Reagents, methods, and systems for detecting therapeutic agents to monitor adherence to nucleoside reverse transcriptase inhibitor metabolites
Inventors
Daughtridge, Giffin • Kardos, Keith • RAJUR, Sharanappa Basappa • HWA-OK, Kim • KADAM, Asharani Dhondiram
Assignees
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Publication Number
US-12099056-B2
Publication Date
2024-09-24
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 uses thereof in monitoring adherence to pre-exposure prophylaxis. Such reagents comprise NRTI derivatives, analogs, NRTI derivatives conjugates, along with antibodies directed to same, which are useful for antibody-based methods, such as a lateral flow immunoassay and other point of care devices.
Core Innovation
The invention relates to immunogen and immunoassay components for detecting tenofovir diphosphate (TFV-DP) and TFV-DP metabolites using antibody reagents that specifically bind TFV-DP. The disclosed antibodies include variable heavy chain and variable light chain CDR amino acid sequences selected from defined sets specified by SEQ ID NOs, and are used as labeled first reagents in lateral flow assay formats to determine the presence or absence of TFV-DP in a patient fluid sample.
The invention also describes immunogenic compositions in which NRTI derivatives, including TFV-DP derivatives, are conjugated to carrier proteins such as TT, DT, CRM197, CRM176, CRM228, KLH, BSA, protein D, OMP, and pneumolysin. Linker chemistries are described for forming conjugates between TFV-DP derivatives and carrier proteins, including thiol-maleimide and NHS/activated esters and disulfide-related linkages. The resulting immunogens support production of antibodies including polyclonal and monoclonal antibody types and related antibody formats.
The immunoassay implementation is further tied to lateral flow device structures comprising a sample pad, a conjugated label pad, a membrane, and a test line with at least one second reagent bound to the membrane. The test line forms a detectable labeled first reagent-second reagent complex by binding interactions, in which the antibody is capable of specifically binding TFV-DP.
Claims Coverage
The independent claims cover four inventive features: an isolated antibody binding tenofovir diphosphate, lateral flow assay methods using TFV-DP-specific antibodies, a lateral flow assay device, and an assay kit including a sample collection receptacle. Across these claims, TFV-DP-specific binding is tied to defined variable heavy and variable light chain CDR amino acid sequence sets selected from SEQ ID NO combinations.
Isolated antibody with defined TFV-DP-specific CDR sets
An isolated antibody that specifically binds to tenofovir diphosphate, wherein the antibody comprises one of the sets of variable heavy chain and variable light chain CDR amino acid sequences selected from the listed SEQ ID NO combinations.
Lateral flow assay method with antibody-labeled first reagent and membrane second reagent
A method for performing a lateral flow assay to determine the presence or absence of tenofovir diphosphate in a fluid sample from a patient, using a labeled first reagent specific for tenofovir diphosphate and a membrane-bound second reagent capable of binding the labeled first reagent to create a detectable signal at a test line.
Lateral flow assay method with membrane-bound TFV-DP-binding antibody as second reagent
A method for performing a lateral flow assay to determine the presence or absence of tenofovir diphosphate in a fluid sample from a patient, including lateral flow from a sample pad to a conjugated label pad and then to a membrane that comprises a second reagent specific for tenofovir diphosphate bound to the membrane to form a test line.
Lateral flow assay device with antibody-based label pad first reagent and membrane test line second reagent
A device for performing a lateral flow assay to detect tenofovir diphosphate in a fluid sample, comprising a sample pad, a conjugated label pad downstream with a labeled first reagent specific for tenofovir diphosphate, and a membrane downstream with at least one second reagent bound to form a test line.
Across the independent claims, the coverage centers on TFV-DP-specific antibody reagents defined by selected variable heavy and variable light chain CDR amino acid sequence sets, and their use in lateral flow assay methods and devices where TFV-DP presence or absence is determined via labeled complex formation at a membrane test line.
Stated Advantages
Detects the presence or absence of tenofovir diphosphate in a patient fluid sample using a lateral flow assay format.
Matrix interference is addressed in documented assay performance in normal human plasma (5% and 10%).
Documented Applications
Lateral flow assay for determining the presence or absence of tenofovir diphosphate in a fluid sample from a patient who is prescribed or administered an NRTI regimen comprising tenofovir, tenofovir disoproxil fumarate, or tenofovir alafenamide.
Point-of-care/lateral-flow diagnostic system formats using lateral flow device/test strip components to generate a detectable signal at a test line.
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