Antibody targeting exposed fibrin epitope for specific detection
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Solution Overview
Problem
Conventional antibodies struggle to specifically detect insoluble fibrin due to its high homology with fibrinogen and soluble fibrin degradation products, requiring an antibody with higher affinity and specificity.
Innovation Solution
Development of monoclonal antibodies that target a specific epitope on the fibrinogen Bβ chain, which becomes exposed during the conversion to insoluble fibrin, allowing for high-affinity binding to insoluble fibrin without binding to fibrinogen or soluble fibrin degradation products.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional antibodies are used to detect fibrin, then detection capability is provided, but specificity is insufficient due to high homology with fibrinogen and FDPs
Solution Approach 1:
The invention divides the fibrin detection task by specifically targeting the Bβ14-30 epitope region, which becomes exposed only during fibrin formation. This segmentation approach allows the antibody to distinguish fibrin from fibrinogen and FDPs that lack this exposed epitope, thereby improving detection specificity while maintaining reliability
Solution Approach 2:
The patent applies local quality by focusing on a specific local region (Bβ14-30 epitope) of the fibrin molecule that undergoes conformational change during polymerization. The antibody 102-10 is designed to bind specifically to this local exposed region, enabling it to recognize fibrin structures while ignoring fibrinogen and degradation products that do not present this epitope configuration
2Strength
If an antibody targets a common epitope on fibrinogen, then high binding affinity is achieved, but specificity to insoluble fibrin is lost
Solution Approach 1:
The invention exploits the dynamic conformational change that occurs when fibrinogen converts to fibrin. The Bβ14-30 epitope is hidden in soluble fibrinogen but becomes exposed during thrombin-mediated cleavage and polymerization. Antibody 102-10 is designed to bind this dynamically exposed epitope, achieving high specificity for insoluble fibrin while maintaining high binding affinity to the exposed configuration
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
Enables sensitive and reliable detection of insoluble fibrin and thrombi, facilitating the diagnosis of thrombus-related diseases and targeted delivery of compounds to thrombi sites, such as tumors.
Implementation Method 1
monoclonal antibodies that target a specific epitope on the fibrinogen Bβ chain, which becomes exposed during the conversion to insoluble fibrin, allowing for high-affinity binding to insoluble fibrin without binding to fibrinogen or soluble fibrin degradation products
Data Source
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AI summary
With the intention of providing an antibody which does not bind to fibrinogen and which has a high affinity for and a high specificity to insoluble fibrin, it is found that a site comprising the amino acids at positions 231 to 246 of the fibrinogen Bβ chain and a site comprising the amino acids at positions 232 to 246 of the fibrinogen γ chain are bound to each other in a fibrinogen molecule. Further, it is shown that when fibrinogen is converted to insoluble fibrin, the binding is released, and these sites are exposed. It is also found that antibodies obtained by immunization with these sites do not bind to fibrinogen and have high affinity for and high specificity to insoluble fibrin.