Title:
THERAPEUTICUM AND PROPHYLACTICUM FOR MALIGNANT DISEASES USING PHENOTYPE SUPPRESSION
Document Type and Number:
WIPO Patent Application WO2003056011
Kind Code:
A3
Abstract:
The invention relates to therapeutic and prophylactic agents for malignant diseases based on phenotype suppression induced by a ds-oligoribonucleotide and/or dsm-RNA or a dsm-RNA fragment, in addition to a method for producing said agents, for testing and monitoring its effects and for selecting and screening novel medicaments. According to the invention, at least one of the phenotypically manifested properties is suppressed and the malignant cells or the malignant tumours are not necessarily killed or eliminated, but are returned to a benign state. The ds-oligoribonucleotide and/or the dsm-RNA or the dsm-RNA fragment, which complement a specific sequence of the gene that is activated with the completion of the malignant process in the cell and whose peptide products are responsible for the selection and the intracellular and transmembrane movement of the transcripts of at least one gene among the genes that are active or have been activated in the malignant cells, are used at least periodically as a universal therapeuticum or prophylacticum on patients with malignant cells or tumours, or on persons with an increased risk of developing cancer. The ds-oligoribonucleotide and/or the dsm-RNA or the dsm-RNA fragment are produced on their own or in a combination of at least two of the above, which complement one of the gene-specific sequences of at least one gene among the genes that contribute directly or indirectly to the malignant process, irrespective of whether said genes also occur in normal cells or are responsible for the high risk of developing cancer. The production is carried out by in vitro synthesis, in defined length and symmetry.
Inventors:
BALAZS VIKTOR (DE)
FROEHLICH MARGIT (DE)
FROEHLICH MARGIT (DE)
Application Number:
PCT/EP2002/014019
Publication Date:
October 02, 2003
Filing Date:
December 10, 2002
Export Citation:
Assignee:
BALAZS VIKTOR (DE)
FROEHLICH MARGIT (DE)
FROEHLICH MARGIT (DE)
International Classes:
C12N15/11; A61K38/00; (IPC1-7): C12N15/11
Other References:
DEMIR G ET AL: "USE OF RNA INTERFERENCE (RNAI) TO DISRUPT C-KIT GENE EXPRESSION IN MALIGNANT HUMAN HEMATOPOIETIC AND NEUROEPITHELIAL CELLS", BLOOD, W.B.SAUNDERS COMPAGNY, ORLANDO, FL, US, vol. 96, no. 11, PART 2, 16 November 2000 (2000-11-16), pages 378B, XP009004894, ISSN: 0006-4971
ELBASHIR SAYDA M ET AL: "Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 411, no. 6836, 24 May 2001 (2001-05-24), pages 494 - 498, XP002206451, ISSN: 0028-0836
MANGO S E: "Stop making nonSense: the C. elegans smg genes", TRENDS IN GENETICS, ELSEVIER, AMSTERDAM, NL, vol. 17, no. 11, 1 November 2001 (2001-11-01), pages 646 - 653, XP004326516, ISSN: 0168-9525
SIEGMUND D ET AL: "SELECTIVE INHIBITION OF FLICE-LIKE INHIBITORY PROTEIN (FLIP) EXPRESSION WITH SMALL INTERFERING RNA OLIGONUCLEOTIDES (SIRNAS) IS SUFFICIENT TO SENSITIZE TUMOR CELLS FOR TRAIL-INDUCED APOPTOSIS", MOLECULAR MEDICINE, BLACKWELL SCIENCE, CAMBRIDGE, MA, US, vol. 8, no. 11, November 2002 (2002-11-01), pages 725 - 732, XP009005569, ISSN: 1076-1551
ELBASHIR SAYDA M ET AL: "Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells", NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, vol. 411, no. 6836, 24 May 2001 (2001-05-24), pages 494 - 498, XP002206451, ISSN: 0028-0836
MANGO S E: "Stop making nonSense: the C. elegans smg genes", TRENDS IN GENETICS, ELSEVIER, AMSTERDAM, NL, vol. 17, no. 11, 1 November 2001 (2001-11-01), pages 646 - 653, XP004326516, ISSN: 0168-9525
SIEGMUND D ET AL: "SELECTIVE INHIBITION OF FLICE-LIKE INHIBITORY PROTEIN (FLIP) EXPRESSION WITH SMALL INTERFERING RNA OLIGONUCLEOTIDES (SIRNAS) IS SUFFICIENT TO SENSITIZE TUMOR CELLS FOR TRAIL-INDUCED APOPTOSIS", MOLECULAR MEDICINE, BLACKWELL SCIENCE, CAMBRIDGE, MA, US, vol. 8, no. 11, November 2002 (2002-11-01), pages 725 - 732, XP009005569, ISSN: 1076-1551
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