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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and neuroprotection was also demonstrated in models of ischemia/reperfusion (Simon et al. 2011) and spinal cord injury (unpublished data).

PATENTS

Erythropoietin fusion protein
granted by: AU 2008217202; CA 2,678,986; CN 200880005733.7; EA 017377; EP 1 961 821; KR 10-1539120; US 9,085,640

PUBLICATIONS

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