HLA-B Allele Detection for Adverse Drug Reaction Risk Prediction

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Solution Overview

Problem

Current methods fail to accurately predict the risk of adverse drug reactions (ADRs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and hypersensitivity syndrome (HSS) in patients, which are often severe and life-threatening, due to the lack of effective genetic markers for identifying susceptible individuals.

Innovation Solution

The use of specific HLA-B alleles, including HLA-B*1502, HLA-B*5801, and HLA-B*4601, as genetic markers to predict the risk of SJS, TEN, and HSS in response to certain drugs, allowing for the identification of patients at risk through genetic testing and pharmacogenomic profiling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current methods are used for predicting adverse drug reactions, then the prediction accuracy is insufficient, but implementing genetic marker-based prediction requires identifying multiple specific HLA alleles and their regions

Engineering Contradiction:
Improveprediction accuracyVSAvoidcomplexity of genetic marker identification
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The HLA-B allele is divided into six distinct regions (Region 1 through Region 6), each containing specific nucleotides that can be independently detected. This segmentation allows for systematic identification of the allele by testing for presence in multiple regions, thereby improving prediction accuracy through comprehensive genetic marker analysis while maintaining a structured approach to the complexity of the task.

Inventive Principle:
Principle #1Segmentation

2Reliability

If multiple regions within HLA-B allele are targeted for accurate determination, then the reliability of ADR risk prediction is improved, but the difficulty of detecting and measuring increases

Engineering Contradiction:
Improvereliability of ADR risk predictionVSAvoiddifficulty of detecting HLA-B allele regions
Core Design Contradiction:
ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The method performs preliminary detection of specific nucleotides in each of the six regions of the HLA-B allele before making a definitive prediction about adverse drug reaction risk. By systematically checking for the presence of characteristic nucleotides in multiple regions beforehand, the method establishes a reliable genetic profile that confirms HLA-B*1502 or HLA-B*5801 status, thereby improving prediction reliability while managing detection complexity through a stepwise approach.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS8142999B2HLA alleles associated with adverse drug reactions and methods for detecting such
Publication Date: 2012.03.27 PHARMIGENE
  • US8142999B2 patent drawing
  • US8142999B2 patent drawing
  • US8142999B2 patent drawing

AI summary

This invention relates to a method of determining the presence of certain HLA alleles, such as HLA-B*1502 or HLA-B*5801, and a kit for carrying out this method. Also disclosed is a method for assessing whether a patient is at risk for developing adverse drug reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, or hypersensitivity syndrome) based on the presence or absence of a genetic marker (e.g., HLA-B*1502, HLA-B*5801, or HLA-B*4601).