Understanding Nanobodies^®

Nanobodies^® are antibody-derived therapeutic proteins that contain the unique structural and functional properties of naturally-occurring heavy-chain antibodies. The Nanobody^® technology was originally developed following the discovery that camelidae (camels and llamas) possess fully functional antibodies that lack light chains. These heavy-chain antibodies contain a single variable domain (VHH) and two constant domains (C_H2 and C_H3). Importantly, the cloned and isolated VHH domain is a perfectly stable polypeptide harbouring the full antigen-binding capacity of the original heavy-chain antibody. These newly discovered VHH domains with their unique structural and functional properties form the basis of a new generation of therapeutic antibodies which Ablynx has named Nanobodies^®.

Ablynx’s Nanobodies^® combine the advantages of conventional antibodies with important features of small molecule drugs. Like conventional antibodies, Nanobodies^® show:

• high target specificity
• high affinity for their target
• low inherent toxicity.

However, like small molecule drugs they have the opportunity to inhibit enzymes and readily access receptor clefts. Furthermore, Nanobodies^®:

• are extremely stable
• have the potential to be administered by means other than injection
• are easy to manufacture.

Ablynx’s Nanobodies^® have a high homology with the VH domains of human antibodies and can be further humanised without any loss of activity. Importantly, Nanobodies^® have a low immunogenic potential, which has been confirmed in primate studies with Nanobody^® lead compounds.