And this, given the inventors, looks like the CIST TPI-2 patent.
Thanks, John.
Cheers! Rick
United States Patent
4,923,807
Webb, et. al.
May 8, 1990
Arg-Serpin human plasminogen activator inhibitor designated PAI-2
Inventors:
Webb; Andrew C. (Wellesley, MA); Auron; Philip E. (Framingham, MA).
Assignee:
New England Medical Center Hospitals Inc. (Boston, MA); Tufts
College (Boston, MA);
Wellesley College (Wellesley, MA); MIT (Cambridge, MA).
Appl. No.:
011,580
Filed:
Feb. 6, 1987
Related U.S. Application Data
Continuation-in-part of Ser No. 4,319, Jan. 8, 1987, Pat. No.
4,766,069, which is a continuation of Ser. No.
611,669, May 18, 1984, abandoned.
Intl. Cl.:
C12P 21/00, C12P 21/02,
C12N 5/00, C12N 1/20
U.S. Cl.:
435/ 69.2; 435/
69.8; 435/240.1; 435/252.3;
435/252.33; 435/255;
435/320; 435/172.3; 536/ 27; 935/
11; 935/
69; 935/ 70; 935/ 72; 935/ 73
Current U.S. Class:
435/69.2
Field of Search:
435/68, 70, 71, 91, 172.1,
172.3, 240.1, 240.2, 252.3,
252.31-252.35, 254, 255,
256, 320; 536/27; 530/350,
380;
935/11, 27, 70, 69, 72-75
References Cited [Referenced By:]
U.S. Patent Documents
4,366,246
Dec., 1982
Riggs
435/ 68
Other References
Houghton et al.; Nucleic Acids Res. 8: 2885 (1980).
Okayama et al.; Molec. Cell. Biol. 3: 280 (1983).
Carrell, R. and J. Travis (1985) Trends Biolog. Sci. 10:20-24,
".alpha.(1) -Antitrypsin and the Serpins:
Variation and Countervariation".
Travis, J. and G. S. Salvesen (1983) Ann. Rev. Biochem. 52:655-709,
"Human Plasma Proteinase
Inhibitors".
Carrell, R. W. and M. C. Owen (1985) Nature 317:730-732,
"Plakalbumin, .alpha.(1) -Antitrypsin,
Antithrombin and the Mechanism of Inflammatory Thrombosis".
Morse, J. O. (1978) New Eng. Jour. Med. 299:1045-1048, 1099-1105,
"Alpha(1) -Antitrypsin Deficiency".
Hamsten, A., Wiman, B., deFaire, U. and Blomback, M. (1985) New Eng.
J. Med. 313:1557-1563,
"Increased Plasma Levels of a Rapid Inhibitor of Tissue Plasminogen
Activator in Young Survivors of
Myocardial Infarction".
Pannekoek, H., Veerman, H., Lambers, H., Diergaarde, P., Verweij, C.
L., van Zonneveld, A.-J. and van
Mourik, J. A. (1986) EMBO Jour. 5:2539-2544, "Endothelial
Plasminogen Activator Inhibitor (PAI): A
New Member of the Serpin Gene Family".
Ginsberg, D., Zeheb, R., Yang, A. Y., Rafferty, U. M., Andreasen, P.
A., Nielsen, L., Dano, K., Lebo, R.
V. and Gelehrter, T. D. (1986) J. Clin. Invest. 78:1673-1680, "cDNA
Cloning of Human Plasminogen
Activator-Inhibitor from Endothelial Cells".
Ny, T., Sawdey, M., Lawrence, D., Millan, J. L. and Loskutoff, D. J.
(1986) Proc. Natl. Acad. Sci. USA
83:6776-6780, "Cloning and Sequence of a cDNA Coding for the Human
.beta.-Migrating
Endothelial-Cell-Type Plasminogen Activator Inhibitor".
Kruithof, E. K. O., Vassalli, J.-D., Schleuning, W.-D., Mattaliano,
R. J. and Bachmann, F. (1986) J. Biol.
Chem. 261:11207-11213, "Purification and Characterization of a
Plasminogen Activator Inhibitor from
the Histiocytic Lymphoma Cell Line U-937".
Scott, R. W., D. L. Eaton, N. Duran, and J. B. Baker (1983) J. Biol.
Chem. 258:4397-4403, "Regulation of
Extracellular Plasminogen Activator by Human Fibroblasts".
Primary Examiner: Martinell; James
Attorney, Agent or Firm: Saliwanchik; Roman, Saliwanchik; David R.
Abstract
The invention is directed to an Arg-Serpin human plasminogen activator
inhibitor designated PAI-2. This protein is
prepared via recombinant DNA means. The invention also includes other
serpins which can be made by amino acid
substitutions or deletions in conserved regions of PAI-1 and PAI-2, as
shown in FIG. 4. The proteins of the invention
can be used to inhibit, or at least modulate, human plasminogen activator
activity in a variety of physiological
conditions, e.g., fibrinolysis, tumor metastasis, and tumor growth.
13 Claims, 6 Drawing Figures |
