| abstract |
Erythropoietin glycoprotein conjugates are described, wherein the conjugates consist of an erythropoietin glycoprotein containing at least one free amino group and having in vivo biological activity that causes bone marrow cells to increase reticulocyte and red blood cell production, with glycoprotein being selected. a group consisting of human erythropoietin and its analogs, having the primary structure of human erythropoietin, modified by the addition of 1 to 6 glycosylation sites or by rearrangement of at least one glycosylation site; said glycoprotein is covalently linked to form one to three lower alkoxy-poly (ethylene glycol) groups, each poly (ethylene glycol) group being covalently attached to the glycoprotein, via a linker of formula -C (O) -XSY, wherein C (O) from the linker group forms an amide bond with one of said amino groups, and wherein X and Y have the meaning defined in the description of the invention and in the claims, the average molecular weight of each poly (ethylene glycol) residue is from about 20 kilodaltons to about 40 kilodaltons, and the average molecular weight of the conjugate is from about 51 kilodaltons to about 175 kilodaltons. |