VEGFA Promoter SNP Detection for Anti-VEGF Therapy Selection

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Solution Overview

Problem

Current anti-VEGF treatments for cancer and macular degeneration are expensive, have limited activity, and cause severe toxicities, and it is difficult to predict which patients will respond effectively to these therapies due to conflicting reports on the role of VEGFA gene polymorphisms as predictive and prognostic markers.

Innovation Solution

A diagnostic method that identifies specific single nucleotide polymorphisms (SNPs) in the VEGFA gene promoter sequence, such as -2578C, -2549del, -1498T, and -1190G, to determine which patients are more responsive to anti-VEGF treatments, particularly Aflibercept, allowing for targeted therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-VEGF treatments are administered to all patients, then more patients may potentially benefit from the therapy, but the cost increases and unnecessary toxicities are imposed on patients who will not respond

Engineering Contradiction:

Improvetreatment efficacyVSAvoidtoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent performs preliminary genetic testing for VEGFA promoter polymorphisms before administering anti-VEGF therapy. This preliminary action identifies patients with responsive genotypes (e.g., -2578AA, -2549del, -1498TT, -1190GG) in advance, ensuring that only pre-selected patients receive the treatment, thereby avoiding unnecessary toxicities in non-responders while maintaining high treatment efficacy in the target population.

Inventive Principle:

Principle #10Preliminary action

2Measurement precision

If genetic testing for VEGFA polymorphisms is performed to identify responsive patients, then treatment precision is improved, but the diagnostic complexity increases

Engineering Contradiction:

Improvepredictive accuracyVSAvoiddiagnostic method complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the complex genetic analysis into detection of specific, discrete polymorphic sites in the VEGFA promoter region (positions -2578, -2549, -1498, -1190). Rather than performing comprehensive genomic sequencing, the method focuses on these key segmented locations, simplifying the diagnostic process while maintaining high predictive accuracy for treatment response.

Inventive Principle:

Principle #1Segmentation

3Productivity

If anti-VEGF therapy is restricted to genetically selected patients, then treatment cost-effectiveness is improved, but the number of patients receiving therapy decreases

Engineering Contradiction:

Improvecost-effectivenessVSAvoidnumber of treated patients

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent changes the selection parameter from broad clinical criteria to specific genetic parameters (VEGFA promoter polymorphisms). This parameter change identifies a precise patient subset with high treatment responsiveness, improving cost-effectiveness by concentrating resources on patients most likely to benefit, rather than diluting resources across a larger, less responsive population.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP2678441B1Single nucleotide polymorphisms in the promoter of vegfa gene and their use as predictive markers for Anti-VEGF treatments

Publication Date: 2017.10.18 SANOFI SA(FR)

AI summary

The invention relates to the treatment and the diagnosis of a group of patients bearing specific alleles of single nucleotide polymorphisms in the promoter region of the VEGFA gene. These patients are more responsive to Aflibercept and more likely to be efficiently treated by anti-VEGF therapy.