Monoclonal Antibody for sAPPβ Quantification

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Solution Overview

Problem

Current methods for quantifying sAPP β are not accurate and sensitive enough, particularly in detecting C-terminal fragments in biological samples, which affects the assessment of BACE1 activity and diagnosis of related diseases.

Innovation Solution

Development of monoclonal antibodies specifically recognizing C-terminal fragments of sAPP β, allowing for precise detection of both full-length and fragmented forms of sAPP β in biological samples, enabling accurate quantification and screening for BACE1 inhibitors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional antibodies are used for sAPP β quantification, then the method is simple to operate, but the measurement precision and sensitivity are insufficient to detect C-terminal fragments

Engineering Contradiction:
ImprovesAPP β quantification accuracyVSAvoidantibody system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention uses two different monoclonal antibodies that recognize different epitopes on sAPP β: one antibody (first monoclonal antibody) recognizes the N-terminal region while the other (second monoclonal antibody) recognizes the C-terminal region. This segmentation approach enables the detection of both full-length sAPP β and C-terminal fragments through a sandwich assay format, thereby improving measurement precision without requiring complex instrumentation

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the binding parameters by selecting monoclonal antibodies with specific epitope specificities. The first monoclonal antibody is selected from antibodies recognizing amino acid sequences in the N-terminal region (SEQ ID NO: 28), while the second monoclonal antibody recognizes C-terminal sequences (SEQ ID NO: 37). This parameter change in antibody specificity enables precise detection of sAPP β forms that were previously undetectable

Inventive Principle:
Principle #35Parameter changes

2Reliability

If antibodies recognizing only full-length sAPP β are used, then the assay is simple, but the reliability of BACE1 activity assessment is compromised due to undetected fragments

Engineering Contradiction:
ImproveBACE1 activity assessment accuracyVSAvoidC-terminal fragment detection difficulty
Core Design Contradiction:
ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The invention introduces a second monoclonal antibody as an intermediary detection tool that specifically binds to C-terminal fragments of sAPP β. This intermediary antibody enables the detection of fragment forms that would otherwise be invisible to conventional assays, thereby improving the reliability of BACE1 activity assessment by providing a complete picture of sAPP β processing

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

By dividing the detection task into two segments—one antibody for N-terminal recognition and another for C-terminal recognition—the invention overcomes the difficulty of detecting fragments. The segmented approach allows each antibody to be optimized for its specific target, improving overall detection reliability

Inventive Principle:
Principle #1Segmentation

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 monoclonal antibodies enable accurate quantification of sAPP β in biological samples, improving the assessment of BACE1 activity and aiding in the diagnosis and screening for diseases related to sAPP β, such as Alzheimer's disease.

Implementation Method 1

A monoclonal antibody or a part thereof, recognizing C-terminal fragments of sAPP β

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP2811018B1ANTI-sAPPß ANTIBODY
Publication Date: 2017.03.22 SHIONOGI & CO LTD
  • EP2811018B1 patent drawingFigure 1(a)~2
  • EP2811018B1 patent drawingFigure 3~4
  • EP2811018B1 patent drawingFigure 5~6

AI summary

Provided are a monoclonal antibody capable of specifically recognizing a specific region of sAPP β or a fragment of said antibody and an assay method and an assay kit using the same, in order to accurately assay sAPPβ contained in a biological sample.