G-CSF CONJUGATES
The invention relates to polypeptide conjugates comprising a polypeptide exhibiting G-CSF activity and having an amino acid sequence that differs from the amino acid sequence of human G-CSF in at least one specified introduced and/or removed amino acid residue comprising an attachment group for a non-polypeptide moiety, and having at least one non-polypeptide moiety attached to an attachment group of the polypeptide. The attachment group may e.g. be a lysine, cysteine, aspartic acid or glutamic acid residue or a glycosylation site, and the non-polypeptide moiety may e.g. be a polymer such as polyethylene glycol or an oligosaccharide. The conjugate, which has a reduced in vitro bioactivity compared to hG-CSF, has one or more improved properties such as increased biological half-life and increased stimulation of neutrophils.
1 .- 23 . (canceled)
24 . A method for preparing a G-CSF conjugate having reduced receptor-mediated clearance compared to hG-CSF, the method comprising preparing a polypeptide with an amino acid sequence that differs in at least one amino acid residue from the amino acid sequence of hG-CSF shown in SEQ ID NO:1, and attaching to an attachment group of said polypeptide at least one non-polypeptide moiety to result in a conjugate having an in vitro bioactivity in the range of about 2-30% of the bioactivity of non-conjugated hG-CSF as determined by the luciferase assay described herein.
25 . (canceled)