Herpesvirus compositions and related methods
Inventors
Anderson, Stephen • Delagrave, Simon • Hamberger, John • Li, Qinglian • Mundle, Sophia • Rahman, Nausheen
Assignees
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Publication Number
US-12214035-B2
Publication Date
2025-02-04
Expiration Date
Abstract
The present disclosure relates to liquid and dried compositions comprising a live, attenuated or genetically modified herpesvirus and methods of preparing such compositions, in one aspect, the composition comprises at least two or more pharmaceutically acceptable excepients, at least one of which is histidine and at least one of which is a sugar or sugar alcohol. The compostions retain a sufficiently high infectious titre following storage or large-scale manufacturing steps, such as lyophilization.
Core Innovation
The described invention relates to formulations and manufacturing of a dried composition comprising a live, attenuated or genetically modified herpesvirus selected from live, attenuated or genetically modified herpes simplex virus type-2 (HSV-2) or herpes simplex virus type-1 (HSV-1). The method comprises admixing the herpesvirus with histidine or glutamine and sucrose or trehalose, and further includes sodium chloride and glutamate, to produce a mixture having a pH of about 6.5 to 7.5, followed by drying.
The core of the formulation is the combination of histidine or glutamine with sucrose or trehalose together with sodium chloride and glutamate, in a specified pH window. The dried product consists of the live herpesvirus, 1 mM to 50 mM histidine or glutamine, sucrose or trehalose, sodium chloride, glutamate, and has a pH of about 6.5 to 7.5.
The described manufacturing approach dries the admixed herpesvirus formulation to yield a low-residual-moisture dried composition, using drying options including lyophilization, foam-drying, or spray-drying as indicated by the claim set. The partial content further reports improved infectious titre retention after manufacturing and storage, including after lyophilization and storage under refrigerated and ambient conditions, using stability criteria tied to dried titre retention.
Claims Coverage
Two independent claims are identified. The inventive coverage centers on manufacturing dried HSV-1 or HSV-2 compositions by admixing live, attenuated or genetically modified herpesviruses with histidine or glutamine plus sucrose or trehalose, together with sodium chloride and glutamate, followed by drying, and maintaining a defined pH range and defined component contents.
Admixing HSV-1 or HSV-2 with histidine or glutamine plus sucrose or trehalose
A method of manufacturing a dried composition comprising a live, attenuated or genetically modified herpesvirus, wherein the method comprises admixing the live, attenuated or genetically modified herpesvirus with histidine or glutamine and sucrose or trehalose.
Drying to form a defined dried composition
Drying the admixture to form a dried composition, wherein the dried composition consists of HSV-2 or HSV-1, 1 mM to 50 mM histidine or glutamine, sucrose or trehalose, sodium chloride, and glutamate, and has a pH of about 6.5 to 7.5.
Admixing with defined components including sodium chloride and glutamate
A method of manufacturing a dried composition comprising a live, attenuated or genetically modified herpesvirus, wherein the method comprises admixing the live, attenuated or genetically modified herpesvirus with histidine, sucrose or trehalose, sodium chloride, and glutamate.
Drying to form an approximately defined dried composition
Drying the admixture, wherein the dried composition consists of HSV-2 or HSV-1, about 10 mM 1 mM, about 10% w/v sucrose or trehalose, sodium chloride, and about 50 mM glutamate, and has a pH of about 6.5 to 7.5.
The independent-claim scope is directed to producing dried HSV-1/HSV-2 compositions by admixing live, attenuated or genetically modified herpesviruses with histidine or glutamine plus sucrose or trehalose, together with sodium chloride and glutamate, then drying to yield a composition limited to HSV-1 or HSV-2 having a pH about 6.5 to 7.5, with specified ranges or approximate amounts for histidine or glutamine, sugar, sodium chloride, and glutamate.
Stated Advantages
Improved infectious titre retention after manufacturing steps such as lyophilization and storage under refrigerated and ambient conditions, with dried titre retention described by specified log10 PFU/mL ranges.
Documented Applications
Formulations and kit formats for dried compositions comprising live, attenuated or genetically modified HSV-1 or HSV-2, including reconstitution.
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