Novo Nordisk A/s

Maxygen Holdings Ltd.

Maxygen, Inc.

Jan Moller Mikkelsen

Kim Vilbour Andersen

Torben Lauesgaard Nissen

Christian Hansen

Hans Thalsgaard Schambye

Flemming M Christensen

Per L Joergensen

Torben K Nielsen

Joergen Petersen

Torben Halkier

Henrik Dalbo Slashedge

Kurt Dorreich

Henrik Dalboge

Marcel Mischler

Hans Thalsgard Schambye

Kurt D Orreich

Lone K Hansen

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 low in 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-conjugated recombinant human G-CSF.

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 has one or more improved properties such as increased biological half-life and reduced side effects.

G-CSF polypeptides and 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.

A process for the microbial production of a protein susceptible to inactivation in a fluid production medium by continuously and reversibly protecting said protein against said inactivation during the production stage, separating the protein from the production medium, deprotecting the protein, and recovering the protein product. The process is especially useful for obtaining substantially increased yields of the protein in question by continuously precipitating said protein.

Method for protection of proteolysis-susceptible protein during protein

Rhamnogalacturonase, corresponding DNA sequence, rhamnogalacturonase

The invention relates to a detergent composition comprising a protease and one or more other enzymes, as well as comprising a reversible protease inhibitor of the peptide or protein type.

Enzymatic detergent composition and method for enzyme stabilization

.beta.-1,4-galactanase and a DNA sequence

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Gentofte, Denmark

Jan Moller Mikkelsen