US 12,012,629 B2
Continuous processing methods for biological products
Thomas C. Ransohoff, Lexington, MA (US); and Marc A. T. Bisschops, Breda (NL)
Assigned to Sartorius Stedim Chromatography Systems Ltd., (GB)
Filed by Sartorius Stedim Chromatography Systems Ltd., Royston (GB)
Filed on Sep. 24, 2020, as Appl. No. 17/030,731.
Application 17/030,731 is a continuation of application No. 13/991,604, abandoned, previously published as PCT/US2011/063598, filed on Dec. 6, 2011.
Claims priority of provisional application 61/420,066, filed on Dec. 6, 2010.
Prior Publication US 2021/0017561 A1, Jan. 21, 2021
Int. Cl. C12M 3/00 (2006.01); B01D 15/18 (2006.01); B01D 15/38 (2006.01); B01L 1/00 (2006.01); C07K 1/36 (2006.01); C07K 16/00 (2006.01); C12M 1/00 (2006.01); C12P 21/00 (2006.01); G01N 30/02 (2006.01)
CPC C12P 21/00 (2013.01) [B01D 15/1821 (2013.01); B01D 15/3804 (2013.01); C07K 1/36 (2013.01); C07K 16/00 (2013.01); C12M 23/44 (2013.01); C12M 47/10 (2013.01); C12M 47/12 (2013.01); G01N 30/02 (2013.01)] 8 Claims
OG exemplary drawing
 
1. A continuous processing system comprising:
(a) a first apparatus for carrying out a first unit operation comprising:
(1) a plurality of valve modules, each module having a central channel traversing the module and a plurality of branch channels connecting the central channel with an outside of the valve module, wherein each of the channels has at least one independently actuatable valve for independently opening or closing the channel, wherein the valve of the central channel separates an inlet end of the central channel from an outlet end of the central channel, wherein at least two branch channels connect separate inlets to the valve module with the central channel on an inlet side of the central channel valve and at least two branch channels lead from the central channel on an outlet side of the central channel valve to separate outlets from the valve module;
(2) a plurality of solution conduits, each conduit connecting to a separate branch channel of each valve module, and
(3) a plurality of chromatography columns, each column having an inlet and an outlet, wherein the column inlet is connected to the inlet end of a valve module central channel and the column outlet is connected to the outlet end of the central channel of a different valve module, such that the plurality of columns is connected in series through intervening valve modules and wherein the outlet of the last column in the series is connected, via an intervening valve module, to the inlet of a first column in the series;
(b) a second apparatus for carrying out a second unit operation comprising:
(1) one or more incubation receptacles each having at least one inlet and at least one outlet, wherein collectively the one or more incubation receptacles has at least the capacity to hold an output of the first unit operation;
(2) a valve module comprising an inlet and an outlet, an inlet channel connected to the valve module inlet, and one or more inlet branch channels connecting with the inlet channel, wherein each inlet branch channel leads from the inlet channel and connects to an inlet of one of the one or more incubation receptacles, wherein each of the inlet branch channels has at least one independently actuatable valve for independently opening or closing the channel, the valve module further comprising an outlet channel leading to the valve module outlet, and one or more outlet branch channels connecting with the outlet channel, wherein each outlet branch channel leads from the outlet channel and connects to an outlet of one of the one or more incubation receptacles, wherein each of the outlet branch channels has at least one independently actuatable valve for independently opening or closing the channel; and
(c) a third apparatus, for connecting the output of the first apparatus to the inlet of the second apparatus, the third apparatus comprising:
(1) a valve module providing at least five fluid transmission channels comprising a central channel traversing the valve module and having an inlet end and an outlet end, a priming channel connecting a separate inlet with the central channel, a surge receptacle inlet channel connecting a separate inlet with the central channel, a surge receptacle outlet channel connecting a separate outlet with the central channel, and a bypass channel connecting a separate outlet with the central channel, each of the five channels having at least one independently actuatable valve for independently opening or closing the channel, wherein the central channel inlet is connected to an outlet branch channel of each of the plurality of valve modules of the apparatus of the first unit operation, the priming channel inlet being suitable for receiving fluid for filling the priming channel and the central channel,
(2) at least one surge receptacle for regulating flow between unit operations and relieving back pressure, the surge receptacle having at least one inlet and at least one outlet, wherein the at least one inlet of the surge receptacle is connected to the surge receptacle outlet channel of the valve module, and the at least one outlet of the surge receptacle is connected to the surge receptacle inlet channel of the valve module, and wherein the at least one surge receptacle has the capacity to hold the output of the apparatus of the first unit operation, and wherein the central channel outlet of the valve module is connected to the inlet of the valve module of the apparatus for carrying out the second unit operation;
wherein the at least one surge receptacle further comprises a vent outlet, the vent outlet communicating an inside of the receptacle with the ambient environment.
