Processes for the preparation of t-PA mutants

Details Processes for the preparation of t-PA mutants Processes for the preparation of t-PA mutants

1988-04-29

1990-06-19

Stone, Jacqueline

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

424 9463, 435219, 435226, 435 691, 4351723, 935 14, A61K 37547, C12N 950, C12N 964

Patent

active

049352377

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-file of 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:
Collen et al, Circ. vol. 70, No. 6, Dec. 1984, pp. 1012-1017.
Kagitani et al, FEBS Letters, vol. 189, No. 1, Sep. 1985, pp. 145-149.
Rijken et al, Biochem. J. vol. 238, 1986, pp. 643-646.
Tate et al, Biochemistry, vol. 26, No. 2, Jan. 1987, pp. 338-343.
Browne, et al., J. Biol. Chem. 263 #4, 1599 (1988).
Kalyan et al., J. Biol. Chem. 263 #8, 3971 (1988).

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