VHL Gene Detection for PD-1/PD-L1 Therapy Response

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Solution Overview

Problem

Current PD-1/PD-L1 targeting agents for cancer treatment have limited antitumor response rates and are expensive, with adverse reactions, necessitating the identification of predictive biomarkers for patient selection to improve therapeutic efficacy.

Innovation Solution

An in vitro or ex vivo method detects the loss of function of the von Hippel-Lindau (VHL) gene in tumor cells to predict responsiveness to PD-1/PD-L1 targeting agents, specifically using PD-1 or PD-L1 antagonists like Nivolumab, Pembrolizumab, and Atezolizumab for patients with VHL gene alterations, particularly in clear cell renal cell carcinoma.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PD-1/PD-L1 targeting agents are used for cancer treatment, then antitumor activity is enhanced, but the response rate remains limited and costs are high

Engineering Contradiction:
Improveantitumor response rateVSAvoidtreatment cost
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies preliminary action by detecting VHL gene loss of function status before initiating PD-1/PD-L1 targeting therapy. This predictive biomarker assessment allows clinicians to pre-identify patients most likely to respond to treatment, thereby improving the overall response rate and avoiding unnecessary treatment costs for patients who would not benefit.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention enables self-service by using the patient's own tumor tissue to detect VHL gene status. The method utilizes readily available clinical samples (tumor biopsies) to generate predictive information, eliminating the need for external or complex diagnostic systems while providing cost-effective patient selection.

Inventive Principle:
Principle #25Self-service

2Strength

If PD-1/PD-L1 targeting agents are administered, then T-cell response is enhanced, but adverse reactions occur

Engineering Contradiction:
ImproveT-cell responseVSAvoidadverse reactions
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by assessing VHL gene status before treatment to identify patients with high likelihood of response. This allows for targeted therapy administration only to suitable candidates, thereby enhancing T-cell response in responders while minimizing adverse reactions in non-responders who would not benefit from the immunotherapeutic mechanism.

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If patient selection is performed without predictive biomarkers, then treatment accessibility is maintained, but therapeutic efficacy is reduced

Engineering Contradiction:
Improvetreatment accessibilityVSAvoidtherapeutic efficacy
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The invention enables self-service by using the patient's own tumor tissue to detect VHL gene status. This approach maintains ease of operation because it utilizes readily available clinical samples that are already collected during standard diagnostic procedures, while simultaneously improving therapeutic efficacy through accurate patient selection based on predictive biomarker status.

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP3391054B1Method for assessing the response to PD-1/PDL-1 targeting drugs
Publication Date: 2019.09.25 INSTITUT GUSTAVE ROUSSY
  • EP3391054B1 patent drawingFigure 1A~1C
  • EP3391054B1 patent drawingFigure 2A~2E
  • EP3391054B1 patent drawingFigure 3A~3C

AI summary

The present invention relates to a method for assessing the response of a patient to a treatment with anti-PD-1/PDL-1 drugs based on the status of the VHL gene (von Hippel-Lindau).