Modified Sandwich ELISA for Antibody-Antigen Complex Quantification

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Solution Overview

Problem

Current methods for detecting and monitoring therapeutic antibody:antigen complexes and soluble antigens in patients undergoing immunotherapy are limited in effectively measuring the efficacy of antibody-based therapies and monitoring hyperproliferative diseases, such as cancer, due to the inability to accurately quantify circulating immune complexes and their impact on therapeutic antibody availability.

Innovation Solution

A modified sandwich ELISA technique is employed to detect and quantify soluble leukocyte surface molecules, therapeutic antibodies, and antibody:antigen complexes in patient samples, allowing for the monitoring of hyperproliferative diseases and the adjustment of antibody dosages to ensure therapeutic levels reach target cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current detection methods are used, then the measurement process is simple, but the measurement precision of circulating immune complexes and soluble antigens is insufficient

Engineering Contradiction:
Improvemeasurement precision of circulating immune complexesVSAvoidcomplexity of detection method
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The detection method is divided into multiple sequential steps: first capturing soluble antigen with a capture antibody, then detecting therapeutic antibody:antigen complexes with a detection antibody, and finally quantifying results. This segmentation allows each step to be optimized for specific measurement precision while maintaining overall process manageability

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A capture antibody is introduced as an intermediary component that specifically binds to soluble antigen, enabling the detection and quantification of circulating immune complexes. This intermediary facilitates precise measurement by creating a stable platform for subsequent detection steps

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If antibody dosages are not adjusted based on circulating complexes, then the treatment protocol is simple, but the therapeutic efficacy is reduced

Engineering Contradiction:
Improvetherapeutic efficacy of antibody-based therapyVSAvoidease of dosage adjustment
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The method establishes a feedback loop where circulating immune complex levels are measured and used to guide therapeutic antibody dosage adjustments. This feedback mechanism ensures reliable therapeutic efficacy by preventing antibody neutralization while maintaining simplicity through standardized measurement protocols that provide clear actionable data

Inventive Principle:
Principle #23Feedback

3Loss of information

If circulating immune complexes are not monitored, then the monitoring process is simple, but the understanding of therapeutic antibody availability is insufficient

Engineering Contradiction:
Improveinformation on therapeutic antibody availabilityVSAvoidproductivity of disease monitoring
Core Design Contradiction:
Loss of informationVSProductivity

Solution Approach 1:

The detection method serves multiple functions simultaneously: it quantifies soluble antigen, measures therapeutic antibody:antigen complexes, and assesses circulating immune complex levels. This multi-functionality comprehensively captures information on therapeutic antibody availability while maintaining productivity through a single integrated assay platform

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

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 enables precise monitoring of hyperproliferative diseases and improves the efficacy of antibody-based therapies by quantifying soluble antigens and antibody:antigen complexes, helping to design more effective therapeutic strategies and adjust dosages accordingly.

Implementation Method 1

A modified sandwich ELISA technique is employed to detect and quantify soluble leukocyte surface molecules, therapeutic antibodies, and antibody:antigen complexes in patient samples

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentUS7718387B2Measuring circulating therapeutic antibody, antigen and antigen/antibody complexes using ELISA assays
Publication Date: 2010.05.18 BOARD OF RGT THE UNIV OF TEXAS SYST
  • US7718387B2 patent drawing
  • US7718387B2 patent drawing
  • US7718387B2 patent drawing

AI summary

The present invention relates to the field of immunology and hyperproliferative diseases. More specifically, the present invention relates to a method of detecting and monitoring therapeutic antibody:antigen complex, soluble antigen and soluble therapeutic antibody, wherein a patient has undergone at least one course of immunotherapy. Yet further, levels of therapeutic antibody:antigen complexes, soluble antigens or soluble therapeutic antibodies may be measured and used to stage or monitor a hyperproliferative disease.