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:
December 14, 2015
Date of Patent:
December 19, 2017
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Lee Lim, Guillaume Chorn, Aarron T. Willingham, Lihong Zhao
Abstract: Disclosed herein is a modular composition comprising 1) an oligonucleotide; 2) one or more tetraGalNAc ligands of Formula (I), which may be the same or different; optionally, 3) one or more linkers, which may be the same or different; 4) one or more peptides independently selected from Table 3, which may be the same or different; and optionally, 5) one or more targeting ligands, solubilizing agents, pharmacokinetics enhancing agents, lipids, and/or masking agents.
Type:
Grant
Filed:
April 7, 2017
Date of Patent:
December 12, 2017
Assignee:
Sirna Therapeutics, Inc.
Inventors:
David Tellers, Steven L. Colletti, Vadim Dudkin, Jeffrey Aaronson, Aaron Momose, Thomas Joseph Tucker, Yu Yuan, Kathleen B. Calati, Lu Tian, Rubina G. Parmar, Anthony W. Shaw, Weimin Wang, Rachel Anne Storr, Marina Busuek, Robert A. Kowtoniuk
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 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:
June 4, 2015
Date of Patent:
September 26, 2017
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
James McSwiggen, Leonid Beigelman, Chandra Vargeese
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:
April 10, 2017
Date of Patent:
August 22, 2017
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Leonid Beigelman, James McSwiggen, Chandra Vargeese
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:
March 30, 2016
Date of Patent:
August 15, 2017
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Leonid Beigelman, James McSwiggen, Chandra Vargeese
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: 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 with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.
Type:
Grant
Filed:
September 20, 2011
Date of Patent:
June 6, 2017
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Matthew G. Stanton, Brian W. Budzik, Gregory L. Beutner, Hongbiao Liao
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 is susceptible to hydrolytic instability that may translate into reduced liver residence times and reduced hepatocellular toxicity. The present invention employs acetals and ketals to provide a low pH sensitive chemical handle for degradation.
Type:
Grant
Filed:
January 19, 2011
Date of Patent:
June 6, 2017
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Steven L. Colletti, Zhengwu James Deng, Matthew G. Stanton, Weimin Wang, Ivory Hills
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:
September 22, 2015
Date of Patent:
May 23, 2017
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Leonid Beigelman, James McSwiggen, Chandra Vargeese
Abstract: Disclosed herein is a modular composition comprising 1) an oligonucleotide; 2) one or more tetraGalNAc ligands of Formula (I), which may be the same or different; optionally, 3) one or more linkers, which may be the same or different; 4) one or more peptides independently selected from Table 3, which may be the same or different; and optionally, 5) one or more targeting ligands, solubilizing agents, pharmacokinetics enhancing agents, lipids, and/or masking agents.
Type:
Grant
Filed:
May 1, 2013
Date of Patent:
May 23, 2017
Assignee:
Sirna Therapeutics, Inc.
Inventors:
David Tellers, Steven L. Colletti, Vadim Dudkin, Jeffrey Aaronson, Aaron Momose, Thomas Joseph Tucker, Yu Yuan, Kathleen B. Calati, Lu Tian, Rubina G. Parmar, Anthony W. Shaw, Weimin Wang, Rachel Anne Storr, Marina Busuek, Robert A. Kowtoniuk
Abstract: The instant invention provides for novel cationic lipids of Formula A 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 coupled with inclusion of hydrolysable functionality in the lipid chains 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 siRNA, to facilitate the cellular uptake and endosomal escape, and to knockdown target mRNA both in vitro and in vivo.
Type:
Grant
Filed:
October 6, 2015
Date of Patent:
May 9, 2017
Assignee:
SIRNA THERAPEUTICS, INC.
Inventors:
Mark Cameron, Jennifer R. Davis, Andrea R. Geiser, Matthew G. Stanton, Vladislav V. Telyatnikov, Lu Tian, Weimin Wang
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:
March 22, 2016
Date of Patent:
May 9, 2017
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 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:
Application
Filed:
March 22, 2016
Publication date:
February 23, 2017
Applicant:
SIRNA THERAPEUTICS, INC.
Inventors:
Brian W. BUDZIK, Steven L. COLLETTI, Jennifer R. DAVIS, Ivory D. HILLS, Darla Danile SEIFRIED, Matthew G. STANTON
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 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: Disclosed herein is a modular composition comprising 1) an oligonucleotide; 2) one or more tetraGalNAc ligands of Formula (I), which may be the same or different; optionally, 3) one or more linkers, which may be the same or different; and optionally, 4) one or more targeting ligands, solubilizing agents, pharmacokinetics enhancing agents, lipids, and/or masking agents.
Type:
Grant
Filed:
May 1, 2013
Date of Patent:
January 10, 2017
Assignee:
Sirna Therapeutics, Inc.
Inventors:
David Tellers, Steven Colletti, Vadim Dudkin, Norihiro Ikemoto, Hongbiao Liao, Craig Parish, Tao Pei, Anthony Shaw, Quang Truong, Lijun Wang, Yu Yuan, Man Zhu
Abstract: Disclosed herein are 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. The cationic lipids can demonstrate 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 coupled with inclusion of hydrolysable functionality in the lipid chains to enhance the efficiency and tolerability of in vivo delivery of siRNA.
Type:
Application
Filed:
September 19, 2016
Publication date:
January 5, 2017
Applicant:
SIRNA THERAPEUTICS, INC.
Inventors:
Matthew G. STANTON, Brian W. BUDZIK, Steven L. COLLETTI