Medically important proteins can take many forms. They can be ligands that are being overproduced by genetically damaged cells and generating uncontrolled cell division. They can stimulate an unmediated, aggressive attack by the immune system that causes excessive inflammation. They can be receptor proteins that are being over-expressed and catalyzing a dangerous surplus of regulatory proteins inside the cell.
Five Prime has developed a suite of screening and characterizing technologies that can identify these medically-relevant proteins without the limitations of traditional protein screening methods.
We design complex cell-based screens that better model the fundamental biological processes underlying the disease of interest, and adapt them to be compatible with our protein library. We have undertaken what we believe to be some of the most complex cell-based screens in high throughput with protein libraries, including screens with rare stem cells and combinations of diseased primary human cell types. We execute these screens on automated, state-of-the-art screening systems designed and built in-house and analyzed using software developed by us. To date, we have screened each of the proteins in our protein library in screens using approximately 50 different cell types.
Rapid In Vivo Protein Production System (RIPPS®)
Our rapid in vivo protein production system, or RIPPS®, enables us to produce and test the proteins in our library directly in vivo in virtually any rodent model of disease and in high throughput. RIPPS technology identifies new targets that cannot be easily identified in other ways. Further, RIPPS not only identifies novel targets for protein therapeutics—for example, targets for therapeutic antibodies—it can also identify proteins that are new therapeutics themselves because each protein in the library is tested for its ability to affect a disease in a rodent model. RIPPS avoids the costly and time-consuming process required for conventional in vivo testing of efficacy and safety that includes expression, scale up, purification, characterization and formulation of each protein one at a time. Using RIPPS, we have identified and validated dozens of new targets and protein drug candidates in rodent models of cancer, inflammatory disorders, muscle disease and other conditions.
Some proteins are referred to as ligands and exert their actions by binding to a receptor on a cell surface. In order to optimally treat some diseases, one must know the identity of both the receptor and the ligand. Our comprehensive collection of protein ligands and extracellular domains of cell surface receptors provides us with the ability to identify ligand and receptor pairs. Historically, this information has led to new therapeutic targets by identifying the best target in a disease pathway and has increased the probability of success of drug development by enhancing understanding of the mechanism of action of a therapeutic candidate. One early validation of our approach was our discovery of a new cytokine (interleukin 34) and identification of its surface receptor (colony stimulating factor receptor 1). This discovery spurred development of our antibody drug candidate FPA008, which entered into human clinical trials in late 2013.