Thermostable Live HSV-1 Powder Compositions for Ambient Storage
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Solution Overview
Problem
Live viruses, such as herpes simplex virus, are unstable at temperatures above -80°C, leading to operational and commercial challenges in storage, transportation, and handling, and lyophilization processes can damage the virus, causing loss of potency and complexity in manufacturing.
Innovation Solution
A lyophilized composition comprising a live, attenuated virus, recombinant human serum albumin, a sugar other than lactose, a sugar alcohol, a source of phosphate, and a source of chloride, which is stable at cold and ambient temperatures, maintaining viral potency and flexibility in handling and transportation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If live attenuated herpes simplex virus is stored at temperatures above -80°C, then storage and transportation become simpler, but viral stability and infectivity deteriorate
Solution Approach 1:
The patent changes the physical state parameter of the virus from liquid to solid through lyophilization, transforming it into a stable powder form that can be stored at ambient temperatures without losing viral potency, thus resolving the contradiction between storage simplicity and viral stability
Solution Approach 2:
The patent introduces protective excipients (sugars, amino acids, buffers) as intermediary substances that mediate between the virus and the storage environment, forming a protective matrix that maintains viral integrity during lyophilization and storage at non-frozen temperatures
2Duration of action of stationary object
If lyophilization is used to improve storage stability, then shelf life is extended, but viral potency is reduced due to process damage
Solution Approach 1:
The patent applies preliminary protective measures by formulating the virus with specific excipients (sugars, amino acids, buffers) before lyophilization, creating a protective environment that prevents viral damage during the freezing and drying process, thereby maintaining high viral potency after lyophilization
Solution Approach 2:
The patent optimizes the lyophilization process parameters (freezing rate, drying temperature, vacuum level) to minimize viral stress and damage, achieving a balance between extended shelf life and preserved viral potency
3Reliability
If strict frozen storage protocols are implemented, then viral stability is maintained, but manufacturing flexibility and supply chain complexity increase
Solution Approach 1:
The patent changes the storage temperature parameter from -80°C frozen to ambient temperatures through lyophilization, eliminating the need for complex frozen storage infrastructure and protocols while maintaining viral stability, thus reducing supply chain complexity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition ensures minimal virus inactivation and maintains at least 30-40% viral potency after lyophilization, allowing for flexible manufacturing and reduced product loss, while being suitable for storage and transport at non-frozen temperatures.
Implementation Method 1
Lyophilization is a freeze-drying process that removes water from a drug product after it is frozen and placed under a vacuum. During this process, water sublimes changing from ice to vapor without passing through the liquid phase.
Data Source
AI summary
Provided herein is a powder comprising a live, attenuated virus, recombinant human serum albumin (rHSA), a sugar other than lactose, a sugar alcohol, a source of phosphate, a source of chloride, wherein the composition is substantially free of lactose, gelatin, antibiotic, and free amino acids. In exemplary aspects, the powder is a lyophilizate of a liquid composition. Related liquid compositions, methods of preparing an oncolytic virus for administration and methods of treating melanoma are also provided herein.