CD19 Exon 2 Splice Variant Testing for Immunotherapy Resistance

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Solution Overview

Problem

Relapse occurs in CD19 CAR therapy due to CD19 antigen loss or alternative spliced mRNA species, leading to treatment resistance in B-cell malignancies such as acute lymphoblastic leukemia, with existing methods failing to predict therapeutic response effectively.

Innovation Solution

Measure CD19 exon2del transcript expression levels in malignant B-cells to predict resistance to CD19 immunotherapy, using a kit with primer oligonucleotides and probes to identify elevated expression, and select CD19-independent treatments when necessary.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CD19 CAR therapy is used to treat B-cell malignancies, then therapeutic efficacy is improved, but treatment resistance develops due to CD19 antigen loss or alternative splicing

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidtreatment resistance

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies preliminary action by measuring CD19 exon2del transcript expression levels before initiating CD19 CAR therapy. This pre-treatment assessment identifies patients who are likely to develop resistance through alternative splicing, allowing clinicians to select alternative treatments beforehand rather than waiting for treatment failure. The method performs the diagnostic action in advance to prevent the worsening of treatment resistance.

Inventive Principle:

Principle #10Preliminary action

2Ease of operation

If CD19 immunotherapy is administered without predictive testing, then treatment is simplified, but ineffective treatments are administered leading to increased toxicity and costs

Engineering Contradiction:

Improvetreatment simplicityVSAvoidtoxicity and costs

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent implements preliminary action by performing CD19 exon2del transcript expression measurement before treatment decisions are made. This preliminary diagnostic step identifies patients who would benefit from CD19-targeted therapy and those who would not, preventing the administration of ineffective treatments. By doing so, it avoids the harmful effects of unnecessary toxicity and healthcare costs while maintaining relatively simple operational procedures through a single pre-treatment test.

Inventive Principle:

Principle #10Preliminary action

3Device complexity

If existing methods are used to predict therapeutic response, then diagnostic procedures are simple, but prediction accuracy is insufficient

Engineering Contradiction:

Improvediagnostic procedure simplicityVSAvoidresponse prediction accuracy

Core Design Contradiction:

Device complexityVSMeasurement precision

Solution Approach 1:

The patent applies parameter changes by measuring a specific molecular parameter (CD19 exon2del transcript expression level) that directly correlates with alternative splicing and treatment resistance. Instead of using complex multi-parameter diagnostic systems, this method focuses on a single critical parameter that provides high prediction accuracy for therapeutic response. The quantitative measurement of exon2del transcripts offers a precise biomarker that simplifies the diagnostic approach while maintaining or improving prediction accuracy compared to existing methods.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12516384B2Methods and kit for analyzing responsiveness of patients to CD19 immunotherapy

Publication Date: 2026.01.06 ST JUDE CHILDRENS RES HOSPITAL INC

AI summary

Kits and methods for determining resistance of a B-cell malignancy to blinatumomab immunotherapy and selecting a treatment for a subject with a B-cell malignancy based upon the expression level of an exon 2 intra-exonic splice variant of CD19 are provided.