Calpain inhibitors and their applications

Chemistry: molecular biology and microbiology – Process of mutation – cell fusion – or genetic modification – Introduction of a polynucleotide molecule into or...

Reexamination Certificate

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C435S440000, C435S456000

Reexamination Certificate

active

07001770

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 transciption of a therapeutic transgene from the CMV promoter. The present invention also provides a method of suppress the in vivo CTL response to viral vectors by the use of calpain inhibitors. The present invention further provides a pharmaceutical formulations 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.

REFERENCES:
patent: 6015787 (2000-01-01), Potter et al.
Atencio, I. A. et al., “Calpain Inhibitor 1 Activates p53-dependent Apoptosis in Tumor Cell Lines” Cell Growth & Differentiation, vol. 11, pp. 247-253, May 2000.
Friedmann, T. “Overcoming the Obstacles to Gene Therapy” Scientific American, pp. 96-101, Jun. 1997.
Gonen, H. et al., “On the involvement of calpains in the degradation of the tumor suppressor protein p53” FEBS Letters, vol. 406, pp. 17-22, 1997.
Hodgson, C. P. “Advances in vector systems for gene therapy” Exp. Opin. Ther. Patents, vol. 5, pp. 459-468, May 1995.
Orkin S. H. and Motulsky A. G. ,“Report and Recommendations of the Panel to assess the NIH investment in research on Gene therapy”, Dec. 7, 1995.
Verma, I. M. and Somia N. ,“Gene therapy- promises, problems and prospects” Nature, vol. 389, pp. 239-242, Sep. 18, 1997.
Claudio et al. (1996) Molecular mechanisms of TNFalpha cytotoxicity: Activation of NF-kappaB and nuclear translocation. Experimental Cell Research 224(1): 63-71.

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