Soluble gp130 Dimer Formulation for High-Concentration Stability
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Solution Overview
Problem
Existing formulations for gp130 dimers, such as IM001, face challenges in achieving stability at high concentrations and pH levels, making it difficult to develop suitable formulations for treating IL-6-mediated conditions like inflammatory diseases and cancer.
Innovation Solution
A formulation comprising a histidine salt buffer system at pH 7.6, with trehalose and polysorbate 80, stabilizes the gp130 dimer, allowing for concentrations up to 30 mg/mL and maintaining stability over time, even at elevated temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If gp130 dimer formulation is developed at high concentration, then dosage efficiency is improved, but formulation stability deteriorates
Solution Approach 1:
The patent applies parameter changes by optimizing the pH level (set to 7.6) and incorporating specific stabilizing excipients (trehalose at 220-280 mM, polysorbate 80 at 0.01-0.03%) to maintain gp130 dimer stability at high concentrations up to 30 mg/mL. The histidine salt buffer system is specifically designed to work at this pH level to prevent aggregation and degradation.
Solution Approach 2:
The patent creates a composite formulation system combining gp130 dimer with multiple stabilizing components: histidine salt buffer, trehalose (a sugar stabilizer), and polysorbate 80 (a surfactant). This composite approach leverages the protective effects of each component working together to maintain stability at high concentrations and elevated temperatures.
2Stability of the object's composition
If gp130 dimer formulation is maintained at elevated pH levels, then protein stability is improved, but compatibility with biological systems deteriorates
Solution Approach 1:
The patent carefully optimizes the pH parameter to 7.6, which is slightly alkaline but within the physiological range compatible with human blood (pH 7.35-7.45). This specific pH level provides sufficient stability for the gp130 dimer while avoiding excessive alkalinity that would cause biological incompatibility or adverse reactions.
3Duration of action of stationary object
If formulation stability is maintained over time, then product shelf life is improved, but manufacturing complexity increases
Solution Approach 1:
The patent uses trehalose and polysorbate 80 as intermediary stabilizing agents that mediate between the gp130 dimer and the storage environment. These excipients act as protective intermediaries that prevent direct interaction between the protein and potentially harmful factors like aggregation, degradation, or contamination, thereby extending shelf life without requiring overly complex formulation systems.
Data Source
AI summary
Provided in the present invention is an aqueous formulation containing a dimer of two single-stranded gp130-Fc fusion proteins, and histidine salt, trehalose and polysorbate 80. The aqueous formulation can be used to treat inflammatory diseases or IL-6-mediated conditions.