Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG.

ABSTRACT: Bispecific antibodies enable unique therapeutic approaches but it remains a challenge to produce them at the industrial scale, and the modifications introduced to achieve bispecificity often have an impact on stability and risk of immunogenicity. Here we describe a fully human bispecific IgG devoid of any modification, which can be produced at the industrial scale, using a platform process. This format, referred to as a ??-body, is assembled by co-expressing one heavy chain and two different light chains, one ? and one ?. Using ten different targets, we demonstrate that light chains can play a dominant role in mediating specificity and high affinity. The ??-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Thus, the ??-body represents a unique, fully human format that exploits light-chain variable domains for antigen binding and light-chain constant domains for robust downstream processing, to realize the potential of bispecific antibodies.

SUBMITTER: Fischer N 

PROVIDER: S-EPMC4339886 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature