Anti-Factor V Antibody for Targeted Anticoagulation and Diagnosis
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Solution Overview
Problem
Current anticoagulant therapies, such as heparins and vitamin K antagonists, have limitations including heparin-induced thrombocytopenia, delayed onset and offset of action, genetic variations, and interactions with food and drugs, while direct oral anticoagulants face concerns of bleeding risks and the need for antidotes. Additionally, aptamers for coagulation factors face challenges with short half-life and renal clearance.
Innovation Solution
Development of a fully human monoclonal antibody specifically targeting Factor V and Va, isolated via phage display technology, which minimizes off-target effects and has a longer half-life, inhibiting clot formation and associated thrombotic events.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If heparins and vitamin K antagonists are used as anticoagulants, then thromboembolism treatment and prevention are achieved, but heparin-induced thrombocytopenia occurs and long-term parenteral administration is limited
Solution Approach 1:
The patent extracts and targets a specific component (Factor V) of the coagulation cascade rather than using broad-spectrum anticoagulants. By developing an antibody that specifically inhibits Factor V, the therapy addresses thromboembolism treatment while avoiding the harmful effects of non-specific anticoagulants like heparin-induced thrombocytopenia.
Solution Approach 2:
The patent changes the mechanism of action from traditional anticoagulant parameters (heparin binding to antithrombin, vitamin K dependency) to a novel antibody-based mechanism that directly targets and inhibits Factor V. This parameter change in the therapeutic approach eliminates the harmful side effects associated with conventional agents while maintaining treatment efficacy.
2Reliability
If vitamin K antagonists are used, then thromboembolic disorders are treated, but delayed onset and offset of action occur requiring frequent monitoring and dose adjustments
Solution Approach 1:
The patent employs an antibody that is pre-formed and ready for immediate administration. Unlike vitamin K antagonists that require time to synthesize and activate, the monoclonal antibody against Factor V can be administered directly and immediately begins inhibiting the coagulation cascade, eliminating the delayed onset problem.
Solution Approach 2:
The patent replaces the biochemical mechanism of vitamin K-dependent clotting factor synthesis with a direct protein inhibition mechanism. The antibody binds to and inhibits Factor V directly, substituting the slow enzymatic regulation mechanism with an immediate protein-protein interaction, thereby eliminating delayed onset and offset.
3Ease of operation
If direct oral anticoagulants are used, then monitoring is eliminated, but bleeding risk remains with case-fatality rate of major bleeding of 8%
Solution Approach 1:
The patent introduces a specific intermediary substance (monoclonal antibody against Factor V) that mediates the anticoagulant effect. This targeted intermediary approach allows for precise control of the coagulation cascade at the Factor V level, reducing off-target effects and bleeding risk while maintaining ease of administration without monitoring requirements.
Solution Approach 2:
The patent applies local quality by targeting a specific location in the coagulation cascade (Factor V) rather than using broad-spectrum anticoagulants. This localized inhibition at the Factor V level provides anticoagulant activity where needed while minimizing systemic bleeding effects, thus reducing the case-fatality rate of major bleeding.
4Measurement precision
If aptamers targeting coagulation factors are used, then high affinity and specificity binding is achieved, but short half-life and rapid renal clearance occur
Solution Approach 1:
The patent creates a composite molecular structure by combining the high-affinity binding capability of aptamer-like recognition with the extended half-life properties of monoclonal antibodies. The resulting antibody against Factor V maintains the specific binding characteristics needed for precise coagulation factor targeting while achieving a longer circulation half-life through antibody pharmacokinetics.
Solution Approach 2:
The patent changes the molecular size and structural parameters from small aptamers to larger monoclonal antibodies. This parameter change in molecular weight and structure fundamentally alters the pharmacokinetic properties, extending half-life and reducing renal clearance while preserving the high affinity and specificity binding capability through the antibody's variable regions.
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 effectively prolongs activated partial thromboplastin time and reduces Factor V levels, demonstrating its ability to interfere with the coagulation cascade, thereby reducing clot formation and thrombotic events without significant cross-reactivity to other coagulation factors.
Implementation Method 1
A fully human monoclonal antibody specific for Factor V was isolated by using an innovative strategy of selection based on phage display, starting from a large human scFv-phage library
Implementation Method 2
The antibody effectively prolongs activated partial thromboplastin time and reduces Factor V levels, demonstrating its ability to interfere with the coagulation cascade
Data Source
Figure 1
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Figure 3A~3C
AI summary
The present invention discloses an anti-factor V antibody useful as an anticoagulant agent and as a tool for diagnostic and research applications. The antibody or its fragments can be conveniently used as anticoagulant agents inhibiting Factor V and/or Factor Va, particularly to reduce clot formation and associated thrombotic events, or they can be used in vitro to measure the levels of Factor V in a blood sample. Other aspects of the invention regard nucleic acids encoding the antibody or fragments thereof as well as expression vectors and host cells containing them.