Carbamylated Epo-Fc Fusion Protein
Polymun has developed a fusion protein consisting of the Fc domain and hinge region of human IgG1 and of two recombinant human EPO molecules. Carbamylation of EPO-FC fusion protein (cEPO-FC) retains the tissue protective action but prevents hematopoietic actions. This allows continuous therapy concepts without risk of thrombosis.
Fusions protein containing the constant region of IgG show prolonged half-lives compared with the parent protein and Fc regions allow receptor mediated uptake through the lungs which enables dosing by inhalation.
CEPO-FC was investigated in several animal models showing tissue- and neuroprotective effects. Impressive results were obtained for the treatment of Parkinson’s disease using the most accepted 6-OHDA rat model. In this model CEPO-FC conferred neuroprotective and neurorescue beneﬁts without the side effects associated with polycythemia (Tayra et al. 2013).
Tissue and neuroprotection was also demonstrated in models of ischemia/reperfusion (Simon et al. 2011) and spinal cord injury (unpublished data).
Erythropoietin fusion protein
granted by: AU 2008217202; CA 2,678,986; CN 200880005733.7; EA 017377; EP 1 961 821; IN 295813; KR 10-1539120; US 9,085,640
Hooshmandi E, Motamedi F, Moosavi M, Katinger H, Zakeri Z, Zaringhalam J, Maghsoudi A, Ghasemi R, Maghsoudi N (2018) CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Aβ-induced Memory Deterioration: A Behavioral and Molecular Study in a Rat Model of Aβ Toxicity. Neuroscience 388:405-417
Simon FH, Erhart P, Vcelar B, Scheuerle A, Schelzig H, Oberhuber A (2016) Erythropoietin preconditioning improves clinical and histologic outcome in an acute spinal cord ischemia and reperfusion rabbit model. J Vasc Surg 64(6):1797-1804
Matějková Š, Scheuerle A, Wagner F, McCook O, Matallo J, Gröger M, Seifritz A, Stahl B, Vcelar B, Calzia E, Georgieff M, Möller P, Schelzig H, Radermacher P, Simon F (2013) Carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine kidney ischemia/reperfusion injury. Intensive Care Med39(3):497-510
Thomas Tayra J, Kameda M, Yasuhara T, Agari T, Kadota T, Wang F, Kikuchi Y, Liang H, Shinko A, Wakamori T, Vcelar B, Weik R, Date I (2013) The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease. Brain Res 1502:55-70
Simon F, Scheuerle A, Gröger M, Vcelar B, McCook O, Möller P, Georgieff M, Calzia E, Radermacher P, Schelzig H (2011) Comparison of carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury. Intensive Care Med 37(9):1525-33
Schriebl K, Trummer E, Lattenmayer C, Weik R, Kunert R, Müller D, Katinger H, Vorauer-Uhl K (2006) Biochemical characterization of rhEpo-Fc fusion protein expressed in CHO cells. Protein Expr Purif 49(2):265-75
Trummer E, Fauland K, Seidinger S, Schriebl K, Lattenmayer C, Kunert R, Vorauer-Uhl K, Weik R, Borth N, Katinger H, Müller D (2006) Process parameter shifting: Part I. Effect of DOT, pH and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors. Biotechnol Bioeng 94(6):1033-44
Trummer E, Fauland K, Seidinger S, Schriebl K, Lattenmayer C, Kunert R, Vorauer-Uhl K, Weik R, Borth N, Katinger H, Müller D (2006) Process parameter shifting: Part II. Biphasic cultivation - a tool for enhancing the volumetric productivity of batch processes using Epo-Fc expressing CHO cells. Biotechnol Bioeng 94(6):1045-52