Processes for the treatment of vascular disease

Details Processes for the treatment of vascular disease Processes for the treatment of vascular disease

1990-06-18

1991-08-06

Stone, Jacqueline

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

424 9463, 435212, 435215, 435217, 435219, 4351723, 435 691, 935 14, A61K 37547, C12N 1558, C12N 964

Patent

active

050376462

ABSTRACT:
Disclosed herein are improved processes for preparing variant human t-PA proteins exhibiting improved pharmacokinetic properties relative to natural t-PA. One such illustrated variant, devoid of amino acids corresponding to amino acids 1 through 44 of natural t-PA, is shown to exhibit a plasma half-life of greater than about 15 times the plasma half-life to natural t-PA, as well as a clearance rate of less than about 1/10 the clearance rate of natural t-PA. Also disclosed are improved processes for treating vascular disease employing pharmaceutical compositions which incorporate therapeutically effective amounts of such t-PA variants with pharmaceutically acceptable diluents or excipients.

REFERENCES:
patent: 4935237 (1990-06-01), Higgins et al.
Browne et al., J. Biol. Chem., 263, (#4), p. 1599, (1988).
Kaylan et al., J. Biol. Chem., 263, (#8), p. 3971, (1988).
Kagitani et al., Fed. of Euro. Biochem. Studies, 189, (#1), p. 145, (1985).
Rijken et al., Biochem. J., 238, p. 643, (1986).
Tate et al., Biochemistry, 26, p. 338, (1987).
Collen et al., Circulation, 79, (#6), 1012, (1984).

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