Research & Development
The molecular biochemistry department supports other departments by conducting analysis and developing assays to look at the functions of different proteins. For example, we have developed assays to look at fibrinogen fibres under a microscope; used a flow chamber model to investigate VWF under flow; and developed glycan assays to analyse post-translational modifications. We support our colleagues in production by analysing samples and identifying proteins by their molecular weight. We use a mass spectrometer for this, which also enables us to identify unknown proteins. We have also developed cell-based assays to understand the immunological properties of plasma proteins in general.
We play an important role in basic research for new product development, most recently in the development of a new subcutaneous recombinant FVIII product. It all started with a discussion and an idea of Christoph Kannicht, General Manager of Octapharma Biopharmaceuticals, to administer FVIII subcutaneously. When you inject small molecules, like peptides, they can go directly into the blood vessels, however large proteins like FVIII and VWF need to enter the circulation via the lymphatic system. The major challenge in the case of FVIII is to transport it into the blood. Because it is so “sticky”, when injected subcutaneously, FVIII adheres to membranes in the epidermis. When administered alone, FVIII has almost zero bioavailability, because it binds to cell membranes. Our idea was to administer FVIII with VWF because VWF blocks this binding, so allowing the FVIII to reach the patient’s bloodstream.
Sometimes you can become entirely absorbed in the laboratory or in your research, but we should never forget the real people we are helping.
Since I have worked extensively on VWF, we discussed what would be the perfect VWF part for this product. The VWF molecule contains different binding domains, one of which is the FVIII binding domain. You can make this domain longer or shorter and, depending on its size, its efficiency at blocking FVIII phospholipid binding domains is changed. We tested a number of fragments and discovered one to be especially good. This most dutiful fragment was tested in the first experiments for the proof of concept. In our R&D facility in Heidelberg, we produced recombinant fragments and tested them again. With recombinant production, you have the benefit of being able to improve your fragment. We modified the structure of the final fragment so that it has better properties; it is released slowly into the circulation and has prolonged half-life, meaning it circulates longer in the body, which in turn leads to half-life prolongation of the FVIII molecule.
Today, several parts of the development are running in parallel: the pharmacology and toxicology studies, upstream process development, development of purification, formulation development and R&D production batches.
Our work is never routine. I enjoy new challenges and working on new products. We have different fields of our research and co-operate and publish studies with excellent scientists outside of our company. Seeing the stories of the children whose lives are determined from the beginning by their illness, is very powerful. As a relatively new mother myself, this was a powerful reminder of the importance of our work. Sometimes you can become entirely absorbed in the laboratory or in your research, but we should never forget the real people we are helping. It’s amazing to do what you love, research and science, and help other people – it’s the ideal combination for me.
Research & Development