In Vitro Drug Combination Efficacy Prediction via Statistical Distribution Analysis

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Solution Overview

Problem

Current methods for predicting the effectiveness of combination chemotherapeutic therapies in cancer treatment lack a suitable approach to account for synergistic and antagonistic effects, relying on separate testing of individual drugs and not effectively measuring the efficacy of drug combinations.

Innovation Solution

The CTR-Test method measures the effectiveness of chemotherapeutic agents by determining the best concentration and distribution curve parameters for individual substances, allowing for the assessment of combination therapies using reduced concentrations and calculating synergistic and antagonistic effects through mean, median, and standard deviation analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If separate testing of individual drugs is performed, then the efficacy of each medication can be determined, but the synergistic and antagonistic effects of combination therapies cannot be accurately predicted

Engineering Contradiction:
Improveefficacy prediction accuracyVSAvoidcombination therapy assessment capability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent merges the assessment of individual drug efficacies with the evaluation of combination effects by integrating multiple drugs into a single in vitro test system. This allows simultaneous determination of both individual and combined therapeutic effects, enabling accurate prediction of synergistic and antagonistic interactions while maintaining the ability to assess each medication's contribution separately.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The in vitro test system is designed to perform multiple functions: it can evaluate individual drug efficacies, assess combination therapy effects, and predict synergistic or antagonistic interactions using the same experimental platform. This multi-functional approach eliminates the need for separate testing protocols and provides comprehensive efficacy prediction for both monotherapy and combination regimens.

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

2Productivity

If the most effective individual medications are selected for combination, then the assumption is that this will produce the best combination therapy, but this approach does not account for synergistic or antagonistic interactions

Engineering Contradiction:
Improvetherapy development efficiencyVSAvoidcombination efficacy prediction
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent implements a feedback mechanism where the in vitro test results for combination therapies provide direct information about synergistic or antagonistic effects. This feedback allows researchers to adjust combination selections based on actual measured interactions rather than relying solely on individual drug efficacy rankings, thereby improving the reliability of combination therapy predictions while maintaining efficient drug development processes.

Inventive Principle:
Principle #23Feedback

3Ease of manufacture

If conventional in vitro methods are used for individual drugs, then established protocols can be applied, but no readily available alternative exists for measuring combination therapy efficacy

Engineering Contradiction:
Improvetesting protocol availabilityVSAvoidcombination therapy measurement capability
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent segments the combination therapy assessment into manageable components that can be evaluated using established in vitro methodologies. By dividing the complex combination effect into measurable parameters (such as synergistic index, antagonistic index, and combined efficacy scores), the system leverages existing test protocols while extending their applicability to combination therapies, thus maintaining ease of implementation while achieving versatile measurement capability.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP3583421B1Novel in vitro system for predicting the efficacy of drug combinations in tumor cells or other target cells
Publication Date: 2022.02.09 KISCHKEL FRANK CHRISTIAN
  • EP3583421B1 patent drawingFigure 1A~1B
  • EP3583421B1 patent drawingFigure 1C~1D
  • EP3583421B1 patent drawingFigure 2A~2C

AI summary

1. The invention relates to a method for predicting the efficacy of drug combinations by individual in vitro testing. 2.1 Combination therapies are increasingly used in the treatment of cancers. The individual substances are hitherto measured individually, without taking any synergistic or antagonistic effects into consideration, to determine the efficacy of their combination. Cancer therapy could be optimized by using a suitable method for predicting the efficacy of drug combinations. 2.2 The conditions for the individual measurements are used to be able to reach a conclusion about the efficacy of the combination. In order to test the efficacy of a given combination that consists of x substances the corresponding drugs are used at 1/x of the determined optimum concentration. The efficacy of the combination is determined by means of the average values and standard deviations of the new distribution curve or of the distribution curve of the individual substances. 2.3 The method according to the invention can be used in oncology and medicine in general whenever drug combinations are used and living target cells are present.