Factor VIII Complex with Von Willebrand Factor Peptides
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Solution Overview
Problem
Current treatments for bleeding disorders like haemophilia A and Von Willebrand's disease require frequent intravenous infusions of Factor VIII and Von Willebrand Factor, which are cumbersome, painful, and associated with risks such as infection and scar formation, and have limitations in bioavailability and immunological reactions.
Innovation Solution
A composition comprising a complex of Factor VIII and Von Willebrand Factor peptides, where the peptides are fragments excluding specific amino acid sequences and have affinity binding constants for heparin, collagen, and phospholipids, enhancing stability and bioavailability while reducing immunological reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If frequent intravenous infusions of Factor VIII are administered to maintain therapeutic levels, then bleeding symptoms are controlled, but patient quality of life deteriorates due to pain, infection risk, and scar formation
Solution Approach 1:
The patent uses Von Willebrand Factor peptides as an intermediary carrier molecule that binds to Factor VIII and mediates its transport and delivery to target sites. This intermediary approach allows Factor VIII to be administered via non-intravenous routes while maintaining therapeutic efficacy, thereby eliminating the harmful effects of repeated intravenous injections.
Solution Approach 2:
The patent changes the administration route parameter from intravenous to non-intravenous (such as subcutaneous or intranasal) by modifying the formulation to include Von Willebrand Factor peptides. This parameter change enables the same therapeutic effect to be achieved without the harmful side effects associated with intravenous administration.
2Duration of action of moving object
If the half-life of Factor VIII is extended through complexation with Von Willebrand Factor, then dosing frequency can be reduced, but the molecular complexity of the preparation increases
Solution Approach 1:
The patent segments the full-length Von Willebrand Factor into specific peptide fragments (such as D' domain peptides) that retain the essential blood-pooling and stabilizing functions. This segmentation reduces the molecular complexity compared to using full-length Von Willebrand Factor while still achieving the desired extension of Factor VIII half-life.
Solution Approach 2:
The patent extracts and utilizes only the essential functional domains of Von Willebrand Factor (specifically the D' domain) that are responsible for stabilizing Factor VIII and extending its half-life. By taking out only the necessary portions rather than using the complete protein, the molecular complexity is reduced while maintaining the therapeutic benefit.
3Object-affected harmful factors
If Von Willebrand Factor is used to shield Factor VIII from antibody binding, then immunological reactions are reduced, but the cost of production increases
Solution Approach 1:
The patent employs relatively short peptide sequences from Von Willebrand Factor instead of the full-length protein. These shorter peptides are cheaper to produce through recombinant methods while still providing the essential shielding function against antibody binding. The peptides can be produced more efficiently and at lower cost compared to full-length Von Willebrand Factor.
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 composition improves the stability and bioavailability of Factor VIII, reduces the risk of immunological reactions, and allows for non-intravenous administration with increased efficacy and prolonged half-life, making it suitable for chronic treatment and emergency situations.
Implementation Method 1
the Von Willebrand Factor peptides have an affinity binding constant for heparin of KD≥2,43 nM
Data Source
Figure 1A~1B
Figure 2
Figure 3A~3B
AI summary
A composition comprising a complex of Factor VIII and one or more Von Willebrand Factor peptides, wherein the Von Willebrand Factor peptides comprise at least the amino acids 764 to 1035 and 1691 to 1905 of SEQ ID No. 1 but not amino acids 2255 to 2645 of SEQ ID No. 1.