Gene Expression Classifier for Kidney Transplant Monitoring

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Solution Overview

Problem

Current methods for monitoring kidney transplant function and immunological status are invasive, insensitive, and non-specific, leading to unnecessary risks and challenges in detecting sub-clinical acute rejection (subAR) and chronic rejection.

Innovation Solution

A method involving mRNA or cDNA derived from blood samples of kidney transplant recipients on immunosuppressant treatment, followed by microarray or sequencing assays to determine gene expression levels. A trained algorithm is applied to these levels to distinguish between transplant excellent kidneys and those with subAR or other non-transplant excellent conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If surveillance biopsies are used to monitor kidney transplant function, then detection precision of rejection is improved, but patient safety deteriorates due to invasive risks and sampling error

Engineering Contradiction:

Improvedetection precisionVSAvoidpatient safety

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the mechanical biopsy procedure with a molecular diagnostic system that analyzes gene expression patterns in blood samples. The classifier system uses computational algorithms to interpret molecular data, substituting invasive mechanical tissue sampling with non-invasive molecular analysis that eliminates biopsy-related risks while maintaining detection capability

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces blood-based molecular markers as an intermediary between the transplant kidney and the diagnostic system. Instead of directly sampling kidney tissue, the system analyzes gene expression products circulating in blood, which serve as mediators that convey information about kidney status without requiring direct tissue invasion

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of operation

If serum creatinine and immunosuppression levels are used for monitoring, then ease of operation is improved, but measurement precision deteriorates due to insensitivity and non-specificity

Engineering Contradiction:

Improveease of operationVSAvoidmeasurement precision

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the monitored parameters from conventional serum creatinine and immunosuppression levels to gene expression levels of specific markers. This parameter transformation enables detection of sub-clinical rejection states that conventional parameters miss, while maintaining the ease of blood sample collection and laboratory analysis

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If repeated surveillance biopsies are performed, then detection precision is improved, but loss of time and productivity deteriorates due to procedural complexity

Engineering Contradiction:

Improvedetection precisionVSAvoidloss of time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces repeated mechanical biopsy procedures with a single or infrequent molecular profiling event. The gene expression analysis can be performed on stored blood samples or routine blood draws, eliminating the need for repeated invasive procedures while maintaining surveillance capability through stable molecular markers

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20250051846A1Genome-wide classifiers for detection of subacute transplant rejection and other transplant conditions

Publication Date: 2025.02.13 THE SCRIPPS RES INST

AI summary

This disclosure provides methods of detecting sub-acute rejection and other categories of rejection in kidney transplant recipients using unique sets of gene expression markers.