Functional ligands to drug compounds
Inventors
Jackson, George W. • Batchelor, Robert • Nguyen, Truong • Drabek, Rafal • Chiu, Alexander S. • Thirunavukarasu, Deepak • Sankarapani, Vinoth
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Assignees
Member
Base Pair BiotechnologiesBase Pair Biotechnologies specializes in custom aptamer discovery and development for research, diagnostics, therapeutics, and industrial applications. The company leverages proprietary multiplex selection, advanced bioinformatics, and chemical modification techniques to develop high-affinity and selective nucleic acid aptamers. Base Pair enables affinity reagent development, biosensor design, and molecular detection for a broad range of targets and partners across academia and industry.
Base Pair Biotechnologies specializes in custom aptamer discovery and development for research, diagnostics, therapeutics, and industrial applications. The company leverages proprietary multiplex selection, advanced bioinformatics, and chemical modification techniques to develop high-affinity and selective nucleic acid aptamers. Base Pair enables affinity reagent development, biosensor design, and molecular detection for a broad range of targets and partners across academia and industry.
Publication Number
US-11427825-B2
Publication Date
2022-08-30
Expiration Date
Abstract
The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules, such as drug compounds, such as levamisole and cocaine.
Core Innovation
The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules, more particularly to functional ligands with binding affinity to target molecules such as drug compounds, such as levamisole and cocaine.
The background identifies that aptamers are nucleic acid ligands capable of binding molecular targets and that levamisole has increasingly been used as a cutting agent in cocaine with associated clinical complications such as neutropenia, agranulocytosis and vasculitis, and that levamisole and cocaine may be quantified in blood, plasma, or urine for diagnostic or medicolegal investigations. The invention addresses generating functional biomolecules that bind with functional activity to targets and provides multiplexed methods for selecting and identifying binding ligands to multiple targets simultaneously to enable identification, tagging and isolation of binding members for subsequent analysis.
Claims Coverage
This patent includes one independent claim. Five main inventive features are identified in the claims.
Artificial ligand binding to cocaine
An artificial ligand binding to cocaine consisting essentially of a non-naturally occurring nucleic acid sequence having the sequence selected from the group consisting of SEQ IDs 50, 191-195, and 200-203.
Substitution with a non-natural analog
At least one nucleotide of the non-naturally occurring nucleic acid sequence is substituted with a non-natural analog.
Appended 5′ sequence
The non-naturally occurring nucleic acid sequence is appended with a 5′-sequence selected from the group consisting of SEQ IDs 291-292.
Appended 3′ sequence
The non-naturally occurring nucleic acid sequence is appended with a 3′-sequence selected from the group consisting of SEQ IDs 291-292.
Appended 5′ and 3′ sequences
The non-naturally occurring nucleic acid sequence is appended with a 5′-sequence and a 3′-sequence selected from the group consisting of SEQ IDs 291-292.
The claims cover an artificial cocaine-binding nucleic acid ligand defined by specific SEQ IDs and claim variations including substitution with non-natural analogs and appending SEQ IDs 291-292 at the 5′ and/or 3′ ends.
Stated Advantages
High capacity, multiplexed identification procedures may save time, expense, and physical space for the process over single target identification processes.
The methods may be utilized to identify and/or eliminate biomolecules that bind or have a tendency to bind to multiple targets.
Performing only the final binding and marking/tagging procedure on an array may be desirable because complex target arrays may generally be more expensive and/or difficult to make or utilize than solutions of target molecules.
Tagging identifiers to bound members enables associating a given member with a particular target while preserving the particular sequence of the member, which may be desirable for resolving multiple binders to a single target or members that bind multiple targets.
Functional ligands to levamisole, cocaine and related molecules may be utilized for detection, quantification, and diagnostic applications such as detecting levamisole in body fluids or tissues, identifying levamisole as an adulterant in drugs, and quantification in clinical poisoning or medicolegal investigations.
Documented Applications
Detection, quantification, and/or other diagnostic applications for levamisole in body fluids or tissues, including identifying levamisole as an adulterant in drugs such as cocaine and quantification in clinical poisoning situations or medicolegal investigations.
Detection of cocaine in bodily fluids or tissue for ascertaining the use of cocaine by a person.
Use of functional ligands (aptamers) as sensors, therapeutic tools, to regulate cellular processes, and to guide drugs to their specific cellular targets.
Application in diverse assay formats including electrochemical sensors, gold nanoparticle assays, enzyme linked aptamer sorbent assays (ELASA), pull down assays (immunoprecipitation), microplate/well assays, lateral flow assays, and aptamer beacons that change signal upon target binding.
Use of multiplexed target arrays and histology sections as target sets for generating and identifying binding nucleic acids, and subsequent tagging/identifier strategies to associate binders with spatially resolved targets.
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