Methods for the prevention of aggregation of viral components
Inventors
van't OEVER, Arend Gesinus • BAKKER, Wilfridus Adrianus Maria • THOMASSEN, Yvonne Elisabeth
Assignees
Nederlanden Volksgezondheid Welzijn en Sport VWS • Intravacc BV
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Publication Number
US-10080793-B2
Publication Date
2018-09-25
Expiration Date
Abstract
The present invention relates to a method for prevention and/or reduction of aggregation of viral components.
Core Innovation
The patent describes that aggregation of Enteroviral particles during purification is prevented or reduced by having a basic amino acid or a derivative thereof present at a defined concentration during at least a part of the purification. The basic amino acid or derivative is selected from arginine, lysine, histidine, arginine-HCl, lysine-HCl, histidine-HCl, agmatine, L-arginine ethyl ester dihydrochloride, tranexamic acid, DL-5-hydroxylysine hydrochloride, L-lysine methyl ester dihydrochloride, 3-methyl-L-histidine, salts thereof and combinations thereof, and is present between 0.5-1000 mM.
The method can include sequential steps of purifying Enteroviral particles, optionally inactivating the Enteroviral particles, and formulating the Enteroviral particles. The purification process maintains the basic amino acid or derivative during at least a part of the sequential steps to prevent or reduce aggregation of the Enteroviral particles.
The composition can be formulated as a vaccine or medicament, and an inactivated polio vaccine embodiment is described for Enteroviral particles. The description also states that aggregation reduction can be demonstrated and assessed for viral components, and that aggregation is reversible when the basic amino acid is removed by diafiltration.
Embodiments are described for non-enveloped and enveloped viruses, including poliovirus/IPV and influenza virus, in which improved viral recovery and purity are reported as outcomes of adding the basic amino acid or derivative during purification.
Claims Coverage
The patent includes two independent claims centered on using a basic amino acid or derivative at a defined concentration during purification to prevent or reduce aggregation of Enteroviral particles. Across the dependent claims, the inventive features are refined by specifying when the concentration is maintained, adding concentration thresholds and ranges, narrowing the Enteroviral particles to particular Enteroviruses or poliovirus serotypes, and specifying an Inactivated Polio Vaccine (IPV) embodiment.
Enteroviral particle purification with basic amino acid to prevent aggregation
Purifying Enteroviral particles from a medium containing Enteroviral particles during at least a part of the purification while a basic amino acid or a derivative thereof is present at a concentration between 0.5-1000 mM to prevent or reduce aggregation of the Enteroviral particles; wherein the basic amino acid or derivative is selected from arginine, lysine, histidine, arginine-HCl, lysine-HCl, histidine-HCl, agmatine, L-arginine ethyl ester dihydrochloride, tranexamic acid, DL-5-hydroxylysine hydrochloride, L-lysine methyl ester dihydrochloride, 3-methyl-L-histidine, salts thereof and combinations thereof; optionally inactivating the Enteroviral particles; and formulating the Enteroviral particles.
Adding basic amino acid during purification to prevent or reduce Enteroviral aggregation
Preventing or reducing aggregation of Enteroviral particles during purification by adding to a composition comprising Enteroviral particles a basic amino acid or derivative thereof selected from arginine, lysine, histidine, arginine-HCl, lysine-HCl, histidine-HCl, agmatine, L-arginine ethyl ester dihydrochloride, tranexamic acid, DL-5-hydroxylysine hydrochloride, L-lysine methyl ester dihydrochloride, 3-methyl-L-histidine, salts thereof and combinations thereof, wherein during at least a part of the purification the basic amino acid or derivative thereof is present at a concentration between 0.5-1000 mM to prevent or reduce aggregation of the viral component.
Across both independent claims, the core claim coverage is directed to maintaining or adding a basic amino acid or a derivative thereof at a concentration between 0.5-1000 mM during purification of Enteroviral particles to prevent or reduce aggregation, with optional inactivation and formulation and dependent refinements specifying particular Enteroviruses/poliovirus serotypes and an Inactivated Polio Vaccine (IPV) embodiment.
Stated Advantages
Prevents or reduces aggregation of Enteroviral particles during purification.
Improved viral recovery and reported outcomes including higher D-antigen yield/potency and better purity.
Aggregation is reversible when the additive is removed by diafiltration.
Documented Applications
Production of a composition comprising Enteroviral particles, including optional inactivation and formulation, for a vaccine or medicament; an Inactivated Polio Vaccine (IPV) embodiment is described.
Purification and formulation contexts described for Enteroviral particles and viral components, including non-enveloped and enveloped viruses, notably poliovirus/IPV and influenza virus.
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