Title:
CALPAIN INHIBITORS AND THEIR APPLICATIONS
Document Type and Number:
WIPO Patent Application WO2000021575
Kind Code:
A3
Abstract:
The present invention provides a method to enhance apoptosis in a cell by the administration of p53 in combination with a calpain inhibitor. The present invention provides a method of increasing the infectivity of a cell to a viral vector by treatment of the cell with a calpain inhibitor. The present invention further provides a method of enhancing transcription of a therapeutic transgene from the CMV promoter. The present invention also provides a method of suppressing the in vivo CTL response to viral vectors by the use of calpain inhibitors. The present invention further provides a pharmaceutical formulation of p53 and a calpain inhibitor in a pharmaceutically acceptable carrier. The present invention provides a method of ablating neoplastic cells in a mammalian organism in vivo by the co-administration of a calpain inhibitor and p53. The present invention also provides a method of ablating neoplastic cells in a population of normal cells contaminated by said neoplastic cells ex vivo by the administration of a recombinant adenovirus in combination with a calpain inhibitor to said population.
Inventors:
ATENCIO ISABELLA A
LAFACE DRAKE M
RAMACHANDRA MURALIDHARA
SHABRAM PAUL W
LAFACE DRAKE M
RAMACHANDRA MURALIDHARA
SHABRAM PAUL W
Application Number:
PCT/US1999/021453
Publication Date:
November 23, 2000
Filing Date:
October 14, 1999
Export Citation:
Assignee:
CANJI INC (US)
International Classes:
A61K38/55; A61K38/57; A61K48/00; (IPC1-7): A61K38/57; A61K38/17; A61K48/00; A61P35/00
Other References:
SHINOHARA K ET AL: "Apoptosis induction resulting from proteasome inhibition.", BIOCHEMICAL JOURNAL, (1996 JUL 15) 317 ( PT 2) 385-8., XP000906742
KUBBUTAT M H ET AL: "Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability.", MOLECULAR AND CELLULAR BIOLOGY, (1997 JAN) 17 (1) 460-8., XP000906747
PARIAT M ET AL: "Proteolysis by calpains: a possible contribution to degradation of p53", MOLECULAR AND CELLULAR BIOLOGY,US,WASHINGTON, DC, vol. 17, no. 5, May 1997 (1997-05-01), pages 2806 - 2815, XP002110841, ISSN: 0270-7306
HAMADA KATSUYUKI ET AL: "Adenovirus-mediated transfer of a wild-type p53 gene and induction of apoptosis in cervical cancer.", CANCER RESEARCH 1996, vol. 56, no. 13, 1996, pages 3047 - 3054, XP002137540, ISSN: 0008-5472
EASTHAM J A ET AL: "IN VIVO GENE THERAPY WITH P53 OR P21 ADENOVIRUS FOR PROSTATE CANCER", CANCER RESEARCH,US,AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, vol. 55, no. 22, 15 November 1995 (1995-11-15), pages 5151 - 5155, XP000606345, ISSN: 0008-5472
LIU T -J ET AL: "APOPTOSIS INDUCTION MEDIATED BY WILD-TYPE P53 ADENOVIRAL GENE TRANSFER IN SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK", CANCER RESEARCH,US,AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, vol. 55, 15 July 1995 (1995-07-15), pages 3117 - 3122, XP002027381, ISSN: 0008-5472
KUBBUTAT M H ET AL: "Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability.", MOLECULAR AND CELLULAR BIOLOGY, (1997 JAN) 17 (1) 460-8., XP000906747
PARIAT M ET AL: "Proteolysis by calpains: a possible contribution to degradation of p53", MOLECULAR AND CELLULAR BIOLOGY,US,WASHINGTON, DC, vol. 17, no. 5, May 1997 (1997-05-01), pages 2806 - 2815, XP002110841, ISSN: 0270-7306
HAMADA KATSUYUKI ET AL: "Adenovirus-mediated transfer of a wild-type p53 gene and induction of apoptosis in cervical cancer.", CANCER RESEARCH 1996, vol. 56, no. 13, 1996, pages 3047 - 3054, XP002137540, ISSN: 0008-5472
EASTHAM J A ET AL: "IN VIVO GENE THERAPY WITH P53 OR P21 ADENOVIRUS FOR PROSTATE CANCER", CANCER RESEARCH,US,AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, vol. 55, no. 22, 15 November 1995 (1995-11-15), pages 5151 - 5155, XP000606345, ISSN: 0008-5472
LIU T -J ET AL: "APOPTOSIS INDUCTION MEDIATED BY WILD-TYPE P53 ADENOVIRAL GENE TRANSFER IN SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK", CANCER RESEARCH,US,AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, vol. 55, 15 July 1995 (1995-07-15), pages 3117 - 3122, XP002027381, ISSN: 0008-5472
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