Pfizer Corporation

Wave Life Sciences Ltd.

Xiayun Cheng

Chandra Vargeese

Joseph Walter Strohbach

Genliang Lu

Scott William Bagley

Jennifer Elizabeth Davoren

John Isidro Trujillo

Naoki Iwamoto

Subramanian Marappan

David Charles Donnell Butler

Frank Eldridge Lovering

Brian Stephen Gerstenberger

Agustin Casimiro-Garcia

Jason Jingxin Zhang

Mihir D Parikh

Rajiah Aldrin Denny

Young Jin Cho

Vinod Vathipadiekal

Luciano Henrique Apponi

Hanna Maria Wisniewska

The invention relates to benzimidazoles of Formula (I) and pharmaceutically acceptable salts thereof, wherein Rto Rare as defined in the description; to their use in medicine; to compositions containing them; to processes for their preparation; and to intermediates used in such processes. The benzimidazoles of Formula (I) are ITK inhibitors and are therefore potentially useful in the treatment of a wide range of disorders including, atopic dermatitis.

Benzimidazole derivative compounds and uses thereof

Among other things, the present disclosure provides designed PNPLA3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or N patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in RNA interference and/or RNase H-mediated knockdown.

Oligonucleotide compositions and methods of use thereof

Growing community of inventors

Old Saybrook, CT, United States of America

Xiayun Cheng