Abstract: It is an object of the instant invention to provide a method for the rapid evaluation of novel sugar modifications to be used in siRNA synthesis including the rapid evaluation of chemical modification patterns within the siRNA to effectuate increased stability and ultimately increased efficacy of a siRNA therapeutic. It is a further object of the instant invention to provide novel nucleosides useful for siRNA therapy.
Type:
Grant
Filed:
October 3, 2014
Date of Patent:
December 6, 2016
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Gabor Butora, Ian W. Davies, William Michael Flanagan, Wenlang Fu, Denise M. Kenski, Ning Qi
Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of HBV gene expression and/or activity, and/or modulate a HBV gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against HBV gene expression.
Type:
Grant
Filed:
April 9, 2015
Date of Patent:
October 11, 2016
Assignee:
Sirna Therapeutics, Inc.
Inventors:
Steven Bartz, Duncan Brown, Michael Robinson
Abstract: The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.
Abstract: The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids comprising at least one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.
Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of CTNNB1 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against CTNNB1 gene expression.
Type:
Grant
Filed:
July 23, 2014
Date of Patent:
September 20, 2016
Assignee:
Sirna Therapeutics, Inc.
Inventors:
Duncan Brown, James J. Cunningham, Marian Gindy, Victoria Pickering, Matthew G. Stanton, Steven M. Stirdivant, Walter R. Strapps
Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against target gene expression.
Type:
Application
Filed:
December 30, 2015
Publication date:
September 15, 2016
Applicant:
SIRNA THERAPEUTICS, INC.
Inventors:
Mark Cancilla, James John Cunningham, Michael William Flanagan, Henry J. Haringsma, Denise M. Kenski, Matthew G. Stanton, Steven M. Stirdivant, Aarron T. Willingham
Abstract: This invention relates to a 2?-modified RNA agent comprising at least one RNA strand containing a 2?-O substituent having an alkyne functional group attaching to the O atom at the 2?-position on one or more ribose rings, wherein the 2?-O substituent is located at one or more of positions 2, 3, 4, 7, 8, 9, 10, 11, 13, 14, and 16, from 5?-end of the RNA strand. This invention also relates to a 2?-modified RNA agent comprising at least one RNA strand containing a 2?-O substituent having a triazole functional group attaching to the O atom at the 2?-position on one or more ribose rings, wherein the 2?-O substituent is located at one or more of positions 2, 3, 4, 7, 8, 9, 10, 11, 13, 14, and 16, from 5?-end of the RNA strand.
Abstract: The present invention provides methods comprising the in vivo delivery of small nucleic acid molecules capable of mediating RNA interference and reducing the expression of myostatin, wherein the small nucleic acid molecules are introduced to a subject by systemic administration. Specifically, the invention relates to methods comprising the in vivo delivery of short interfering nucleic acid (siNA) molecules that target a myostatin gene expressed by a subject, wherein the siNA molecule is conjugated to a lipophilic moiety, such as cholesterol. The myostatin siNA conjugates that are delivered as per the methods disclosed are useful to modulate the in vivo expression of myostatin, increase muscle mass and/or enhance muscle performance. Use of the disclosed methods is further indicated for treating musculoskeletal diseases or disorders and/or diseases or disorders that result in conditions in which muscle is adversely affected.
Type:
Application
Filed:
November 10, 2014
Publication date:
September 8, 2016
Applicant:
SIRNA THERAPEUTICS, INC.
Inventors:
Marija Tadin-Strapps, Tayeba Khan, Walter Richard Strapps, Laura Sepp-Lorenzino, Vasant Jadhav, Duncan Brown
Abstract: Single-stranded RNA molecules comprise one or more internal, non-nucleotide spacers, covalently linked with nucleotide portions of the molecule are provided. The single-stranded RNA molecules function as guide or antisense strands that are capable of inhibiting gene expression via an RNA interference mechanism, and thus represent single-stranded RNAi agents. The single-stranded RNAi molecules can be used in methods for a variety of therapeutic, diagnostic, target validation, genomic discovery, genetic engineering, and pharmacogenomic applications.
Type:
Application
Filed:
December 14, 2015
Publication date:
August 4, 2016
Applicant:
SIRNA THERAPEUTICS, INC.
Inventors:
Lee Lim, Guillaume Chorn, Aarron T. Willingham, Lihong Zhao
Abstract: The present invention provides membrane lytic poly(amido amine) polymers, polyconjugates, compositions and methods for the delivery of oligonucleotides for therapeutic purposes.
