Monogram Biosciences, Inc.

Other

Douglas Richman

Wei Huang

Neil T Parkin

Christos J Petropoulos

Jeannette Whitcomb

Mary T Wrin

Susan Little

Karl Y Hostetler

James R Beadle

Eyal Raz

Ganesh D Kini

Andre Rosowsky

Anthony A Horner

Hearn Jay Cho

Jeannette M Whitcomb

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

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

The invention provides lipophilic phosphonoacid/nucleoside conjugates that exhibit exceptional antiviral activity, including activity against drug-resistant HIV strains. Compounds of the invention include phosphonoacid/nucleoside conjugates where the carboxyl group and phosphonyl groups of the phosphonacid are esterified whereby the compound contains at least one lipophilic group and at least one nucleoside group.

Antiviral compounds and methods of administration

The invention provides methods for T helper-independent activation of an antigen-specific cytotoxic T lymphocyte response in an individual. The methods generally involve administering to an individual an immunostimulatory nucleic acid molecule in an amount effective to increase an antigen-specific CTL response in the individual. The invention further provides methods for increasing chemokine secretion, which can block HIV infection.

Methods for increasing a cytotoxic T lymphocyte response in vivo

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La Jolla, CA, United States of America

Douglas Richman