Anti-Sclerostin Antibody Formulation Stability
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Solution Overview
Problem
Protein-based pharmaceuticals, such as anti-sclerostin antibodies, face significant challenges in maintaining stability and preventing aggregation and degradation during formulation, filling, shipping, storage, and administration due to their physical and chemical instabilities, which can lead to loss of function and adverse immunogenic reactions.
Innovation Solution
A pharmaceutical composition comprising an anti-sclerostin antibody, a buffer (glutamic acid, histidine, or succinic acid), and a polyol (like sorbitol) at specific concentrations, maintaining a pH between 4 and 7, which enhances stability and reduces aggregation and denaturation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protein-based pharmaceuticals are formulated for storage and administration, then therapeutic benefit is achieved, but physical and chemical instability leads to aggregation and degradation
Solution Approach 1:
The patent employs multiple excipients as intermediary substances to protect the anti-sclerostin antibody from aggregation and degradation. Specifically, surfactants (polysorbate 20 or polysorbate 80) act as mediators to prevent surface-induced aggregation, while amino acids (arginine, glycine, or L-proline) serve as protective intermediaries that maintain protein structure stability during storage and handling
Solution Approach 2:
The formulation utilizes controlled parameter changes to optimize stability. The pH is maintained within a specific range (5.0-7.0) using buffers to prevent acid-base induced degradation. The concentrations of all excipients are precisely controlled: surfactant at 0.01-5% w/v, amino acid at 1-250 mM, and polysaccharide at 0.1-10% w/v, creating an optimized parameter space where the antibody remains stable
2Productivity
If high concentration of anti-sclerostin antibody is formulated, then dosing efficiency is improved, but aggregation and loss of function increase
Solution Approach 1:
At high antibody concentrations, the patent uses excipients as protective intermediaries that prevent intermolecular aggregation. The surfactant molecules intercalate between antibody molecules, while amino acids form protective hydration shells, allowing high concentrations to be maintained without loss of functional activity
Solution Approach 2:
The formulation incorporates excipients that provide beforehand cushioning against aggregation stresses. The polysaccharides and amino acids create a protective matrix that cushions the antibody molecules from each other, preventing aggregation even at high concentrations before administration
Data Source
AI summary
The present disclosure is directed to pharmaceutical compositions comprising an anti-sclerostin antibody.