US 12,110,330 B2
Compositions of programmed death receptor 1 (PD-1) antibodies and methods of obtaining the compositions thereof
Mark A. Brower, Bound Brook, NJ (US); Chung-Jr Huang, Berkeley Heights, NJ (US); Brian Wai Kwan, Parsippany, NJ (US); William Nicholas Napoli, Wayland, MA (US); Bhumit A. Patel, Edison, NJ (US); Nuno J. Dos Santos Pinto, Long Branch, NJ (US); Douglas Dennis Richardson, II, Collegeville, PA (US); and Sen Xu, Pine Brook, NJ (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US)
Filed on Jan. 27, 2022, as Appl. No. 17/586,109.
Claims priority of provisional application 63/143,461, filed on Jan. 29, 2021.
Prior Publication US 2022/0251205 A1, Aug. 11, 2022
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C12N 15/85 (2006.01)
CPC C07K 16/2818 (2013.01) [A61P 35/00 (2018.01); A61K 2039/505 (2013.01); C07K 2317/565 (2013.01); C07K 2317/94 (2013.01); C12N 2015/8518 (2013.01)] 32 Claims
 
1. A method of obtaining a purified composition comprising anti-human PD-1 antibodies or antigen-binding fragments thereof, wherein the anti-human PD-1 antibodies or antigen binding fragments thereof comprise a light chain variable region comprising three light chain CDRs comprising CDRL1 of SEQ ID NO:1, CDRL2 of SEQ ID NO:2 and CDRL3 of SEQ ID NO:3 and a heavy chain variable region comprising three heavy chain CDRs of CDRH1 of SEQ ID NO:6, CDRH2 of SEQ ID NO:7 and CDRH3 SEQ ID NO:8, comprising the steps of:
a) perfusing Chinese Hamster Ovary host cells in cell culture medium in a perfusion bioreactor by providing fresh medium at a rate of at least about 0.25-6.0 vessel volume per day (vvd), wherein the host cell comprises a polynucleotide encoding the light chain variable domain and a polynucleotide encoding the heavy chain variable domain, or a polynucleotide encoding the light chain variable domain and the heavy chain variable domain, of the anti-human PD-1 antibodies or antigen-binding fragments thereof, wherein a cell culture broth is formed in the perfusion bioreactor;
b) continuously harvesting the antibodies or antigen-binding fragments thereof from the cell culture broth to obtain a harvest cell culture fluid medium at a rate of at least about 0.25-6.0 vessel volume per day (vvd); and
c) continuously purifying the harvest cell culture fluid with an affinity chromatography step to obtain the purified composition.