rAAV Pharmaceutical Composition for Stable Refrigerated Storage
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Solution Overview
Problem
Existing recombinant adeno-associated virus (rAAV) gene therapy products require storage at low temperatures (-20°C or -60°C), which poses logistical challenges for distribution and increases costs, necessitating a stable formulation suitable for refrigeration (2-8°C) and room temperature storage for extended periods.
Innovation Solution
A pharmaceutical composition comprising rAAV, ionic salts, buffers, stabilizers, and surfactants, specifically sodium chloride, Tris-HCl, sucrose, and poloxamer 188, maintains stability and biological activity for over a year at refrigeration temperatures and two weeks at room temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rAAV is stored at low temperatures (-20°C or -60°C), then stability and biological activity are maintained, but logistics complexity and storage costs increase
Solution Approach 1:
The patent changes the storage temperature parameter from -20°C or -60°C to 2-8°C, enabling refrigeration storage instead of frozen storage. This parameter change resolves the contradiction by maintaining virus stability while simplifying logistics and reducing storage costs.
Solution Approach 2:
The patent introduces a specific formulation composition containing stabilizers and surfactants as intermediary substances that protect rAAV during storage. These intermediaries enable the virus to remain stable at higher temperatures (2-8°C), thus resolving the contradiction between maintaining stability and simplifying logistics.
2Reliability
If rAAV is stored at low temperatures (-20°C or -60°C), then biological activity is maintained, but storage costs increase
Solution Approach 1:
The patent changes the storage temperature parameter from -20°C or -60°C to 2-8°C, eliminating the need for frozen storage. This parameter change reduces energy consumption and storage costs while maintaining biological activity through the optimized formulation.
Solution Approach 2:
The patent introduces stabilizers and surfactants as intermediary substances in the formulation that protect rAAV biological activity during refrigeration storage. These intermediaries enable cost-effective storage at 2-8°C by preventing virus inactivation, thus resolving the contradiction between maintaining biological activity and reducing storage costs.
3Device complexity
If rAAV is stored at refrigeration temperature (2-8°C), then logistics is simplified, but stability and biological activity may deteriorate
Solution Approach 1:
The patent introduces stabilizers and surfactants as intermediary substances that specifically protect rAAV from deterioration at refrigeration temperatures. These intermediaries enable the virus to remain stable and biologically active during storage at 2-8°C, thus resolving the contradiction between logistics simplicity and maintaining reliability.
4Ease of manufacture
If conventional rAAV formulation is used, then manufacturing is simple, but storage stability at refrigeration temperature is insufficient
Solution Approach 1:
The patent creates a composite formulation system combining rAAV with stabilizers and surfactants. This composite material approach enhances storage stability at refrigeration temperatures while maintaining manufacturing feasibility, resolving the contradiction between ease of manufacture and storage stability.
Data Source
AI summary
The present invention belongs to the field of formulation of a recombinant adeno-associated virus vector, in particular relating to a pharmaceutical composition of a recombinant adeno-associated virus vector, comprising a recombinant adeno-associated virus (rAAV), an ion salt, a buffering agent, a stabilizer, and a surfactant, and its use. The rAAV vector carries hFIX and can be used to treat hemophilia B. The pharmaceutical composition can be stored at a refrigeration temperature, such as 2-8° C., for more than 1 year, maintain stable for such as genome titer and biological activity, and also has good stability when stored at room temperature for two weeks.