Humanized Antibody Liquid Formulation Stability
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Solution Overview
Problem
Current formulations for humanized anti-interleukin 6 receptor antibodies face challenges in maintaining stability and activity over time, leading to issues such as aggregation, degradation, and insoluble microparticle formation during storage and temperature variations, which affects their efficacy in treating IL-6 related diseases like rheumatoid arthritis.
Innovation Solution
A stable liquid formulation comprising a humanized anti-interleukin 6 receptor antibody, a buffer system formed by histidine salt and sodium acetate, a surfactant like polysorbate-80, and a stabilizer such as arginine hydrochloride or mannitol, optimized to prevent acidic peaks, dimers, aggregates, and degradants, ensuring stability through 5 freeze-thaw cycles and long-term storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If the antibody formulation is stored for long periods, then the treatment duration is extended, but the antibody stability deteriorates due to aggregation and degradation
Solution Approach 1:
The patent optimizes formulation parameters including pH (5.0-7.0), buffer concentration (5-20 mM histidine salt), stabilizer concentration (30-400 mM), and surfactant concentration (0.1-1 g/L) to maintain antibody stability during long-term storage. These parameter changes prevent aggregation and degradation while extending storage duration.
Solution Approach 2:
The patent introduces intermediary substances including buffer systems (histidine salt, sodium acetate), stabilizers (arginine hydrochloride, mannitol, sucrose), and surfactants (polysorbate-80, poloxamer 188) that mediate between the antibody and storage conditions. These intermediaries protect the antibody from environmental factors and prevent aggregation during storage.
2Adaptability or versatility
If the antibody formulation undergoes temperature variations, then the adaptability to storage conditions is improved, but the antibody stability deteriorates due to aggregation and insoluble microparticle formation
Solution Approach 1:
The patent incorporates stabilizing agents and surfactants beforehand that cushion the antibody against temperature variations. The buffer system and stabilizers are pre-added to prevent aggregation and insoluble microparticle formation before temperature changes occur, maintaining stability during temperature cycling.
Solution Approach 2:
The patent formulates the antibody with optimized pH (5.0-7.0), buffer concentration (5-20 mM), and stabilizer concentration (30-400 mM) to create a formulation that resists temperature-induced changes. These parameter optimizations enable the formulation to withstand temperature variations without aggregation or degradation.
3Ease of operation
If the antibody formulation is subjected to freeze-thaw cycles, then the ease of operation during storage and transport is improved, but the antibody stability deteriorates due to aggregation and degradation
Solution Approach 1:
The patent adds stabilizers and surfactants beforehand that cushion the antibody against freeze-thaw damage. The buffer system and stabilizing agents are pre-included to prevent aggregation and degradation during freeze-thaw cycles, making the formulation easier to store and transport while maintaining stability.
Solution Approach 2:
The patent introduces intermediary substances including stabilizers (arginine hydrochloride, mannitol, sucrose) and surfactants (polysorbate-80, poloxamer 188) that mediate between the antibody and freeze-thaw conditions. These intermediaries protect the antibody during temperature cycling and prevent aggregation.
4Reliability
If the antibody formulation maintains high monomer purity, then the treatment efficacy is improved, but the formulation complexity increases due to required stabilizers and buffers
Solution Approach 1:
The patent optimizes formulation parameters including pH (5.0-7.0), buffer concentration (5-20 mM), stabilizer concentration (30-400 mM), and surfactant concentration (0.1-1 g/L) to achieve high monomer purity. These parameter optimizations ensure treatment efficacy while managing formulation complexity through systematic parameter control.
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 formulation maintains the antibody's stability and biological activity for at least 6 months at room temperature and 36 months at 4°C, effectively inhibiting disease progression in IL-6 related conditions by maintaining the antibody's monomer purity and reducing insoluble particles, thus enhancing treatment efficacy.
Implementation Method 1
a buffer system formed by histidine salt and sodium acetate
Implementation Method 2
a surfactant like polysorbate-80
Implementation Method 3
a stabilizer such as arginine hydrochloride or mannitol, optimized to prevent acidic peaks, dimers, aggregates, and degradants
Data Source
AI summary
The invention relates to a liquid formulation of humanized antibody for treating IL-6 related diseases. The liquid formulation contains 2-100 mg/ml recombinant humanized anti-human interleukin 6 receptor monoclonal antibody, 5-20 mM histidine salt buffer (or a buffer of a combination of 5-20 mM histidine salt and 5-20 mM sodium acetate), 0.025-0.075% (by volume) surfactant, and 3-5% (by mass to volume) stabilizer and water for injection. The antibody formulation enhances the stability of the recombinant anti-human interleukin 6 receptor monoclonal antibody, prevents the monoclonal antibody from aggregation, degradation, and acidic isomer increases. This formulation can be used for stabilizing the structure and function of the humanized antibody.