Monogram Biosciences, Inc.

Medimmune Vaccines, Inc.

Aviron

Virologic, Inc.

Neil T Parkin

Christos J Petropoulos

Wei Huang

Mary T Wrin

Rainer Ziermann

Jeannette Whitcomb

Douglas Richman

Colombe Chappey

Susan Little

Ellen Paxinos

Jeanette Whitcomb

Kathleen L Coelingh

Signe Fransen

Soumi Gupta

Eoin Coakley

Andrea Gamarnik

Jeannette M Whitcomb

This invention relates to methods for determining hypersusceptibility of HIV-1 viruses to non-nucleoside reverse transcriptase inhibitors (NNRTIs) based on the viral genotypes. The methods generally comprise detecting, in a gene encoding reverse transcriptase of the HIV-1, the presence of a mutation at codon 65, 69, or 74 alone or in combination with one or more mutations at certain other codons. Combinations of mutations associated with hypersusceptibility to NNRTIs are also disclosed.

Methods for determining hypersusceptibility of HIV-1 to non-nucleoside reverse transcriptase inhibitors

Provided are methods for identifying whether a compound inhibits entry of a virus into a cell. The method may include obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus and co-transfecting it into a first cell along with a viral expression vector which lacks a nucleic acid encoding the envelope protein. The method may further include contacting the viral particles produced by the first cell with a second cell to which the virus binds in the absence and presence of the compound and measuring the amount of signal produced by the second cell.

Methods for evaluating viral receptor/co-receptor usage and inhibitors of virus entry using recombinant virus assays

The present invention provides a method for identifying whether a compound inhibits entry of a virus into a cell which comprises: (a) obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus; (b) co-transfecting into a first cell (i) the nucleic acid of step (a), and (ii) a viral expression vector which lacks a nucleic acid encoding an envelope protein, and which comprises an indicator nucleic acid which produces a detectable signal, such that the first cell produces viral particles comprising the envelope protein encoded by the nucleic acid obtained from the patient; (c) contacting the viral particles produced in step (b) with a second cell in the presence of the compound, wherein the second cell expresses a cell surface receptor to which the virus binds; (d) measuring the amount of signal produced by the second cell in order to determine the infectivity of the viral particles; and (e) comparing the amount of signal measured in step (d) with the amount of signal produced in the absence of the compound, wherein a reduced amount of signal measured in the presence of the compound indicates that the compound inhibits entry of the virus into the second cell.

Methods for determining the presence of antibodies blocking viral infection

This invention relates, in part, to methods and compositions for determining altered susceptibility of a human immunodeficiency virus ('HIV') to the non-nucleoside reverse transcriptase inhibitors ('NNRTIs') efavirenz (&#x201c;EFV&#x201d;), nevirapine (&#x201c;NVP&#x201d;), and delavirdine (&#x201c;DLV&#x201d;), the nucleoside reverse transcriptase inhibitor AZT, and the integrase strand transfer inhibitors diketo acid 1, diketo acid 2, and L-870,810 by detecting the presence of a mutation or combinations of mutations in the gene encoding HIV reverse transcriptase that are associated with altered susceptibility to the anti-HIV drugs.

Methods and compositions for determining altered susceptibility of HIV-1 to anti-HIV drugs

This invention relates to methods for determining hypersusceptibility of HIV-1 viruses to non-nucleoside reverse transcriptase inhibitors (NNRTIs) based on the viral genotypes. The methods generally comprise detecting, in a gene encoding reverse transcriptase of the HIV-1, the presence of a mutation at codon 65, 69, or 74 alone or in combination with one or more mutations at certain other codons. Combinations of mutation associated with hypersusceptibility to NNRTIs are also disclosed.

Methods and compositions for determining hypersusceptibility of HIV-1 to non-nucleoside reverse transcriptase inhibitors

The present invention provides an approach for developing an algorithm for determining the effectiveness of anti-viral drugs based on a comprehensive analysis of paired phenotypic and genotypic data guided by phenotypic clinical cut-offs. In one aspect, the algorithm allows one to provide a patient with effective treatment. It helps predict whether an infected individual will respond to treatment with an anti-viral compound, thereby allowing an effective treatment regimen to be designed without subjecting the patient to unnecessary side effects. Also, by avoiding the administration of ineffective drugs, considerable time and money is saved.

Compositions and methods for determining the susceptibility of a pathogenic virus to protease inhibitors

Method for determining human immunodeficiciency virus type 1 (HIV-1) hypersusceptibility to the protease inhibitor amprenavir

The invention provides a method for identifying whether a compound inhibits entry of a virus into a cell which comprises: (a) obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus; (b) co-transfecting into a first cell (i) the nucleic acid of step (a), and (ii) a viral expression vector which lacks a nucleic acid encoding an envelope protein, and which comprises an indicator nucleic acid which produces a detectable signal, such that the first cell produces viral particles comprising the envelope protein encoded by the nucleic acid obtained from the patient; (c) contacting the viral particles produced in step (b) with a second cell in the presence of the compound, wherein the second cell expresses a cell surface receptor to which the virus binds; (d) measuring the amount of signal produced by the second cell in order to determine the infectivity of the viral particles; and (e) comparing the amount of signal measured in step (d) with the amount of signal produced in the absence of the compound, wherein a reduced amount of signal measured in the presence of the compound indicates that the compound inhibits entry of the virus into the second cell.

Method of evaluating a patient antibody response to envelope proteins of a virus

Methods of evaluating cell surface receptor binding of a patient derived population of viral envelope protein constructs

This invention relates to antiviral drug susceptibility and resistance tests to be used in identifying effective drug regimens for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), particularly treatment regimens including a protease inhibitor. The invention further relates to the means and methods of monitoring the clinical progression of HIV infection and its response to antiretroviral therapy using phenotypic or genotypic susceptibility assays.

Means and methods for monitoring protease inhibitor antiretroviral therapy and guiding therapeutic decisions in the treatment of HIV/AIDS

Methods of evaluating viral entry inhibitors using patient derived envelope protein constructs

Growing community of inventors

Belmont, CA, United States of America

Neil T Parkin