Neo-Epitope Immunoassay for Elastin Fragment Detection

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Solution Overview

Problem

Current methods for detecting and quantifying elastin degradation in pulmonary diseases are limited, as they primarily measure intact proteases or intact elastin, failing to effectively assess the neo-epitopes generated during proteolytic degradation, which are crucial for diagnosing and prognosing conditions like COPD and IPF.

Innovation Solution

Development of an immunoassay method using monoclonal antibodies specifically reactive with neo-epitopes formed at cleavage sites of elastin by HNE or MMP7, allowing for the quantification of peptide fragments in biological samples, which provides a more specific and sensitive measure of elastin degradation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ELISA kits quantify intact elastin or intact proteases, then the concentration of these molecules can be measured, but the neo-epitopes generated during elastin degradation cannot be detected

Engineering Contradiction:
Improvedetection of elastin degradationVSAvoiddetection capability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The invention extracts and detects only the specific neo-epitope regions generated by proteolytic cleavage of elastin, rather than measuring intact elastin or proteases. This is achieved by using antibodies that specifically bind to the cleaved regions, thereby isolating the detection target to the degradation products themselves.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention applies local quality by targeting specific local regions (neo-epitopes) of the elastin molecule that are generated upon cleavage. The antibodies are designed to recognize specific amino acid sequences at the cleavage sites, providing localized detection of degradation events rather than global measurement of intact molecules.

Inventive Principle:
Principle #3Local quality

2Reliability

If monoclonal antibodies are developed for specific neo-epitopes, then diagnostic specificity is improved, but the complexity of assay development increases

Engineering Contradiction:
Improvediagnostic specificityVSAvoidassay development complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention performs preliminary action by pre-selecting and characterizing specific neo-epitope targets based on known protease cleavage sites of elastin. This preliminary identification of target regions guides the subsequent antibody development process, reducing the complexity of screening and validation compared to developing antibodies against unknown or multiple potential targets.

Inventive Principle:
Principle #10Preliminary action

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 enables accurate diagnosis and prognosis of pulmonary diseases by quantifying specific elastin fragments, offering a higher degree of specificity and sensitivity compared to existing methods, and aiding in monitoring disease progression and treatment response.

Implementation Method 1

an immunological binding partner having specific binding affinity for a said neo-epitope

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP3094979B1Biochemical markers for pulmonary and other diseases
Publication Date: 2020.08.12 NORDIC BIOSCIENCE AS
  • EP3094979B1 patent drawingFigure 1~2
  • EP3094979B1 patent drawingFigure 3~4
  • EP3094979B1 patent drawingFigure 5~6

AI summary

A method of bioassay for the quantification of peptide fragments elevated in lung diseases such as COPD, SCC, or IPF, comprising a neo-epitope formed at a cleavage site by cleavage in vivo of elastin by a proteinase by contacting a sample with an antibody having specific binding affinity for a the neo-epitope amino acid sequence and determining the level of binding, where the antibody binds one of the following terminal sequences:.......FGPGVV.......VPGLGV IKAPKL........ and antibodies and immunoassay kits for use in such methods.