Method and apparatus for antibody production and purification
Inventors
HIRSCHEL, Mark • Wojciechowski, Robert J. • Adams, Grant • Page, Darrell P. • ARNESON, KIMBERLY • JORGENSEN, JEFF • WANIGER, SCOTT
Assignees
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Publication Number
US-10570434-B2
Publication Date
2020-02-25
Expiration Date
Abstract
The subject invention pertains to methods and apparatus for the production and purification of cell products, such as immunoglobulins. One aspect of the invention is an integrated cell culture and purification apparatus for the growth and maintenance of cells and the harvest and purification of cell products, such as immunoglobulins. Thus, the apparatus integrates a cell culture function with a purification function. Other aspects of the invention pertain to an automated method for producing immunogenic compositions such as vaccines.
Core Innovation
The invention provides an automated method for producing cells and cell products and purifying them in a contaminant-free environment. The method uses a first disposable cultureware module with a cell growth chamber that forms part of a cell culture unit, supported by a first reusable instrumentation base device including microprocessor control and a pump for circulating cell culture medium through the cell growth chamber.
A second disposable cultureware module with a selection device forms part of a purification unit, and is supported by a second reusable instrumentation base device that receives fluid from the cell growth chamber through a fluid flow path between the cell culture unit and the purification unit. The reusable hardware includes valves and dual pumps for chromatography, and the purification unit includes a chromatography device, a diafiltration module that utilizes tangential flow filtration, an anion exchange filter, and a size-exclusion virus filter connected to the cell growth chamber by the fluid flow path.
The integrated workflow includes separating a component using the chromatography device, separating a component using the diafiltration module, separating a component using the anion exchange filter, and separating virus using the size-exclusion virus filter. The chromatography step includes loading culture medium containing the cell products onto the chromatography device to absorb a cell product, eluting the absorbed cell product into an aqueous medium, and collecting the cell product in a pre-sterilized disposable collection vessel to form a purified cell product.
Claims Coverage
The document contains one independent claim with multiple dependent claims that narrow or specify aspects of the cell product and purification devices.
Automated contaminant-free cell production and purification with disposable cultureware
An automated method for the production of cells and cell products and purification thereof in a contaminant-free environment, comprising providing a first disposable cultureware module including a cell growth chamber and providing a second disposable cultureware module including a selection device.
Modular reusable instrumentation with microprocessor control and fluid circulation
Providing a first reusable instrumentation base device incorporating hardware to support cell culture growth, the first reusable instrumentation base device including a microprocessor control and a pump for circulating cell culture medium through the cell growth chamber; wherein the first disposable cultureware module and the first reusable instrumentation base device are components of a cell culture unit.
Dual pump chromatography and valve-controlled circulation
The pump comprises dual pumps for chromatography, and the hardware of the first reusable instrumentation base device further comprises a plurality of valves; wherein the dual pumps and the plurality of valves circulate cell culture medium into and out of the cell growth chamber through the ports of the cell growth chamber.
Connected cell culture and purification units by a fluid flow path
Wherein the cell culture unit and the purification unit are connected by a fluid flow path there between, wherein the hardware of the second reusable instrumentation device receives fluid from the cell growth chamber through the fluid flow path.
Integrated purification train with chromatography, tangential flow diafiltration, anion exchange, and size-exclusion virus filtration
Wherein the selection device comprises a chromatography device, wherein the second disposable cultureware module further includes a diafiltration module that utilizes tangential flow filtration, an anion exchange filter, and a size-exclusion virus filter, wherein the chromatography device, diafiltration module, anion exchange filter, and size-exclusion virus filter are connected to the cell growth chamber of the cell culture unit by the fluid flow path.
Purification sequence resulting in collection in a pre-sterilized disposable vessel
Wherein the chromatography device separates a component from fluid received from the cell growth chamber; wherein the diafiltration module separates a component from fluid received from the chromatography device; wherein the anion exchange filter separates a component from fluid received from the diafiltration module or the chromatography device; and wherein the size-exclusion virus filter separates virus from fluid received from the chromatography device, the diafiltration module, or the anion exchange filter; and collecting the cell product in a pre-sterilized disposable collection vessel to form a purified cell product.
Chromatography-based capture and elution of cell product in aqueous medium
Loading the culture medium containing the cell products onto the chromatography device to absorb a cell product onto the chromatography device; eluting the absorbed cell product into an aqueous medium.
Independent inventive refinements for antibody-defined products and purification options
The dependent claims specify that the cell product is an antibody, and that the antibody comprises IgM, IgG, IgD, IgE, or IgA; and that the chromatography device includes hydroxyapatite resin. The dependent claims also specify selectable chromatography device modalities including affinity chromatography, immuno-affinity chromatography, ionic exchange chromatography, hydrophobic interaction chromatography, size-exclusion chromatography, or a combination of two or more of these.
Overall claim coverage centers on an automated contaminant-free method that integrates a disposable cell growth chamber supported by reusable microprocessor-controlled circulation hardware with a connected purification unit using chromatography, tangential flow diafiltration, anion exchange, and size-exclusion virus filtration, ending with collection of a purified cell product in a pre-sterilized disposable collection vessel. Dependent claims narrow the cell product to antibodies, specify particular chromatography options including hydroxyapatite resin, and provide named adjuvant options for conjugation where applicable.
Stated Advantages
Purifies cells and cell products in a contaminant-free environment.
Produces purified cell product by integrated purification steps connected to the cell growth chamber.
Uses a pre-sterilized disposable collection vessel to collect the purified cell product.
Separates virus using a size-exclusion virus filter as part of the purification train.
Documented Applications
Automated vaccine production using antibody purification and conjugation to adjuvants such as KLH.
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