Anti-TNFα domain antibody construct CEP-37247 Full antibody functionality at half the size

We report preclinical data for CEP-37247, the first human framework domain antibody construct to enter the clinic. At approximately 11-13 kDa, domain antibodies or dAbs are the smallest antibody domain able to demonstrate the antigen-recognition function of an antibody, e.g., high selectivity and affinity for target antigen. CEP-37247 is a bivalent antitumor necrosis factor (TNF)alpha domain antibody protein construct combining the antigen-recognition function of a dAb with the pharmacological advantages of an antibody Fc region. As a homodimer, with each chain comprising V-L dAb, truncated C(H)1, hinge, C(H)2 and C(H)3 domains, CEP-37247 has a molecular mass of approximately 78 kDa, which is about half the size of a conventional IgG molecule. Surface plasmon resonance data demonstrate that CEP-37247 possesses high selectivity and affinity for TNF alpha. CEP-37247 is a potent neutralizer of TNF alpha activity in vitro in the L929 TNF mediated cytotoxicity assay. In a human TNF alpha-overexpressing mouse model of polyarthritis, CEP-37247 prevents development of disease and is at least as effective as the marketed product etanercept. Fc functionality is intact-CEP-37247 is capable of mediating antibody-dependent cell-mediated cytotoxicity and has a circulating half-life of approximately 4.5 days in cynomolgus macaques. Given the favorable properties outlined above and its high expression levels (approaching 7 g/L) in a CHOK1 based-expression system, CEP-37247 is progressing into the clinic where other potential advantages, such as enhanced efficacy due to improved tissue distribution and beneficial immunogenicity profile, will be evaluated.