Anti-IL-4R Antibody Liquid Formulation for Storage Stability
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Solution Overview
Problem
Therapeutic antibodies, such as those targeting the human interleukin-4 receptor alpha (hIL-4Rα), face challenges in maintaining stability during storage and administration due to degradation, aggregation, and chemical modifications in liquid formulations, necessitating improved pharmaceutical formulations.
Innovation Solution
A liquid pharmaceutical formulation comprising a human antibody that binds to hIL-4Rα, combined with a buffer, organic cosolvent, thermal stabilizer, and viscosity reducer, at specific concentrations and pH, to maintain stability and suitable viscosity for administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If therapeutic antibodies are formulated in liquid solution, then they are suitable for administration to patients, but they are prone to degradation, aggregation, or undesired chemical modifications during storage
Solution Approach 1:
The patent modifies formulation parameters by adjusting pH to specific ranges (e.g., pH 5.0-6.5), controlling temperature (e.g., 2-8°C refrigerated storage), and optimizing excipient concentrations to prevent degradation while maintaining administerability
Solution Approach 2:
The patent introduces stabilizing excipients as intermediary substances including sugars (sucrose, trehalose, mannitol), amino acids (arginine, histidine, acetate), and surfactants (polysorbates, poloxamers) that mediate between the antibody and storage conditions, preventing direct harmful interactions
2Quantity of substance
If the concentration of antibody in the formulation is increased, then the effectiveness is improved, but the viscosity of the solution increases
Solution Approach 1:
The patent adjusts formulation parameters including pH (5.0-6.5), ionic strength, and excipient concentrations to optimize the balance between antibody concentration and viscosity, enabling higher concentrations while maintaining acceptable flow characteristics for injection
Solution Approach 2:
The patent uses viscosity-modifying excipients such as amino acids (arginine hydrochloride, histidine hydrochloride, acetate) and surfactants that act as intermediaries to reduce protein-protein interactions and maintain solution flowability even at high antibody concentrations
3Duration of action of stationary object
If the formulation is stored at higher temperatures, then the storage stability is improved, but the antibody undergoes degradation and aggregation
Solution Approach 1:
The patent incorporates stabilizing excipients beforehand that provide protective effects against thermal stress, pH shifts, and mechanical stress, cushioning the antibody against degradation pathways even during temperature excursions or long-term storage
Solution Approach 2:
The patent optimizes formulation parameters including pH (5.0-6.5), ionic strength, and excipient concentrations to create a formulation that maintains antibody integrity across a range of storage temperatures, with preferred storage at 2-8°C but acceptable stability at elevated temperatures due to the stabilizing excipients
Data Source
AI summary
The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human interleukin-4 receptor (hIL-4R). The formulations may contain, in addition to an anti-hIL-4R antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.