The therapeutic potential of many ADCs that are currently in pre-clinical or clinical development, including FDA-approved ado-trastuzumab emtansine (Kadcyla®) suffered from very narrow therapeutic window. There is constant need in the ADC field for further improvement.

Many ADCs that are currently in pre-clinical or clinical development including FDA approved ado-trastuzumab emtansine (Kadcyla®), have very narrow therapeutic window and further improvements may be required to enhance the therapeutic potential. Many of those ADCs were produced by random conjugation to the surface lysines on an antibody to yield heterogeneous mixture that is very difficult to characterize and ensure batch to batch consistency. Site-specific conjugation has recently shown to eliminate heterogeneity, improve conjugate stability, and increase the therapeutic window. Herein, we developed a proprietary K-Lock™ conjugation method that is a linker-controlled, site-selective conjugation technology targeting 2 native Lys sites out of 80-90 Lys present in an antibody WITHOUT the need of antibody modification for cell engineering or enzymatic modification steps that are used in various site-specific conjugation strategies use of engineered cysteine residues, unnatural amino acids, and enzymatic conjugation through glycosyltransferases and transglutaminases. The generated ADCs have fewer regioisomers and lower DAR while maintaining comparable potency to ADCs generated from standard conjugation methods.