Amgen Inc.
DOWNSTREAM PROCESSING OF BISPECIFIC ANTIBODY CONSTRUCTS

Abstract:

The present invention provides an improved manufacturing method for the production of bispecific antibody products, which comprise at least two binding domains. The process comprises at least the method comprising a step of refolding the construct, wherein one or more of the domains comprise a disulfide bond, and wherein the construct is contacted with a refolding buffer to refold the construct to its native form, the buffer comprising (i) a redox and/or oxidizing agent having a concentration of at least 0.1 mM and (ii) a chaotropic agent having a concentration >1 M, and wherein the pH of the refolding buffer corresponds to +/-4.5 of the pI value of the first domain or +/-4.0 of the pI value of the entire construct.