The present invention relates to a separation of viruses of an essentially spherical shape from viruses with a rod-like shape that are comprised in a sample, wherein the sample comprising the viruses is subjected to filtration.

The present invention provides a method for purification of a virus or virus antigen comprising providing a virus preparation and centrifugation of said virus preparation in a gradient of a sugar established by the addition of two or more buffered sugar layers of different concentration. The method leads to higher yields and reduces unwanted aggregation of the virus or virus antigen by increasing the volume of the peak pool.

A method for stably and easily producing a parvovirus having a high infectivity titer is provided. The problem is solved by a method for producing a parvovirus having an infectivity titer as high as 10.sup.8 TCID.sub.50/mL or more in a culture supernatant, comprising the steps of inoculating a seed virus of the parvovirus into a culture substrate comprising host cells having a cell density of 1/500 to 1/20 of the cell density of the host cells confluently grown and a medium at a multiplicity of infection of 0.0001 to 0.1, culturing for a period of 5 to 11 times the doubling time of the host cells, and recovering a culture supernatant.

The present invention provides a reproducible, effective and scalable process for the purification of (infectious) parvovirus H-1 particles. The purification process allows the separation of empty particles from particles containing a full genome and is compatible with large-scale H-1PV production for clinical applications.

The present invention provides a robust single clone Master Cell Bank (MCB) for an optimized production of H-1 parvovirus (H-1 PV) which is suitable to increase infectious parvovirus production compared to standard producer NB-324K mixed cells.

Described is an optimized process for parvovirus production including an essentially serum-free medium which is suitable to increase parvovirus production compared to a standard medium, preferably for H-1PV production.

The present invention is directed to methods for increasing the efficiencies with which recombinant adeno-associated virus (rAAV) are packaged, so as to increase their production titers. More specifically, the invention relates to a method for increasing the production titer of rAAV by transfected cells by increasing the ionic strength of the cell culture media through the administration of additional ions.

The invention provides methods of reducing fouling of ultrafiltration membranes in processes wherein virus particles are removed from aqueous solutions comprising virus particles and at least one protein by adding a surfactant or non-surfactant, non-ionic agent to the aqueous solution prior to filtration. The invention also provides methods to dissociate protein aggregates or to reduce the formation of protein aggregates by adding a surfactant or non-surfactant, non-ionic agent to the protein solution.

The embodiments provide a modified filter membrane for separating a crude solution of a biological product and a viral contaminant. The filter membrane has a cellulosed based porous surface, and at least one divalent metal ion bound to the cellulose based porous surface of the filter membrane to form a modified filter membrane cellulose based porous surface, wherein the modified cellulose based porous surface separates the crude solution by retaining a viral contaminant greater than 15 nm in diameter while allowing a biological product smaller than 15 nm in diameter to pass through. The embodiments also provide a method of filtering a crude solution of a biological product and a viral contaminant using a modified filter membrane by adding a divalent metal ion to a filter membrane porous surface to form a modified filter membrane porous surface with a pore size in the range of 1 to 15 nm in size, and filtering the crude solution of the biological product and the viral contaminant through the porous surface of the modified filter membrane, wherein the modified filter membrane retains the viral contaminant on the porous surface while allowing the biological product to pass through.

Provided are a parvovirus derived from an unconcentrated cell culture supernatant, having a infectivity titer of 10.sup.9 TCID.sub.50/mL or more and an {infectivity titer (TCID.sub.50/mL)}:{impurity protein concentration (ng/mL)} ratio more than 5000:1; and a method of producing such a high-infectivity titer and high-purity parvovirus.