AOC GMP Manufacture For A FIH Study

The successful development of antibody oligonucleotide conjugates (AOCs) for First-in-Human (FIH) trials requires robust Good Manufacturing Practice (GMP) processes and efficient scale-up. Manufacturing an AOC for a muscular dystrophy treatment involving a fragment antibody (fAb) conjugated to a phosphorodiamidate morpholino oligonucleotide (PMO) serves as a compelling example.

A key part of this process is developing the fAb intermediate, which involves selecting the optimum molecule based on manufacturability, immunogenicity, and function, supported by a specialized analytical platform. The fAb is manufactured using a platform process developed in-house. The overall AOC conjugation process is typically conducted over four to five days, involving pre-reaction to form a linker-oligo, conjugation with the fAb via lysine conjugation, and purification by ion exchange chromatography. Utilizing in-process checks (IPCs) throughout the entire conjugation process is vital for monitoring the course of the reaction, maximizing yields, and ensuring product stability, especially given the high cost of input materials.

Explore the full process flow and key considerations for cGMP bioconjugation.