EXT1/EXT2 Kidney Tissue Markers for Membranous Nephropathy Risk

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Solution Overview

Problem

Current methods fail to accurately predict the progression of membranous nephropathy to end-stage kidney disease, limiting effective treatment strategies.

Innovation Solution

Identify kidney tissue expression of EXT1 and EXT2 polypeptides using immunohistochemistry or laser microdissection and mass spectrometry to classify membranous nephropathy as likely or unlikely to progress to end-stage kidney disease, and administer immunosuppressive agents like corticosteroids or Rituximab to slow progression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic methods are used to identify membranous nephropathy, then diagnosis can be made, but accurate prediction of disease progression to end-stage kidney disease cannot be achieved

Engineering Contradiction:
Improvedisease progression prediction accuracyVSAvoidtreatment strategy effectiveness
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent performs preliminary classification of membranous nephropathy into EXT1/EXT2-positive and EXT1/EXT2-negative types before treatment initiation. This preliminary action enables accurate prediction of disease progression and guides appropriate treatment selection, resolving the contradiction between diagnostic capability and progression prediction accuracy.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces EXT1 and EXT2 polypeptide detection as an intermediary marker system. This intermediary enables the connection between initial diagnosis and future disease progression outcomes, allowing clinicians to predict progression to end-stage kidney disease with high accuracy while maintaining reliable treatment strategy formulation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If immunosuppressive agents are administered without disease progression classification, then treatment is provided, but treatment effectiveness is reduced due to inability to identify high-risk patients

Engineering Contradiction:
Improvetreatment effectivenessVSAvoiddiagnostic classification system
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent implements preliminary risk stratification based on EXT1/EXT2 polypeptide status before administering immunosuppressive therapy. This preliminary classification identifies high-risk patients likely to progress to end-stage kidney disease, ensuring that intensive treatment is targeted to those who will benefit most, thereby improving overall treatment effectiveness without excessive complexity.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If EXT1 and EXT2 polypeptide detection is implemented, then accurate disease progression prediction is achieved, but diagnostic process complexity increases

Engineering Contradiction:
Improveprogression prediction accuracyVSAvoiddetection methodology
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs EXT1 and EXT2 polypeptide detection as intermediary biomarkers that bridge initial diagnosis and progression prediction. These intermediaries provide accurate progression prediction through relatively straightforward detection methods, resolving the contradiction between achieving high measurement precision and maintaining acceptable diagnostic process complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Accurately predicts disease progression and enables targeted treatment to reduce the risk of end-stage kidney disease, allowing for effective management of membranous nephropathy.

Implementation Method 1

determining if kidney tissue from the mammal expresses a polypeptide, wherein the polypeptide is an exostosin 1 (EXT1) polypeptide or an exostosin 2 (EXT2) polypeptide

Methodology Applied
Scientific EffectImmunohistochemistry: Absorption (physical)

Implementation Method 2

laser microdissection and mass spectrometry

Methodology Applied
Scientific EffectLaser microdissection: Laser Ablation

Implementation Method 3

laser microdissection and mass spectrometry

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentEP4244375B1Methods and materials for identifying and treating membranous nephropathy
Publication Date: 2025.12.17 MAYO FOUNDATION FOR MEDICAL EDUCATION & RESEARCH
  • EP4244375B1 patent drawingFigure 1
  • EP4244375B1 patent drawingFigure 2A~2F
  • EP4244375B1 patent drawingFigure 3A~3F

AI summary

This document provides methods and materials involved in identifying and treating mammals (e.g., humans) having membranous nephropathy. For example, methods and materials for determining the likelihood that a mammal (e.g., a human) having membranous nephropathy (e.g., lupus membranous nephropathy) will progress to end stage kidney disease are provided. Methods and materials for treating membranous nephropathy likely to develop end stage kidney disease also are provided.