title: Production and clinical development of a Hansenula polymorpha-derived PEGylated hirudin.
abstract: This article describes the expression of the hirudin gene heterologously in the methylotrophic yeast Hansenula polymorpha, the establishment of an industrial-scale production process and the subsequent clinical development of polyethylene glycol (PEG)-hirudin. PEGylation increases the molecular weight of hirudin, thereby reducing its kidney filtration rate and immunogenicity and increasing its half-life in the circulation.
authors.affiliation: Abbott Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA. avgerig@Abbott.com
authors.forename: G C
authors.initials: GC
authors.lastname: Avgerinos
authors.forename: B G
authors.initials: BG
authors.lastname: Turner
authors.forename: K J
authors.initials: KJ
authors.lastname: Gorelick
authors.forename: A
authors.initials: A
authors.lastname: Papendieck
authors.forename: U
authors.initials: U
authors.lastname: Weydemann
authors.forename: G
authors.initials: G
authors.lastname: Gellissen
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000138:chemical synthesis / Q000235:genetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000235:genetics; D006801:Humans; D007218:Industrial Microbiology; D010599:Pharmacokinetics; D010843:Pichia / Q000235:genetics*; D014170:Transformation, Genetic
chemical_list: D000991:Antithrombins; D006629:Hirudins; C104614:polyethyleneglycol-hirudin