Arrowhead Pharmaceuticals, Inc.

Arrowhead Madison, Inc.

Empirico Inc.

Lauren Almeida

Darren H Wakefield

David L Lewis

David B Rozema

Steven B Kanner

Christine I Wooddell

Tao Pei

Zhen Li

Aaron Almeida

Andrei V Blokhin

So Wong

Jeffrey Carlson

Rui Zhu

Anthony Nicholas

Jonathan D Benson

Weijun Cheng

Bruce D Given

Justin Woods

Vladimir S Trubetskoy

Nicholas A Rossi

Stacey Melquist

Anthony L Perillo-Nicholas

Omri Gottesman

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

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

RNAi Therapy for Hepatitis B Virus Infection

Growing community of inventors

Madison, WI, United States of America

Lauren Almeida