Human tissue plasminogen activator variants

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase

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4351723, 435212, C12N 1558, C12N 1500

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active

053148185

ABSTRACT:
Disclosed are novel variants of tissue plasminogen activator (t-PA) that have surprising biological/pharmacokinetic properties compared with native t-PA. For example, certain of the variants hereof demonstrate increased half-life profiles, and show good fibrin binding activity even though fibrin binding regions of the molecule are deleted. All associated means and methods for preparing such variants recombinantly and for using such variants are also disclosed.

REFERENCES:
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Higgins, et al. Thrombosis and Haemostatis 58 (1), 287 (1987) Abstract 1043.
Kagitani, et al. Febs Letters 189 (1), 145-149 (1985).
Hansen, et al. Journal of Biological Chemistry 263 (30), 15713-15719 (1988).
Harris, Protein Engineering vol. 1, 449-458 (1987).
Van Zonneveld et al., J. Biol. Chem. vol. 261 (30), 14214-14218 (1986).
Zoller et al., Methods in Enzymology, vol. 154, Part E, 329-350 (1987).
Dayhoff et al., Atlas of Protein Sequence and Structure vol. 5, 89-99 (1972).

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