Aronex Pharmaceuticals, Inc.

Biochem Pharma Inc.

Other

Shire Biochem, Inc.

National Institutes of Health, a Component of the US Dept. of Health & Human Services

Columbia University

The United States of America As Represented by the Department of Health

Research Development Foundation

The Wistar Institute

Ptc Therapeutics, Inc.

Robert F Rando

Michael E Hogan

Joshua O Ojwang

Joseph G Zendegui

Susan Fennewald

Francis J Giles

Jean B&eacute;dard

Zhengxian Gu

Neil Gregory Almstead

Yves Pommier

Ellen Welch

Bharat B Aggarwal

Guy Falardeau

Cy Aaron Stein

Stanley A Plotkin

Thomas L Wallace

Ganapathi R Revankar

Klara Berencsi

Arthur F Lewis

Robert P Ricciardi

Jean-Francois Lavall&eacute;e

Ewa Gonczol

Jean Bédard

Abhijit Mazumder

Joshua O Ojwaug

Paul A Cossum

Mathew C Pellegrini

Joshua O Oiwana

Susan M Fennewald

Paul Cossum

Rodrigo V Devivar

Birendra K Bhattacharya

The present invention relates to a method for screening and identifying compounds that modulate premature translation termination and/or nonsense-mediated messenger ribonucleic acid ('mRNA') by interacting with a preselected target ribonucleic acid ('RNA'). In particular, the present invention relates to identifying compounds that bind to regions of the 28S ribosomal RNA (&#x201c;rRNA&#x201d;) and analogs thereof. Direct, noncompetitive binding assays are advantageously used to screen libraries of compounds for those that selectively bind to a preselected target RNA. Binding of target RNA molecules to a particular compound is detected using any physical method that measures the altered physical property of the target RNA bound to a compound. The structure of the compound attached to the labeled RNA is also determined. The methods used will depend, in part, on the nature of the library screened. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads.

Methods for identifying small molecules that modulate premature translation termination and nonsense mediated mRNA decay

This invention provides an antisense oligonucleotide or analog thereof comprising 10 or more contiguous bases or base analogs from the sequence of bases of sequence A, B, C, D, E, F, G, H, I, J, K, L, or M of FIG.This invention also provides the above-described antisense oligonucleotides, wherein the nucleotide sequence comprises nucleotide sequence A, A', B, C, C&#x2032;, D, E, E, E&#x2032;, F, G, G&#x2032;, H, H&#x2032;, I, I&#x2032;, J, K, K&#x2032;, L, L&#x2032;, M, or M&#x2032; of FIGS.A andB. This invention also provides the above-described antisense oligonucleotides, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention also provides the above-described antisense oligonucleotides, wherein the phosphate backbone comprises phosphorothioate bonds. In addition, this invention provides a method of treating cancer, comprising introducing into a tumor cell an effective amount of the the above-described antisense oligonucleotide, thereby reducing the levels of bcl-xL protein produced and treating cancer. This invention also provides the above-described methods, wherein the introducing comprises using porphyrin or lipofectin as a delivery agent. This invention also provides the above-described pharmaceutical compositions, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention further provides the above-described pharmaceutical compositions, wherein the pharmaceutical composition comprises tetra meso-(4-methylpyridyl)porphine or tetra meso-(anilinium)porphine or a combination thereof.

Oligonucleotide inhibitors of bcl-xL

Viral infections selected from the group consisting of herpes simplex virus, varicella zoster virus, respiratory syncytial virus and cytomegalovirus can be treated by administering to the host a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof;wherein Y, Ra, and R1 are as defined herein. The compounds and salts can also be used to inhibit viral replication of these viruses in cells.

Method for the treatment or prevention of viral infection using nucleoside analogues

In accordance with the present invention there is provided a pharmaceutical combination useful for the treatment of viral infections comprising a at least one antiviral active compound of formula (1):and at least one further therapeutic agent chosen from nucleoside analogues; NNRTIs; and protease inhibitors.

