Biotech Values

[DewDiligence]

Structural difference between Lucentis and Avastin:



[Source: NEJM]

Following is an edited version of the caption
to the above graphic in the NEJM article:

“Ranibizumab [Lucentis] is a recombinant humanized monoclonal IgG1 kappa-isotype antibody fragment with a molecular weight of about 48 kD. It is produced in an E coli expression system (and thus is not glycosylated) and is designed for intraocular use. Bevacizumab [Avastin] is a recombinant humanized monoclonal IgG1 antibody with a molecular weight of about 149 kD [i.e. 3x the molecular weight of Lucentis]. It is produced in a Chinese-hamster-ovary mammalian-cell expression system (and thus is glycosylated) and is designed for intravenous infusion. Both the antibody fragment and the full-length antibody bind to and inhibit all the biologically active forms of VEGF-A and are derived from the same mouse monoclonal antibody. However, ranibizumab has been genetically engineered through a process of selective mutation to increase its affinity for binding and inhibiting the growth factor. The Fab domain of ranibizumab differs from the Fab domain of bevacizumab by six amino acids, five on the heavy chain (four of which are in the binding site) and one on the light chain. Not all the intermediate Fabs between the mouse monoclonal antibody and ranibizumab are shown [in this graphic].”