US 12,110,312 B2
Integrated continuous manufacturing of therapeutic protein drug substances
Konstantin Konstantinov, Bridgewater, NJ (US); Rahul Godawat, Bridgewater, NJ (US); Veena Warikoo, Bridgewater, NJ (US); and Sujit Jain, Bridgewater, NJ (US)
Assigned to Genzyme Corporation, Cambridge, MA (US)
Filed by Genzyme Corporation, Cambridge, MA (US)
Filed on Jun. 22, 2020, as Appl. No. 16/908,401.
Application 16/908,401 is a continuation of application No. 15/493,523, filed on Apr. 21, 2017, granted, now 10,711,034.
Application 15/493,523 is a continuation of application No. 14/645,138, filed on Mar. 11, 2015, granted, now 9,657,056, issued on May 23, 2017.
Application 14/645,138 is a continuation of application No. 14/195,481, filed on Mar. 3, 2014, granted, now 9,650,412, issued on May 16, 2017.
Claims priority of provisional application 61/856,390, filed on Jul. 19, 2013.
Claims priority of provisional application 61/775,060, filed on Mar. 8, 2013.
Prior Publication US 2020/0317726 A1, Oct. 8, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. B01D 15/18 (2006.01); B01D 15/32 (2006.01); B01D 15/34 (2006.01); B01D 15/36 (2006.01); B01D 15/38 (2006.01); B01D 15/42 (2006.01); C07K 1/16 (2006.01); C07K 1/18 (2006.01); C07K 1/22 (2006.01); C07K 1/36 (2006.01); C07K 16/00 (2006.01); C12M 1/00 (2006.01); C12N 9/00 (2006.01); C12N 9/24 (2006.01); C12N 9/40 (2006.01); C12P 21/00 (2006.01)
CPC C07K 1/22 (2013.01) [B01D 15/1807 (2013.01); B01D 15/1864 (2013.01); B01D 15/1871 (2013.01); B01D 15/327 (2013.01); B01D 15/34 (2013.01); B01D 15/362 (2013.01); B01D 15/363 (2013.01); B01D 15/3809 (2013.01); B01D 15/3814 (2013.01); B01D 15/422 (2013.01); C07K 1/16 (2013.01); C07K 1/18 (2013.01); C07K 1/36 (2013.01); C07K 16/00 (2013.01); C12M 23/52 (2013.01); C12M 47/10 (2013.01); C12M 47/12 (2013.01); C12N 9/00 (2013.01); C12N 9/2402 (2013.01); C12N 9/2465 (2013.01); C12P 21/00 (2013.01); C12P 21/005 (2013.01); C12Y 302/01022 (2013.01); C12Y 302/01045 (2013.01); C07K 2317/14 (2013.01)] 14 Claims
 
1. A process for manufacturing a recombinant therapeutic protein drug substance, the process comprising:
(a) introducing one or both of liquid culture medium or nutrients into a cell culture disposed in a perfusion bioreactor, wherein cells in the cell culture secrete a recombinant therapeutic protein;
(b) monitoring cell density in the cell culture disposed in the perfusion bioreactor;
(c) continuously flowing the cell culture from the perfusion bioreactor into a cell retention system;
(d) continuously removing a liquid comprising the recombinant therapeutic protein that is substantially free of cells from the cell retention system;
(e) feeding the liquid into a first multi-column chromatography system (MCCS);
(f) capturing the recombinant therapeutic protein in the liquid using the first MCCS; and
(g) purifying and polishing the recombinant therapeutic protein using a second MCCS, wherein the purifying is performed using a resin in the second MCCS that is different in chemical structure compared to the resin in the second MCCS used to perform the polishing.