bradley L. Merner
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Publication number: 20150366894Abstract: 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?-OCH3 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 nucleotide of the oligomer has a modified sugar and/or backbone modification.Type: ApplicationFiled: April 17, 2015Publication date: December 24, 2015Applicant: ISIS PHARMACEUTICALS, INC.Inventor: Stanley T. Crooke
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Publication number: 20150368288Abstract: Provided herein are methods for the synthesis of oligomeric compounds wherein the standard coupling protocols are modified when coupling bicyclic nucleosides of Formula I. More particularly, the modified coupling protocols provide for a decrease in the ratio of phosphoramidite solution to activator solution in the coupling reagent with an increased contact time. The modified coupling protocols provide for oligomeric compounds having comparable yields to similar oligomeric compounds having modified nucleosides other than bicyclic nucleosides of Formula I.Type: ApplicationFiled: January 30, 2014Publication date: December 24, 2015Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Isaiah E. Cedillo, Michael T. Migawa, W. Brad Wan
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Publication number: 20150353929Abstract: 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: ApplicationFiled: December 29, 2014Publication date: December 10, 2015Applicants: COLD SPRING HARBOR LABORATORY, ISIS PHARMACEUTICALS, INC.Inventors: Brenda F. Baker, Adrian R. Krainer, Yimin Hua
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Publication number: 20150344879Abstract: 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: ApplicationFiled: April 28, 2015Publication date: December 3, 2015Applicant: 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
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Publication number: 20150337303Abstract: Disclosed herein are antisense compounds and methods for decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) or Lp(a). Certain diseases, disorders or conditions related to apo(a) or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The antisense compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.Type: ApplicationFiled: November 24, 2014Publication date: November 26, 2015Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Rosanne M. Crooke, Mark J. Graham, Susan M. Freier, Marc Lim, Andrew Dibble