Accelerate biotechnology

The E. coli platform for production of therapeutic antibody fragments

Meet the Expert: Pranav, Microbial Bioprocess Scientist

E. coli has been used as a platform for the production of therapeutic proteins since the late 1970’s. The organism is a well-known and cost-effective biological production factory for which many genetic tools and scale up cultivation strategies are available. As a matter of fact, around 30% of approved therapeutic products, mainly used for treatment of diabetes, cancer, cardiovascular diseases and infectious diseases are produced using E. coli. However, the E. coli machinery lacks certain enzymes pivotal for complex post translational modifications and therefore the platform is less suitable for the production of complex recombinant proteins and full-length antibodies.

Production of antibody fragments in E. coli

Full length recombinant antibodies represent one of the fastest growing classes of biopharmaceuticals. The downside is that the manufacturing of these antibodies is expensive, requires extensive production times, and yield relatively low product as they are currently made on mammalian cells. Therefore, the scientific community is actively pursuing research to identify whether antibody fragments can be engineered, that maintain the properties of full length antibodies, but which are significantly cheaper to manufacture. It is therefore that genetically improved E. coli strains are highly sought after. Next to mere price advantages, antibody fragments can also exert additional advantages over full length antibodies. For instance, in terms of tissue penetration, antibody fragments are smaller, generally lacking the Fc domain. Also, these characteristics can be an advantage for specific applications in therapeutics, like oncology and neurodegenerative diseases as well as in diagnostics, like radioimmunotherapy and radiology, where shorter serum half-lives are preferred. Finally, new technologies involving conjugation of antibodies fragments to other proteins, toxins or chemicals, and engineering multimeric forms (i.e. diabodies, triabodies) or new variants (i.e. minibodies) have helped to improve stability, increase avidity and broaden the therapeutic applications. Thus, for many indications, antibody fragments potentially provide an attractive alternative to full length antibodies.

Batavia Biosciences creates very cost-effective manufacturing processes for antibody fragments or any antibody that requires only limited post translational modifications. Hereto, my team and I have developed SCOPE® microbial fermentation technology, which allows for highly controlled protein expression and high yield production of functional antibody fragments.

SCOPE® technology

Our SCOPE® microbial fermentation technology comprises a set of unique, regulatory compliant, DNA expression vectors that can be used in combination with our pharmaceutical grade E. coli Coliath strains or any other E. coli strain. The DNA expression vectors are modular build, allowing rapid exchange of diverse elements such as promoters, origin of replication, leader sequences and antibiotic resistance markers. This results in a set of plasmids that can be used to rapidly adapt SCOPE® to any specific need based on the characteristics of the antibody fragment or other protein to be expressed. The SCOPE® technology has proven to provide high product yield and tight control of expression for proteins previously considered difficult for expression in E. coli. Our SCOPE® technology works seamlessly with our upstream-downstream process development know-how and corresponding analytics. We are thus well set to provide a complete manufacturing package for antibody fragment based products.

As a company dedicated to help bringing biopharmaceuticals to the market at higher speed, with reduced costs, and with a higher success rate, Batavia Biosciences has vast experience in developing microbial strains and corresponding bioprocesses. With our team of experienced researchers, using the newest technologies and techniques, we are well equipped to take on any challenge associated with microbial based biopharmaceuticals.

 

SCOPE® technology: recombinant protein production

Microbial vaccines & proteins

Cell Culture & Microbial Medium Optimization