Structural understanding of stabilization patterns in engineered bispecific Ig-like antibody molecules
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Updated: Jun 21, 2026

Laboratory Scale Production and Purification of a Therapeutic Antibody
Published on: January 24, 2017
Jacob L Jordan1, Joseph W Arndt, Karl Hanf
1Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Abstract:
Bispecific immunoglobulin-like antibodies capable of engaging multiple antigens represent a promising new class of therapeutic agents. Engineering of these molecules requires optimization of the molecular properties of one of the domain components. Here, we present a detailed crystallographic and computational characterization of the stabilization patterns in the lymphotoxin-beta receptor (LTbetaR) binding Fv domain of an anti-LTbetaR/anti-TNF-related apoptosis inducing ligand receptor-2 (TRAIL-R2) bispecific immunoglobulin-like antibody. We further describe a new hierarchical structure-guided approach toward engineering of antibody-like molecules to enhance their thermal and chemical stability.
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