Pharmaceutical combination of antiviral agents

Antiviral compounds

A method and compositions for treating viral infection (IV) vitro and in vivo using a guanosine-rich oligonucleotide. The oligonucleotides have sufficient guanosine to form a guanosine tetrad. Also provided are oligonucleotides of at least two runs of at least two guanosines. Also provided are guanosine-rich oligonucleotides and methods for treating viral infections in humans, and a method for designing guanosine-rich oligonucleotides having anti-viral activity and integrase inhibition activity.

Guanosine-rich oligonucleotide integrase inhibitors

A method and compositions for treating viral infection in vitro and in vivo using a guanosine-rich oligonucleotide. The oligonucleotides have sufficient guanosine to form a guanosine tetrad. Also provided are oligonucleotides of at least two runs of at least two guanosines. Also provided are guanosine-rich oligonucleotides and methods for treating viral infections in humans, and a method for designing guanosine-rich oligonucleotides having anti-viral activity and integrase inhibition activity.

Anti-viral guanosine-rich oligonucleotides and method of treating HIV

Guanosine-rich oligonucleotides having sequences that favor the formation under physiological conditions of a stable four-stranded structure containing two stacked guanosine quartets (G4s) are disclosed. These oligonucleotides demonstrate enhanced nuclease resistance, cellular uptake and biological efficacy. Methods and composition for treating viral infection using these guanosine-rich oligonucleotides are also disclosed. Certain embodiments of the new oligonucleotides are 16-17 nucleotides long and contain at least one C-5 propynyl dU substitution. A method for designing anti-viral oligonucleotides is also disclosed.

Anti-viral guanosine-rich tetrad forming oligonucleotides

The oligonucleotides have sufficient guanosine to form a guanosine tetrad and can be composed of at least about 40% guanosine nucleotides, the nucleotide sequence containing at least two runs of at least two guanosines. Some of the new oligonucleotides also contain phosphorothioate backbones and 3&prime; end modifications. Representative guanosine-rich oligonucleotides of the present invention demonstrate anti-viral activity in tissue culture against HSV-2, HIV-1, HCMV and FMLV, and show specific inhibition of bacterial RNA polymerase enzymes T7 and T3, the FMLV and HIV-1 reverse transcriptase enzyme and eukaryotic RNA polymerase.

Anti-viral guanosine-rich oligonucleotides

A method and compositions for treating viral infection in vitro and in vivo using a guanosine-rich oligonucleotides. The oligonucleotides have sufficient guanosine to form a guanosine tetrad. They can be composed of at least about 40% guanosine nucleotides. Also provided are oligonucleotides of at least two runs of at least two guanosines. Also provided are guanosine-rich oligonucleotides and methods for treating viral infections in humans, and a method for designing guanosine-rich oligonucleotides having anti-viral activity.

The present invention provides novel methods of treating anti-neoplastic and non-neoplastic cell proliferative diseases. The present methods involve administration of triplex forming oligonucleotides to humans to inhibit the biological activity of tumor necrosis factor. Also provided are methods of treating neuro-oncologic states and renal cancer.

Uses of triplex forming oligonucleotides for the treatment of human

A method and compositions for treating viral infection in vitro and in vivo using a guanosine-rich oligonucleotides. The oligonucleotides are composed of at least about 50% guanosine nucleotides. Also provided are guanosine-rich oligonucleotides and methods for treating viral infections in humans, and a method for designing guanosine-rich oligonucleotides having anti-viral activity.

The present invention provides a non-defective adenovirus recombinant expression system for the expression of the HCMV gB subunit, an immunogenic fragment of the gB subunit, and for the expression of non-structural immediate-early exon 4 proteins, said recombinant HCMV-expressing adenovirus being useful as a vaccine.

Recombinant cytomegalovirus vaccine

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Annandale, NJ, United States of America

Robert F Rando