Adenovirus Vector Stability via Anionic Polymer Formulation
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Solution Overview
Problem
Adenovirus vector formulations have limited stability during prolonged storage and at ambient temperatures, requiring refrigeration for maintenance, which restricts shelf-life and practicality for use as vaccines or in gene therapy.
Innovation Solution
An aqueous formulation comprising an adenovirus vector and sodium carboxymethyl cellulose, along with other additives like dextran sulfate and buffers, enhances the stability of adenovirus vectors, allowing for storage at 2-8°C for at least twelve months and up to 25°C for three months without significant loss of infectivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If adenovirus vectors are formulated conventionally as liquid compositions, then the formulation can be administered by injection or infusion, but the virus stability during prolonged storage and at ambient temperature is insufficient
Solution Approach 1:
The patent changes the chemical parameters of the formulation by introducing specific excipients including sodium carboxymethyl cellulose (0.1-10 mg/mL), dextran sulfate (0.1-10 mg/mL), buffers (pH 5.0-8.0), and other stabilizing agents. These parameter changes enable the virus to maintain stability at higher temperatures and extend shelf-life without requiring frozen storage conditions
Solution Approach 2:
The patent creates a composite formulation system combining adenovirus vectors with multiple excipients working synergistically: sodium carboxnymethyl cellulose as a primary stabilizer, dextran sulfate as a secondary stabilizer, buffers for pH control, surfactants to prevent aggregation, and antioxidants. This composite material approach provides enhanced protection against degradation during storage
2Stability of the object's composition
If adenovirus vectors are stored at less than -60 °C, then good virus stability is ensured, but the requirement for frozen storage reduces practicality and increases complexity
Solution Approach 1:
The formulation parameters are optimized to enable storage at refrigerated temperatures (2°C to 8°C) rather than requiring ultra-low temperature frozen storage (<-60°C). This parameter change in storage temperature dramatically simplifies the storage infrastructure requirements while maintaining virus stability through the use of specialized excipients
Solution Approach 2:
The patent introduces intermediary substances (excipients such as sodium carboxnymethyl cellulose, dextran sulfate, and other stabilizers) that mediate between the virus and the storage environment. These intermediaries protect the virus from degradation during storage at higher temperatures, eliminating the need for complex frozen storage infrastructure
3Stability of the object's composition
If adenovirus vectors are stored at 2 °C - 8 °C, then improved stability is achieved compared to ambient temperature, but the shelf-life is still limited to less than twelve months
Solution Approach 1:
The patent optimizes formulation parameters including excipient concentrations, pH levels, and ionic strength to achieve extended shelf-life of at least twelve months at 2°C to 8°C. Specific parameters such as sodium carboxnymethyl cellulose concentration (0.1-10 mg/mL) and buffer composition are tuned to maximize long-term stability
Solution Approach 2:
The formulation includes preliminary protective measures through the addition of stabilizing excipients that prevent degradation pathways before they can occur during storage. This preliminary protection extends the shelf-life from less than twelve months to at least twelve months, and in some cases up to twenty-four months, at refrigerated temperatures
Data Source
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AI summary
The present invention is based on the surprising discovery that the inclusion of an anionic polymer in the adenovirus formulation enhances long-term stability of the vector composition. An aqueous formulation comprising an adenovirus vector and at least one anionic polymer is provided, together with methods of the preparation of a storage stable adenovirus aqueous formulation.