Since 2004, we have been working on the development of a totally new way to engineer antibodies. We have realized that is it possible to introduce antigen binding sites into constant domains of antibodies by randomizing certain loop sequences in these domains and then selecting specifically binding domains from large surface display libraries. By this, it is possible to design so-called Fcabs, which are Fc fragments with antigen binding sites. An Fcab combines all attractive properties of a complete antibody (antigen binding, effector functions and long in vivo half life) in a molecule of only one third the size.
When an Fcab is used as a module in a complete immunoglobulin, an antibody is generated that has, in addition to its natural binding sites in the variable domains, an additional binding site in the constant domains. Due to this added functionality, which can be used for the design and engineering of bispecific or oligovalent monoclonal antibodies, this novel antibody format is called mab2.
It is also possible to engineer constant domains in Fab fragments, thus creating bispecific or bivalent Fabs with two independent binding sites.
We are using knowledge-based protein engineering methods as well as in vitro directed evolutionary methods to select and improve Fcabs with specific antigen binding properties. To achieve these aims, we employ yeast surface display as well as phage display methods, bacterial, yeast and mammalian cell expression systems, as well as standard biochemical and immunological analytical and preparative methods. An important aspect of our work is to analyze and improve the biophysical properties of selected antibodies and antibody fragments, by employing state of the art methods such as differential scanning calorimetry, circular dichroism spectroscopy, UV-VIS and fluorescence spectroscopy surface plasmon resonance and biolayer interferometry methods, isothermal titration calorimetry and many more.
Our Modular Antibody Engineering technology has led to the creation of f-star GmbH, a BOKU spin-off company (www.f-star.com) which was founded in 2006 by Florian Rüker, Gordana Wozniak-Knopp, Gottfried Himmler and Geert Mudde. f-star currently employs a staff of more than 20 and has raised more than 20 million Euro in public funding and venture capital.