Creative Biolabs is proud to introduce a unique therapeutic antibody discovery service: Humanization of Bovine Ultralong CDR3 Antibodies.
By merging the ultralong CDR3s discovered in bovine with human IgG scaffolds, novel therapeutic antibodies against challenging hot antigen families, including GPCRs and other intra-membrane targets on the cell surface are possible. Humanized IgG scaffolds that accommodate ultralong CDR3s may target small proteins with desirable therapeutic properties, which are challenging for conventional antibodies.
Advantage of Ultralong CDR3s
Evidence has shown that antibodies with unusually long CDR H3 regions may be a more effective defense against disease than typical antibodies. In cattle, 10% of antibodies have such ultralong CD3 H3 regions. Deep sequencing reveals a remarkable complexity of cysteines. Correspondingly, crystal structure reveals these CDR H3s form a very unusual architecture composed of a β strand “stalk” that supports a structurally diverse, disulfide-bonded “knob” domain, that can be elicited to recognize defined antigens. Through combinations of somatically generated disulfides, these ultralong CDR H3s can fold into a diversity of minidomains. These cow antibodies look interesting for their potential to zero on those targets that haven’t been successfully targeted by traditional antibodies, for example, the GPCRs, that have been intractable for antibody therapeutic development in the past.
Fig. 1 Model for Ultralong CDR H3 Diversification into Minifolds. (Wang et al. 2013)
Besides developing therapeutic monoclonal antibodies with ultralong CDR3s, Creative Biolabs has also established a platform to raise bovine monoclonal antibodies with ultralong CDR3s.