Multi-omics Platform for Rapid Drug Mechanism Identification

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Solution Overview

Problem

Current drug development processes are inefficient and costly, with a high failure rate of drug candidates in clinical trials due to inadequate understanding of molecular mechanisms of action, particularly in predicting efficacy and safety, and existing methods fail to comprehensively identify biological effects of drugs at early stages.

Innovation Solution

A method involving a multi-omics platform that rapidly identifies biological mechanisms of drugs or toxins by determining optimal dosage and exposure time, assessing biological parameters, and applying bioinformatic analysis to determine mechanisms of action within 30 days, utilizing techniques such as RPLC, HILIC chromatography, RNA sequencing, and mass spectrometry.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If targeted medium to high-throughput approaches (RPMA, PCA, HCT) are used to measure hundreds to thousands of pre-selected proteins, then measurement capability is improved, but comprehensiveness of biological mechanism identification deteriorates because only pre-selected targets are probed

Engineering Contradiction:
Improvemeasurement capabilityVSAvoidcomprehensiveness of biological mechanism identification
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent employs a multi-omics platform that simultaneously performs transcriptomics, proteomics, and metabolomics analyses to universally capture comprehensive biological mechanisms across multiple molecular levels, rather than being limited to pre-selected protein targets

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent extends the analysis from single-omics (one dimension) to multi-omics (multiple dimensions) by integrating transcriptomics, proteomics, and metabolomics data, thereby achieving comprehensive coverage of biological mechanisms that cannot be obtained by probing pre-selected targets alone

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Productivity

If current toxicology screens are used to evaluate potential toxicity based on structural and physiochemical properties, then toxicity prediction efficiency is improved, but ability to define full mechanism of action deteriorates because only known toxicity profiles are evaluated

Engineering Contradiction:
Improvetoxicity prediction efficiencyVSAvoidfull mechanism of action definition
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The patent performs preliminary multi-omics profiling during pre-clinical development stages to comprehensively characterize the mechanism of action before clinical trials, enabling early identification of both known and novel toxicity mechanisms rather than relying solely on structural property evaluation

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses multi-omics data integration as an intermediary approach that bridges the gap between rapid toxicity screening and comprehensive mechanism elucidation, combining the speed of high-throughput screening with the depth of mechanistic investigation

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If reductionist approach focusing on single target affinity optimization is used, then drug development efficiency is improved, but success rate deteriorates because off-target effects and multiple attributes are not simultaneously optimized

Engineering Contradiction:
Improvedrug development efficiencyVSAvoidsuccess rate of drug candidates
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent employs a multi-functional evaluation platform that simultaneously assesses multiple attributes including target affinity, off-target effects, and mechanistic characteristics across transcriptomics, proteomics, and metabolomics, enabling comprehensive optimization rather than single-target focus

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent implements feedback mechanisms by using multi-omics data to identify off-target effects and mechanistic issues early in development, providing information that feeds back into compound optimization to improve success rate before clinical trials

Inventive Principle:
Principle #23Feedback

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

This approach enables a comprehensive understanding of a compound's mechanism of action, reducing the time and cost of drug development by identifying potential issues early on and improving the prediction of drug success, while also providing insights into resistance mechanisms and metabolic changes.

Implementation Method 1

utilizing techniques such as RPLC, HILIC chromatography

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

mass spectrometry

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 3

RNA sequencing

Methodology Applied
Scientific EffectRNA sequencing:

Data Source

PatentUS10607721B2High-throughput, multi-omics approach to determine and validate de novo global mechanisms of action for drugs and toxins
Publication Date: 2020.03.31 VANDERBILT UNIV
  • US10607721B2 patent drawing
  • US10607721B2 patent drawing
  • US10607721B2 patent drawing

AI summary

The present disclosure provides for rapid identification of mechanism of action (MOA) for drugs and toxins, and does so in a rapid (30 days or less) fashion. The methods use a combination of high throughput bioinformatics and pathway analysis that examine a wide variety of biological parametics.