FDA-approved ADC, brentuximab vedotin (Adcetris®), is produced through reduction of four inter-chain disulfide bonds followed by partial maleimide conjugation to the exposed sulfhydryl groups. ADCs generated with this approach are polydisperse and the drug-antibody ratios (DAR) ranges from 0–8.
Our proprietary C-Lock™ conjugation method utilizes novel linker chemistry to reconnect the antibody heavy and light chains following the reduction of the inter-chain disulfide bonds. The crosslinking introduces one payload per reduced disulfide bond. The resultant ADCs possess enhanced stability in vitro and in vivo, with a probable improvement in PK and PD profile. The cross linking conjugation process can be optimized to consistently produce an ADC with DAR 4 in very high yield, thereby simplifying the purification and characterization process in ADC production.