12 Key Areas of Research and Development – Advancements in Healthcare Will Be Sweet ProBioGen AG is a specialist for the development and manufacturing of complex therapeutic glycoproteins and cell-based vaccines for clinical use. Combining both state-of-the-art development platforms together with intelligent product-specific technologies yields biologics with optimized properties. In the field of glycobiotechnology, the company has developed the GlymaxX ® technology to optimize cell lines producing therapeutic antibodies. Antibodies produced by GlymaxX ® -engineered cells contain a reduced amount of core-fucose and show an increased ability to recruit natural killer cells, a type of cytotoxic lymphocytes, mediating an efficient antibody dependent cellular cytotoxicity response. In addition, ProBioGen is based on a variety of proprietary technologies, e.g. to modulate the degree of galactosylation and sialylation to calibrate the desired glycosylation pattern of biosimilars and new biological entities. UGA Biopharma, a CRO in cell line development, offers ready-to-use biosimilar expressing cell lines and customized cell line development services for new biological entities (NBEs). Bioprocess optimization, downstream development and analytics are included. The success is based on the choice of an appropriate host cell line, optimized expression vectors and use of a proprietary, high-performance cell culture medium (optimized for the CHO platform). Chinese Hamster Ovary (CHO) clones are the most commonly used cell lines for the production of recombinant proteins. With a very streamlined workflow in hand, UGA Biopharma is seeking new cooperation partners for out-licensing existing research cell lines from the portfolio or starting a new development project for a biosimilar/ NBE expressing cell line together with clients. At the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Christian Hackenberger and his group study the biological role of protein glycosylation and other post-translational modifications and decorate proteins with fluorescent moieties that permit their visualization. In collaboration with Stephan Hinderlich, Beuth University of Applied Sciences Berlin, the scientists generate a repertoire of unnaturally modified glycoproteins by metabolic oligosaccharide engineering. These novel biopolymers will be investigated for the development of new diagnostic and therapeutic glycoproteins. Both groups also investigate the functional contribution of sialic acids to disease development. Research efforts focus on a specific enzyme, N-acetylmannosamine kinase, which plays a key role in the biosynthesis of sialic acids and glycosylation of proteins. Sialylated glycoconjugates affect a large number of biological processes, including immune modulation and cancer transformation. In searching for effective inhibitors of N-acetylmannosamine kinase the scientists apply high-throughput screening of drug-like small molecules. The comprehensive competence in the glycoengineering area has been enhanced by pronounced collaborative efforts of regional players in industry and academia that also include Charité – Universitätsmedizin Berlin, HTW Berlin – University of Applied Sciences, Max Planck Institute for Colloids and Interfaces, Fraunhofer Institute for Cell Therapy and Immunology and others.
Key Areas of Research and Development – Advancements in Healthcare Will Be Sweet 13 Carbohydrate Vaccines – A Promising Way to Prevent Infectious Diseases Vaccines represent the most powerful tool to combat infectious diseases and are indispensable in modern medicine. The benefits of immunization have saved millions of lives and today more than 70 vaccines are available to prevent infections from about 30 pathogens. Despite all medical progress, infectious diseases still remain a challenge. Carbohydrate vaccines open up a new pathway for rational vaccine design. Modern vaccination reaches back to the late 18th century when Edward Jenner first used a vaccine against smallpox. It was he who introduced the term “vaccine” since his inoculant derived from a virus affecting cows (Latin: vacca for cow). A hundred years later the Charité became renowned for this field of research. Robert Koch, Emil von Behring and Paul Ehrlich – all of them Nobel Prize Laureates in Physiology or Medicine in the first decade of the 20th century – received worldwide recognition for their breakthrough achievements in immunology. With the advancements of glycomics in recent times, the potential of glyco-conjugate vaccines soon became apparent as carbohydrates have a huge impact on pathogen-host interactions. The surface of microbes is covered with carbohydrates and the sugar residues build unique glycan epitopes which are key for the development of protective antibodies. The Max Planck Institute of Colloids and Interfaces (MPICI) is among the pioneers exploiting this area of research. In Peter Seeberger’s group “Glycobiology and Vaccine Development” scientists synthesize pathogen surface carbohydrates and evaluate them for potential applications in the field of vaccine development. The group currently focuses on chemical synthesis and biological evaluation of carbohydrates present on the bacteria Streptococcus pneumoniae, Klebsiella pneumoniae, Yersinia pestis, Chlamydia, Haemophilus influenzae, Neisseria meningitidis and Clostridium difficile as well as on surface carbohydrates of unicellular protozoa like Leishmania and Plasmodium falciparum which causes malaria. The most advanced project aims at developing a vaccine against Streptococcus pneumoniae a bacterium that causes lung infections. The Paul Ehrlich Institute already gave its go-ahead for a first clinical trial. Due to the promising results of research efforts, in 2015 the spin-off Vaxxilon AG was founded to drive forward the development and commercialization of carbohydrate vaccines. Peter Seeberger is also co-founder of BDW Berliner Diagnostik Werke GmbH, a company developing carbohydrate-based microarrays to determine general vaccination status as well as companion diagnostics for the vaccination status related to specific vaccines. Other regional players committed to vaccine development are the Beuth University of Applied Sciences and the Technical University of Applied Sciences Wildau. Their joint “Ipo- Gly” project aimed at developing glycoengineered vaccines integrating antigen and adjuvant functions in one molecule. Improved vaccine efficacy was achieved by atypical glycosylation of a recombinant protein of the respiratory syncytial virus, a pathogen causing severe infections of the respiratory tract in infants and in the elderly. “The German capital region is a global center of the glycosciences that span from basic research at universities and institutes to companies that translate those scientific breakthroughs into products. Access to defined glycans by automated chemical assembly has been the basis for the development of novel research tools, diagnostics and vaccines. Carbohydrate-conjugate vaccines can protect people from many bacteria including those that are responsible for resistant hospital acquired infections. The ability to protect millions of lives creates a multi-billion Euro market globally. Berlin provides a perfect stage for top scientists and entrepreneurs to pursue their dreams.” Peter Seeberger Director Max Planck Institute of Colloids and Interfaces / Co-Founder Vaxxilon AG