Silicon Dioxide Adsorption for Safer Plasma Protein Purification
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Solution Overview
Problem
Existing plasma-derived protein compositions contain high levels of serine proteases and serine protease zymogens, such as FXI, FXIa, FXII, and FXIIa, which can lead to thromboembolic events, necessitating the development of methods to reduce their presence.
Innovation Solution
Treatment of plasma-derived protein compositions with finely divided silicon dioxide (SiO2) to bind and remove serine proteases and zymogens, followed by separation to achieve reduced activity and content.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If plasma-derived protein compositions are used to treat medical conditions, then therapeutic efficacy is improved, but thromboembolic events occur due to high levels of serine proteases and zymogens
Solution Approach 1:
The patent applies extraction by removing serine proteases and zymogens from plasma-derived protein compositions through treatment with activated carbon or silica gel. This selectively extracts the harmful proteolytic components while retaining the therapeutic proteins, thereby eliminating the cause of thromboembolic events while preserving therapeutic efficacy.
Solution Approach 2:
The patent converts the harmful proteolytic activity into a beneficial purification process. By utilizing the binding affinity of activated carbon or silica gel for serine proteases, the harmful contaminants are selectively captured, transforming the presence of these enzymes from a therapeutic risk into an opportunity for enhanced product safety and purity.
2Stability of the object's composition
If serine proteases and zymogens are present in plasma-derived compositions, then the composition maintains natural plasma composition, but safety is reduced due to thromboembolic risk
Solution Approach 1:
The patent selectively extracts serine proteases and zymogens from plasma-derived compositions using activated carbon or silica gel treatment. This removal process maintains the natural composition of therapeutic proteins while eliminating the specific harmful components, achieving a balance between compositional integrity and safety.
Solution Approach 2:
The patent applies local quality by selectively targeting and removing only serine proteases and zymogens from the plasma composition, while leaving other plasma proteins intact. This localized modification approach preserves the overall natural composition characteristics while addressing the specific safety concern related to proteolytic activity.
3Reliability
If activated carbon or silica gel is used to remove serine proteases, then safety is improved by reducing thromboembolic risk, but processing complexity increases
Solution Approach 1:
The patent employs disposable activated carbon or silica gel adsorbent materials that are added to the plasma-derived composition, perform their purification function, and are then removed. These single-use adsorbents simplify the process by eliminating the need for complex regeneration or reuse systems, reducing overall processing complexity while maintaining safety improvements.
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 method effectively reduces serine protease activity and content, thereby minimizing the risk of thromboembolic events and enhancing the safety of plasma-derived therapies.
Implementation Method 1
treatment with finely divided silicon dioxide... under conditions suitable to bind at least one serine protease or serine protease zymogen
Data Source
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AI summary
The present invention provides novel methods for reducing the serine protease and/or serine protease zymogen content of a plasma-derived protein composition. Also provided are methods for manufacturing plasma-derived protein compositions having reduced serine protease and/or serine protease zymogen content. Among yet other aspects, the present invention provides aqueous and lyophilized compositions of plasma-derived proteins having reduced serine protease and/or serine protease zymogen content. Yet other aspects include methods for treating, managing, and/or preventing a disease comprising the administration of a plasma-derived protein composition having a reduced serine protease or serine protease zymogen content.