Anti-PD1 Antibody Formulation Stability via Citrate Buffer
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Solution Overview
Problem
There is a need for stable pharmaceutical formulations of anti-PD1 antibodies that are safe for human administration, as existing formulations may not maintain the physical, chemical, and biological stability of the antibodies during storage and use.
Innovation Solution
A liquid pharmaceutical composition comprising an anti-human PD1 antibody, one or more amino acids other than histidine, a non-ionic surfactant, and a citrate buffer, with a pH between 5.0 and 5.8, specifically using polysorbate 20 or polysorbate 80 as the surfactant and arginine or lysine as the amino acids, to create a stable formulation for cancer treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If existing formulations (containing histidine buffer, polysorbate 80, and sucrose) are used, then the formulation provides basic stability, but the antibody fails to maintain physical, chemical, and biological stability during storage and use
Solution Approach 1:
The patent changes the buffer system from histidine to citrate buffer and adjusts the pH range to 5.0-5.8, which significantly improves antibody stability. This parameter change in the formulation composition directly addresses the instability problem while maintaining safety for human administration.
Solution Approach 2:
The patent creates a composite formulation system combining citrate buffer, amino acids (arginine and/or lysine), polysorbate 20 or 80, and the anti-PD1 antibody. This composite material approach provides synergistic stabilization effects that individual components cannot achieve alone, ensuring physical, chemical, and biological stability.
2Stability of the object's composition
If the formulation uses citrate buffer with amino acids other than histidine and polysorbate, then the antibody maintains stability during storage, but the formulation complexity increases
Solution Approach 1:
The citrate buffer serves multiple functions: it maintains pH within the optimal range (5.0-5.8) for antibody stability, provides ionic strength control, and works synergistically with the amino acids and polysorbate. This multi-functionality reduces the need for additional separate stabilizing agents, thereby managing formulation complexity while achieving enhanced stability.
Solution Approach 2:
The amino acids (arginine and/or lysine) act as intermediaries between the citrate buffer and the antibody, providing additional stabilization through electrostatic interactions and solvation effects. This intermediary role enhances stability without requiring complex formulation structures.
Data Source
AI summary
The present invention relates to pharmaceutical compositions of an anti-PD1 antibody comprising acitrate buffer, one or more amino acids other than histidine and a surfactant.