Anti-IL1R1 Antibody Formulation for High-Concentration Stability
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Solution Overview
Problem
The formulation of monoclonal antibodies for pharmaceutical applications faces challenges with elevated viscosity and stability issues, particularly at high protein concentrations, due to their macromolecular nature and unique physicochemical properties, necessitating a tailored approach for each antibody.
Innovation Solution
A stable formulation for anti-Interleukin 1 Receptor 1 (IL1R1) antibodies is developed with a pH range of 4.4-6.5 and arginine concentration below 130 mM, which stabilizes the antibodies, reducing high molecular weight species formation and viscosity, allowing concentrations above 80 mg/ml.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high protein concentration is used in antibody formulations, then volume limitations for subcutaneous administration are addressed, but viscosity increases significantly
Solution Approach 1:
The patent applies parameter changes by systematically optimizing multiple formulation parameters including pH (4.0-7.4), ionic strength (10-200 mM), buffer type, and excipient concentrations to achieve the desired balance between high protein concentration and acceptable viscosity. This involves adjusting physical and chemical states of the formulation components to prevent intermolecular interactions that cause viscosity increase.
Solution Approach 2:
The patent uses excipients as intermediary substances to mediate between the antibody molecules and the formulation environment. These excipients prevent direct intermolecular interactions between antibodies, thereby maintaining low viscosity at high concentrations. The excipients act as spacers or protective agents that reduce the tendency of macromolecules to aggregate.
2Quantity of substance
If high protein concentration is used in antibody formulations, then dose requirements are met, but stability decreases due to intermolecular interactions
Solution Approach 1:
The patent employs parameter changes by optimizing pH, ionic strength, and excipient concentrations to stabilize the antibody structure at high concentrations. The specific pH range (4.0-7.4) and ionic strength (10-200 mM) are selected to minimize conformational changes and intermolecular interactions that lead to aggregation and degradation.
Solution Approach 2:
The patent applies beforehand cushioning by incorporating stabilizing excipients and buffers in advance to prevent degradation and aggregation. These protective agents are included in the formulation to cushion against potential destabilizing factors such as pH shifts, ionic interactions, and molecular collisions that occur at high concentrations.
3Ease of operation
If arginine is used at high concentration to reduce viscosity, then viscosity decreases, but antibody destabilization occurs
Solution Approach 1:
The patent applies parameter changes by optimizing the arginine concentration within a specific range (10-200 mM) rather than using high concentrations. This balanced approach allows arginine to effectively reduce viscosity through its charge-neutralizing properties while avoiding the destabilizing effects that occur at excessive concentrations. The optimal concentration is determined based on the specific antibody's physicochemical properties.
Data Source
AI summary
The present invention provides, among other things, stable formulations comprising an anti-Interleukin 1 Receptor 1 (IL1R1) antibody at a concentration of between than 50-200 mg/ml, wherein the formulation comprises less than 130 mM arginine and a pH of 4.4-6.5, wherein the amount of HMW species in the formulation increases less than 2% upon storage at 25° C. for at least 4 weeks.