Polyalkoxy Fatty Acyl Surfactant for Protein Aggregation Control
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Solution Overview
Problem
Protein denaturation and aggregation occur during ultrafiltration and diafiltration processes due to shear stress and surfactant interactions with filtration membranes, limiting the effectiveness of surfactants like polysorbate 80 and poloxamer 188 in stabilizing proteins during purification and concentration.
Innovation Solution
A method involving a polyalkoxy fatty acyl surfactant of specific formula, which reduces protein aggregation by passing through separation membranes during ultrafiltration and diafiltration, allowing for its use upstream in protein production to mitigate aggregation and particle formation, thereby improving protein yields.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If polysorbate 80 is used to stabilize protein during ultrafiltration and diafiltration, then protein aggregation is reduced, but the surfactant is concentrated and does not effectively pass through the filtration membrane
Solution Approach 1:
The patent changes the molecular weight parameter of the surfactant from conventional high molecular weight polysorbate 80 to a lower molecular weight polyalkoxy fatty acyl surfactant (e.g., C8-16-EO1-5-OL). This parameter change enables the surfactant to pass through ultrafiltration membranes while maintaining its protein stabilization function, resolving the contradiction between protein stability and surfactant retention.
2Stability of the object's composition
If polysorbate 80 is used at higher concentrations to protect protein from aggregation, then protein stability improves, but interaction with processing equipment increases causing membrane fouling
Solution Approach 1:
The patent changes the molecular weight and structure parameters of the surfactant to create a lower molecular weight compound that is less prone to adsorption and fouling of processing equipment. This allows effective protein stabilization at lower concentrations without the harmful membrane fouling effects of conventional surfactants.
3Stability of the object's composition
If conventional surfactants are used during upstream processing, then protein stability is improved, but removal during downstream processing becomes difficult
Solution Approach 1:
The patent changes the molecular weight parameter of the surfactant to a lower value that enables easy removal during downstream processing steps such as ultrafiltration and diafiltration. The lower molecular weight surfactant can be effectively separated from the protein product, simplifying the manufacturing process while maintaining protein stability throughout upstream processing.
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 polyalkoxy fatty acyl surfactant effectively reduces protein aggregation and passes through membranes, maintaining protein stability and concentration, with a lower critical micelle concentration facilitating faster interface stabilization and improved surfactant retention, enhancing protein purification and concentration processes.
Implementation Method 1
contacting the aqueous solution with a separation membrane, and subjecting the aqueous solution to a diafiltration step to reduce the concentration of soluble low molecular weight components or to introduce one or more soluble low molecular weight components therein and/or to an ultrafiltration step
Implementation Method 2
subjecting the aqueous solution to a diafiltration step to reduce the concentration of soluble low molecular weight components or to introduce one or more soluble low molecular weight components therein
Implementation Method 3
whereby the compound of formula I reduces aggregation of the protein in method steps (a)-(c) and whereby the compound of formula I passes through the separation membrane in step (c)
Data Source
AI summary
This disclosure relates to a method which involves the steps of: (a) providing an aqueous solution comprising a protein and a polyalkoxy fatty acyl surfactant of general formula Iwherein R1—C(═O) is a fatty acyl group, R2 is H or a substituted or unsubstituted hydrocarbyl group, X1 is S, O or NH, X2 is S, O or NH, n is 0 or an integer of 1-5, R3 is a polymeric group comprising polymerized units of general formula II and III(b) contacting the aqueous solution with a separation membrane, and (c) subjecting the aqueous solution to a diafiltration step and/or to an ultrafiltration step to produce a retentate product which is an aqueous solution comprising the protein, whereby the compound of formula I reduces aggregation of the protein in method steps (a)-(c) and whereby the compound of formula I passes through the separation membrane in step (c).