Stabilised Protein Solutions With Sucrose During Ultrafiltration
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Solution Overview
Problem
Highly concentrated protein solutions, particularly antibody solutions, denature and precipitate during ultrafiltration due to wall concentration, leading to discrepancies in calculated and measured concentrations and reduced yield.
Innovation Solution
Adding sucrose to the protein solution before ultrafiltration stabilizes proteins, reducing aggregation and precipitation, thereby improving yield and reducing turbidity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If ultrafiltration is used to concentrate protein solutions to high concentrations, then productivity is improved, but the protein denatures and precipitates due to wall concentration
Solution Approach 1:
A stabilization peptide is introduced as an intermediary substance that binds to the protein surface and prevents denaturation and aggregation during ultrafiltration. The peptide acts as a protective mediator between the protein and the harsh concentration conditions, allowing high concentration to be achieved without protein precipitation.
Solution Approach 2:
The invention changes the chemical parameters of the solution by adding stabilization peptides, which modify the surface properties and interaction characteristics of the protein. This parameter change enables the system to withstand higher concentration levels without losing protein stability.
2Reliability
If sucrose is added to stabilize protein during ultrafiltration, then protein stability is improved, but the risk of infection increases
Solution Approach 1:
The invention replaces long-term stabilizing agents like sucrose with short-acting stabilization peptides that are added temporarily during the ultrafiltration process. The peptides perform their stabilizing function during concentration and can be removed or degraded, eliminating the need for prolonged presence of potentially problematic additives.
Solution Approach 2:
The invention changes the type of stabilizing agent from carbohydrates (sucrose) to peptides, fundamentally altering the chemical nature of the stabilization mechanism. This parameter change maintains protein stability while eliminating infection risks associated with sucrose addition.
3Productivity
If wall concentration is allowed to increase during ultrafiltration, then productivity is improved, but protein aggregation and precipitation occur
Solution Approach 1:
The stabilization peptide serves as an intermediary layer on the protein surface that prevents direct protein-protein interactions that lead to aggregation. This mediator allows high wall concentration to be maintained without the harmful effects of precipitation.
Solution Approach 2:
The stabilization peptide is added before ultrafiltration begins, providing preliminary protection against aggregation. This preemptive measure prevents the formation of aggregates before they can occur during the concentration process, even at high wall concentrations.
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 enhances the correlation between calculated and measured protein concentrations, increases recovery to above 99%, and maintains low levels of high molecular weight protein aggregates.
Implementation Method 1
the protein solution is stabilized during the ultrafiltration by addition of sucrose to the solution
Implementation Method 2
After purification of the antibody in solution, the concentration of the antibody is increased by use of ultrafiltration (UF)
Data Source
AI summary
The invention relates to a method of stabilizing highly concentrated protein solutions during ultrafiltration by addition of sucrose to the highly concentrated protein solution, in particular, but not exclusively to a method of stabilizing highly concentrated antibody solutions during ultrafiltration by addition of sucrose to the highly concentrated antibody solution.