Transgenic plants are a novel route for production of protein-based APIs, including antibodies. Martin Lobedann, Ph.D., now a process expert at Bayer Technology Services. described work done for his doctoral thesis at the Fraunhofer Institute on the purification of a recombinant anti-HIV antibody, 2G12, which is manufactured in transgenic tobacco plants.
These plant-made pharmaceuticals (PMPs) may offer an economic route to biopharmaceuticals in the future. Partnered with the University of Aachen, this work is part of the EU-funded Pharma-Planta project that aims to advance PMPs.
Dr. Lobedann described the various downstream processing steps he developed for the purification of 2G12. First there was a dispersion and extraction step, followed by a four-step filtration. The first filtration stage removed fiber from the antibody-containing crude extract, followed by clarification with disposable filters. Antibody capture by protein A affinity chromatography, followed by ion-exchange chromatography in combination with virus filtration, was used for 2G12 isolation.
Finally, Dr. Lobedann carried out an UF/DF step for buffer exchange and concentration adjustment. Overall yield was 60%, which is 3.6 g of antibody from 216 kg of tobacco leaves; and 250 kg of leaf material can be processed in one working day. 2G12 is expected to enter Phase I soon.
The Pharma-Planta project, which has 39 partners, is not trying to compete with mammalian systems but rather aims to show that plants can produce antibodies under GMP conditions to initiate clinical trials. Possibilities for the future include using plants as vehicles for making vaccines as commodities or for manufacturing them simply and cheaply in emerging countries.