Arrowhead Pharmaceuticals, Inc.

Arrowhead Madison, Inc.

Mirus Bio Corporation

Empirico Inc.

Roche Madison Inc.

Mirus Corporation

Hoffmann-la Roche Inc.

Nanosur LLC

Wisconsin Alumni Research Foundation

Mirns Bio Corporation

F. Hoffmann-la Roche Ag

Arrowhead Research Corporation

David B Rozema

Darren H Wakefield

David L Lewis

Jon Asher Wolff

James E Hagstrom

Sean D Monahan

Vladimir G Budker

Andrei V Blokhin

Lauren Almeida

Jonathan D Benson

Peter Mohr

Philipp Hadwiger

Torsten Hoffmann

Eric Argirios Kitas

Jeffrey Carlson

Omri Gottesman

Vladimir S Trubetskoy

Paul Michael Slattum

Ingo Roehl

So Wong

Aaron Almeida

Tao Pei

Zhen Li

Hans Martin Mueller

Shannon Bruse

Brian Cajes

Christine I Wooddell

Kerstin Jahn-Hofmann

Guenther Ott

Steven B Kanner

Kirk Ekena

Weijun Cheng

Jason Klein

Linda Valis

Rui Zhu

Anthony Nicholas

Lori Higgs

Bruce D Given

Juan P Arhancet

Sreevishnu Cheerla

Graciela B Arhancet

Paul Buske

Justin Woods

Fred J Fleitz

Nicholas A Rossi

Wilma Thuer

Stacey Melquist

Anthony L Perillo-Nicholas

Samuel Helmer Gellman

Hans Herweijer

Paul Slattum

Aaron G Loomis

Lisa J Hanson

Ingo Röhl

Sarah Kleinstein

Günther Ott

Kerstin Jahn-Hoffmann

Larry F Whitesell

Matthew R Wolff

Torsten Hoffman

David Jakubosky

John Vekich

Erik Kitas

Lauren J Almeida

Eric A Kitas

Jeffrey C Carlson

Andrei Blokhin

Vladimir Trubetskoy

Weijun Chen

Anthony L Nicholas

Linda Christine Valis

Aaron M Almeida

Provided herein are oligonucleotide compositions that inhibit ANGPTL7 and reduce intraocular pressure when administered to an eye. The oligonucleotide compositions contain nucleoside modifications.

Treatment of angiopoietin like 7 (ANGPTL7) related diseases

Disclosed herein are compositions comprising an oligonucleotide that targets MST1. The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating conditions associated with MST1 variants that include providing an oligonucleotide that targets MST1 to a subject.

Treatment of MST1 related diseases and disorders

Provided herein, are compositions comprising GalNAc moieties that may be conjugated to an oligonucleotide. The oligonucleotide may be a small interfering RNA or an antisense oligonucleotide. Also provided herein are methods of treatment that include administering the composition to a subject.

GalNAc compositions for improving siRNA bioavailability

Disclosed herein are compositions comprising modified oligonucleotides. In some embodiments, the oligonucleotide includes a hydrophobic moiety. In some embodiments, the oligonucleotide includes a vinyl phosphonate. In some embodiments, the oligonucleotide includes modified oligonucleotide sugars such as 2' modified ribose molecules. In some embodiments, the oligonucleotide includes modified internucleoside linkages such as phosphorothioate linkages. In some embodiments, the oligonucleotide includes an siRNA. In some embodiments, the siRNA comprises a duplex region with overhangs on either end.

Modified oligonucleotides

Described are novel targeting ligands that may be linked to compounds, such therapeutic compounds, that are useful in directing the compounds to the target in vivo. The targeting ligands disclosed herein can serve to target expression-inhibiting oligomeric compounds, such as RNAi agents, to liver cells to modulate gene expression. The targeting ligands disclosed herein, when conjugated to an expression-inhibiting oligomeric compound, may be used in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Compositions including the targeting ligands disclosed herein when linked to expression-inhibiting oligomeric compounds are capable of mediating expression of target nucleic acid sequences in liver cells, such as hepatocytes, which may be useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.

Targeting ligands for therapeutic compounds

Provided herein, are compositions comprising GaINAc moieties that may be conjugated to an oligonucleotide. The oligonucleotide may be a small interfering RNA or an antisense oligonucleotide. Also provided herein are methods of treatment that include administering the composition to a subject.

RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2&#x3b1; (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2&#x3b1; RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2&#x3b1; RNAi triggers to tumor cells in vivo provides for inhibition of Hif2&#x3b1; gene expression and treatment of cancer.

Compositions and methods for inhibiting gene expression of Hif2alpha

Described herein are compounds and pharmaceutical compositions containing such compounds which are prodrugs of ALOX-15 inhibitors. Also described herein are methods for using such compounds in the treatment of disease.

Prodrugs of ALOX-15 inhibitors and methods of using the same

Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B virus gene are described. The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection.

RNAi agents for hepatitis B virus infection

Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hepatitis B virus gene are described. Pharmaceutical compositions comprising one or more HBV RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi triggers to infected liver in vivo provides for inhibition of HBV gene expression and treatment.

RNAi therapy for hepatitis B virus infection

RNAi agents for Hepatitis B virus infection

Provided are compositions comprising an oligonucleotide that targets Thymic stromal lymphopoietin (TSLP). The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating an airway disorder by providing an oligonucleotide that targets TSLP to a subject in need thereof. In some embodiments, the oligonucleotide targeting is specific for a long isoform of TSLP (1fTSLP).

Treatment of thymic stromal lymphopoietin (TSLP) related diseases by inhibition of long-form TSLP transcripts

Provided are compositions comprising an oligonucleotide that targets Angiopoietin-like 4 (ANGPTL4). The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating a metabolic or cardiovascular disorder by providing an oligonucleotide that targets ANGPTL4 to a subject in need thereof.

Oligonucleotides for treatment of angiopoietin like 4 (ANGPTL4) related diseases

Described are post transcriptionally chemically modified double strand RNAs (MdsRNAs) having more than 30 base pairs. The MdsRNAs inhibit gene expression in target organisms. Also described are methods of making and using MdsRNAs.

Post-transcriptionally chemically modified double strand RNAs

Growing community of inventors

Madison, WI, United States of America

David B Rozema