TTRV30M Affinity Trap for Amyloidogenic TTR Detection

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for detecting transthyretin (TTR) monomers in biological samples are inadequate, particularly for diagnosing transthyretin amyloidosis, as they lack specificity and clinical validation, and existing diagnostic tools do not effectively measure the severity of the disease or the efficacy of TTR stabilization drugs.

Innovation Solution

A method involving a variant TTR with a valine to methionine substitution at position 30 (TTRV30M) linked with an affinity moiety, such as biotin, is used to bind with TTR monomers in a biological sample, forming a detectable complex, which can then be detected using streptavidin and subsequent detection reagents like antibodies or aptamers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Difficulty of detecting and measuring

If monoclonal antibodies are used to detect TTR monomers, then detection capability is provided, but specificity and clinical validation are insufficient

Engineering Contradiction:

Improvedetection capabilityVSAvoidspecificity

Core Design Contradiction:

Difficulty of detecting and measuringVSMeasurement precision

Solution Approach 1:

The patent uses TTRV30M as an intermediary binding reagent that specifically recognizes and binds to TTR monomers. This intermediary approach allows indirect detection of TTR monomers through the TTRV30M-TTR monomer complex, providing both detection capability and enhanced specificity compared to direct antibody detection methods

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs a variant TTR (TTRV30M) with a specific amino acid substitution (valine to methionine at position 30) to create a binding reagent with altered properties. This parameter change in the protein structure enables specific recognition of TTR monomers while maintaining structural similarity to endogenous TTR, thereby improving measurement precision

Inventive Principle:

Principle #35Parameter changes

2Productivity

If existing diagnostic tools are used, then general TTR measurement is possible, but they do not effectively measure disease severity or drug efficacy

Engineering Contradiction:

Improvediagnostic capabilityVSAvoidprognostic information

Core Design Contradiction:

ProductivityVSLoss of information

Solution Approach 1:

The patent replaces conventional diagnostic approaches with a novel TTRV30M-based binding system that provides more sensitive and specific detection of TTR monomers. This substitution enables the measurement of clinically relevant parameters including disease severity and treatment response, thereby reducing information loss

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent establishes a diagnostic system that provides feedback on TTR monomer levels, which correlates with disease severity and treatment efficacy. By monitoring TTRV30M-TTR monomer complex formation, the system enables continuous assessment of disease progression and therapeutic response, preventing loss of prognostic information

Inventive Principle:

Principle #23Feedback

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach allows for accurate detection of TTR monomers, providing prognostic data on disease severity and evaluating the efficacy of TTR stabilization drugs by forming stable complexes that can be easily quantified, thereby improving diagnostic accuracy and clinical outcomes.

Implementation Method 1

contacting the sample with a TTR binding reagent for a sufficient time for the TTR binding reagent to bind to TTR monomers in the sample and form a complex comprising the TTR binding reagent and oligomerized TTR monomers

Methodology Applied

Scientific EffectProtein-protein binding:

Implementation Method 2

the affinity moiety is biotin... the method further comprises binding the complex to streptavidin

Methodology Applied

Scientific EffectAffinity binding:

Data Source

PatentUS20230184788A1A synthentic poly-transthyretin affinity trap for detecting amyloidogenic transthyretin forms in plasma samples oftranthyretin amyloidosis patients

Publication Date: 2023.06.15 NORTHWESTERN UNIV

AI summary

Disclosed herein are methods for detecting the presence of transthyretin monomers in a subject sample.