Emory University

Digene Corporation

Hoffmann-la Roche Inc.

Roche Palo Alto LLC

Pharmasset, Inc.

Abel De La Rosa

Gregory R Bluemling

George R Painter

Dennis C Liotta

Attila T Lorincz

James G Lazar

Inna Williams

Christina M Strange

Clayton D Collier

Joan M Zakel

Williamson Ziegler Bradford

Steven B Porter

Ellen S Yetzer

Alexander Kolykhalov

Michael D Rogers

William T Symonds

Damien Kuiper

Patrick F Smith

This disclosure related to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the nucleotide or nucleoside is a compound having the formula:

Substituted nucleosides and nucleotides for treating viral infections

Disclosed are compounds to the treatment of infectious diseases and methods of treating such diseases. The compounds are derivatives of clevudine.

Phosphoramidates for the treatment of hepatitis B virus

This disclosure relates therapeutic compositions containing a compound of Formula Im: or a pharmaceutically acceptable salt thereof, wherein Ris as defined herein.

Pharmaceutical compositions comprising substituted nucleotides and nucleosides for treating viral infections

Disclosed are compounds and compositions to the treatment of infectious diseases and methods of treating such diseases. The compounds and compositions include derivatives of clevudine. The compounds and compositions include derivatives of clevudine in combination with another antiviral agent. The compounds and compositions include derivatives of clevudine in combination with a phosphoramidate of lamivudine, adefovir, tenofovir, telbivudine, entecavir, or combinations thereof.

This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the nucleotide or nucleoside is defined by Formula I below, 

Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto

This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating viral infections, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether. The nucleotide or nucleoside is defined by Formula Ia below: 

Substituted nucleotides and nucleosides for treating viral infections

This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

Nucleotide and nucleoside therapeutic compositions and uses related thereto

Embodiments disclosed in the present application relate to a composition that can include a hepatitis C viral polymerase inhibitor, or pharmaceutically acceptable salt or prodrug thereof and a hepatitis C viral protease inhibitor, or pharmaceutically acceptable salt or prodrug thereof. Additional embodiments disclosed relate to methods for treating a disease condition such as a hepatitis C virus infection, liver fibrosis and/or impaired liver function with a hepatitis C viral polymerase inhibitor, or pharmaceutically acceptable salt or prodrug thereof and a hepatitis C viral protease inhibitor, or pharmaceutically acceptable salt or prodrug thereof.

Therapeutic composition

The present invention provides a hybridization method and kit for the detection and measurement of biological molecules. A test sample containing the biological molecules of interest is hybridized with an unlabeled or optionally a detectably-labeled complementary biomolecule to form a double-stranded hybrid immobilized to a solid phase. The immobilized hybrid may be detected with an entity which specifically recognizes an RNA:DNA hybrid, followed by analyses and quantification. Therefore, the present invention provides a method and kit to detect and measure biological molecules that is simple to use, highly specific, sensitive, and accurate for screening a plurality of biological molecules.

Immunological detection of RNA:DNA hybrids on microarrays

The present invention provides a hybridization method and kit for the detection and measurement of biological molecules. A test sample containing the biological molecules of interest is hybridized with an unlabeled or optionally a detectably labeled complementary biomolecule to form a double-stranded hybrid immobilized to a solid phase. The immobilized hybrid may be detected with an entity which specifically recognizes an RNA:DNA hybrid, followed by analyses and quantification. Therefore, the present invention provides a method and kit to detect and measure biological molecules that is simple to use, highly specific, sensitive, and accurate for screening a plurality of biological molecules.

Disclosed is a method of detecting RNA molecules of interest in which reverse transcription primers unique to the RNA molecule of interest are used for reverse transcribing the RNA with a reverse transcriptase lacking RNAse H function and the resulting RNA/DNA hybrid is detected with an antibody specific for RNA/DNA hybrids. The primers are immobilized on a solid support in order to associate the RNA/DNA hybrid with the solid support. This allows easy separation of hybrids form sample solution and specific detection of RNA molecules based on the position of the hybrid on the solid support. This method can be used to detect the presence of one or many specific RNA molecules which may be present in a sample, including RNA from different organisms (such as viruses, bacteria, fungi, plants, and animals), or RNA indicative of an infection, a disease state, or predisposition to a disease in an animal. The specificity of detection is increased relative to current detection methods involving probe hybridization since the reverse transcription primers are shorter and less subject to non-specific hybridization. Specificity of the disclosed method can also be increased by using a thermostable reverse transcriptase and performing reverse transcription at a high temperature. The disclosed method can also be used to detect reverse transcriptase activity in a sample and to identify inhibitors of reverse transcriptase. Also disclosed is a method for sequencing target RNA molecules using reverse transcriptase lacking an RNAse H function.

Direct detection of RNA mediated by reverse transcriptase lacking RNAse H function

Continuous amplification reaction provide a method of amplifying a specific nucleic acid without the need to cycle a reaction. The method produces RNA transcripts which can be detected by a variety of methods. Amplification and detection kits are also provided.

Promoter-primer mediated nucleic acid amplification

Disclosed is a method of detecting RNA molecules of interest in which reverse transcription primers unique to the RNA molecule of interest are used for reverse transcribing the RNA with a reverse transcriptase lacking RNAse H function and the resulting RNA/DNA hybrid is detected with an antibody specific for RNA/DNA hybrids. This method can be used to detect the presence of one or many specific RNA molecules which may be present in a sample, including RNA from different organisms (such as viruses, bacteria, fungi, plants, and animals), or RNA indicative of an infection, a disease state, or predisposition to a disease in an animal. The specificity of detection is increased relative to current detection methods involving probe hybridization since the reverse transcription primers are shorter and less subject to non-specific hybridization. Specificity of the disclosed method can also be increased by using a thermostable reverse transcriptase and performing reverse transcription at a high temperature. The disclosed method can also be used to detect reverse transcriptase activity in a sample and to identify inhibitors of reverse transcriptase. Also disclosed is a method for sequencing target RNA molecules using reverse transcriptase lacking an RNAse H function.

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Alpharetta, GA, United States of America

Abel De La Rosa