Type:
Grant
Filed:
October 3, 2014
Date of Patent:
August 2, 2016
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Marina Busuek, Rubina G. Parmar, Michael Steven Poslusney, Weimin Wang, J. Michael Williams
Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of IDH1 and mutant IDH1 gene expression and/or activity, and/or modulate an IDH1 or mutant IDH1 gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules, including small nucleic acid molecules such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules, that are capable of mediating or that mediate RNA interference (RNAi) against IDH1 or mutant IDH1 gene expression.
Abstract: The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.
Type:
Grant
Filed:
May 13, 2015
Date of Patent:
April 19, 2016
Assignee:
Sirna Therapeutics, Inc.
Inventors:
Brian W. Budzik, Steven L. Colletti, Jennifer R. Davis, Ivory D. Hills, Darla Danile Seifried, Matthew G. Stanton
Abstract: The present invention relates to RNAi molecules, and compositions thereof, comprising a 2? internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5? end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5? modified nucleotides that comprise, among other potential modifications, a 2? internucleoside linkage. The invention further relates to 5? modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.
Type:
Application
Filed:
February 20, 2014
Publication date:
March 10, 2016
Applicant:
SIRNA THERAPEUTICS, INC.
Inventors:
Wonsuk Chang, Erin N. Guidry, Matthew G. Stanton, Daniel Zewge
Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against target gene expression.
Type:
Grant
Filed:
October 25, 2011
Date of Patent:
February 16, 2016
Assignee:
Sirna Therapeutics, Inc.
Inventors:
Mark Cancilla, James J. Cunningham, Michael W. Flanagan, Henry J. Haringsma, Denise Kenski, Matthew G. Stanton, Steven M. Stirdivant, Aarron Willingham
Abstract: Single-stranded RNA molecules comprise one or more internal, non-nucleotide spacers, covalently linked with nucleotide portions of the molecule are provided. The single-stranded RNA molecules function as guide or antisense strands that are capable of inhibiting gene expression via an RNA interference mechanism, and thus represent single-stranded RNAi agents. The single-stranded RNAi molecules can be used in methods for a variety of therapeutic, diagnostic, target validation, genomic discovery, genetic engineering, and pharmacogenomic applications.
Type:
Grant
Filed:
August 19, 2011
Date of Patent:
January 26, 2016
Assignee:
Sirna Therapeutics, Inc.
Inventors:
Lee Lim, Guillaume Chorn, Aarron Willingham, Lihong Zhao
Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of PHD2 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsR-NA), micro-RNA (miRNA), and short hair-pin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against PHD2 gene expression.
Type:
Grant
Filed:
August 24, 2011
Date of Patent:
January 12, 2016
Assignee:
Sirna Therapeutics, Inc.
Inventors:
Brandon Ason, Duncan Brown, Walter Strapps
Abstract: This invention relates generally to segmented oligonucleotides capable of modulating gene expression. Specifically, the instant invention relates to segmented microRNA (miRNA) oligonucleotides, including segmented miRNA precursors and segmented pre-microRNAs. The invention also relates to compositions comprising such segmented oligonucleotides, as well as to methods of making and using such oligonucleotides for diagnosis and treatment of diseases associated or causally linked to aberrant levels or activities of gene expression, including aberrant levels of coding and/or non-coding RNA.
Abstract: This invention relates to the post-synthetic chemical modifications of RNA at the 2?-position on the ribose rings via orthogonal chemistry involving amidation reactions plus metal catalyzed alkyne-azide cycloaddition (click) reactions.
Type:
Application
Filed:
December 18, 2013
Publication date:
November 12, 2015
Applicant:
SIRNA THERAPEUTICS, INC.
Inventors:
Daniel Zewge, Gregory T. Copeland, Zhen LI, Joseph D. Armstrong
Abstract: The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.
Type:
Grant
Filed:
October 14, 2014
Date of Patent:
November 10, 2015
Assignee:
Sirna Therapeutics, Inc.
Inventors:
James McSwiggen, Leonid Beigelman, Chandra Vargeese
Abstract: The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with siRNA, to facilitate the cellular uptake and endosomal escape, and to knockdown target mRNA both in vitro and in vivo.
Type:
Grant
Filed:
August 18, 2010
Date of Patent:
November 10, 2015
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Mark Cameron, Jennifer R. Davis, Andrea R. Geiser, Matthew G. Stanton, Vladislav V. Telyatnikov, Lu Tian, Weimin Wang