Novira Therapeutics, Inc.

Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Janssen Sciences Ireland Unlimited Company

Istituto Di Richerche Di Biologia Molecolare P. Angeletti S.p.a.

Osvaldo A Flores

George D Hartman

Steven W Ludmerer

Robert L LaFemina

Donald J Graham

Klaus G Klumpp

Jay A Grobler

Jan Martin Berke

Amy L Simcoe

Man Iu Lam

Maura Pizzuti

Cinzia Traboni

Eric J Markel

Edward M Murray

Paul D Zuck

The present disclosure is directed to capsid assembly inhibitor compositions and methods for use in the treatment of hepatitis B virus infection.

Combinations and methods comprising a capsid assembly inhibitor

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.

Hepatitis B antiviral agents

The present invention features methods for enhancing the ability of a genotype 2b NS5B sequence to function in a replicon, for producing replicons containing a functional genotype 2b NS5B, and for using replicons to measure the ability of a compound to affect HCV replication that is sustained with the genotype 2b polymerase. Also featured is a genotype 1b NS4B adaptive mutation. The ability to produce replicons containing a functional genotype 2b NS5B is illustrated by the production of chimeric replicons based on HCV genotype 1b where substantially all the NS5B sequence is replaced with a genotype 2b NS5B.

HCV replicons containing NS5B from genotype 2B

The present invention features methods for producing HCV replicons using HCV encoding sequences from different isolates. The featured methods are based on the discovered importance of NS3 amino acid position 470 in conferring cell culture replication activity to different HCV isolates.

Method to confer cell culture replication activity to different Hepatitis C virus isolates

The present invention features assays employing a beta-lactamase reporter system, an HCV replicon enhanced cell, and/or a chimeric HCV replicon containing a 3' UTR based on the HCV-1a 3&#x2032; UTR. These features can be employed alone or together, and are preferably combined together to measure HCV replicon activity and the affect of compounds on such activity.

Hepatitis C virus assay systems

The present invention features NS5B polypeptides from different clinically important HCV genotypes. The polypeptides can be used individually, or as part of a panel of RNA-dependent RNA polymerases, to evaluate the effectiveness of a compound to inhibit NS5B activity.

HCV RNA-dependent RNA polymerase

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Doylestown, PA, United States of America

Osvaldo A Flores