Method and apparatus for virus and vaccine production
Inventors
HIRSCHEL, Mark • GANGEMI, JOSEPH DAVID
Assignees
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Publication Number
US-9732313-B2
Publication Date
2017-08-15
Expiration Date
Abstract
The invention concerns a bioreactor for production of virus and virus-like particles (VLPs), methods for production of virus and VLPs, methods for regulating the concentration of molecules inhibitory to viral and VLP yield in a cell culture chamber of a bioreactor, such as the extracapillary space of a hollow fiber bioreactor.
Core Innovation
The invention provides a method for the production of virus and virus-like particles (VLP) by culturing virus-infected cells in an apparatus having a hollow fiber bioreactor with an intracapillary space, an extracapillary space, and a hollow fiber membrane separating the intracapillary space and the extracapillary space. Cells are cultured in a culture medium in the extracapillary space, and the culture medium is circulated so that it passes through the hollow fiber membrane.
During circulation, the method reduces the concentration of a molecule in the culture medium that is inhibitory to virus or VLP yield from the cells in the extracapillary space. The reduction is performed by diluting or removing the inhibitory molecule from the extracapillary space, or by increasing or removing culture medium from the extracapillary space in a manner such that the inhibitory molecule is a size that prevents passage through the hollow fiber membrane to the intracapillary space.
Alternatively, the method reduces the inhibitory molecule by passing the culture medium through a membrane filter that specifically binds the inhibitory molecule. After the reduction step, the culture medium is recirculated through the bioreactor to improve virus or VLP yield by controlling molecules inhibitory to virus production within the bioreactor.
Claims Coverage
The document includes one independent claim covering the overall hollow-fiber perfusion bioreactor process for producing virus and/or VLP while reducing an inhibitory molecule to improve yield. The dependent claims further define how the inhibitory molecule is handled, refine inhibitory-molecule characteristics, and specify example virus contexts.
Hollow fiber bioreactor with IC/EC separation and circulating medium
Culturing virus-infected cells in a hollow fiber bioreactor comprising an intracapillary space, an extracapillary space, and a hollow fiber membrane separating the intracapillary space and the extracapillary space; circulating culture medium through the bioreactor such that the culture medium passes through the hollow fiber membrane, with cells cultured in the extracapillary space.
Reducing inhibitory molecule concentration from the extracapillary space
Reducing the concentration of a molecule inhibitory to virus or VLP yield from the cells in the extracapillary space by diluting or removing the inhibitory molecule, increasing or removing culture medium so that the inhibitory molecule is a size that prevents passage through the hollow fiber membrane to the intracapillary space, or passing the culture medium through a membrane filter that specifically binds the inhibitory molecule and recirculating the culture medium through the bioreactor.
Claim coverage centers on producing virus and/or VLP in an IC/EC hollow fiber bioreactor with recirculating culture medium and improving yield by reducing an inhibitory molecule concentration from the extracapillary space. The dependent claim set refines the inhibitory-molecule reduction by specifying dilution or removal, size-based blocking via membrane passage limits, or specific binding by a membrane filter.
Stated Advantages
Improves virus or VLP yield by reducing the concentration of a molecule inhibitory to virus or VLP yield.
Documented Applications
Production of virus and virus-like particles (VLP), including influenza virus (H1N1 and H5N1) as examples.
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