Biomarker Panel for Predicting Integrin Therapy Response

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Solution Overview

Problem

Current treatments for complex multifactorial diseases lack personalized approaches, leading to variable efficacy and side effects, necessitating the development of specific biomarkers for predicting patient response to therapies, particularly for αvβ6-integrin mediated disorders like lung fibrosis and cancer.

Innovation Solution

Identification of biomarkers such as ALOX5, FN1, OLR1, PAI-1, TGM2, and TREM1 in bronchoalveolar lavage fluid to predict responsiveness to αvβ6-integrin inhibitors, allowing for tailored therapy and monitoring of treatment effectiveness.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional histological and clinical features are used to correlate with prognosis, then general treatment guidance can be provided, but specific parameters to determine responsiveness to therapy and individualized treatment outcomes cannot be obtained

Engineering Contradiction:
Improveprediction precision of treatment responseVSAvoidcomplexity of biomarker analysis system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the complex disease prognosis problem into specific gene expression markers (e.g., HSP90AA1, HSP90AB1, PGK1, TBP) that can be independently measured and analyzed. This segmentation allows precise prediction of treatment response by focusing on key molecular indicators rather than attempting to analyze all clinical features simultaneously.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces gene expression levels as intermediary biomarkers that mediate between conventional clinical features and treatment outcomes. These molecular markers serve as intermediate indicators that provide more precise information about drug responsiveness, bridging the gap between general clinical assessment and individualized treatment prediction.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If a one-size-fits-all therapy approach is used, then treatment simplicity is maintained, but variable efficacy and severe side effects occur in different individuals

Engineering Contradiction:
Improvetreatment efficacy reliabilityVSAvoidtreatment implementation simplicity
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent applies local quality by tailoring treatment to individual patients based on their specific gene expression profiles. Instead of uniform treatment, patients are stratified into responders and non-responders based on molecular characteristics, allowing customized therapy selection that optimizes efficacy for each individual's specific disease phenotype.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent performs preliminary action by conducting gene expression analysis before treatment initiation to predict patient response. This pre-treatment molecular profiling allows clinicians to identify likely responders and select appropriate therapies in advance, avoiding ineffective treatments and reducing side effects before they occur.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If biomarker analysis is implemented to predict treatment response, then personalized medicine can be achieved, but additional testing requirements and complexity increase

Engineering Contradiction:
Improvetreatment personalization capabilityVSAvoiddiagnostic system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent employs universal gene expression markers that can be measured using standard molecular biology techniques (qPCR, RNA sequencing) already widely available in clinical laboratories. These multi-functional markers provide information about multiple aspects of disease biology and treatment response simultaneously, reducing the need for multiple specialized tests.

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

Solution Approach 2:

The patent uses gene expression levels as molecular copies or proxies for complex biological processes and drug response mechanisms. Instead of directly measuring treatment response or disease mechanisms, the expression levels of specific genes serve as simplified surrogate markers that replicate the information needed for treatment prediction in a more accessible format.

Inventive Principle:
Principle #26Copying

Data Source

PatentEP2831104B1Biomarkers for use in integrin therapy applications
Publication Date: 2021.04.21 BIOGEN MA INC
  • EP2831104B1 patent drawingFigure 1
  • EP2831104B1 patent drawingFigure 2A
  • EP2831104B1 patent drawingFigure 2B

AI summary

The present invention relates to biomarkers for use in determining the sensitivity of patients to therapy with alphavbeta6 integrin inhibition or therapy with TGF-beta pathway inhibitors. The biomarker profiles disclosed herein provide individualized gene and protein profiles which will aid in treating diseases and disorders which are amenable to treatment with therapies designed against alphavbeta6-integrin and/or TGF-beta pathway inhibitors.