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Title:
MUTATED ANTHRAX TOXIN PROTECTIVE ANTIGEN PROTEINS THAT SPECIFICALLY TARGET CELLS CONTAINING HIGH AMOUNTS OF CELL-SURFACE METALLOPROTEINASES OR PLASMINOGEN ACTIVATOR RECEPTORS
Document Type and Number:
WIPO Patent Application WO2001021656
Kind Code:
A3
Abstract:
The present invention provides methods of specifically targeting compounds to cells overexpressing matrix metalloproteinases, plasminogen activators, or plasminogen activator receptors, by administering a compound and a mutant protective antigen protein comprising a matrix metalloproteinase or a plasminogen activator-recognized cleavage site in place of the native protective antigen furin-recognized cleavage site, wherein the mutant protective antigen is cleaved by a matrix metalloproteinase or a plasminogen activator overexpressed by the cell, thereby translocating into the cell a compound comprising a lethal factor polypeptide comprising a protective antigen binding site.

Inventors:
LEPPLA STEPHEN H (US)
LIU SHI-HUI (US)
NETZEL-ARNETT SARAH (US)
HANSEN-BIRKEDAL HENNING (US)
BUGGE THOMAS (US)
Application Number:
PCT/US2000/026192
Publication Date:
January 17, 2002
Filing Date:
September 22, 2000
Export Citation:
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Assignee:
US GOV HEALTH & HUMAN SERV (US)
LEPPLA STEPHEN H (US)
LIU SHI HUI (US)
NETZEL ARNETT SARAH (US)
HANSEN BIRKEDAL HENNING (US)
BUGGE THOMAS (US)
International Classes:
A61K39/07; A61K39/108; A61K47/48; A61K48/00; C07K14/25; C07K14/32; C07K19/00; A61K38/00; (IPC1-7): C07K14/32; C07K19/00; C07K14/25; A61K39/07; A61K48/00; A61K39/108
Foreign References:
US5677274A1997-10-14
US5817771A1998-10-06
Other References:
LIAW L ET AL: "FUNCTIONS OF THE EXTRACELLULAR MATRIX AND MATRIX DEGRADING PROTEASES DURING TUMOR PROGRESSION", BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH,BR,RIBEIRAO PRETO, vol. 32, no. 7, July 1999 (1999-07-01), pages 805 - 812, XP000872134, ISSN: 0100-879X
MAZAR ET AL: "High-affinity, small cyclic peptide urokinase plasminogen activator receptor (uPAR)-targeting ligands localize reporter and therapeutic conjugates to the surfaces of tumor cells and stimulated endothelial cells", PROCEEDINGS OF THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH,US,PHILADELPHIA, PA: AACR, vol. 40, March 1999 (1999-03-01), pages 22, XP002131000
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