Merck Sharp + Dohme Corp.

Sirna Therapeutics, Inc.

Msd R&d (china) Co., Ltd.

Alnylam Pharmaceuticals, Inc.

Sima Therapeutics, Inc.

Merck Msd (r&d) China Co., Ltd.

Msd R&d Co., Ltd.

David M Tellers

Steven L Colletti

Weimin Wang

Thomas Joseph Tucker

Rubina G Parmar

Anthony W Shaw

Yu Yuan

Kathleen B Calati

Vadim Y Dudkin

Marina Busuek

Robert A Kowtoniuk

Jianming Bao

Ling Tong

Michael Man-Chu Lo

Michael T Rudd

Robert D Mazzola, Jr

Chunsing Li

Lu Tian

Melissa S Egbertson

Xiaolei Gao

Scott T Harrison

Oleg B Selyutin

Matthew G Stanton

Rob Burke

Vasant R Jadhav

Francis Gosselin

Rachel Anne Storr

Aaron Momose

Jeffrey Aaronson

John J Acton, Iii

Timothy J Henderson

Sandra Lee Knowles

Zhaoyang Meng

Fengqi Zhang

Boyoung Kim

Tao Pei

Meng Na

Jeffrey G Aaronson

Qiaolin Deng

Hongbiao Liao

Denise M Kenski

Aarron T Willingham

Ronald Dale Ferguson, Ii

Jenny Miu-Chun Wai

Lijun Wang

Man Zhu

Craig Parish

Robert M Garbaccio

Takao Suzuki

Zhiguo Jake Song

James J Mulhearn

Quang T Truong

Jing Liao

Laura Marie Artino

Yaling Wang

Vanessa L Rada

J Michael Williams

David R Lieberman

Stanley F Barnett

Kevin Matthew Schlosser

Daniel Zewge

Brian Allen Carr

Quang Truong

Norihiro Ikemoto

Jeffrey W Schubert

Craig A Parish

Erin Guidry

Sandra C Tobias

Vadim Dudkin

Jeffery G Aaronson

René Bartz

Jacob H Waldman

Stephanie E Barrett

Aaron A Momose

Rene Bartz

Robert D Mazzola

Ronald Iii Ferguson

Sandra L Knowles

Scott Timothy Harrison

John J Iii Acton

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

The present invention is directed to cinnolinyl and quinolinyl pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

3-(1H-pyrazol-4-yl)pyridine allosteric modulators of the M4 muscarinic acetylcholine receptor

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.

Short interfering nucleic acid (siNA) compositions

The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

The present invention is directed to 5-(pyridine-3-yl)oxaxole compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

5-(pyridin-3-yl)oxazole allosteric modulators of the M4 muscarinic acetylcholine receptor

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

The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine 5 receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

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

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Lansdale, PA, United States of America

David M Tellers