US 12,459,986 B2
System and method for characterizing drug product impurities
Shunhai Wang, Ossining, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Feb. 22, 2022, as Appl. No. 17/677,499.
Application 17/677,499 is a division of application No. 16/223,463, filed on Dec. 18, 2018, abandoned.
Claims priority of provisional application 62/743,632, filed on Oct. 10, 2018.
Claims priority of provisional application 62/610,029, filed on Dec. 22, 2017.
Prior Publication US 2022/0169704 A1, Jun. 2, 2022
Int. Cl. C07K 16/00 (2006.01); B01D 15/30 (2006.01); C07K 16/06 (2006.01); C12Q 1/6872 (2018.01); G01N 30/02 (2006.01); G01N 30/88 (2006.01); G01N 33/15 (2006.01); G01N 33/68 (2006.01)
CPC C07K 16/00 (2013.01) [B01D 15/305 (2013.01); C07K 16/065 (2013.01); G01N 33/15 (2013.01); G01N 33/6857 (2013.01); C07K 2317/14 (2013.01); C07K 2317/41 (2013.01); C07K 2317/50 (2013.01); C07K 2317/515 (2013.01); C07K 2317/55 (2013.01); C07K 2319/00 (2013.01); C12Q 1/6872 (2013.01); C12Y 305/01052 (2013.01); G01N 2030/027 (2013.01); G01N 2030/8831 (2013.01); G01N 33/6848 (2013.01)] 8 Claims
 
1. A method for characterizing low molecular weight protein drug impurities in a protein drug product sample comprising:
i) deglycosylating the protein drug product sample, wherein the protein drug product sample comprises a protein drug, low molecular weight protein drug impurities, and an excipient;
ii) separating deglycosylated protein components of the deglycosylated protein drug product sample by hydrophilic interaction chromatography;
iii) analyzing the separated deglycosylated protein components by mass spectroscopy to characterize the low molecular weight protein drug impurities in the protein drug product sample,
wherein the protein drug product sample comprises between 0.05% and 30.0% (w/w) of low molecular weight protein drug impurities, and
wherein the low molecular weight protein drug impurity is characterized as a low molecular weight protein drug impurity selected from the group consisting of free light chain, half antibody, H2L, H2, HL, HC, or a combination thereof.