Cell-Free DNA Risk Assessment for Early Transplant Rejection

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Solution Overview

Problem

Current methods for quantitative analysis of nucleic acids in samples are limited, particularly in detecting low levels of cell-free DNA for early detection of transplant rejection or adverse transplant outcomes.

Innovation Solution

A method involving the determination and comparison of total and specific cell-free nucleic acid levels, such as DNA, using PCR and next-generation sequencing, to assess transplant rejection risk by providing values in reports that include threshold indicators for clinical intervention.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current quantitative analysis methods are used, then measurement capability is maintained, but detection sensitivity for low levels of cell-free DNA is insufficient

Engineering Contradiction:

Improvedetection sensitivityVSAvoidearly detection capability

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent segments the analysis into two distinct measurements: total cell-free DNA levels and donor-specific cell-free DNA levels. This segmentation allows for more precise detection of low levels of donor-specific DNA by comparing it against the total background, thereby improving detection sensitivity for early rejection detection

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes the measurement parameters by quantifying both absolute total cell-free DNA levels and relative donor-specific percentages. This dual-parameter approach enables detection of subtle changes that indicate early rejection, improving both measurement precision and early detection capability

Inventive Principle:

Principle #35Parameter changes

2Reliability

If total and specific cell-free DNA measurements are performed, then early detection capability is improved, but measurement complexity increases

Engineering Contradiction:

Improveearly detection capabilityVSAvoidmeasurement complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs universal quantitative PCR and next-generation sequencing methodologies that can simultaneously measure both total and donor-specific cell-free DNA. These multi-functional techniques reduce measurement complexity by consolidating multiple measurements into integrated assay platforms

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent uses donor-specific genetic markers as intermediaries to bridge the measurement of total DNA and rejection detection. By targeting specific donor alleles within the total cell-free DNA pool, the method simplifies the complex task of detecting rejection through standardized molecular assays

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

Enables early detection of transplant rejection and adverse outcomes by accurately measuring and interpreting cell-free DNA levels, facilitating timely therapeutic interventions and improving clinical outcomes.

Implementation Method 1

using PCR and next-generation sequencing

Methodology Applied

Scientific EffectPolymerase Chain Reaction (PCR):

Implementation Method 2

using PCR and next-generation sequencing

Methodology Applied

Scientific EffectNext-generation sequencing:

Data Source

PatentEP3535413B1Methods for assessing risk using total and specific cell-free DNA

Publication Date: 2026.01.28 MEDICAL COLLEGE OF WISCONSIN INC

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AI summary

This invention relates to methods and compositions for assessing risk by measuring total and specific cell-free nucleic acids (such as DNA) in a subject. The methods and compositions provided herein can be used to determine risk of a condition, such as transplant rejection.