Fusion Protein with Transferrin for Factor VII Half-Life
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for hemorrhagic disorders caused by deficiencies in blood coagulation factors, such as hemophilia A and B, face challenges due to the short half-life of factor VIIa, requiring frequent injections and high treatment costs, and the emergence of alloantibodies against replacement factors, which reduces therapeutic efficacy.
Innovation Solution
A fusion protein comprising factor VII and transferrin, where transferrin is linked to the C-terminus of factor VII, is developed, along with a DNA coding for this fusion protein and a recombinant vector for expression, to enhance the in-vivo half-life while maintaining biological activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If factor VIIa is administered to treat hemorrhagic disorders, then hemostasis is achieved, but the short half-life requires frequent injections and increases treatment cost
Solution Approach 1:
The patent combines factor VII with transferrin to create a fusion protein. This merging of two functional proteins allows the factor VII to retain its hemostatic activity while gaining the extended circulation time characteristic of transferrin, thereby reducing the frequency of administration
Solution Approach 2:
The fusion protein represents a composite biological material that integrates the functional domains of factor VII (for hemostasis) and transferrin (for extended half-life). This composite structure enables simultaneous achievement of therapeutic efficacy and prolonged duration of action
2Reliability
If plasma-derived or recombinant factor concentrates are used for hemophilia treatment, then coagulation deficiency is corrected, but alloantibodies are generated against the replacement factors
Solution Approach 1:
The transferrin portion of the fusion protein acts as an intermediary that modifies the immunogenicity profile of factor VII. By fusing factor VII to transferrin, the patent creates a novel molecular structure that may reduce recognition by alloantibodies while maintaining the essential coagulation function of factor VII
3Duration of action of moving object
If factor VII is fused with other proteins to extend half-life, then in-vivo duration is improved, but biological activity is lost
Solution Approach 1:
The patent strategically positions the factor VII and transferrin domains within the fusion protein to preserve the local functional quality of each component. The factor VII domain maintains its catalytic activity for activating factor X, while the transferrin domain provides the extended half-life, with each domain functioning optimally in its designated location
Solution Approach 2:
The fusion protein is segmented into distinct functional domains: the factor VII portion retains its enzymatic function for hemostasis, while the transferrin portion provides circulation stability. This segmentation allows independent optimization of each domain's function while maintaining overall protein integrity
Data Source
AI summary
A fusion protein comprising factor VII (FVII) and transferrin according to the present invention has an improved specific activity of FVII compared to existing FVII fusion proteins comprising other fusion partners than transferrin, and thus can be effectively used in a therapy using FVII.