Sirna Therapeutics, Inc.

Merck Sharp + Dohme Corp.

Alnylam Pharmaceuticals, Inc.

Merck Sharpe & Dohme Corp.

Weimin Wang

Chandra Vargeese

Steven L Colletti

Rubina G Parmar

David M Tellers

Thomas Joseph Tucker

Tongqian Chen

Marina Busuek

Kathleen B Calati

Lu Tian

Matthew G Stanton

Anthony W Shaw

Yu Yuan

Robert A Kowtoniuk

Kurt Vagle

Vadim Y Dudkin

Peter Haeberli

Rob Burke

Leonid Beigelman

James A McSwiggen

Vasant R Jadhav

Jeffrey Aaronson

Aaron Momose

Ye Zhang

Rachel Anne Storr

Boyoung Kim

J Michael Williams

Jeffrey G Aaronson

Michael Steven Poslusney

Jennifer R Davis

Mark Cameron

Christopher Shaffer

Andrea R Geiser

Vladislav V Telyatnikov

Nassim Usman

Robert M Garbaccio

James D Thompson

Quang T Truong

Zhengwu James Deng

Shawn Patrick Zinnen

Jing Liao

Pamela Pavco

David Morrissey

Kathy L Fosnaugh

Bharat Chowrira

Stanley F Barnett

Ivory Hills

Kevin Matthew Schlosser

Erin Guidry

Craig A Parish

Tao Pei

Dennis G Macejak

Narendra K Vaish

Stephanie E Barrett

Sandra C Tobias

Jacob H Waldman

Sharon F Jamison

Jeffery G Aaronson

René Bartz

Aaron A Momose

Vadim Dudkin

Rene Bartz

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.

Tetragalnac and peptide containing conjugates and methods for delivery of oligonucleotides

Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)-(G); wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)-(L)-(G); wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

Dual molecular delivery of oligonucleotides and peptide containing conjugates

Disclosed herein is a peptide containing conjugate comprising (P)-(L)-(G), wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if present, is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. The conjugate can be administered to a subject either alone or in combination with a composition comprising R-(L)-(G), wherein R is an oligonucleotide as defined herein, to inhibit expression of a gene of the subject.

Peptide containing conjugates for dual molecular delivery of oligonucleotides

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.

Cationic lipids for oligonucleotide delivery

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.

Cationic lipids with various head groups for oligonucleotide delivery

The present invention provides membrane lytic poly(amido amine) polymers, polyconjugates, compositions and methods for the delivery of oligonucleotides for therapeutic purposes.

Membrane lytic poly(amido amine) polymers for the delivery of oligonucleotides

The present invention provides poly(amide) polymers, polyconjugates, compositions and methods for the delivery of oligonucleotides for therapeutic purposes.

Poly(amide) polymers for the delivery of oligonucleotides

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.

RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)

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Churchville, PA, United States of America

Weimin Wang