Products and methods for monitoring adherence to nucleoside reverse transcriptase inhibitor therapy
Inventors
Daughtridge, Giffin • Kardos, Keith
Assignees
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Publication Number
US-11795239-B2
Publication Date
2023-10-24
Expiration Date
Abstract
The invention provides novel compounds, reagents, systems, and methods for detecting a metabolite related to a NRTI in a biological sample, and use thereof in monitoring adherence to pre-exposure prophylaxis or anti-retroviral treatment. Such reagents comprise NRTI derivatives, analogs, NRTI derivatives conjugates, along with antibodies directed to same, which are useful for anti-body-based methods, such as a lateral flow immunoassay and other point of care devices.
Core Innovation
The invention relates to isolated antibodies that specifically bind to tenofovir. The antibodies are defined by immunoglobulin variable light chain CDRs and immunoglobulin variable heavy chain CDRs, with the CDRs specified according to sets of SEQ ID NOs. The disclosed antibody format includes immunoglobulin variable regions and CDR-defined binding specificity for tenofovir.
The invention also relates to nucleic acids encoding the antibody heavy and light chains and transformed cells containing the nucleic acids. The disclosed variable-region sequence content includes full variable-region sequences and CDR amino-acid sequences for multiple antibody clones, including monoclonal and polyclonal antibody configurations.
A further aspect of the invention concerns lateral flow immunoassay concepts for detecting tenofovir in a fluid sample. The assay architecture includes a sample pad, a conjugate label pad with a labeled first reagent specific for tenofovir, and a downstream membrane with a second reagent bound to form a test line. Detectable label at the test line indicates the presence or absence of tenofovir, including competitive readout logic.
The disclosed assay implementations include membrane support concepts such as nitrocellulose and a control-line concept based on a third reagent that generates a detectable signal to indicate proper performance. The described use context includes detecting tenofovir in biological fluid samples, including urine from patients, including those on FTC/TAF, and provides cross-reactivity profiling and competition ELISA performance concepts for tenofovir detection.
Claims Coverage
The partial claim set includes three independent claims directed to tenofovir-specific antibodies defined by particular CDR sequence sets, a lateral flow assay method with conditional test-line signal behavior, and a lateral flow assay device with defined test-line components and interfaces. Across these independent claims, the main inventive features are the CDR-defined antibody specificity to tenofovir and the lateral-flow strip architecture that links labeled tenofovir-binding reagent behavior with test-line detectable signal formation.
CDR-defined tenofovir-specific antibody
An isolated antibody that specifically binds to tenofovir, wherein the antibody comprises immunoglobulin variable light chain CDRs and immunoglobulin variable heavy chain CDRs specified according to SEQ ID NOs in four alternative sets.
Lateral flow assay with labeled tenofovir-binding reagent and test line
A method for performing a lateral flow assay to detect tenofovir in a fluid sample by applying the fluid sample to a sample pad, flowing laterally to a conjugated label pad with a labeled first reagent specific for tenofovir, forming a labeled first reagent-tenofovir complex if tenofovir is present, flowing to a membrane forming a test line with a second reagent bound to the membrane that can bind the labeled first reagent, forming a labeled first reagent-second reagent complex at the test line, and detecting the label at the test line, wherein the first reagent is an antibody comprising immunoglobulin variable light chain CDRs and immunoglobulin variable heavy chain CDRs specified according to SEQ ID NOs in four alternative sets.
Lateral flow assay device with sample pad, conjugated label pad, and test line
A device for performing a lateral flow assay to detect tenofovir in a fluid sample comprising a sample pad, a conjugated label pad downstream with a labeled first reagent specific for tenofovir where a first interface forms between the sample pad and the conjugated label pad, a membrane downstream forming a second interface where the membrane comprises a second reagent bound to form a test line and can bind the labeled first reagent, and a test-line pathway such that the first and second interfaces allow the fluid sample to flow, contact the labeled first reagent, and form a labeled first reagent-second reagent complex to cause a detectable signal at the test line, wherein the first reagent is an antibody comprising immunoglobulin variable light chain CDRs and immunoglobulin variable heavy chain CDRs specified according to SEQ ID NOs in four alternative sets.
Overall, the independent claims cover CDR-defined isolated antibodies that specifically bind tenofovir, and lateral-flow assay systems (method and device) that use a tenofovir-specific labeled first reagent and defined test-line complex formation to generate a detectable signal indicating tenofovir presence or absence.
Stated Advantages
Enables monitoring adherence to NRTI therapy by detecting tenofovir (TFV) or tenofovir-related metabolites in a subject’s biological fluid sample.
Provides a lateral flow assay and point-of-care style device architecture with detectable signals at a test line for tenofovir detection.
Uses tenofovir-specific antibodies defined by defined immunoglobulin variable CDR SEQ ID NO sets to support consistent tenofovir binding in the assay formats.
Documented Applications
Monitoring adherence to NRTI therapy (including PrEP/ART) by detecting tenofovir (TFV) or tenofovir-related metabolites in a subject’s biological fluid sample.
A lateral flow assay for detecting tenofovir in a fluid sample using a test line readout with a labeled tenofovir-specific first reagent and a membrane-bound second reagent.
A lateral flow assay device configured for performing the tenofovir detection workflow using a sample pad, conjugated label pad, and membrane with a test line.
Detecting tenofovir in biological fluid samples, including urine from patients, including those on FTC/TAF.
POCT.
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