Production and clinical development of a Hansenula polymorpha-derived PEGylated hirudin

被引:21
作者
Avgerinos, GC
Turner, BG
Gorelick, KJ
Papendieck, A
Weydemann, U
Gellissen, G
机构
[1] Abbott Biores Ctr, Worcester, MA 01605 USA
[2] Rhein Biotech GmbH, Dusseldorf, Germany
关键词
hirudin; PEG-hirudin; Hansenula polymorpha; manufacturing; clinical development;
D O I
10.1055/s-2001-16889
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This article describes the expression of the hirudin gene heterologously in the methylotrophic yeast Hansenula polymorpba, 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.
引用
收藏
页码:357 / 371
页数:15
相关论文
共 46 条
[1]   Comparison of the antithrombotic effect of PEG-hirudin and heparin in a human ex vivo model of arterial thrombosis [J].
Bossavy, JP ;
Sakariassen, KS ;
Rübsamen, K ;
Thalamas, C ;
Boneu, B ;
Cadroy, Y .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (05) :1348-1353
[2]   Relationship between molecular mass and duration of activity of polyethylene glycol conjugated granulocyte colony-stimulating factor mutein [J].
Bowen, S ;
Tare, N ;
Inoue, T ;
Yamasaki, M ;
Okabe, M ;
Horii, I ;
Eliason, JF .
EXPERIMENTAL HEMATOLOGY, 1999, 27 (03) :425-432
[3]  
BRAKE AJ, 1984, P NATL ACAD SCI-BIOL, V81, P4642, DOI 10.1073/pnas.81.15.4642
[4]   Inhibition of neointimal proliferation after coronary angioplasty by low-molecular-weight heparin (clivarine) and polyethyleneglycol-hirudin [J].
Buchwald, AB ;
Hammerschmidt, S ;
Stevens, J ;
Goring, J ;
Nebendahl, K ;
Unterberg, C .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1996, 28 (04) :481-487
[5]   AN EFFICIENT TRANSFORMATION PROCEDURE ENABLING LONG-TERM STORAGE OF COMPETENT CELLS OF VARIOUS YEAST GENERA [J].
DOHMEN, RJ ;
STRASSER, AWM ;
HONER, CB ;
HOLLENBERG, CP .
YEAST, 1991, 7 (07) :691-692
[6]   CLONING OF THE SCHWANNIOMYCES-OCCIDENTALIS GLUCOAMYLASE GENE (GAM1) AND ITS EXPRESSION IN SACCHAROMYCES-CEREVISIAE [J].
DOHMEN, RJ ;
STRASSER, AWM ;
DAHLEMS, UM ;
HOLLENBERG, CP .
GENE, 1990, 95 (01) :111-121
[7]  
Esslinger H.-U., 1998, Annals of Hematology, V76, pA97
[8]  
Esslinger HU, 1997, THROMB HAEMOSTASIS, V77, P911
[9]  
ESSLINGER HU, 1991, THROMB HAEMOSTASIS, V65, P1291
[10]  
ESSLINGER HU, 1997, EUR J CLIN PHARMACOL, V52, P83