EP0317874A2
Expired / Lapsed
EP
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Continuous cell dispersion, cultivation and substance recovery system
Assignee: Bayer Corp
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Filing: 1988-11-15
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Granted: —
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Expires: 2008-11-15
Abstract
Abstract A system for continuous production and removal of a biological substance from a dispersed cell culture. The system comprises a reactor adapted to maintain the cell culture under incubating conditions and means for pumping limited volumes of the culture fluid from the reactor and through an external substance separation device adapted to extract the substance in a limited time on a continuous basis without collection of, or damage to, the dispersed cells. Less than 5% of the total culture fluid volume is outside the reactor (Volume outside or Vo) at any time and a given dispersed cell is outside the protective environment of the reactor for less than about two minutes, as expressed by the following relationship, In preferred embodiments the external device comprises a plurality of substance-extracting, porous, hollow fibers through which the culture fluid, substance, and dispersed cells are continuously passed. In other preferred embodiments, separate means for continuously dialyzing the culture fluid prior to its return to the reactor are provided.
Inventors
- 👤 Jürgen Trawinski
- 👤 Detmar Redeker
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-02 17:31
CPC Classifications
C; C12; C12M; C12M29/00; C12M29/18; C12M27/00; C12M27/02; C12M29/16; Y; Y10; Y10S; Y10S435/00; Y10S435/803; Y10S435/813
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
133 words
A system for continuously producing and separating a substance from a population of suspended cells expressing the substance, the system comprising: (a) a reactor including at least a portion of the cells in a culture fluid maintained under conditions sufficient to promote expression of the substance by the cells; (b) external means for continuously and relatively quickly moving a relatively small volume of the fluid, expressed substance, and dispersed cells through a separating device in fluid communication with and outside of the reactor, the device adapted to continuously separate at least a portion of the substance from the fluid while permitting substantially all cells to pass with at least a portion of the fluid through the device; and (c) means for returning the cells and fluid from the reactor to the first reactor.
Claim 2
Independent Claim
133 words
A system for continuously producing and separating a substance from a population of suspended cells expressing the substance, the system comprising: (a) a reactor including at least a portion of the cells in a culture fluid maintained under conditions sufficient to promote expression of the substance by the cells; (b) external means for continuously and relatively quickly moving a relatively small volume of the fluid, expressed substance, and dispersed cells through a separating device in fluid communication with and outside of the reactor, the device adapted to continuously separate at least a portion of the substance from the fluid while permitting substantially all cells to pass with at least a portion of the fluid through the device; and (c) means for returning the cells and fluid from the reactor to the first reactor.
Claim 3
Dependent Claim
29 words
The system of claim 1 wherein the relatively small volume of fluid outside the reactor at any given time is less than about 5% of the total culture fluid.
Claim 4
Dependent Claim
22 words
The system of claim 1 wherein the dispersed cells of step (b) are outside the reactor for less than about two minutes.
Claim 5
Dependent Claim
36 words
The system of claim 1 wherein the reactor is a stirred tank fermentor and the separating device comprises porous hollow fibers adapted to separate continuously at least about 40% of the substance passing through the device.
Claim 6
Dependent Claim
22 words
The system of claim 4 wherein the hollow fibers have an average pore diameter ranging from about to 0.2 to 0.6 um.
Claim 7
Dependent Claim
33 words
The system of claim 1 wherein dialysis means are included between the separator device exit and the reactor, the dialysis means being adapted to provide nutrients and remove wastes from the cultivation medium.
Claim 8
Dependent Claim
25 words
The system of claim 1 wherein the substance is a protein and the cells are mammalian cells that have been adapted to express the protein.
Claim 9
Dependent Claim
20 words
The system of claim 1 wherein the substance is an antibody and the cells are capable of expressing monoclonal antibodies.
Claim 10
Dependent Claim
15 words
The system of claim 1 wherein step (b) includes means adapted to disperse aggregated cells.
Claim 11
Independent Claim
116 words
A method of continuously producing and separating a biological substance comprising the steps of: (a) introducing into a reactor a dispersed cell culture and incubation fluid which includes a cell population capable of expressing the substance and maintaining the reactor under conditions to assure the expression of the substance; (b) continuously moving a portion of the fluid, including dispersed cells and the substance, through a separation device adapted to continuously separate at least some of the substance from the fluid while allowing the majority of the moving fluid and substantially all of the dispersed cells to pass through the separation device; (c) continuously returning the majority of the fluid and the dispersed cells to the reactor.
Claim 12
Independent Claim
116 words
A method of continuously producing and separating a biological substance comprising the steps of: (a) introducing into a reactor a dispersed cell culture and incubation fluid which includes a cell population capable of expressing the substance and maintaining the reactor under conditions to assure the expression of the substance; (b) continuously moving a portion of the fluid, including dispersed cells and the substance, through a separation device adapted to continuously separate at least some of the substance from the fluid while allowing the majority of the moving fluid and substantially all of the dispersed cells to pass through the separation device; (c) continuously returning the majority of the fluid and the dispersed cells to the reactor.
Claim 13
Dependent Claim
47 words
The method of claim 10 wherein the volume of culture fluid outside of the reactor is less than about 5% of the total culture fluid volume and a given dispersed cell is outside the reactor for less than about two minutes, as determined by the following relationship
Claim 14
Dependent Claim
36 words
The method of claim 10 wherein the reactor is a stirred tank reactor and the separating device comprises porous hollow fibers adapted to separate continuously at least about 40% of the substance passing through the device.
Claim 15
Dependent Claim
21 words
The method of claim 10 wherein the hollow fibers have an average pore diameter ranging from about 0.2 to 0.6 um.
Claim 16
Dependent Claim
10 words
The system of claim 10 wherein the substance is proteinaceous.
Claim 17
Dependent Claim
11 words
The system of claim 13 wherein the substance is an antibody.
Claim 18
Dependent Claim
20 words
The method of claim 10 wherein means for dispersing cell aggregates are disposed between the reactor and the separation device.
Claim 19
Dependent Claim
12 words
The method of claim 16 wherein the dispersing means is a pump.
References Cited (Backward Citations)
No citation records indexed.
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