Behringwerke Aktiengesellschaft

Chiron Corporation

Hoechst Marion Roussel Deutschland Gmbh

Eric P Paques

Guy T Mullenbach

Nancy L Haigwood

Ernst-Guenter Afting

Norbert Heimburger

Werner Stuber

Peter Fuhge

Hartmut Lobermann

Ernest-Guenter Afting

Novel polypeptide compositions based on the amino acid sequence of tissue plasminogen activator (tPA) are provided having improved properties over natural tissue plasminogen activator. Particularly, enhanced specific activity, reduced response to inhibition by plasminogen activator inhibitor, fibrin stimulation of plasminogenolytic activity and/or enhanced affinity to fibrin surfaces are provided by modifying one or more loci by deletions or substitutions. One or both of the N- or C-termini may be modified.

Peptide plasminogen activators

Novel polypeptide compositions based on the amino acid sequence of tissue plasminogen activator (tPA) are provided having improved properties over natural tissue plasminogen activator. Particularly, reduced fibrin stimulation of plasminogenolytic activity and/or enhanced affinity to fibrin surfaces are provided by modifying the C-terminus by deletions.

Protease absorbent for isolating and purifying proteases, a process for

In the preparation of parenteral solutions for the therapy and prophylaxis of thromboses and embolisms, because of the poor solubility of t-PA hitherto either the infusion of very large volumes has been necessary, or else a solution with a low volume and a high t-PA concentration has been prepared at the expense of setting up a non-physiologically low pH of 2 to 5. Hence, the present invention relates to a process for the preparation of a solution of high concentration of a protein having plasminogen activator activity, where an increase in stability and solubility is achieved by adding at least two substances from the group of D- and/or L-amino acids, their salts, derivatives or homologs. This invention also relates to a process for the pasteurization of a protein solution having t-PA activity, and to a t-PA-containing solution prepared by the claimed process, and to the use of this solution as a fibrinolytic in human and veterinary medicine.

t-PA solution of high concentration and use of the solution in human and

Insulin derivatives of the general formulae I and II

Insulin derivatives, a process for their preparation, and their use

A process is described for the purification of plasminogen activator (PA), wherein a solution containing such as plasminogen activator is brought into contact with a carrier-bound polysulfate of a saccharide or sulfated sugar, the liquid is removed, and the PA bound by this material is eluted.

Process for the purification of plasminogen activators (PA)

A method for the determination of urokinase (UK) or tissue plasminogen activator (t-PA) is described, in which the activator is incubated with plasminogen, with a polysulfuric ester of a saccharide or with a sulfated sugar and, where appropriate, fibrin or fibrin degradation products, and the conversion of plasminogen into plasmin is determined, and agents suitable for this method are described.

Method for the determination of plasminogen activators (PA)

A process for the production of an unnative and biologically active bonded collagen fiber sheet from human placentae is described, in which process collagen-containing material from placentae is treated with a neutral salt solution, a solution of citric acid and with pepsin. The degraded collagen material obtained in this manner is, where appropriate, treated with a crosslinking agent. The collagen material produced in this manner is used for producing bonded collagen fiber sheets which can be used, for example, as covering for wounds.

Growing community of inventors

Marburg, Germany

Eric P Paques