United Kingdom (UK)
Recombinant monoclonal antibody to ADAMTS5. Manufactured using AbAb’s Recombinant Platform with variable regions (i.e. specificity) from the hybridoma 7B4.
UniProt Accession Number of Target Protein: Q9UNA0
Alternative Name(s) of Target: A disintegrin and metalloproteinase with thrombospondin motifs 5; Aggrecanase; ADAM-TS 5; ADAM-TS5; ADAMTS-5; A disintegrin and metalloproteinase with thrombospondin motifs 11; ADAM-TS 11; ADAMTS-11; ADMP-2; Aggrecanase-2; 7B4.1E11
Specificity: The antibody is specific for ADAMTS5 and it recognises an epitope within the catalytic and disintegrin domains (amino acids 262-576). ADAMTS-5 is a protease involved in cartilage degradation in human OA patients.
Application Notes: The antibody was characterized for binding affinity, species cross-reactivity and domain specificity. The antibody showed inhibitory potency (IC50) of 41.26 nM and humanization improved potency to 11.12 nM. The affinity of the original antibody and humanized version was measured, Kd= 0.280 nM and 0.205 nM respectively. Epitope mapping and selective binding to purified recombinant ADAMS5 were profiled by DELFIA. Selective binding of the antibody is demonstrated by immunocytochemistry using ADAMTS-5 and CHO cells. The antibody inhibited aggrecanolysis from human OA cartilage explants. The ability of the antibody to engage its target in vivo was assessed using labeled antibody in a preclinical OA model and whole body imaging was used to monitor biodistribution and cartilage penetration. The antibody treatment suppressed joint disease severity and mechanical allodynia. The crystal structure of the Fab fragment was determined (Larkin et al., 2015; PMID: 25800415).
Antibody first published in:
Larkin et al. Translational development of an ADAMTS-5 antibody for osteoarthritis disease modification. Osteoarthritis Cartilage. 2015 Aug;23(8):1254-66. PMID:25800415
Note on publication:
The paper describes the generation and characterization of the antibody.