	US 12,070,502 B2
	Process for reducing subvisible particles in a pharmaceutical formulation
Hanne Bak, New York, NY (US); John Mattila, Nyack, NY (US); Ning Li, New Canaan, CT (US); Xiaolin Tang, Old Tappan, NJ (US); Daniel B. Dix, LaGrangeville, NY (US); Chen Li, Pleasantville, NY (US); and William Markis, Passaic, NJ (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Apr. 8, 2019, as Appl. No. 16/377,371.
Application 16/377,371 is a continuation of application No. 14/878,079, filed on Oct. 8, 2015, granted, now 10,342,876.
Claims priority of provisional application 62/061,797, filed on Oct. 9, 2014.
Prior Publication US 2019/0231877 A1, Aug. 1, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/395 (2006.01); A61K 47/22 (2006.01); A61K 47/26 (2006.01)

CPC A61K 47/22 (2013.01) [A61K 39/39591 (2013.01); A61K 47/26 (2013.01)]

48 Claims

1. A method of preparing a formulated drug substance,

the method comprising:

co-purifying an antibody and a phospholipase B-like 2 protein (PLBL2) from a host cell to produce a composition comprising the antibody and the PLBL2;

separating the PLBL2 from the composition using hydrophobic interaction chromatography (HIC) to form an antibody composition;

combining the antibody composition with a fatty acid ester; and

storing a volume of the formulated drug substance at about 5° C. for 6 months, after which less than 10,000 particles having an average mean diameter of 2 microns or more are detectable in the stored volume,

wherein the formulated drug substance comprises:

the antibody at a concentration of at least 150 mg/ml; and

the fatty acid ester, present in an amount of about 0.2% by weight, based on a total weight of the formulated drug substance.