Amino Acid Formulation for Polypeptide Surface Adsorption Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Recombinant biomolecules, such as therapeutic proteins and viral vectors, adsorb to various surfaces during handling and administration, leading to loss of potency and aggregation, which can be exacerbated by hydrophobic and electrostatic interactions, and current additives like polysorbates and albumins pose risks of contamination and degradation.
Innovation Solution
A method involving a composition of at least two different amino acids, including one with negatively charged R groups and one with aromatic R groups, is used to reduce or prevent the adsorption of polypeptides on surfaces like metals and polymers by contacting the surfaces with a concentration ranging from 10 mM to 550 mM.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If polysorbates or albumins are added to compositions to reduce polypeptide adsorption on surfaces, then adsorption is reduced, but contamination and degradation risks increase
Solution Approach 1:
Amino acids serve as intermediary substances that compete with polypeptides for surface binding sites. The amino acid composition (containing at least one aromatic amino acid and one amino acid with hydroxyl, carboxyl, or amino group in the R group) acts as a mediator that prevents direct interaction between polypeptides and hydrophobic surfaces, thereby reducing adsorption without introducing contaminants like polysorbates or albumins
Solution Approach 2:
The invention changes the chemical composition parameters of the liquid formulation by incorporating specific amino acids with defined concentrations (0.1-100 mM aromatic amino acids and 0.1-100 mM amino acids with hydroxyl, carboxyl, or amino groups). This parameter modification alters the surface interaction dynamics, reducing polypeptide adsorption through competitive binding and electrostatic repulsion mechanisms
2Ease of manufacture
If hydrophobic surfaces are used for medical devices and containers, then manufacturing and handling are simplified, but polypeptide adsorption and aggregation increase
Solution Approach 1:
Amino acids act as intermediary substances in the liquid composition that prevent direct contact between polypeptides and hydrophobic surface interfaces. The aromatic amino acids (phenylalanine, tyrosine, tryptophan) specifically interact with hydrophobic surfaces through pi-stacking and hydrophobic interactions, forming a protective barrier that maintains polypeptide stability while allowing the use of simple hydrophobic materials for medical devices
Solution Approach 2:
The invention converts the harmful hydrophobic interaction between amino acids and surfaces into a beneficial effect. By including aromatic amino acids in the composition, the hydrophobic effect is harnessed to protect polypeptides from adsorption - the amino acids preferentially bind to hydrophobic surfaces, thereby preventing polypeptide adsorption and aggregation while maintaining the simplicity of hydrophobic medical device materials
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
Effectively reduces polypeptide adsorption on surfaces, maintaining therapeutic potency and stability without the need for additional stabilizing proteins, thus minimizing aggregation and contamination risks.
Implementation Method 1
Adsorption of mAbs to glass vials has been shown to be due predominantly to electrostatic interactions
Implementation Method 2
surface adsorption-desorption of misfolded protein that reveal hydrophobic residues, and thereby facilitate protein aggregation through hydrophobic interactions
Data Source
Figure 1
Figure 2A~2B
Figure 3A~3B
AI summary
The invention relates to a method of reducing or preventing the adsorption of a polypeptide on a surface, or the aggregation of a polypeptide in a liquid composition in contact with a surface comprising the steps of a) providing a composition comprising the polypeptide and at least two different amino acids; b) contacting the composition with the surface. Furthermore, the invention relates to medical devices comprising a composition comprising the polypeptide and at least two different amino acids.