Gruenenthal Gmbh

Gerd J Steffens

Stephan Wnendt

Regina Heinzel-Wieland

Derek John Saunders

Johannes Schneider

Wolfgang Werner Strassburger

Wolfgang Hillen

Elke Janocha

Martin R Wilhelm

Leopold Flohe'

Regina E Brigelius-Flohe'

Chimeric proteins with fibrinolytic and thrombin-inhibiting properties having a plasminogen-activating amino acid sequence which is linked at its C-terminal end to a thrombin-inhibiting amino acid sequence.

Chimeric proteins having fibrinolytic and thrombin-inhibiting properties

Proteins having fibrinolytic and coagulation-inhibiting properties which are linked at the N- and/or C-terminal end of the plasminogen-activating amino acid sequence to a thrombin- or factor Xa-inhibiting amino acid sequence. The proteins, which are produced by genetic engineering, are useful as thrombolytic agents.

Proteins having fibrinolytic and coagulation--inhibiting properties

Bifunctional urokinase variants possessing improved fibrinolytic properties and thrombin inhibitory activities, plasmids used in the production of these polypeptides, as well as thrombolytic agents containing one of the bifunctional urokinase variants as active ingredient are described.

Bifunctional urokinase variants with improved fibrinolytic

Plasmids containing synthetic DNA sequences are described which are suitable for the expression of the intermediate protein of the recombinant scu-PA (i.e., the unglycosylated protein moiety of the single chain prourokinase) in Enterobacteriaceae, especially in E. coli, with expression rates far higher than those obtainable according to prior methods. The plasmids comprise operons that include a regulatable, optionally synthetic, promotor, a Shine-Dalgarno sequence, a start codon, a synthetic structural gene with selected codon usage, and downstream of the structural gene, 1 to 2 transcription terminators. The preparation of the plasmids and of synthetic DNA-sequences starting from commercially available plasmids and intermediates is described. The intermediate protein, expressed in high yields by using the plasmids for transforming suitable hosts, may be refolded to produce the therapeutically useful plasminogen activator recombinant scu-PA. This protein also may serve as a starting material for obtaining the recombinant two chain unglycosylated urokinase protein (rtcu-PA) on a large scale by splitting the single chain product.

Plasmids, their construction and their use in the manufacture of a

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Aachen, Germany

Gerd J Steffens