Arrowhead Pharmaceuticals, Inc.

Arrowhead Madison, Inc.

Roche Madison Inc.

Mirus Bio Corporation

Empirico Inc.

Mirns Bio Corporation

F. Hoffmann-la Roche Ag

Arrowhead Research Corporation

Darren H Wakefield

David B Rozema

David L Lewis

Lauren Almeida

Jon Asher Wolff

James E Hagstrom

Steven B Kanner

Andrei V Blokhin

Jonathan D Benson

So Wong

Christine I Wooddell

Peter Mohr

Philipp Hadwiger

Torsten Hoffmann

Tao Pei

Eric Argirios Kitas

Zhen Li

Jeffrey Carlson

Aaron Almeida

Sean D Monahan

Ingo Roehl

Lori Higgs

Nicholas A Rossi

Vladimir S Trubetskoy

Hans Martin Mueller

Jason Klein

Kirk Ekena

Linda Valis

Eric A Kitas

Rui Zhu

Anthony Nicholas

Guenther Ott

Bruce D Given

Dan Sheik

Justin Woods

Vladimir G Budker

Paul Michael Slattum

Omri Gottesman

Weijun Cheng

Kerstin Jahn-Hofmann

Fred J Fleitz

Alexander V Sokoloff

Wilma Thuer

Stacey Melquist

Aaron G Loomis

Jeffrey C Carlson

James Ludtke

Magdolna G Sebestyén

Anthony L Perillo-Nicholas

Hans Herweijer

Ingo Röhl

Günther Ott

Kerstin Jahn-Hoffmann

Torsten Hoffman

Erik Kitas

Linda Christine Valis

Jon A Wolff

Lauren J Almeida

Andrei Blokhin

Vladimir Trubetskoy

Weijun Chen

Anthony L Nicholas

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

The invention relates to a RNA interference triggers for inhibiting the expression of an AAT gene through the mechanism of RNA interference. The invention also relates to a pharmaceutical composition comprising the AAT RNAi trigger together with an excipient capable of improving delivery of the RNAi trigger to a liver cell in vivo. Delivery of the AAT RNAi trigger to liver cells in vivo provides for inhibition of AAT gene expression and treatment of alpha 1-antitrypsin deficiency and associated diseases.

Compositions and methods for inhibiting gene expression of alpha-1 antitrypsin

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 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

Compositions and methods for inhibiting gene expression of alpha-1 AntiTrypsin

RNA interference (RNAi) triggers for inhibiting the expression of Factor XII (F12) gene through the mechanism of RNA interference are described. Pharmaceutical compositions comprising one or more F12 RNAi triggers together with one or more excipients capable of delivering the RNAi trigger(s) to a liver cell in vivo are also described. Delivery of the F12 RNAi trigger(s) to liver cells in vivo provides for inhibition of F12 gene expression and treatment of angioedema, including hereditary angioedema (HAE) and venous thromboembolism (VTE), and diseases associated with angioedema.

Compositions and methods for inhibiting gene expression of factor XII

RNA interference (RNAi) agents and RNAi agent conjugates for inhibiting the expression of the LPA (apo(a)) gene are described. Pharmaceutical compositions comprising one or more LPA RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described LPA RNAi agents to liver cells in vivo provides for inhibition of LPA gene expression and treatment of cardiovascular and cardiovascular-related diseases.

Compositions and methods for inhibiting gene expression of LPA

Growing community of inventors

Fitchburg, WI, United States of America

Darren H Wakefield