AAV Antibody Titer Screening for High-Throughput Therapy Selection

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Solution Overview

Problem

Existing methods for screening patients for adeno-associated virus (AAV) therapy are low throughput, labor-intensive, and suffer from high variability and low sensitivity, making it difficult to effectively exclude patients with high levels of pre-existing neutralizing AAV-specific antibodies.

Innovation Solution

A method using enzyme-linked immunosorbent assay (ELISA) to measure the titer of anti-AAV antibodies in biological samples, allowing for the identification of subjects suitable for AAV therapy by administering the therapy only to those with low titers of anti-AAV antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If cell-based neutralizing antibody assays are used to screen patients, then patient selection accuracy is improved, but throughput and efficiency deteriorate due to low throughput and labor-intensive procedures

Engineering Contradiction:

Improvepatient selection accuracyVSAvoidthroughput

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent replaces the manual, labor-intensive cell-based neutralizing antibody assay with an automated ELISA-based screening method. This substitution transforms a mechanical/manual process into an automated biochemical assay, achieving both high throughput and accurate patient selection by measuring anti-AAV antibody titers in serum samples without requiring live cells or complex manual operations

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the measurement parameter from functional neutralizing activity (requiring cell-based assays) to antibody titer concentration (measurable by ELISA). This parameter transformation enables automated, high-throughput screening while maintaining patient selection accuracy, as the ELISA quantifies anti-AAV antibody levels that correlate with neutralizing capacity

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If cell-based neutralizing antibody assays are used to screen patients, then measurement sensitivity is improved, but operational complexity and labor requirements worsen

Engineering Contradiction:

Improvedetection sensitivityVSAvoidassay complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the complex cell-based assay system with a simpler ELISA system. The cell-based method requires maintaining live cells, preparing complex media, and performing multiple manual steps, whereas the ELISA uses standardized reagents, automated plate readers, and simplified protocols, reducing operational complexity while maintaining detection sensitivity through precise antibody titer measurement

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If large numbers of patients are screened, then patient selection quality is improved, but time and resource requirements worsen due to low throughput

Engineering Contradiction:

Improvescreening qualityVSAvoidscreening time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent changes the screening approach from functional assays to titer-based ELISA measurements. This parameter change allows parallel processing of numerous samples simultaneously in 96-well or 384-well plates, reducing screening time while maintaining quality through automated data collection and analysis of antibody titer levels

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent substitutes manual cell-based screening with automated ELISA processing, enabling high-throughput screening of large patient cohorts. The automated system processes multiple samples in parallel, significantly reducing the time and resources required while maintaining screening quality through consistent, reproducible measurements

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach provides a high-throughput, robust, and sensitive method for patient selection, enhancing the efficacy of AAV therapy by reducing the impact of neutralizing antibodies and enabling large-scale screening.

Implementation Method 1

measuring a titer of an antibody or antigen-binding portion thereof that specifically binds to an AAV ('anti-AAV antibody') in a biological sample obtained from the subject using an enzyme-linked immunosorbent assay (ELISA)

Methodology Applied

Scientific EffectAntibody-antigen binding:

Data Source

PatentUS20250340621A1Methods of AAV therapy

Publication Date: 2025.11.06 BRISTOL MYERS SQUIBB CO

AI summary

This disclosure provides methods for identifying a subject suitable for an adeno associated virus (AAV) therapy. In some embodiments, the method comprises measuring a titer of an antibody or antigen-binding portion thereof that specifically binds to an AAV (“anti-AAV antibody”) in a biological sample obtained from the subject using an enzyme-linked immunosorbent assay (ELISA).