Schering Corporation

Merck Sharp + Dohme Corp.

Bruce A Malcolm

Brian M Beyer

Corey Strickland

Wenyan Wang

Eileen Wilson

F George Njoroge

Patricia C Weber

Hung V Le

Nanhua Hugh Yao

Robert Palermo

Boris Feld

Xiao Tong

S Shane Taremi

Viyyoor Moopil Girijavallabhan

Zhaoning Zhu

Ashok Arasappan

Srikanth Venkatraman

Raymond G Lovey

Kevin X Chen

Zhong-Yue Sun

Rumin Zhang

William T Windsor

Wing-Kee Philip Cho

Zhihui Qiu

James P Durkin

Prudence K Bradley

Anastasia Pavlovsky

The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of &#x3b2;-secretase (BACE) polypeptide. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

Refolded recombinant &#x3b2;-secretase crystals and methods for preparing and using the same

The present invention provides methods for treating infections, in a host, by viruses belonging to the Flaviviridae family, such as HCV, comprising administering an Ara-C homologue to the host.

Treatments for Flaviviridae virus infection

Pharmaceutical formulations containing at least one compound of Formulae I-XXVI herein and at least one surfactant. Pharmaceutically acceptable carriers and excipients may also be included in the formulations. The formulations of the present invention are suited for use in single unit dosages.

Pharmaceutical formulations and methods of treatment using the same

The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of &#x3b2;-secretase (BACE) polypeptide. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding human BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

Method for making &#x3b2;-secretase co-crystals complexed with a ligand

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The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of &#x3b2;-secretase (BACE) polypeptide. Polypeptides used herein are derived from human BACE which is also known by the synonyms 'mamapsin 2', 'human &#x3b2;-site APP-cleaving enzyme, and Asp2'. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

Codon-optimized &#x3b2;-secretase and methods of refolding and processing

The present invention is directed to certain diaryl amide compounds as NS3-Serine protease inhibitors of hepatitis C virus. A particularly preferred compound is of the formula:

Diaryl peptides as NS3-serine protease inhibitors of hepatitis C virus

Covalent HCV NS4A-NS3 complexes comprising the central hydrophobic domain of native HCV NS4A peptide, a linker, and the HCV NS3 serine protease domain, wherein the hydrophobic domain of native HCV NS4A peptide is tethered by the linker to the amino terminus of the HCV NS3 protease domain.

Single-chain recombinant complexes of hepatitis C virus NS3 protease and NS4A cofactor peptide

Novel chromogenic, fluorogenic and fluorescence polarization substrates which are useful in HCV NS3 protease and inhibitor assays.

Peptide substrates for HCV NS3 protease assays

Growing community of inventors

Paoli, PA, United States of America

Bruce A Malcolm