Lyophilized Antibody Formulation Stability
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Solution Overview
Problem
Developing stable pharmaceutical formulations for therapeutic antibodies, particularly anti-OX40 antagonist antibodies, is challenging due to stability issues during storage and administration, requiring effective excipients and buffering agents to maintain potency and safety.
Innovation Solution
A stable pharmaceutical formulation comprising an anti-OX40 antagonist antibody or antibody fragment, a buffer (such as acetate, L-histidine, citrate, or phosphate), and stabilizing or tonicity agents (like sucrose, Polysorbate 80, and Poloxamers) is developed, which is either liquid or lyophilized, ensuring stability at various temperatures for extended periods and suitable for subcutaneous or intravenous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional pharmaceutical formulations are used for therapeutic antibodies, then the formulation can be prepared and administered, but the antibody loses potency and stability during storage and administration
Solution Approach 1:
The patent applies parameter changes by optimizing the pH range (5.0-7.0) and concentrations of excipients including buffer (1-10 mM), stabilizing agents (0.001-10%), and tonicity agents. These parameter optimizations maintain antibody structural integrity and prevent degradation during long-term storage at various temperatures, directly resolving the contradiction between reliability and storage duration.
Solution Approach 2:
The formulation uses a composite approach by combining multiple excipients with specific functions: buffers (acetate, L-histidine, citrate, or phosphate) for pH control, stabilizing agents (such as Polysorbate 80, Poloxamers, sucrose) for protein protection, and tonicity agents (sodium chloride, potassium chloride, calcium chloride) for osmotic balance. This composite formulation synergistically maintains antibody stability over extended storage periods.
2Quantity of substance
If high concentration antibody formulations are developed to reduce administration volume, then the potency per volume increases, but the formulation stability and safety become more challenging to maintain
Solution Approach 1:
The patent optimizes parameters for high concentration formulations (20-80 mg/mL) by adjusting buffer concentrations (1-10 mM), stabilizing agent percentages (0.001-10%), and tonicity agent levels. These parameter changes prevent aggregation and maintain solubility at high concentrations while ensuring formulation stability and safety for clinical administration.
Solution Approach 2:
The formulation employs intermediary substances including Polysorbate 80 (0.001-0.1%), Poloxamers (0.001-10%), and other stabilizing agents that act as mediators between the high concentration antibody and the aqueous environment. These intermediaries prevent protein-protein interactions that lead to aggregation, enabling stable high-concentration formulations.
3Reliability
If multiple excipients are added to maintain antibody stability, then the storage stability improves, but the formulation complexity increases
Solution Approach 1:
The patent applies multi-functionality by selecting excipients that perform multiple roles: buffers (acetate, L-histidine, citrate, phosphate) simultaneously control pH and provide ionic strength; stabilizing agents like Polysorbate 80 and Poloxamers provide both surface activity and protein stabilization; tonicity agents contribute to osmotic balance and solubility. This reduces the need for separate additives while maintaining comprehensive stability.
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 physical and chemical stability, retaining biological activity for at least 24 months at +5±3° C, 12 months at +25±2° C, and 3 months at +40±2° C, and is suitable for reconstitution and further dilution, making it effective for treating OX40-mediated disorders.
Implementation Method 1
a buffer (such as acetate, L-histidine, citrate, or phosphate)
Implementation Method 2
stabilizing or tonicity agents (like sucrose, Polysorbate 80, and Poloxamers)
Implementation Method 3
Polysorbate 80
Implementation Method 4
said pharmaceutical formulation is liquid or lyophilized
Data Source
AI summary
The present invention relates to a stable pharmaceutical formulation comprising an antibody; preferably the pharmaceutical formulation is lyophilized.