abstract |
The invention relates to polypeptide with G-CSF activity comprising at least 15 amino acid sequences of different residues compared with the Hg-CSF amino acid sequence as shown in SEQ ID NO:1 and substituted K16R, K34R, K40R, T105K and S159K compared with SEQ ID NO:1. Polypeptide conjugates with G-CSF activity comprising a polypeptide having at least one introduced lysine residue and at least one removed lysine residue compared to the sequence of human G-CSF, and which are conjugated to 2-6 polyethylene glycol moieties. The conjugates have a lowin vitro bioactivity, a long in vivo half-life, a reduced receptor-mediated clearance, and provide a more rapid stimulation of production of white blood cells and neutrophils than non-conjugates recombinant human G-CSF. |