Donor-Specific cfDNA Analysis for Transplant Rejection Detection

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Solution Overview

Problem

Current methods for monitoring organ transplant rejection are invasive, expensive, and lack sensitivity, making it challenging to detect rejection in its early stages.

Innovation Solution

A non-invasive method involving the analysis of cell-free nucleic acids from transplant recipients, specifically measuring polymorphic nucleic acid targets to identify donor-specific alleles, using algorithms to determine transplant status without prior genotyping of the donor or recipient.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current surveillance methods are used to detect transplant rejection, then monitoring can be performed, but the methods are invasive, expensive, and lack sensitivity

Engineering Contradiction:
Improvedetection sensitivityVSAvoidinvasiveness of procedure
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts and analyzes cell-free nucleic acids (specifically donor-specific DNA) from the recipient's bloodstream as a non-invasive biomarker for rejection detection, separating the diagnostic function from invasive tissue sampling procedures

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses cell-free nucleic acids as an intermediary substance that carries information about organ health status from the transplanted organ to the bloodstream, allowing indirect monitoring without direct organ access

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If current surveillance methods are used to detect transplant rejection, then monitoring can be performed, but the methods are expensive

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcost of monitoring
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent employs standard PCR amplification and sequencing technologies that are relatively inexpensive and widely available, replacing costly specialized surveillance methods with accessible molecular biology techniques

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Loss of time

If current surveillance methods are used to detect transplant rejection, then monitoring can be performed, but rejection is difficult to detect in early stages

Engineering Contradiction:
Improvedetection timingVSAvoidearly detection capability
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent establishes baseline allele frequency measurements from the donor's nucleic acid profile before transplantation, enabling comparison with post-transplant samples to detect rejection at its earliest stages before significant organ damage occurs

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS20210301342A1Methods, and systems to detect transplant rejection
Publication Date: 2021.09.30 SEQUENOM INC
  • US20210301342A1 patent drawing
  • US20210301342A1 patent drawing
  • US20210301342A1 patent drawing

AI summary

This application provides methods and systems for determining transplant status. In some embodiments, the method comprises obtaining a biological sample from an organ transplant recipient who has received an organ; isolating cell-free nucleic acids from the biological sample; measuring the amount of each allele of one or more polymorphic nucleic acid targets in the biological sample; identifying the donor specific allele using a computer algorithm based on the measurements of the one or more polymorphic nucleic acid targets, whereby detecting one or more donor-specific circulating cell-free nucleic acids, detecting tissue injury based on the presence or amount of said one or more donor-specific nucleic acids, thereby determining transplant status.