Human tissue plasminogen activator variants

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

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4351723, 435212, 935 27, 935 56, 536 27, C12N 964, C12N 1500, C12N 1558

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active

050949535

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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Harris, Protein Engineering, vol. 1, pp. 449-458, 1987.
van Zonneveld et al., J. Biol. Chem., vol. 261, No. 30, pp. 14214-14218, Oct. 25, 1986.
Zoller et al., Methods in Enzymology, vol. 154 Part E, pp. 329-350, 1987.
Tate et al., Biochemistry 26 (2), 338-343 (1987).
Higgins et al., Thrombosis and Heamostasis 58 (1), 287 (1987) Abstract 1043.
Kagitani et al., Febs Letters 189 (1), 145-149 (1985).

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