Antibody Binding Affinity Complex for Vitamin D Detection

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Solution Overview

Problem

Current methods for measuring small substances like 25OH vitamin D3 and 25OH vitamin D2 face challenges in sensitivity and specificity, particularly with the competitive inhibition method, and the sandwich method is hindered by steric hindrance when dealing with small substances.

Innovation Solution

Development of a full-length monoclonal antibody capable of specifically binding to an affinity complex comprising 25OH vitamin D3 and/or 25OH vitamin D2, produced using a DT40 cell line, which allows for high sensitivity and specificity in measuring these substances using a sandwich method.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the competitive inhibition method is used to measure small substances like 25OH vitamin D3, then measurement can be performed, but measurement sensitivity and accuracy are low

Engineering Contradiction:
Improvemeasurement sensitivityVSAvoidmeasurement accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

Instead of using a single antibody to directly bind the small substance (which has low affinity), the invention inverts the approach by using an antibody that binds to the complex formed between the small substance and another antibody. This indirect binding approach achieves high measurement sensitivity and accuracy that cannot be obtained by direct binding methods.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The invention employs a nested structure where the first antibody binds to the small substance (25OH vitamin D3), forming an affinity complex. Then, the second antibody (anti-idotype antibody) binds to this complex, creating a nested antibody-antigen-antibody structure. This nested arrangement enables the sandwich method to effectively measure small substances with high sensitivity.

Inventive Principle:
Principle #7Nested doll (Nesting)

2Measurement precision

If the sandwich method is used to measure small substances, then measurement sensitivity improves, but steric hindrance occurs between two antibodies

Engineering Contradiction:
Improvemeasurement sensitivityVSAvoidsteric hindrance
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The small substance (25OH vitamin D3) acts as an intermediary that bridges the two antibodies. The first antibody binds to the small substance, and the second antibody binds to the first antibody, forming a stable sandwich complex. This intermediary approach allows two antibodies to cooperate without direct steric conflict, enabling high-sensitivity measurement of small substances.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If an antibody with high specificity is required for competitive inhibition method, then measurement specificity improves, but huge amount of effort is required for antibody selection

Engineering Contradiction:
ImprovespecificityVSAvoideffort for antibody selection
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The invention performs preliminary action by pre-forming the affinity complex between the small substance and the first antibody. This pre-formed complex serves as the target for the second antibody, eliminating the need for extensive screening to find antibodies with perfect specificity. The anti-idotype antibody naturally recognizes the first antibody's binding site, ensuring high specificity without extensive selection effort.

Inventive Principle:
Principle #10Preliminary action

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

The antibody enhances measurement sensitivity and specificity, simplifies the measurement process, and facilitates the construction of a rapid and cost-effective measurement system, enabling accurate quantification of 25OH vitamin D3 and 25OH vitamin D2.

Implementation Method 1

an antibody against an affinity complex, and an assay for a factor that constitutes the affinity complex using the antibody against the affinity complex

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP2759551B1Antibodies binding to an affinity complex comprising 25oh vitamin d2 or d3 and an antibody thereto
Publication Date: 2019.05.22 FUJIREBIO CO LTD
  • EP2759551B1 patent drawingFigure 1
  • EP2759551B1 patent drawingFigure 2
  • EP2759551B1 patent drawingFigure 3

AI summary

The present invention provides a means and a method for specifically measuring a substance such as a small substance with high sensitivity by a sandwich method. Specifically, the present invention provides an antibody capable of specifically binding to an affinity complex and a method of measuring of the affinity complex comprising measuring the affinity complex using the antibody capable of specifically binding to the affinity complex. The antibody of the present invention may be a full-length antibody. The antibody of the present invention may also have a region derived from an immunoglobulin from an animal having an ability of gene conversion (e.g., a complementarity-determining region, a framework region, or a variable region). Examples of at least one factor that constitutes the affinity complex include a small substance or a protein (e.g., antibody).