Six-Gene Biomarker Panel for IL7R Modulator Response
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Solution Overview
Problem
Current methods lack effective biomarkers to accurately predict a patient's response to IL7R modulators, such as IL7R antagonists or agonists, leading to inefficiencies in clinical trials and a need for personalized therapy.
Innovation Solution
A method for analyzing gene expression profiles in human peripheral blood mononuclear cells to identify a limited set of biomarkers, including BCL2, CISH, PTGER2, and DPP4 genes, to assess the efficacy of IL7R modulators, allowing for personalized treatment selection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If comprehensive gene expression profiling is performed to identify biomarkers, then measurement precision is improved, but device complexity and loss of time increase
Solution Approach 1:
The patent extracts and isolates a specific subset of 6 genes (BCL2, CISH, PTGER2, DPP4, SOCS2, FLT3LG) from the broader gene expression profile. This extraction approach maintains measurement precision by focusing on the most relevant biomarkers while significantly reducing analysis complexity compared to comprehensive profiling of all genes.
Solution Approach 2:
The patent segments the gene expression analysis into a focused panel of 6 specific genes rather than analyzing the entire transcriptome. This segmentation strategy allows for precise biomarker identification while managing complexity through targeted analysis of only the most informative genes.
2Measurement precision
If comprehensive gene expression profiling is performed to identify biomarkers, then measurement precision is improved, but loss of time increases
Solution Approach 1:
The patent extracts and isolates a specific subset of 6 genes (BCL2, CISH, PTGER2, DPP4, SOCS2, FLT3LG) from the broader gene expression profile. This extraction approach maintains measurement precision by focusing on the most relevant biomarkers while significantly reducing analysis time compared to comprehensive profiling of all genes.
Solution Approach 2:
The patent performs preliminary identification and validation of the 6 biomarker genes through in vitro studies before implementing the assay in clinical settings. This preliminary action ensures that the selected genes are the most informative and can be measured efficiently, reducing overall analysis time while maintaining precision.
3Device complexity
If in vitro gene signature analysis on mouse models is performed, then device complexity is reduced, but measurement precision deteriorates due to poor translatability
Solution Approach 1:
Instead of performing in vitro analysis on mouse models and attempting to translate findings to human patients, the patent inverts the approach by directly performing gene expression profiling on human peripheral blood mononuclear cells. This inversion eliminates the translatability problem while maintaining relatively simple in vitro conditions for sample collection and analysis.
Solution Approach 2:
The patent uses human peripheral blood mononuclear cells as a accessible copy of the human biological system, avoiding the need for complex animal models. This copying approach allows for direct study of human biomarkers under controlled in vitro conditions, maintaining measurement precision while simplifying the experimental system.
Data Source
AI summary
The present invention relates to a method of evaluating or predicting a therapeutic response to the treatment with an II, 7R modulator such as IL 7R antagonist or agonist in a patient, more particularly to the identification of biomarkers for evaluating or predicting whether an II, 7R modulator would be effective for treating a patient. The present invention also relates to a method for screening a compound that would be effective for treating a patient. The biomarkers are BCL2, CISH, SOCS2, FLT3LG, PTGER2 and DPP4.


