CRTH2 Receptor Antagonist Response Genetic Markers

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Solution Overview

Problem

Current asthma treatments with CRTH2 receptor antagonists show variable therapeutic effects among patients, necessitating a method to identify individuals who would benefit most from these therapies to enhance treatment efficacy and cost-effectiveness.

Innovation Solution

Identification of specific genetic polymorphisms, such as the C/T polymorphism at rs12748961, and other SNPs on human chromosome 1, which are associated with improved responses to CRTH2 receptor antagonist therapy, allowing for personalized treatment approaches by testing patients for these markers before administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CRTH2 receptor antagonist therapy is administered to all asthma patients, then some patients may experience therapeutic benefit, but treatment efficacy varies widely among patients due to lack of patient selection

Engineering Contradiction:
Improvetreatment efficacyVSAvoidpatient responsiveness
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies preliminary action by performing genetic testing for CRTH2 receptor polymorphisms before administering CRTH2 antagonist therapy. This advance identification of patients with responsive genotypes (e.g., those with minor alleles at rs12748961, rs12118655, rs6679073) allows clinicians to pre-select patients who are likely to benefit from the therapy, thereby improving treatment efficacy while avoiding unnecessary treatment of non-responsive patients.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If genetic testing for CRTH2 antagonist response markers is performed, then patient selection for therapy can be optimized, but additional testing steps and complexity are introduced

Engineering Contradiction:
Improvetreatment response predictionVSAvoidtesting procedure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex clinical trial methodologies and empirical patient selection approaches with a genetic biomarker-based selection system. By identifying specific CRTH2 receptor polymorphisms (such as rs12748961, rs12118655, rs6679073) that predict treatment response, the invention substitutes objective genetic testing for subjective clinical assessment, thereby improving reliability while actually simplifying the patient selection process through standardized genetic markers.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If CRTH2 receptor antagonists are used as alternative oral therapy, then treatment options are expanded for patients not controlled on standard therapy, but compliance and effectiveness remain problematic

Engineering Contradiction:
Improvetreatment optionsVSAvoidcompliance and effectiveness
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies local quality by tailoring the treatment approach to specific patient subgroups based on their genetic characteristics. Rather than applying CRTH2 antagonist therapy universally or as a blanket alternative, the invention identifies patients with specific CRTH2 polymorphism profiles (e.g., carrying responsive alleles at rs12748961, rs12118655, or rs6679073) who are most likely to respond. This personalized approach improves both compliance and effectiveness by ensuring that oral CRTH2 antagonist therapy is directed at patients who will genuinely benefit from it.

Inventive Principle:
Principle #3Local quality

Data Source

PatentEP3337803B1Genetic markers associated with response to CRTH2 receptor antagonists
Publication Date: 2022.08.17 MERCK SHARP & DOHME LLC
  • EP3337803B1 patent drawingFigure 1
  • EP3337803B1 patent drawingFigure 2
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AI summary

The present invention provides genetic markers on human chromosome 1 that are associated with a beneficial response to CRTH2 receptor antagonists. These CRTH2 receptor antagonist response markers are useful, inter alia, to identify patients who are most likely to benefit from treatment with CRTH2 receptor antagonist compositions and drug products, in methods of treating patients having a disease susceptible to treatment with a CRTH2 receptor antagonist, and in methods for selecting the most appropriate therapy for such patients.