Fusion Protein Aqueous Composition Stabilization
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Solution Overview
Problem
Aqueous pharmaceutical compositions containing proteins as active ingredients, such as linked antibodies and lysosomal enzymes, face stability challenges during storage, requiring additional stabilizing agents like amino acids and surfactants, but a stable formulation for marketing has not been consistently achieved.
Innovation Solution
An aqueous pharmaceutical composition is developed with a fusion protein of an antibody and a lysosomal enzyme, stabilized using sucrose and a nonionic surfactant, within specific concentration ranges and pH levels, to maintain stability and usability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If aqueous pharmaceutical composition is used for convenience, then ease of operation is improved, but stability of the protein is worsened during storage
Solution Approach 1:
The patent optimizes specific parameter ranges including sucrose concentration (5-50% w/v), nonionic surfactant concentration (0.01-5% w/v), pH (5.0-7.5), and buffer concentration (3-30 mM) to achieve both aqueous stability and storage stability of the fusion protein
Solution Approach 2:
The patent uses a composite stabilizing system combining multiple components: sucrose as a stabilizing agent, nonionic surfactant (such as polysorbate 80) to prevent aggregation, and buffer systems to maintain pH, creating a synergistic effect that preserves protein stability in aqueous form
2Reliability
If stabilizing agents are added to enhance protein stability, then reliability is improved, but device complexity is worsened due to multiple additives
Solution Approach 1:
The patent selects stabilizing agents that serve multiple functions: sucrose provides both stabilization and osmotic balance, nonionic surfactants prevent aggregation and maintain solubility, and buffers maintain pH - each component performs multiple roles to reduce the total number of additives needed
Data Source
AI summary
Aqueous pharmaceutical compositions containing a fusion protein of an antibody and a lysosomal enzyme as an active ingredient, which are stable enough to be marketed, are disclosed. The aqueous pharmaceutical composition, for example, comprises the fusion protein of the antibody and the lysosomal enzyme at a concentration of 0.5 to 20 mg/mL, sodium chloride at a concentration of 0.3 to 1.2 mg/mL, sucrose at a concentration of 50 to 100 mg/mL, a nonionic surfactant at a concentration of 0.15 to 3 mg/mL, a buffer at a concentration of 3 to 30 mM, and is adjusted to pH 5.0 to 7.5.