Development of long-acting polymer-single domain antibody conjugates to inhibit neutrophil elastase in COPD

Mireille Dumoulin – Research Associate, ULiège; Francisco Javier Morales Yánez – Postdoctoral researcher, ULiège; Rita Vanbever – Professor and Research Director, UCLouvain; Jessica Vanderstraeten – Postdoctoral researcher, UCLouvain

Introduction: Neutrophil elastase (NE) causes lung destruction and perpetuates inflammation in chronic obstructive pulmonary disease (COPD) [1]. We generated a single domain antibody (sdAb), NbE201, able to tightly, selectively and competitively inhibit NE [2]. However, its small size is responsible for its rapid clearance in vivo. To increase NbE201 half-life, we conjugated it to a polymer: PAS, XTEN or polyethylene glycol (PEG) [3,4]. The first two are polypeptides, whereas the last one is a non-biodegradable polymer. The production of the polymer-NbE201 conjugates has been optimized and we have characterized their physico-chemical and biological properties in vitro.