Stable virus-containing composition

Inventors

SEDIQ, Ahmad Shakeb • TONNIS, Wouter Frank • Capelle, Martinus Anne Hobbe

Assignees

Bavarian Nordic AS • Janssen Vaccines and Prevention BV

Abstract

Described herein are compositions and pharmaceutical compositions including poxviruses, in particular vaccinia virus such as modified vaccinia Ankara (MVA) virus, a sulfate salt at a concentration between about 5 mM and 300 mM and a buffer, wherein the composition has a pH of between about 6.0 and 8.5. Also described are methods for stabilizing a poxvirus composition by preparing said viral formulation.

Core Innovation

The invention relates to stable pharmaceutical compositions comprising a poxvirus, a buffer, and a sulfate salt. The composition has a pH between about 6.0 and 8.5, and the sulfate salt is present at a concentration between about 5 mM and 300 mM. The disclosed formulation concept is directed to maintaining virus stability during storage and stress conditions.

The patent describes characterization that supports the stabilization aims, including intrinsic fluorescence, anisotropy, and measurements of aggregation and turbidity. Colloidal and particle properties are determined by DLS including Z-average and PDI, and potency and infectivity are assessed using FACS and TCID50, with virus titer and potency expressed using InfU/mL and TCID50/mL.

Sulfate-containing formulations, including sodium sulfate, Na2SO4, and other sulfate salts, are compared with controls without sulfate and with alternative salts. The patent describes reduced aggregation and reduced pH- and turbidity-related changes, together with retained potency and infectivity under accelerated stress, including elevated temperature, freeze-thaw, and agitation. The overall described approach is stabilization of poxvirus pharmaceutical compositions by combining a buffer with a sulfate salt at the specified pH and concentration ranges.

Claims Coverage

The independent claim covers a pharmaceutical composition defined by three elements: poxvirus, buffer, and a sulfate salt, together with defined pH and sulfate concentration ranges. Across the dependent claims, additional inventive features specify the poxvirus identity, buffer types and buffer concentrations, named sulfate salts, and further formulation constraints such as virus titer, liquid versus frozen form, and additional formulation components.

Overall claim coverage centers on stabilizing poxvirus pharmaceutical compositions by combining a buffer with a sulfate salt at defined sulfate and pH ranges, optionally specifying vaccinia or MVA, particular buffer types and concentrations, selected sulfate salts, and constraints on virus titer. A stabilization method is also covered by preparing the claimed composition.

Stated Advantages

Documented Applications