Patent ID: 6620916
Filing Date: 2003-09-16
Classification: A61K,A61P,C07H,C07K

Abstract:
A process for producing a modified physiologically active protein comprising:(a) reacting a physiologically active protein with a terminal amino group of a branched chain ligand, in the presence of transglutaminase obtained from a microorganism, for a time and under conditions effective to form an amide bond between the &ggr;-carboxamide group of a glutamine residue in said protein and the terminal amino group in said branched chain ligand; wherein the physiologically active protein has a molecular weight of 1-200 kD and contains at least one glutamine residue; the branched chain ligand contains a galactose (Gal) or N-acetyl galactosamine (GalNac) group and an amino acid derivative containing an amino group, and said ligand bears a terminal amino group which becomes a substrate for the transglutaminase; and (b) isolating the modified physiologically active protein, of which binding affinity for an asialoglycoprotein receptor present on the surface of a hepatocyte is lower than the binding affinity of an asialoorosomucoid for said receptor, with the proviso that said branched chain ligand is other than that of formula (V) or (XVIII)