abstract |
The present invention relates to a method for modulating (eg, reducing) the mannose content, particularly the high mannose content of recombinant glycoproteins. In one aspect, the present invention regulates the mannose content (ie, on the oligosaccharide side chain) of a recombinant glycoprotein produced in a mammalian host cell by manipulating cell culture conditions, resulting in production by that cell. A method is provided wherein the glycoprotein produced has a low mannose content. In one embodiment, a composition produced by a method of the invention has less than about 10% of the glycoproteins in the composition having more than 4 mannose residues (ie, M5 or higher species). . This low mannose content maintains cell culture conditions at low osmolality (eg, less than about 600 mOsm / Kg, or less than about 500 mOsm / Kg, or less than about 400 mOsm / Kg, eg, about 380-250 mOsm / Kg). Is achieved by doing |