Organic Acid Precipitation for Coagulation Factor Removal
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Solution Overview
Problem
Current methods for removing or inactivating coagulation factors like FXIa from protein preparations are time-consuming and costly, particularly when using chromatography, and there is a risk of unwanted clot formation in therapeutic applications.
Innovation Solution
A method involving the use of organic acids or their salts, such as caprylic acid, to inactivate or remove coagulation factors FXIa, FII, FVII, FVIIa, FIX, FIXa, and FX from solutions containing immunoglobulins or albumin, by stirring at specific temperatures and pH ranges, allowing for the separation of precipitates and subsequent filtration or centrifugation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If chromatography methods are used to remove coagulation factors, then purification effectiveness is improved, but processing time and cost increase
Solution Approach 1:
The patent changes the chemical parameters of the solution by adjusting pH to specific ranges (pH 3.5-6.0) and introducing organic acids or their salts, which alters the solubility and precipitation behavior of coagulation factors, enabling their selective removal without chromatography
Solution Approach 2:
The patent extracts coagulation factors from the protein solution through selective precipitation caused by organic acid addition. The coagulation factors precipitate out of solution while therapeutic proteins remain soluble, allowing separation by simple filtration or centrifugation
2Manufacturing precision
If chromatography methods are used to remove coagulation factors, then purification effectiveness is improved, but manufacturing cost increases
Solution Approach 1:
The patent replaces expensive chromatography resins with inexpensive organic acids (such as acetic acid, propionic acid, butyric acid, or their salts) that can be easily added and removed. These cheap reagents achieve the same purification effect without requiring costly specialized materials
Solution Approach 2:
The patent extracts coagulation factors through selective precipitation using organic acids, eliminating the need for expensive chromatography columns and resins while achieving comparable or superior purification effectiveness
3Ease of operation
If coagulation factors are not removed, then processing simplicity is maintained, but safety risk increases due to thrombotic events
Solution Approach 1:
The patent extracts coagulation factors through selective precipitation, effectively removing the harmful procoagulant activity while maintaining a simple processing approach that avoids complex chromatography
Solution Approach 2:
The patent changes solution parameters (pH, organic acid concentration) to selectively precipitate coagulation factors, achieving safe removal of thrombotic risk factors through a simple, controllable process
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
This method effectively reduces coagulation factors to undetectable levels, preventing procoagulant activity and ensuring the safety of therapeutic preparations by eliminating the risk of thrombotic events, with the ability to integrate into existing protein purification processes.
Implementation Method 1
contacting a coagulation factor containing immunoglobulin G (IgG) solution with an organic acid or its salt while being stirred at a temperature from about 0° C. to about 40° C., in the pH range from about 3.5 to about 6.0, not only inactivated or removed FXIa but also other coagulation factors
Data Source
AI summary
A method for inactivation or removal of coagulation factors FII, FVII, FVIIa, FIX, FIXa, FX, FXI and FXIa in or from protein containing solutions obtained from blood, blood plasma, plasma fractions or by recombinant means wherein the protein containing solution is contacted with an organic acid or its salt while being stirred.