Factor VII Transferrin Fusion Protein Formulation Stability
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Solution Overview
Problem
Current pharmaceutical compositions for factor VII, such as NovoSeven® RT, have stability issues when stored at room temperature or after reconstitution, leading to reduced efficacy and increased treatment costs due to the short half-life of FVIIa, which requires frequent injections and results in patient discomfort.
Innovation Solution
A pharmaceutical composition with improved stability is developed, containing a fusion protein of factor VII and transferrin linked at the C-terminus, using trehalose or glycine as a bulking agent instead of polyols, which maintains biological activity and stability during storage at room temperature, reducing high molecular weight aggregate formation and chemical degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Temperature
If conventional pharmaceutical compositions (e.g., NovoSeven® RT) are used for factor VII, then the product can be stored at room temperature, but the stability is reduced and high molecular weight aggregates form
Solution Approach 1:
The patent changes the chemical composition parameters by replacing polyols with specific excipients (histidine, sucrose, glycylglycine, polysorbate 80) and adjusting their concentrations to achieve stable room temperature storage without aggregate formation
Solution Approach 2:
The patent creates a composite formulation system combining multiple excipients (histidine buffer, sucrose, glycylglycine, polysorbate 80) that work synergistically to maintain protein stability at room temperature while preventing aggregate formation
2Duration of action of moving object
If FVIIa is administered to overcome short half-life, then the therapeutic effect is improved, but frequent injections are required causing patient discomfort and high treatment costs
Solution Approach 1:
The patent merges factor VII with transferrin to create a fusion protein, combining the hemostatic function of FVII with the iron transport and receptor-mediated functions of transferrin, thereby extending half-life through receptor recycling mechanisms
3Duration of action of moving object
If fusion protein of FVII and transferrin is formulated with conventional compositions, then the in-vivo half-life is improved, but the stability is significantly reduced
Solution Approach 1:
The patent optimizes excipient parameters including histidine concentration (5-50 mM), sucrose concentration (1-20%, w/v), glycylglycine concentration (0.1-5%, w/v), and polysorbate 80 concentration (0.01-0.1%, w/v) to achieve both stability and extended half-life
Solution Approach 2:
The patent uses excipients as intermediary substances that mediate between the fusion protein and the environment, with histidine buffering pH, sucrose providing structural support, glycylglycine preventing aggregation, and polysorbate 80 preventing surface adsorption
Data Source
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AI summary
The present invention relates to a pharmaceutical composition with improved stability, containing, as active ingredients, factor VII and transferrin, wherein the transferrin contains a fusion protein linked to the C-terminal of factor VII; and trehalose or glycine as a bulking agent. The composition can stably store factor VII and a modification thereof at room temperature for a long time, and thus can be used as a useful therapeutic agent for patients suffering from hemophilia or congenital factor VII deficiency.