Laboratory Corp of America Holdings has filed a patent for a method to determine resistance of human immunodeficiency virus (HIV) to viral entry inhibitors. The method involves analyzing the inhibition curve of HIV population in the presence of varying concentrations of the inhibitor to determine resistance. GlobalData’s report on Laboratory Corp of America Holdings gives a 360-degree view of the company including its patenting strategy. Buy the report here.
According to GlobalData’s company profile on Laboratory Corp of America Holdings, molecular diagnosis biomarkers was a key innovation area identified from patents. Laboratory Corp of America Holdings's grant share as of September 2023 was 44%. Grant share is based on the ratio of number of grants to total number of patents.
Method for determining resistance of hiv to entry inhibitors
A recently filed patent (Publication Number: US20230313327A1) describes a method for detecting mutations of a virus that are correlated with reduced susceptibility to a virus entry inhibitor. The method involves obtaining biological samples from a subject at different time points during infection, cloning nucleic acid molecules from the samples, and transfecting them into cells to produce pseudoviruses. These pseudoviruses are then tested for infectivity in cells expressing the virus's cell surface receptor. The infectivity of the pseudoviruses is compared when exposed to the virus entry inhibitor and when not exposed to determine if there is reduced susceptibility. The nucleic acid sequence of the pseudoviruses is also determined to identify any mutations in the gene encoding the envelope protein that may be correlated with reduced susceptibility.
The method described in the patent also includes additional steps. Site-directed mutagenesis can be used to generate specific mutant pseudoviruses with mutations in the gene encoding the envelope protein that are correlated with reduced sensitivity to the virus entry inhibitor. These mutant pseudoviruses can then be tested for infectivity upon exposure to the inhibitor. The viral expression vector used in the method may contain an indicator nucleic acid that produces a detectable signal, or the second cell may contain an indicator nucleic acid that produces a detectable signal upon infection with the virus.
The receptor used in the method is CD4, and the second cell may also contain coreceptors such as CXCR4 and CCR5. The nucleic acid encoding the envelope protein can encode various components of the protein, including gp120, gp41, gp160, or fragments thereof. The method can be performed on patients who have been treated with an HIV inhibitor, particularly an entry inhibitor such as an antibody or combination of antibody fragments. The antibody may bind to various regions of the HIV envelope surface glycoprotein or the HIV envelope transmembrane glycoprotein.
In summary, the patent describes a method for detecting mutations in a virus that are correlated with reduced susceptibility to a virus entry inhibitor. The method involves cloning nucleic acid molecules, producing pseudoviruses, testing their infectivity, and determining the nucleic acid sequence of the pseudoviruses. Additional steps include generating mutant pseudoviruses, testing their infectivity, and using indicator nucleic acids to produce detectable signals. The method can be used on patients treated with HIV inhibitors, particularly entry inhibitors.
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