TTR Tetramer Detection via T4-Site Binding for Stability Assessment

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

There is a need for a reliable method to detect and evaluate the stability of transthyretin (TTR) tetramer, as its destabilization is a key factor in amyloidosis, and existing methods are inadequate for this purpose.

Innovation Solution

A method involving the formation of a complex using a compound that binds to the T4 binding site of TTR tetramer, an antibody that binds to TTR monomer, and a labeling substance, followed by signal measurement to detect and assess TTR tetramer stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing screening tests (electrocardiogram, echocardiography) are used for ATTR diagnosis, then patient identification can be performed, but the methods cannot directly evaluate TTR tetramer stability which is the underlying cause of ATTR

Engineering Contradiction:
ImproveATTR diagnosis accuracyVSAvoidTTR tetramer stability information
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

The patent introduces a compound capable of binding to the T4 binding site as an intermediary substance. This compound specifically interacts with TTR tetramer, enabling the detection method to indirectly measure TTR tetramer stability through the binding interaction, thereby recovering the stability information that was lost when using conventional screening tests

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical/physical screening methods (electrocardiogram, echocardiography) with a chemical-based detection system. By using a compound that chemically binds to the T4 binding site and measuring this interaction, the system substitutes physical monitoring with chemical interaction analysis, enabling direct assessment of TTR tetramer stability

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If a detection method using multiple components (compound, antibody, labeling substance) is implemented, then TTR tetramer stability can be evaluated, but the device complexity increases

Engineering Contradiction:
ImproveTTR tetramer stability measurementVSAvoiddetection system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines multiple functional components into an integrated detection system. The compound, antibody, and labeling substance work together in a unified assay format, merging their individual functions into a single measurement process that evaluates TTR tetramer stability without requiring separate analytical steps

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The detection system is designed with multi-functionality, where the same assay platform can detect TTR tetramer presence, evaluate its stability, and potentially quantify dissociation kinetics. This universal approach allows a single complex system to perform multiple measurement functions, reducing the need for separate specialized devices

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

Enables accurate detection and evaluation of TTR tetramer stability, facilitating early identification of ATTR patients and aiding in the development of therapeutic interventions.

Implementation Method 1

a compound capable of binding to the T4 binding site of the TTR tetramer

Methodology Applied
Scientific EffectMolecular binding: Absorption (physical)

Implementation Method 2

an antibody capable of binding to the TTR monomer

Methodology Applied
Scientific EffectAntigen-antibody binding: Absorption (physical)

Implementation Method 3

a labeling substance; and measuring a signal generated by the labeling substance contained in the complex

Methodology Applied
Scientific EffectSignal generation: Luminescence

Data Source

PatentEP4660629A1Method for detecting transthyretin tetramer, and method for evaluating stability
Publication Date: 2025.12.10 SYSMEX CORP
  • EP4660629A1 patent drawingFigure 1A~1B
  • EP4660629A1 patent drawingFigure 2A~2B
  • EP4660629A1 patent drawingFigure 3A~3B

AI summary

An object of the invention is to provide a means capable of detecting transthyretin (TTR) tetramer in a sample. Provided is a method comprising forming a complex comprising the TTR tetramer in the sample, a compound capable of binding to the thyroxine binding site of the TTR tetramer, an antibody capable of binding to the TTR monomer, and a labeling substance, and measuring a signal generated by the labeling substance contained in the complex.