STING Agonist Patient Selection via Genotype Testing

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Solution Overview

Problem

Early clinical studies of STING agonists have failed to demonstrate consistent anti-tumor efficacy due to the impact of human genetic variation in proteins involved in the cGAS-STING pathway, particularly single nucleotide variants that decrease type 1 interferon and cytokine production.

Innovation Solution

Identifying and selecting cancer patients based on specific genotypes, such as TMEM173 V48V, TLR6 S249P, and TLR10 I775V variants, to administer a therapeutically effective amount of a STING agonist like E7766, potentially in combination with checkpoint inhibitors, for personalized treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If STING agonists are administered to all cancer patients, then broad coverage is achieved, but treatment efficacy is reduced due to genetic variation in the cGAS-STING pathway

Engineering Contradiction:

Improvetreatment efficacyVSAvoidpatient selection flexibility

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies preliminary action by performing genotype testing for TMEM173, TLR6, and TLR10 variants before administering STING agonist therapy. This pre-screening identifies patients with genetic profiles likely to respond to treatment, ensuring that the therapeutic intervention is targeted to the appropriate population before treatment begins, thereby improving reliability of treatment efficacy.

Inventive Principle:

Principle #10Preliminary action

2Reliability

If genotype-based patient selection is implemented, then treatment efficacy is improved, but diagnostic complexity increases

Engineering Contradiction:

Improvetreatment efficacyVSAvoidgenotype detection complexity

Core Design Contradiction:

ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies segmentation by dividing the diagnostic process into distinct, testable components: TMEM173 genotype assessment, TLR6 genotype assessment, and TLR10 genotype assessment. Each genetic marker can be evaluated independently through specific assays, allowing the complex diagnostic challenge to be broken into manageable segments that can be performed sequentially or in parallel.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies parameter changes by establishing specific genotype parameters (presence of TMEM173 V48V variant, TLR6 S249P variant, or TLR10 I775V variant) that define treatment eligibility. These discrete genetic parameters transform the continuous complexity of genetic variation into specific, measurable categories that guide therapeutic decision-making.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If personalized medicine approach is adopted, then anti-tumor response is enhanced, but treatment cost and complexity increase

Engineering Contradiction:

Improveanti-tumor responseVSAvoidtreatment regimen complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by tailoring the treatment approach to the specific genetic characteristics of each patient's tumor and immune system. Rather than applying a uniform treatment regimen, the therapy is customized based on the presence or absence of specific genetic variants in the patient's cGAS-STING pathway, ensuring that treatment intensity and type match the individual's biological needs.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20240384356A1Biomarkers for sting agonists and methods of using the same

Publication Date: 2024.11.21 EISAI R&D MANAGEMENT CO LTD

AI summary

The present disclosure relates to methods of identifying, selecting, monitoring, and/or treating a cancer patient with a STING agonist.