Merck + Co., Inc.

Other

Merck Sharp + Dohme Corp.

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

Donald J Graham

Steven W Ludmerer

Osvaldo A Flores

Robert L LaFemina

Amy L Simcoe

Jon H Condra

Leah Gotlib

Maura Pizzuti

Cinzia Traboni

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 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

A chromogenic assay is described for the identification and isolation of drug-resistant HIV protease mutants. Coversely, the assay is useful to screen for new inhibitors of HIV protease, e.g., inhibitors not affected by drug-resistance of the HIV protease. This color screening assay contains a vector comprising a regulatable promoter which controls the transcription of two adjacent structural sequences, one sequence coding for HIV protease or mutant thereof, the other sequence coding for beta-galactosidase with an amino acid substrate insert cleavable by HIV protease. A library of HIV proteases is also described and is isolated in the form of a collection of such vectors, which is a color screen vector library.

Color screening assay for identifying inhibitor resistant HIV protease

A trash entry chute device for mounting on a top-opening trash container, which device supports and holds open a limp plastic film bag for use as a disposable liner for the container. The device comprises a chute having a flange which supports the device on the container and diverts trash into the chute, and bag support means in opposite positions on the outside surface of the chute. When a bag is supported by the device, the chute fits into the mouth of the bag, holding it open to receive trash.

Support device for a disposable trash bag

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Green Lane, PA, United States of America

Donald J Graham