ABSTRACT
Manufacturer: Roche Diagnostics GmbH, Sandhofer Strasse 116, 68305 Mannheim, Germany, https://www.rochediagnostics.com/ (E.U. and U.S.)
Marketing: Roche Registration Limited, 40 Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AY, U.K., https://www.roche.com/ (E.U.) Centocor, Inc., 200 Great Valley Parkway, Malvern, PA 19355, https://www.centocor.com/ (U.S.)
Manufacturing
Rapilysin is a recombinant nonglycosylated form of the human tPA. It consists of the kringle-2 domain, related to the activity of the molecule, and the serine protease domain of the natural protein, while lacking the kringle-1, finger, and epidermal growth factor domains of native tPA. The modified gene is encoded on a plasmid that is transformed into E. coli cells, with a helper vector used to increase the stability of the construct. The protein is expressed in the bacterial strain and aggregates in the cells in the form of inclusion bodies. After isolation of inclusion bodies, protein solubilization and denaturation are carried out under reducing conditions, followed by renaturation in the presence of glutathione in order to obtain the active protein. Misfolded molecules are removed via chromatographic steps and filtration procedures. The final formulation includes the active substance reteplase and the following excipients: tranexamic acid dipotassium-hydrogen phosphate, phosphoric acid, sucrose, and polysorbate 80. The product is presented in a lyophilized form to be reconstituted using the solvent provided
Overview of Therapeutic Properties
Rapilysin a faster plasma clearance and a shorter half-life. This allows for a two-dose administration with a 30-minute interval (which is significantly shorter than the 90minute interval observed with the natural molecule) and for increased efficacy. Furthermore, Rapilysin binds to fibrin less tightly than the natural molecule, thus allowing better diffusion throughout the clot.
