Poster dedicated to Lock Release Technology presented at 14th Annual PEGS Boston Conference
Abstract – Solid-phase mediated antibody-drug conjugation (Lock-Release) was tested for it’s ability to improve process control & product quality (aggregation, level of residuals and overall yield) relative to standard solution phase conjugation.
Conjugations of maytansinoid, auristatin, duocarmycin and PDB payloads to native cysteines, lysines and engineered cysteines of trastuzumab and cetuximab, using 96 well plate, stirred batch and column modes, were used to test the general applicability of this system for antibody-drug conjugate manufacture.
In all combinations of antibody, conjugation method, payload type and Lock-Release mode, the immobilised (locked) antibody was restrained from self-interaction or aggregation during conjugation, consistently resulting in <1.0% soluble dimer over a range of drug-antibody ratios of 0.5 – 4.4. Post conjugation washing of locked ADC removed residual drug and solvent to below the limits of detection. Scalability and batch to batch variation was assessed over 10 lots and a 10 fold scale up, giving an average DAR of 3.6 (SD 0.08) , monomer level of 99.0% (SD 0.1%, all batches >98%). Structural and binding studies of lock-release ADC showed an equivalence to solution phase conjugations.