Cell-Free DNA Quantification for Pro-Inflammatory Severity Assessment

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Solution Overview

Problem

Current methods lack effective means to assess and manage pro-inflammatory responses, particularly in conditions like COVID-19 infections, where inappropriate responses can lead to severe complications, and existing treatments are not adequately monitored for efficacy.

Innovation Solution

Quantifying total cell-free DNA (cf-DNA) levels in a sample to determine the severity and risk of complications associated with pro-inflammatory responses, using cf-DNA inhibitors to treat subjects with excessive DNA levels, and monitoring these levels over time to assess treatment effectiveness.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If total cell-free DNA levels are used to assess pro-inflammatory response severity, then measurement precision and early detection capability are improved, but device complexity and measurement difficulty increase

Engineering Contradiction:

Improveseverity assessment precisionVSAvoidcf-DNA quantification difficulty

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent replaces complex cellular analysis methods with a biochemical assay approach. Instead of directly analyzing cellular responses or inflammatory markers requiring complex processing, the invention uses qPCR-based quantification of cell-free DNA, substituting mechanical/cellular analysis with a chemical amplification and detection system that is more precise and easier to standardize.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces cell-free DNA as an intermediary biomarker that mediates between the actual pro-inflammatory response and the measurement system. Rather than directly measuring inflammatory cells or cytokines, the assay measures cf-DNA levels which serve as a surrogate indicator, simplifying the detection process while maintaining assessment accuracy.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If cf-DNA inhibitors are administered to treat pro-inflammatory responses, then treatment effectiveness is improved, but loss of substance (DNA) and potential off-target effects increase

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidcell-free DNA reduction

Core Design Contradiction:

ReliabilityVSLoss of substance

Solution Approach 1:

The patent implements a feedback-based treatment approach where cf-DNA levels are measured before and after inhibitor administration. This allows clinicians to assess treatment effectiveness by monitoring the reduction in cf-DNA levels, creating a closed-loop system that adjusts treatment based on actual biomarker response rather than relying solely on clinical symptoms.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The patent performs preliminary quantification of cf-DNA levels before initiating inhibitor treatment. This baseline measurement allows for personalized treatment planning and establishes a reference point against which treatment effectiveness can be compared, ensuring that inhibitors are administered only when cf-DNA levels indicate a pro-inflammatory response that would benefit from such treatment.

Inventive Principle:

Principle #10Preliminary action

3Productivity

If total cell-free DNA quantification is implemented for monitoring subjects, then productivity and early identification capability are improved, but loss of time for sample processing and analysis increases

Engineering Contradiction:

Improveearly identification efficiencyVSAvoidsample processing time

Core Design Contradiction:

ProductivityVSLoss of time

Solution Approach 1:

The patent performs preliminary extraction and preparation of cell-free DNA from serum or plasma samples at the time of blood collection. By preparing the sample upfront and storing it appropriately, the actual qPCR quantification can be performed rapidly using pre-prepared reagents and protocols, reducing the critical processing time needed at the point of decision-making.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent replaces time-consuming manual sample processing steps with automated extraction kits and standardized protocols. The use of commercial cf-DNA extraction kits and pre-optimized qPCR assays reduces hands-on processing time and minimizes variability, allowing rapid turnaround from sample collection to results interpretation.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20230138927A1Methods for assessing the severity of, and for inhibiting, pro-inflammatory responses with total cell-free DNA

Publication Date: 2023.05.04 MEDICAL COLLEGE OF WISCONSIN INC

AI summary

This invention relates to methods and compositions for assessing an amount of total cell-free DNA, such as from a subject having a pro-inflammatory response, such as a pro-inflammatory response associated with an infection, such as a COVID-19 infection. This invention also relates to compositions and methods for treating subjects having or suspected of having a pro-inflammatory response, such as a pro-inflammatory response associated with an infection, such as a COVID-19 infection. In embodiments, there is a risk of an inappropriate or detrimental pro-inflammatory response, such as in a subject with a COVID-19 infection. The methods and composition provided herein can be used to determine severity and risk of complications in a subject. The methods and composition provided herein can also be used to assess the effectiveness of a therapy in a subject, such as a COVID-19 subject.