Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Hydrolases
Patent
1985-08-16
1993-06-15
Schwartz, Richard A.
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Hydrolases
424 9464, 435211, 435212, 435215, 435226, A61K 37547, C12N 972
Patent
active
052195694
ABSTRACT:
Novel single-chain protease resistant urokinase derivatives are provided. In particular, derivatives are provided wherein the Lys.sub.135 Lys.sub.136 and Arg.sub.156 to Lys.sub.158 sites are rendered less susceptible to proteolytic cleavage are provided by occluding the sites or by covalently modifying them. Preferred covalent modifications are amino acid sequence variants at the sites where proteolysis of urokinase occurs. These are optimally produced by synthesis of single-chain urokinase mutants in recombinant cell culture. The novel urokinase derivatives herein offer the advantage of avoiding the generation of substantial two-chain urokinase, either in vivo or during recombinant cell culture. However, the derivatives continue function to activate plasminogen in initiating blood clot lysis.
REFERENCES:
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Nelles, L. et al., Chem. Abst. 106:208738m, p. 177, 1987.
Holmes, W. et al., Bio/Technology, vol. 3, pp. 923-929, Oct., 1985.
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Nelles, L. et al., J. Biolog. Chem., vol. 262, pp. 5682-5689, Apr., 1987.
Pennica, D. et al., Nature, vol. 301, pp. 214-221, 1983.
Blaber Michael
Heyneker Herbert L.
Vehar Gordon A.
Dreger Walter H.
Genentech Inc.
Schwartz Richard A.
Vogel Nancy
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