US 12,351,602 B2
Methods of inactivating viral contaminants
Filipa Abrantes, La Chaux-de-Fonds (CH); Sonia Letestu, La Chaux-de-Fonds (CH); Laure Cahuzac, La Chaux-de-Fonds (CH); and Lionel Duarte, La Chaux-de-Fonds (CH)
Assigned to Ichnos Sciences SA., La Chaux-de-Fonds (CH)
Appl. No. 16/641,281
Filed by Ichnos Sciences SA, La Chaux-de-Fonds (CH)
PCT Filed Aug. 27, 2018, PCT No. PCT/IB2018/056502
§ 371(c)(1), (2) Date Aug. 5, 2020,
PCT Pub. No. WO2019/038742, PCT Pub. Date Feb. 28, 2019.
Claims priority of application No. 17188012 (EP), filed on Aug. 25, 2017.
Prior Publication US 2020/0369747 A1, Nov. 26, 2020
Int. Cl. C07K 16/06 (2006.01); A61K 39/395 (2006.01); C07K 1/18 (2006.01); C07K 1/22 (2006.01); C07K 1/34 (2006.01); C07K 1/36 (2006.01); C07K 16/00 (2006.01)
CPC C07K 1/22 (2013.01) [A61K 39/395 (2013.01); A61K 39/39591 (2013.01); C07K 1/18 (2013.01); C07K 1/34 (2013.01); C07K 1/36 (2013.01); C07K 16/00 (2013.01); C07K 16/065 (2013.01); C07K 2317/14 (2013.01); C07K 2317/31 (2013.01)] 12 Claims
 
1. A method of production of a bulk drug substance comprising a therapeutic antibody, wherein the method comprises the steps of:
(a) subjecting a harvested antibody material to Protein A chromatography;
(b) incubating the resulting Protein A eluate at a high pH;
(c) neutralizing the resulting viral inactivated solution to pH 5.5, followed by 0.2 um filtration;
(d) subjecting the neutralized viral inactivated Protein A eluate to cation exchange chromatography, followed by 0.2 um filtration;
(e) concentrating the cation exchange chromatography eluate by ultrafiltration and continuous diafiltration, followed by 0.2 um filtration;
(f) purifying the product by anion exchange chromatography in flow through mode, using membrane adsorption, followed by 0.2 um filtration;
(g) removing virus by nanofiltration;
(h) concentrating the product by ultrafiltration and continuous diafiltration into pre-formulation buffer, followed by 0.2 um filtration;
(i) adding excipients to achieve about 6 mg/mL of the product in the final formulation buffer, by mixing about 5 mM L-Histidine, about 150 mM L-Arginine Monohydrochloride, about 15% Sucrose, and about 0.06% Polysorbate 80, at pH of about 6.0, followed by 0.2 um filtration; and
(j) filling the product into sterile bags, followed by freezing and storage at −80±20° C.