A study conducted by Wacker Biotech GmbH on behalf of MorphoSys AG using Fab fragments, has demonstrated that Wacker's E. coli secretion system can offer a far simpler way of obtaining high yields of antibody fragments, which are used for research, diagnostic and therapeutic applications.
Under the joint agreement, MorphoSys obtains the right to use Wacker's secretion system for antibody-fragment production in research quantities for therapeutic projects both on its own behalf and with its commercial partners.
Wacker's E. coli-based secretion system is a well established system for the production of monomeric proteins.
However, the feasibility study commissioned by MorphoSys proved that production of Fab antibody fragments is also possible.
Wacker's E. coli-based secretion system proved effective in the expression of a MorphoSys antibody fragment with therapeutic potential.
Yields of secreted and active antibody fragments exceeded 2 grams per liter in the supernatant. This result is especially remarkable since the antibody fragments are assembled from two different sub-units and have intramolecular disulfide bridges.
Wacker's system has already been used to produce other proteins in yields as high as 7 grams per liter.
Under the joint agreement, MorphoSys gains access to Wacker's secretion system for producing antibody fragments. MorphoSys application will focus on the research phase for antibody generation, in both of MorphoSys's operating units.
Antibody fragments are engineered parts of whole antibodies and a relatively new class of therapeutics.
Several antibody fragment based medicines are already undergoing phase 3 clinical trials; one therapeutic antibody fragment is currently marketed under the brand name ReoPro®.
“We are very pleased at the positive outcome of our cooperation and the scientifically remarkable results of the joint study,” says Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys AG.
“Wacker's unique secretion system gives us the opportunity to produce antibody fragments even more efficiently for our own purposes and for our partnered projects.”
“The successful cooperation with MorphoSys shows that Wacker Biotech not only offers years of experience in producing actives according to GMP standards, but also provides highly attractive expression systems,” says Dr. Thomas Maier, Managing Director of Wacker Biotech.
“Our innovative technology greatly reduces the cost-of-goods factor, creating substantial added value for customers.”
The study targeted a candidate from the MorphoSys proprietary development pipeline - a HuCAL® -Fab antibody fragment.
HuCAL® stands for Human Combinatorial Antibody Library and is a concept for the in-vitro production of highly specific human antibodies and antibody fragments for diagnostic and therapeutic purposes.
Wacker's proprietary E. coli K12-based expression system transfers recombinant proteins in native form to the fermentation broth during fermentation.
The system consists of specific expression plasmids and a proprietary E. coli K12 strain that transfers proteins from the periplasma into the medium in high yields. The E. coli strain is stable during fermentation.