MorphoSys and Wacker show high yield expression of antibody fragments
Modern protein biopharmaceuticals, for example derived from antibodies, can pose a challenge for biomanufacturing due to the high volumes needed for therapeutic purposes. Compared with the more conventional small molecule pharmaceuticals, these bioproducts are a lot more costly to manufacture, largely because of the high-cost technology required for production. If they are produced using mammalian cell-based processes it adds considerably to the cost.
In future, these issues could become a historical footnote after a recent cooperation between two of Germany's biotech players, MorphoSys AG based in Munich working with Jena-based contract biomanufacturer Wacker Biotech GmbH.
A feasibility study conducted by Wacker Biotech on behalf of MorphoSys AG using Fab fragments, showed Wacker's E. coli secretion system could offer a far simpler and more cost-effective way of obtaining the high yields of antibody fragments needed for research, diagnostic and therapeutic applications. According to the terms of a joint agreement, MorphoSys gained rights 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, well established for production of monomeric proteins, has now shown for the first time by the feasibility study, commissioned by MorphoSys, that production of Fab antibody fragments is also possible.
Wacker's E. coli-based system was found to be highly effective in expressing a MorphoSys antibody fragment with therapeutic potential. Yields of secreted and active antibody fragments exceeded 2 grams per liter in the supernatant. This outcome is particularly interesting considering that the antibody fragments are assembled from two different sub-units while they also possess intramolecular disulfide bridges.
Wacker's system has already produced other proteins in yields as high as 7 grams per liter. Extracellular secretion makes purification of recombinant products comparatively straightforward so that the entire manufacturing process is far more efficient and cost effective.
Antibody fragments, a relatively new class of therapeutic, consist of engineered parts of whole antibodies. Several antibody fragment-based medicines are already undergoing phase III clinical trials. One therapeutic antibody fragment is currently marketed under the brand name ReoPro(R). Fragments have a number of advantages over whole antibodies, in particular, lower manufacturing costs and faster production cycles.
Pleased at the positive outcome of the cooperation and the results of the joint study, Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys AG considers that Wacker's unique secretion system provides the opportunity "to produce antibody fragments even more efficiently for our own purposes and for our partnered projects."
The successful cooperation with MorphoSys illustrates the advantage of Wacker Biotech's many years of experience in producing actives according to GMP standards, while also providing highly attractive expression systems. According to 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 promising candidate from the MorphoSys proprietary development pipeline - a HuCAL(R)-Fab antibody fragment. HuCAL(R) stands for Human Combinatorial Antibody Library and is meanwhile a state-of-the-art concept for the in-vitro production of highly specific human antibodies and antibody fragments for diagnostic and therapeutic purposes. HuCAL(R) technology offers a high-throughput process for the fast generation and selective optimization of antibodies.
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.
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Keywords : Wacker Morphosys Germany Biomanufacturing Contract Partnership Fab Antibody fragments Process improvement High yield Cost effective E. coli K12 secretion system
