Antibody Formulation Stabilization via Specific Salt Selection
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Solution Overview
Problem
Current antibody formulations face issues with stability due to denaturation, oxidation, and aggregation, leading to efficacy loss and potential toxicity or immunogenicity, and are often hindered by high viscosity, which complicates manufacturability and administration.
Innovation Solution
Incorporating specific salts such as magnesium glutamate, magnesium acetate, and lithium sulfate into antibody formulations to enhance stability and reduce viscosity, while maintaining optimal osmolality and pH levels, thereby creating a buffer-free or buffer-inclusive aqueous solution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If traditional excipients (sugars like sucrose) are used to stabilize antibodies, then stability is improved, but viscosity increases
Solution Approach 1:
The patent changes the chemical parameter of the stabilizing agent from traditional sugars (sucrose, trehalose) to specific salts (magnesium acetate, arginine acetate, lysine acetate, etc.). This parameter change maintains the stabilizing function while fundamentally altering the physical property profile, specifically reducing viscosity. The salts provide ionic stabilization through electrostatic interactions with the antibody surface, achieving stability without the high viscosity associated with sugar-based excipients.
2Stability of the object's composition
If traditional excipients (sugars and polyols) are used to stabilize antibodies, then stability is improved, but osmolality increases
Solution Approach 1:
The patent changes the chemical composition parameter from high-osmolality sugars and polyols to low-osmolality salts. The ionic compounds (such as magnesium acetate, arginine acetate, and lysine acetate at concentrations of 1-750 mM) provide effective stabilization through charge interactions while contributing significantly less to osmolality compared to equivalent stabilizing concentrations of sugars. This parameter substitution resolves the contradiction between achieving stability and minimizing osmolality.
3Quantity of substance
If antibodies are formulated at high concentrations, then efficacy is improved, but viscosity increases
Solution Approach 1:
The patent introduces specific salts as intermediary substances that mediate between high antibody concentration and acceptable viscosity. The salts (magnesium acetate, arginine acetate, lysine acetate, etc.) act as molecular spacers and charge shields, reducing protein-protein interactions that lead to viscosity increase at high concentrations. This intermediary allows the formulation to maintain high antibody concentrations (improving efficacy) while the salt mediates reduced intermolecular attraction, keeping viscosity manageable.
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 use of these salts stabilizes antibodies, reduces viscosity, and maintains osmolality, resulting in formulations that are more stable, less toxic, and easier to administer, with improved manufacturability and bioavailability.
Implementation Method 1
antibodies can be stabilized in solution by including a salt selected from the group of magnesium glutamate, magnesium acetate, magnesium aspartate, magnesium sulfate, arginine acetate, arginine aspartate, arginine glutamate, arginine sulfate, lysine acetate, lysine aspartate, lysine glutamate, lysine sulfate, sodium acetate, sodium aspartate, sodium glutamate, sodium sulfate, lithium acetate, lithium aspartate, lithium glutamate, and lithium sulfate
Implementation Method 2
The resulting stabilized antibody solutions are also less viscous compared to formulations which do not include one of these salts or that contain traditional excipients
Data Source
AI summary
Provided herein are aqueous antibody formulations that exhibit improved stability and low viscosity. The formulations include an antibody or an antigen-binding fragment, a buffer, and a salt selected from the group of magnesium glutamate, magnesium acetate, magnesium aspartate, magnesium sulfate, arginine acetate, arginine aspartate, arginine glutamate, arginine sulfate, lysine acetate, lysine aspartate, lysine glutamate, lysine sulfate, sodium acetate, sodium aspartate, sodium glutamate, sodium sulfate, lithium acetate, lithium aspartate, lithium glutamate, or lithium sulfate, where the formulations have a pH of about 4 to about 8 and, optionally an osmolality of about 250 mOsm/kg to about 1500 mOsm/kg