Objective

Blood brain barrier (BBB) remains to be a major hurdle in delivery of antibody-based therapeutics to the brain. The barrier prevents large molecules from penetrating the tissue leaving many therapeutic oncology and neurology targets beyond biologics’ reach. To tackle the BBB penetration, we used proprietary nurse shark-based single domain antibody discovery platform. There are numerous advantages of using variable new antigen receptor (VNAR) platform in therapeutic development process, just to mention small size, reduced complexity, increased stability and consequently the ease of engineering as multi-valent and multi-specific therapeutics. To identify BBB shuttle, we used proprietary phage display libraries in combinatorial in vitro and in vivo selection process. The selected clone (clone C) was shown to bind TfR1 and was cross-species reactive; it efficiently penetrated across BBB into parenchyma, delivering therapeutic antibodies and enzymes.