G-CSF conjugates
AssigneeMaxygen Holdings Ltd.
InventorsTorben Lauesgaard Nissen, Kim Vilbour Andersen, Christian Karsten Hansen, Jan Moller Mikkelsen, Hans Thalsgaard Schambye
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AssigneeMaxygen Holdings Ltd.
InventorsTorben Lauesgaard Nissen, Kim Vilbour Andersen, Christian Karsten Hansen, Jan Moller Mikkelsen, Hans Thalsgaard Schambye
Estimating the term…
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.
A polypeptide conjugate exhibiting at least 2% of the in vitro activity of non-conjugated hG-CSF, comprising (a) a polypeptide comprising an amino acid sequence that differs from the hG-CSF sequence shown in SEQ ID NO:1 in no more than 15 amino acid residues and which comprises the substitutions K16R, K34R, K40R, and T105K and (b) at least one non-polypeptide polymer attached to an attachment group of the polypeptide.
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 from the hG-CSF sequence shown in SEQ ID NO:1 in no more than 15 amino acid residues and which comprises the substitutions K16R, K34R, K40R, and T105K, and attaching at least one non-polypeptide polymer to an attachment group of the polypeptide, wherein the resulting conjugate has an in vitro activity of about 2-30% of the activity of non-conjugated hG-CSF.
Dependencies are inferred from the claim text.