PD-L1 Antibody Formulation Stability via Buffer and Surfactant Optimization
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Solution Overview
Problem
Anti-PD-L1 antibody drugs are unstable due to their large molecular weight and complex structure, leading to degradation and chemical modifications, which complicates their administration and storage stability.
Innovation Solution
A pharmaceutical composition comprising an anti-PD-L1 antibody or antigen-binding fragment, a succinate or acetate buffer, a saccharide such as trehalose or sucrose, and a surfactant like polysorbate 80, formulated to maintain stability at specific concentrations and pH levels, ensuring physical, chemical, and biological stability during storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-PD-L1 antibody is formulated as a pharmaceutical composition, then biological activity and therapeutic effect are improved, but stability during storage and administration deteriorates due to degradation and polymerization
Solution Approach 1:
The patent optimizes multiple formulation parameters including buffer type (succinate or acetate), pH (4.5-6.0), buffer concentration (5-50 mM), antibody concentration (30-80 mg/mL), and adds stabilizing agents (saccharides at 1-10%, surfactants at 0.01-1%). These parameter changes collectively improve storage stability while maintaining biological activity.
Solution Approach 2:
The patent introduces intermediary substances including buffers (succinate/acetate), saccharides (trehalose, sucrose), and surfactants (polysorbate 80, polysorbate 20) that mediate between the antibody and environmental stressors, preventing degradation and polymerization while preserving therapeutic function.
2Productivity
If antibody concentration is increased to improve therapeutic efficacy, then treatment effectiveness is improved, but physical stability and resistance to aggregation deteriorates
Solution Approach 1:
Surfactants (polysorbate 80 or polysorbate 20 at 0.01-1% concentration) are introduced as intermediary substances that adsorb at antibody interfaces, preventing aggregation even at high concentrations (30-80 mg/mL), thus enabling high therapeutic efficacy while maintaining physical stability.
Solution Approach 2:
The patent optimizes antibody concentration within the range of 30-80 mg/mL combined with specific surfactant concentrations (0.01-1%) and pH conditions (4.5-6.0), achieving a balance where high therapeutic efficacy is obtained without sacrificing physical stability.
3Stability of the object's composition
If buffer concentration is increased to maintain pH stability, then pH control is improved, but chemical stability and prevention of undesired modifications deteriorates
Solution Approach 1:
The patent identifies an optimal buffer concentration range of 5-50 mM (preferably 10-30 mM) that provides sufficient pH control while avoiding excessive buffer concentrations that could induce chemical instability or undesired modifications. The pH is optimized to 4.5-6.0 range.
Solution Approach 2:
Saccharides (trehalose, sucrose at 1-10% concentration) are introduced as intermediary substances that form protective complexes with the antibody, stabilizing the protein structure chemically while working synergistically with the buffer system to maintain overall formulation stability.
Data Source
AI summary
The present invention provides a PD-L1 antibody pharmaceutical composition and use thereof. In particular, the present invention provides a pharmaceutical composition comprising the PD-L1 antibody or an antigen-binding fragment thereof in a succinate buffer. In addition, the pharmaceutical composition may also contain a sugar and a nonionic surfactant.