Cholate Surfactants Stabilize Antibodies Without Oxidative Degradation
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Solution Overview
Problem
Current protein stabilizers like polysorbates undergo degradation, leading to the formation of byproducts that increase turbidity and protein aggregation, reducing their protective effect in formulations, necessitating a need for compositions that enhance stability and prevent oxidation and aggregation of proteins.
Innovation Solution
The use of cholate surfactants at concentrations below their critical micelle concentration (CMC) values, such as CHAPS, BigCHAP, SGH, STH, and SCH, which effectively stabilize and reduce aggregation of antibodies and other proteins in therapeutic formulations, offering protection against degradation and oxidation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polysorbates are used as protein stabilizers, then protein aggregation is prevented, but degradation byproducts increase turbidity and reduce protective effect
Solution Approach 1:
The patent changes the chemical composition parameter by replacing polysorbate surfactants with cholate-based surfactants (such as sodium cholate, deoxycholate, or mixtures thereof). This parameter change eliminates the degradation byproduct issue while maintaining the protein stabilization function, as cholate surfactants do not exhibit the same oxidative degradation pathways as polysorbates.
Solution Approach 2:
The patent extracts and removes the problematic polysorbate component from the formulation and replaces it with an alternative surfactant system. By taking out the degradable polysorbate and substituting it with cholate-based surfactants, the harmful degradation byproducts are eliminated while preserving the desired protein protection function.
2Reliability
If polysorbates are used to protect proteins from oxidation, then protein aggregation is reduced, but the protective effect decreases over time due to degradation
Solution Approach 1:
The patent changes the temporal stability parameter by introducing cholate-based surfactants that are resistant to oxidative degradation. This chemical substitution ensures that the protective effect remains consistent over extended storage periods, eliminating the time-dependent decline in efficacy observed with polysorbates.
Solution Approach 2:
The patent replaces the short-lived protective effect of polysorbates (which degrade over time) with cholate-based surfactants that provide long-lasting stability. The cholate surfactants act as a more durable, long-term protective agent that maintains its function throughout the product shelf life.
3Reliability
If conventional surfactants are used at high concentrations, then protein stability is improved, but formulation complexity and potential side effects increase
Solution Approach 1:
The patent changes the concentration parameter by demonstrating that cholate-based surfactants achieve effective protein stabilization at lower concentrations compared to polysorbates. This reduces the overall formulation complexity and minimizes potential side effects associated with high surfactant concentrations, while maintaining adequate protective function.
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
Cholate surfactants maintain protein stability and reduce aggregation even at concentrations below their CMC values, providing enhanced protection against degradation and oxidation, ensuring the integrity of protein formulations over time.
Implementation Method 1
a nonionic detergent (i.e., a surfactant) is often used... This is exemplified by the use of polysorbates... The polysorbates are amphipathic, nonionic surfactants... certain cholate surfactants are useful for stabilizing and/or reducing aggregation of antibodies or other proteins
Implementation Method 2
Proteins undergo varying degrees of degradation during purification and storage, wherein oxidation (including, light-induced oxidation) is one of the major degradation pathways that has a destructive effect on protein stability and potency. Oxidative reactions cause destruction of amino acid residues, peptide bond hydrolysis
Data Source
AI summary
The present invention relates to use of certain cholate surfactant comprising compositions for enhancing the storage stability of antibodies and other proteins in therapeutically useful formulations.