 
8. A continuous processing system comprising:
(a) a first apparatus for carrying out a first unit operation comprising:
(1) a plurality of valve modules, each module having a central channel traversing the module and a plurality of branch channels connecting the central channel with an outside of the valve module, wherein each of the channels has at least one independently actuatable valve for independently opening or closing the channel, wherein the valve of the central channel separates an inlet end of the central channel from an outlet end of the central channel, wherein at least two branch channels connect separate inlets to the valve module with the central channel on an inlet side of the central channel valve and at least two branch channels lead from the central channel on an outlet side of the central channel valve to separate outlets from the valve module;
(2) a plurality of solution conduits, each conduit connecting to a separate branch channel of each valve module, and
(3) a plurality of chromatography columns, each column having an inlet and an outlet, wherein the column inlet is connected to the inlet end of a valve module central channel and the column outlet is connected to the outlet end of the central channel of a different valve module, such that the plurality of columns is connected in series through intervening valve modules and wherein the outlet of the last column in the series is connected, via an intervening valve module, to the inlet of a first column in the series;
(b) a second apparatus for carrying out a second unit operation comprising:
(1) one or more incubation receptacles each having at least one inlet and at least one outlet, wherein collectively the one or more incubation receptacles has at least the capacity to hold an output of the first unit operation;
(2) a valve module comprising an inlet and an outlet, an inlet channel connected to the valve module inlet, and one or more inlet branch channels connecting with the inlet channel, wherein each inlet branch channel leads from the inlet channel and connects to an inlet of one of the one or more incubation receptacles, wherein each of the inlet branch channels has at least one independently actuatable valve for independently opening or closing the channel, the valve module further comprising an outlet channel leading to the valve module outlet, and one or more outlet branch channels connecting with the outlet channel, wherein each outlet branch channel leads from the outlet channel and connects to an outlet of one of the one or more incubation receptacles, wherein each of the outlet branch channels has at least one independently actuatable valve for independently opening or closing the channel; and
(c) a third apparatus, for connecting the output of the first apparatus to the inlet of the second apparatus, the third apparatus comprising:
(1) a valve manifold providing at least three fluid transmission channels comprising a central channel traversing the valve manifold and having an inlet end and an outlet end, a priming channel connecting a separate inlet with the central channel, and a bypass channel connecting a separate outlet with the central channel, each of the channels having at least one independently actuatable valve for independently opening or closing the channel, the central channel inlet being suitable for receiving throughput from an upstream unit operation, and the priming channel inlet being suitable for receiving fluid for filling the priming channel and the central channel,
(2) at least one surge receptacle for regulating flow between unit operations and relieving back pressure, the surge receptacle having at least one inlet and at least one outlet, the at least one inlet of the surge receptacle being connected to the central channel outlet of the valve manifold, and the at least one surge receptacle having the capacity to hold the throughput of a unit operation connected to the valve manifold central channel inlet;
wherein the surge receptacle further comprises a vent outlet, the vent outlet communicating an inside of the receptacle with the ambient environment.