Synageva Expression Platform
The foundation of Synageva’s expression platform is an integrated system of proprietary vectors and methods that allow high levels of expression of the therapeutic protein of interest in hen oviduct cells. This leads to the secretion and packaging of the therapeutic protein into egg white (EW), which is a much more protein friendly environment than the conditioned media of conventional cell culture fermentation. The protein matrix of EW allows bulk storage of unpurified EW for prolonged periods and is one of a number of production advantages of the Synageva platform. In contrast to mammalian cell culture based approaches which utilize immortalized cell lines with high genetic and epigenetic instability, Synageva’s proprietary vectors incorporate the gene of interest into the genome of genetically stable normal oviduct cells. The importance of this cellular environment for therapeutic protein expression is highlighted by the tight consistency of post-translational modification, including glycosylation, seen in proteins manufactured using the Synageva platform. Furthermore, Synageva’s technology yields consistent expression levels and quality of protein across production lines and multiple generations.
Synageva’s proprietary technology allows for the production of proteins with glycosylation patterns that are suitable for many different diseases without a requirement for additional processes either during manufacturing (inhibition of specific glycosylation enzymes) or during post purification (enzymatic removal of terminal sugars) to modify terminal glycan structures impacting biodistribution. Furthermore, unlike some alternative expression platforms, Synageva’s expression system produces proteins with ‘human like’ glycan structures and does not incorporate non-human sugars into glycans.
Manufacturing and Supply
Synageva has demonstrated that its platform has the ability to successfully produce a wide array of therapeutic proteins, including therapeutic enzymes, cytokines, monoclonal antibodies and fusion proteins. In addition, investigational products produced using Synageva’s system have been included in a number of phase 1 studies and a phase 2 study conducted in the U.S., EU, and India. In total, the studies included more than 200 patients. The regulatory clearance for these studies included detailed considerations related to the manufacturing platform resulting in regulatory familiarity with the expression system. The phase II study mentioned above was a global multicenter clinical trial investigating the use of glycosylated recombinant human granulocyte colony stimulating factor (“G-CSF”) in 189 breast cancer patients with chemotherapy induced neutropenia. The overall safety and efficacy profile was comparable to the characteristics of Neupogen® (filgrastim) and no patient dosed with Synageva’s product showed evidence of antibody seroconversion during extended follow-up out to 12 months after initiation of dosing.