Sirna Therapeutics, Inc.

Merck Sharp + Dohme Corp.

Merck + Co., Inc.

Sima Therapeutics, Inc.

Arena Pharmaceuticals, Inc.

Alnylam Pharmaceuticals, Inc.

Steven L Colletti

Matthew G Stanton

David M Tellers

Weimin Wang

Thomas Joseph Tucker

Rubina G Parmar

Anthony W Shaw

Vadim Y Dudkin

Tesfaye Biftu

Rob Burke

James R Tata

Matthew J Wyvratt

Ravi P Nargund

Michael H Fisher

Amjad Ali

Hubert B Josien

Michael W Miller

Hong Shen

Donald W Graham

Fa-Xiang Ding

Duane E DeMong

Cheng Zhu

Purakkattle J Biju

Peter T Meinke

Subharekha Raghavan

De-Yi Yang

Richard Berger

Darby Schmidt

David A Claremon

Nigel J Liverton

William K Hagmann

Qun Dang

Prasun K Chakravarty

Bin Hu

James M Balkovec

Vasant R Jadhav

Dong Xiao

James B Doherty

Francis Gosselin

Brian W Budzik

Yu Yuan

Kathleen B Calati

Lu Tian

Marina Busuek

Robert A Kowtoniuk

Darla Danile Seifried

Ivory Hills

Jeffrey Aaronson

Aaron Momose

Rachel Anne Storr

Jennifer R Davis

Anilkumar G Nair

Boyoung Kim

Richard Beresis

Tao Pei

Jeffrey G Aaronson

Jae-Kyu Jung

Hongbiao Liao

Thomas O Schrader

Nam Fung Kar

Philip J Skinner

Lijun Wang

Rui Liang

Robert M Garbaccio

Helen Y Chen

XiaoXia Qian

Christopher Francis Thompson

Yan Guo

Graeme Semple

Cameron James Smith

Tawfik Gharbaoui

Christopher W Plummer

Dennis M Schmatz

Charles J McIntyre

Quang T Truong

Kevin D Dykstra

Zhengwu James Deng

Gool F Patel

Thomas L Shih

Gui-Bai Liang

Sriram Tyagarajan

Jing Liao

Zhiyong Hu

Jason Eugene Imbriglio

J Michael Williams

Pawan Dhondi

Donald M Sperbeck

Stanley F Barnett

Candido Gude

Mingxiang Cui

Michelle Kasem

Kevin Matthew Schlosser

Daniel Zewge

Erin Guidry

Benjamin R Johnson

Craig A Parish

P Douglas Boatman

Ashley Rouse Lins

Weichun Chen

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

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia Formula (I). 

Antidiabetic bicyclic compounds

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. 

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

Antidiabetic tricyclic compounds

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.

Diester and triester based low molecular weight, biodegradeable cationic lipids for oligonucleotide delivery

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

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.

Tetragalnac containing conjugates and methods for 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 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.

Low molecular weight cationic lipids for oligonucleotide delivery

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Princeton Junction, NJ, United States of America

Steven L Colletti