Peptide plasminogen activators

Details Peptide plasminogen activators Peptide plasminogen activators

1997-02-13

1999-11-02

Jacobson, Dian C.

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

435212, 435226, 4352523, 4353201, 435325, 435476, 536 232, C12N 964, C12N 1555, C12N 113, A61K 3849

Patent

active

059765305

ABSTRACT:
Novel polypeptide compositions based on the amino acid sequence of tissue plasminogen activator (tPA) are provided having improved properties over natural tissue plasminogen activator. Particularly, enhanced specific activity, reduced response to inhibition by plasminogen activator inhibitor, fibrin stimulation of plasminogenolytic activity and/or enhanced affinity to fibrin surfaces are provided by modifying one or more loci by deletions or substitutions. One or both of the N- or C-termini may be modified.

REFERENCES:
patent: 4751084 (1988-06-01), Feder et al.
patent: 4753879 (1988-06-01), Rosa
patent: 5073494 (1991-12-01), Heyneker et al.
patent: 5106741 (1992-04-01), Marotti et al.
patent: 5147643 (1992-09-01), Heyneker et al.
patent: 5344773 (1994-09-01), Wei et al.
patent: 5439679 (1995-08-01), Afting
patent: 5501853 (1996-03-01), Haigwood et al.
Haigwood, Nancy L. et al., "Variants of Human Tissue- AI Type Plasminogen Activator Substituted at the Protein Cleavage Site and Glycosylation Sites, and Truncated at the N- and C-termini," Protein Engineering, vol. 2, No. 8, pp. 611-620 (1989).
Craik, Charles S. et al., "Redesigning Trypsin: Altera- of Substrate Specificity," Science, vol. 228, pp. 291-297 (Apr. 1985).
Rosenberg, Steven et al., "Synthesis in yeast of a functional oxidation-resistant mutant of human .alpha..sub.1 - antitrypsin," Nature, vol. 312, No. 5989, pp. 77-80 (Nov. 1984).
Wilkinson, Anthony J. et al., "A large increase in enzyme- substrate affinity by protein engineerinng," Nature, vol. 307, pp. 187-188 (Jan. 1984).
Andreasen, P.A., "Inactive proenzyme to tissue-type plasminogen activator from human melanoma cells, identified after affinity purification with a mono- clonal antibody," EMBO Journal, vol. 3, pp. 51-55 (1984).
van Zonneveld, A.J., Abstract from ISTH Meeting, Jul. 14-19, 1985, report on the relationship between structure and function of human tissue-type plasminogen activator.
NYE et al., Figure I, Proc. Natl. Acad. Sci. USA, vol. 81, p. 5355 (1984).
OPDENAKKER, G., et al., "The Carbohydrate Side-Chains of Tissue-Type Plasminogen Activator Influences its Activity," EMBO Workshop on Plasminogen Activation, Emalfi, Italy, Oct. 14-18, 1985.
Loskutoff, D.J. et al., "Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells," Proc. Natl. Acad. Sci. USA, vol. 80, pp. 2956-2960 (May 1963).
Loskutoff, D.J., "Thrombosis and Haemostasis," Journal of the International Society of Thrombosis and Haemostasis, vol. 54, No. 1, p. 118 (S699).
Zoller, Mark J. et al., "Oligonucleotide-Directed Mutagenesis of DNA Fragments Cloned into M13 Vectors," Methods in Enzymology, vol. 100, pp. 468-500 (1983).
Pohl, Gunnar et al., "Tissue Plasminogen Activator: Peptide Analyses Confirm an Indirectly Derived Amino Acid Sequence, Identify the Active Site Serine Residue, Establish Glycosylation Sites and Localize Variant Difference," Biochemistry, vol. 23, pp. 3701-3707 (1984).
Zoller, Mark J. et al., "Oligonucleotide-directed mutagenesis using M13-derived vectors; and efficient and general procedure for the production of point mutations in any fragment of DNA," Nucleic Acids Research, vol. 10, No. 2 (Aug. 1982).
Guan, Jun-Lin et al., "Glycosylation Allows Cells-Surface Transport of an Anchored Secretory Protein," Cell, vol. 42, pp. 489-496 (Sep. 1965).
Little, Sheila P. et al., "Functional Properties of Carbohydrate-Depleted Tissue Plasminogen Activator," Biochemistry, vol. 23, pp. 6191-6195 (1984).
Nose, Masato et al., "Biological significance of carbohydrate chains on monoclonal antibodies," Proc. Natl. Acad. Sci. USA, vol. 80, pp. 6632-6636 (Nov. 1983).
Ny, Tor et al., "The structure of the human tissue-type plasminogen activator gene: Correlation of intron and exon structures so functional and structural domains," Proc. Natl. Acad. Sci., vol. 81, pp. 5355-5359 (1984).
Vehar, Gordon A. et al., "Characterization Studies on Human Melanoma Cell Tissue Plasminogen Activator," Biotechnology, vol. 2, pp. 1051-1057 (1986).
Pennica, Diane et al., "Cloning and Expression of Human Tissue-Type Plasminogen Activator cDNA in E.coli," Nature, vol. 301, No. 5897, pp. 214-221 (1983).
Stryer, L., Chapter 8, Zymogen Activation, Biochemistry pp. 165-166, (1988) .

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