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Last Updated: April 19, 2024

Claims for Patent: 5,504,001


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Summary for Patent: 5,504,001
Title: Hybrid plasminogen activator
Abstract:Hybrid proteins comprising a cross-linking domain derived from a protein that acts as an acyl-donor substrate for factor XIIIa, a fibrin-binding domain, and a serine protease domain are disclosed. Host cells transfected or transformed with an expression vector comprising a transcriptional promoter operably linked to a DNA sequence encoding such hybrid proteins are also disclosed, as well as methods for producing the proteins. The proteins may be utilized in combination with a suitable carrier or diluent as pharmaceutical compositions.
Inventor(s): Foster; Donald C. (Seattle, WA)
Assignee: ZymoGenetics, Inc. (Seattle, WA)
Application Number:08/254,485
Patent Claims:1. A hybrid plasminogen activator comprising a human tissue plasminogen activator or a variant thereof having one or more amino acid substitutions within the cleavage site sequence Gln-Phe-Arg-Ile-Lys-Gly-Gly, and an amino-terminal cross-linking domain, wherein the cross-linking domain comprises the amino terminal twelve amino acids of .alpha..sub.2 -plasmin inhibitor.

2. A hybrid plasminogen activator having the sequence Ser-Asn-Gln-Glu-Glm-Val-Ser-Pro-Leu-Thr-Gly-Leu-Lys-Gly-Ser-tPA, wherein tPA is human tissue plasminogen activator or a variant thereof having one or more amino acid substitutions within the cleavage site sequence Gln-Phe-Arg-Ile-Lys-Gly-Gly.

3. The plasminogen activator of claim 1 wherein the Arg residue in the cleavage site sequence is replaced with a Gly residue.

4. The plasminogen activator of claim 1 wherein said activator contains a thrombin cleavage site between the fibrin-binding domain and the serine protease domain.

5. The plasminogen activator of claim 4 wherein the Phe residue in the cleavage site sequence is replaced with a Pro residue.

6. A pharmaceutical composition comprising a plasminogen activator according to claim 1 in combination with a physiologically acceptable carrier or diluent.

7. The composition of claim 6 wherein said carrier or diluent is sterile water or sterile saline.

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