US 12,466,874 B2
Prevention of protein disulfide bond reduction
Sanjeev Ahuja, Gaithersburg, MD (US); Wai Keen Chung, Gaithersburg, MD (US); Deborah Sweet Goldberg, Gaithersburg, MD (US); Michael Handlogten, Gaithersburg, MD (US); Someet Narang, Gaithersburg, MD (US); Brian Russell, Gaithersburg, MD (US); Min Zhu, Gaithersburg, MD (US); Suzanne Hudak, Gaithersburg, MD (US); Kenneth Hwang, Gaithersburg, MD (US); and Jihong Wang, Gaithersburg, MD (US)
Assigned to MEDIMMUNE LLC, Gaithersburg, MD (US)
Filed by MEDIMMUNE LLC, Gaithersburg, MD (US)
Filed on Dec. 8, 2021, as Appl. No. 17/545,262.
Application 17/545,262 is a continuation of application No. 16/300,315, abandoned, previously published as PCT/US2017/031704, filed on May 9, 2017.
Claims priority of provisional application 62/334,136, filed on May 10, 2016.
Prior Publication US 2022/0098282 A1, Mar. 31, 2022
Int. Cl. C07K 16/00 (2006.01); A61K 39/395 (2006.01)
CPC C07K 16/00 (2013.01) [A61K 39/39591 (2013.01); C07K 2317/14 (2013.01); C07K 2317/40 (2013.01)] 13 Claims
 
1. A method for increasing the yield of an intact disulfide bond-containing antibody or antigen-binding fragment thereof in a cell culture or solution, comprising manufacturing the disulfide bond-containing antibody or antigen-binding fragment thereof in the presence of a glutathione reductase inhibitor, a thioredoxin reductase inhibitor, or both a glutathione reductase inhibitor and a thioredoxin reductase inhibitor,
detecting the presence of glutathione reductase and/or thioredoxin reductase in the culture or the solution containing the disulfide bond-containing antibody or antigen-binding fragment thereof, and
adding a glutathione reductase and/or thioredoxin reductase inhibitor to mitigate reduction of the disulfide bond-containing antibody or antigen-binding fragment thereof;
whereby the amount of intact disulfide bond-containing antibody or antigen-binding fragment thereof is higher in the cell culture or solution manufactured in the presence of a glutathione reductase inhibitor, a thioredoxin reductase inhibitor, or a glutathione reductase inhibitor and a thioredoxin reductase inhibitor as compared to the amount of intact disulfide bond-containing antibody or antigen-binding fragment thereof in a cell culture or solution not manufactured in the presence of a glutathione reductase inhibitor, a thioredoxin reductase inhibitor, or a glutathione reductase inhibitor and a thioredoxin reductase inhibitor.