High-Concentration Anti-IL-13R Antibody Formulation for Low Viscosity
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Solution Overview
Problem
Existing formulations of anti-IL13R antibodies, such as eblasakimab, face challenges in achieving high concentration without aggregation, phase separation, and excessive viscosity, making them difficult to handle and store stably for therapeutic use.
Innovation Solution
A formulation comprising 150 to 210 mg/ml of anti-IL13R antibody with specific buffer and surfactant concentrations, including 170 to 250 mM arginine and 20 to 50 mM histidine buffer, maintains high monomer content and low viscosity, ensuring stability and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentration antibody formulation is prepared, then smaller injection volume is achieved, but aggregation and phase separation occur
Solution Approach 1:
The patent optimizes multiple formulation parameters simultaneously including buffer pH (6.0-7.0), excipient concentrations (arginine 170-250 mM, histidine 20-50 mM, sucrose 180-220 mM, phenylalanine 45-85 mM), and surfactant type (polysorbate 20 or 80 at 0.02-0.05%). This multi-parameter optimization resolves the contradiction by finding the specific parameter space where high antibody concentration (150-210 mg/ml) coexists with formulation stability and prevention of aggregation
Solution Approach 2:
The formulation uses a composite approach by combining multiple excipients with different functions: arginine and histidine for pH buffering and solubility, sucrose for osmotic balance and stability, phenylalanine for aggregation prevention, and polysorbate surfactants for surface tension reduction. This composite formulation strategy enables high concentration while maintaining stability
2Quantity of substance
If high concentration antibody formulation is prepared, then smaller injection volume is achieved, but viscosity becomes excessive
Solution Approach 1:
The patent identifies that specific combinations of excipient concentrations and pH values can maintain viscosity in the acceptable range (10-30 cP) even at high antibody concentrations (150-210 mg/ml). The optimized parameter set includes pH 6.0-7.0, arginine 170-250 mM, and polysorbate 0.02-0.05%, which collectively prevent excessive viscosity while enabling high concentration formulation
Solution Approach 2:
The formulation uses arginine and histidine as intermediary substances that mediate between antibody molecules, preventing excessive intermolecular interactions that would lead to high viscosity. These excipients act as spacing agents that maintain proper molecular distribution even at high concentrations
3Quantity of substance
If high concentration antibody formulation is prepared, then therapeutic efficacy is improved, but aggregation occurs reducing monomer content
Solution Approach 1:
The patent optimizes formulation parameters to maintain >98% monomer content at high antibody concentrations. Key parameters include pH 6.0-7.0, sucrose concentration (180-220 mM), and phenylalanine concentration (45-85 mM). These parameter settings create a molecular environment that disfavors aggregation while allowing high therapeutic concentration
Solution Approach 2:
The formulation converts potentially harmful aggregation-prone conditions into beneficial effects by using sucrose and phenylalanine at specific concentrations. These excipients, when present at optimized levels, transform the high concentration environment from aggregation-promoting to aggregation-preventing, maintaining >98% monomer content
Data Source
AI summary
A stable formulation of an anti-IL 13R antibody. Also provided is the use of this formulation for treatment, method of treatment using the formulation and a process of making the formulation.