Bristol-myers Squibb Compnay

Medimmune Vaccines, Inc.

Viiv Healthcare UK Limited

Mark R Krystal

B Narasimhulu Naidu

Yasutsugu Ueda

Jacques Banville

Michael A Walker

John D Matiskella

Timothy P Connolly

Margaret E Sorenson

Francis Beaulieu

Roger Remillard

Serge Plamondon

Carl Ouellet

Nicholas A Meanwell

Rita Civiello

Kathleen F Kadow

Peter M Palese

Jonathan Harry Davis

Kuo-Long Yu

Christopher W Cianci

Stephen E Kurtz

David L Wensel

Richard J Colonno

Jeffrey Parvin

Moira Hagen

Thomas D Chung

The invention encompasses a series of bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

N-[[4-fluoro-2-(5-methy-1H-1,2,4-triazol-1-yl)phenyl]methyl]-4-,6,7,9-tetrahydro-3-hydroxy-9,9-dimethyl-4-oxo-pyrimido[2,1-c][1,4]oxazine-2-carboxamide as an HIV integrase inhibitor

Recombinant negative-strand viral RNA templates are described which may be used with purified RNA-directed RNA polymerase complex to express heterologous gene products in appropriate host cells and/or to rescue the heterologous gene in virus particles. The RNA templates are prepared by transcription of appropriate DNA sequences with a DNA-directed RNA polymerase. The resulting RNA templates are of the negative-polarity and contain appropriate terminal sequences which enable the viral RNA-synthesizing apparatus to recognize the template. Bicistronic mRNAs can be constructed to permit internal initiation of translation of viral sequences and allow for the expression of foreign protein coding sequences from the regular terminal initiation site, or vice versa.

Recombinant negative strand RNA virus expression systems and vaccines

The invention encompasses a series cyclic bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV. 

Bicyclic heterocycles as HIV integrase inhibitors

The invention encompasses a series bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV 

The present invention concerns antiviral compounds, their compositions, and use in the treatment of viral infections. More particularly, the invention provides benzimidazole derivatives for the treatment of respiratory syncytial virus infection.

Substituted benzimidazole antiviral agents

Novel capped oligonucleotides useful in treatment of influenza infection. A synthetically derived 67-nucleotide RNA substrate, containing a �.sup.32 P! labeled cap-1 structure was used to analyze parameters of influenza virus endonuclease activity. This substrate was specifically cleaved by the influenza virus polymerase to yield a single capped 11-nucleotide fragment capable of directly priming transcription. An analysis of systematic truncations of this RNA substrate in cleavage, elongation, and binding reactions demonstrated that the minimum chain length required for cleavage was one nucleotide past the cleavage site. In contrast, the minimum chain length required for priming activity was found to be 9 nucleotides, while a chain length of at least 4 nucleotides was required for efficient binding. Based on these chain length requirements, the present inventors show that a pool of capped oligonucleotides--too short to prime transcription but long enough to bind with high affinity to the viral polymerase--are potent inhibitors of cap-dependent in vitro transcription.

Capped nucleic acid oligomers that inhibit cap-dependent transcription

A modified Saccharomyces cerevisiae cell, wherein the cell expresses the Influenza virus ion channel protein M.sub.2. Also disclosed is a process for detecting modulators of M.sub.2, which comprises (a) treating such modified Saccharomyces cerevisiae cells with a test substance, and (b) assessing growth in the presence of a test substance, wherein a change in growth signals that the test substance is an M.sub.2 modulator. M.sub.2 inhibitors are useful anti-viral agents.

Saccharomyces cerevisiae expressing M.sub.2 protein of influenza A virus

Growing community of inventors

Westport, CT, United States of America

Mark R Krystal