Monogram Biosciences, Inc.

Virologic, Inc.

Laboratory Corporation of America Holdings

Christos J Petropoulos

Neil T Parkin

Wei Huang

Jeannette Whitcomb

Mary T Wrin

Daniel J Capon

Douglas Richman

Colombe Chappey

Susan Little

Jeanette Whitcomb

Signe Fransen

Jonathan Toma

Ellen Paxinos

Andrea Gamarnik

Danielle Ditirro

Jeannette M Whitcomb

Jeanette M Whitcomb

The present disclosure relates to methods, compositions, and systems for detecting whether a subject exposed to a coronavirus has developed a neutralizing antibody response. Also disclosed are methods for determining whether a patient infected by a coronavirus is likely to respond to treatment with an antibody preparation. Also disclosed are methods for detecting the level of neutralizing antibody response in a sample of serum from a subject exposed to a coronavirus or to a coronavirus vaccine.

Methods, compositions, and systems for detecting coronavirus neutralizing antibodies

The invention provides a method for determining whether a human immunodeficiency virus is resistant to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.

Compositions and methods for determining resistance to inhibitors of virus entry using recombinant virus assays

The invention provides a method for determining whether a human immunodeficiency virus is resistance to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.

The present invention provides methods and compositions for determining whether a subject would benefit from co-receptor inhibitor therapy. In certain aspects, the methods can be used to determine whether a subject infected with a dual-mixed tropic population of HIV would benefit from CCCR5-inhibitor therapy or CXCR4-inhibitor therapy, the methods comprising determining whether the HIV population is a homogeneous or heterogeneous population of HIV, wherein the nature of the homogenous or heterogenous population of HIV indicates whether the patient would benefit from co-receptor inhibitor therapy.

Compositions and methods for determining whether a subject would benefit from co-receptor inhibitor therapy

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 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

This invention provides a method for determining susceptibility for an anti-viral drug comprising: (a) introducing a resistance test vector Comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c). This invention also provides a method for determining anti-viral drug resistance in a patient comprising: (a) determining anti-viral drug susceptibility in the patient at a first time using the susceptibility test described above, wherein the patient-derived segment is obtained from the patient at about said time; (b) determining anti-viral drug susceptibility of the same patient at a later time; and (c) comparing the anti-viral drug susceptibilities determined in step (a) and (b), wherein a decrease in anti-viral drug susceptibility at the later time compared to the first time indicates development or progression of anti-viral drug resistance in the patient.

Compositions and methods for determining anti-viral drug susceptibility and resistance and anti-viral drug screening

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.

Growing community of inventors

Half Moon Bay, CA, United States of America

Christos J Petropoulos