Method and apparatus for virus and vaccine production
AssigneeBiovest International, Inc.
InventorsMARK HIRSCHEL, ROBERT J. WOJCIECHOWSKI, JOSEPH DAVID GANGEMI, SCOTT WANIGER, KEVIN TACHENY, CHAD SINKLER, DARRELL P. PAGE, JEFF JORGENSEN, MICHAEL J. GRAMER, KIMBERLY ARNESON, GRANT ADAMS
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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.
Claims20
A method for the production of virus and virus-like particles (VLP), comprising culturing virus-infected cells in a cell culture bioreactor comprising a first compartment, a second compartment, and a membrane separating the first and second compartments, wherein the cells are cultured in the first compartment under conditions that allow for regulating the concentration of a molecule inhibitory to virus or VLP yield from the cells within the first compartment, and allow for production of the virus or VLP at a yield greater than that achieved in the absence of said regulation.
A method for regulating the concentration of a molecule inhibitory to viral yield or virus-like particle (VLP) yield in a first compartment of a bioreactor comprising the first compartment, a second compartment, and a membrane separating the first and second compartments, said method comprising the culturing virus-infected cells in the first compartment by adding cell culture medium to the first compartment and controlling how rapidly culture medium bearing the inhibitor molecule is replaced with fresh culture medium in the first compartment, or by diffusing one or more inhibitor molecules from the first compartment, through the membrane, into the second compartment.
An apparatus selected from among:
- a hollow fiber perfusion bioreactor for production of virus or virus-like particles (VLP), comprising semipermeable hollow fibers within a casing, wherein each of said hollow fibers comprise a lumen defining an intracapillary (IC) space, and wherein each of said hollow fibers have an exterior that, together with said casing, define an extracapillary (EC) space, and wherein at least a portion of said EC space or IC space is occupied by virus-infected cells producing virus or VLP;
- or
- an automated cell culture and purification apparatus for the production of virus and virus-like particles (VLPs), comprising:
- (a) a cell culture unit comprising:
- a first reusable instrumentation base device incorporating hardware to support cell culture growth;
- and
- at least one first disposable cell cultureware module removably attachable to said first instrumentation base device, said first cultureware module including a cell growth chamber;
- and
- (b) a purification unit linked to said cell culture unit, said purification unit comprising:
- a second reusable instrumentation base device incorporating hardware to receive fluid from said cell growth chamber of said cell culture unit;
- and
- at least one second disposable cell cultureware module removably attachable to said second instrumentation base device of said purification unit, said second cultureware module including a selection device.
An automated method for the production of virus and virus-like products (VLP) and purification thereof in a contaminant-free environment, comprising the steps of:
- providing at least one first disposable cultureware module, said first module including a cell growth chamber;
- providing a first reusable instrumentation base device incorporating hardware to support cell culture growth, said base device including a microprocessor control and a pump for circulating cell culture medium through the cell growth chamber;
- providing at least one second disposable cultureware module, said second cultureware module including a selection device (such as a purification column);
- providing a second reusable instrumentation base device incorporating hardware to receive fluid from the cell growth chamber;
- removably attaching said at least one first cultureware module to said first instrumentation base device;
- introducing cells into the cell growth chamber;
- fluidly attaching a source of cell culture medium to said at least one first cultureware module;
- programming operating parameters into the microprocessor control;
- operating the pump to circulate the cell culture medium through the cell growth chamber to grow virus-infected cells therein;
- loading the culture medium containing the virus or VLPs onto the selection device to absorb a virus or VLP onto the selection device;
- eluting the absorbed virus or VLP into an aqueous medium;
- and
- collecting the virus or VLP in a pre-sterilized collection vessel to form a purified product.
An automated method for producing an immunogenic composition such as a vaccine, comprising purifying a virus or virus-like particle (VLP) from a virus-containing fluid medium using an automated method for the production of virus and virus-like products (VLP) and purification thereof in a contaminant-free environment;
- and combining the virus or VLP with a pharmaceutically acceptable carrier, wherein the automated method comprises providing at least one first disposable cultureware module, said first module including a cell growth chamber;
- providing a first reusable instrumentation base device incorporating hardware to support cell culture growth, said base device including a microprocessor control and a pump for circulating cell culture medium through the cell growth chamber;
- providing at least one second disposable cultureware module, said second cultureware module including a selection device (such as a purification column);
- providing a second reusable instrumentation base device incorporating hardware to receive fluid from the cell growth chamber;
- removably attaching said at least one first cultureware module to said first instrumentation base device;
- introducing cells into the cell growth chamber;
- fluidly attaching a source of cell culture medium to said at least one first cultureware module;
- programming operating parameters into the microprocessor control;
- operating the pump to circulate the cell culture medium through the cell growth chamber to grow virus-infected cells therein;
- loading the culture medium containing the virus or VLPs onto the selection device to absorb a virus or VLP onto the selection device;
- eluting the absorbed virus or VLP into an aqueous medium;
- and
- collecting the virus or VLP in a pre-sterilized collection vessel to form a purified product.
Dependencies are inferred from the claim text.