The invention relates to the process for the isolation of biologically activegranulocyte colony stimulating factor (G-CSF), which enables the separation ofcorrectly folded biologically active monomeric molecules of G-CSF from theincorrectly folded, biologically inactive monomeric, oligo- or polymeric andalso from aggregated molecules of G-CSF by using immobilised metal affinitychromatography. The process of the invention, if desired the whole process,can be advantageously performed under native conditions. The biologicallyactive G-CSF with a purity of greater than 95% is thus obtained. Only twoadditional chromatographic steps, cationic exchange chromatography and gelfiltration, are then preferably applied to remove the traces of impurities.The entire process results in the production of higher yields of G-CSF with apurity of greater than 99%. The described process is particularly suitable forthe industrial production of G-CSF.
