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  Antisense oligonucleotides directed to ribonucleotide reductase r2 and uses thereof in the treament of cancerUSPTO Application #: 20060241070Title: Antisense oligonucleotides directed to ribonucleotide reductase r2 and uses thereof in the treament of cancer Abstract: The present invention provides antisense oligonucleotides directed to a mammalian ribonucleotide reductase R2 gene and combinations of the antisense oligonucleotides with one or more chemotherapeutic agents for use in the treatment of cancer. (end of abstract) Agent: Sterne, Kessler, Goldstein & Fox PLLC - Washington, DC, US Inventor: Jim A Wright USPTO Applicaton #: 20060241070 - Class: 514044000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), O-glycoside, , Nitrogen Containing Hetero Ring, Polynucleotide (e.g., Rna, Dna, Etc.) The Patent Description & Claims data below is from USPTO Patent Application 20060241070. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION [0001] The present invention pertains to the field of cancer therapeutics and in particular to the use of antisense oligonucleotides alone or in combination with one or more chemotherapeutic drugs for the treatment of cancer. BACKGROUND [0002] Regulation of ribonucleotide reductase, and particularly the R2 component, is altered in malignant cells exposed to some tumour promoters and to the growth factor TGF-.beta. [Amara, et al., 1994; Chen et al., 1993; Amara et al., 1995b; Hurta and Wright, 1995; Hurta et al., 1991]. Higher levels of enzyme activity have been observed in cultured malignant cells when compared to nonmalignant cells [Weber, 1983; Takeda and Weber, 1981; Wright et al., 1989a], and increased levels of R2 protein and R2 mRNA have been found in pre-malignant and malignant tissues as compared to normal control tissue samples [Saeki et al., 1995; Jensen et al., 1994]. However, these correlative studies did not show a direct role for ribonucleotide reductase in cancer cell transformation and tumour progression, because like so many other enzyme activities found to be altered in cancer cells [e.g. Weber, 1983], the results could easily be explained by the increased cell proliferation and altered cell cycle regulation characteristics of transformed and malignant cell populations [Morgan and Kastan, 1997]. [0003] Antisense oligonucleotides directed to the R1 or R2 component of ribonucleotide reductase have been shown to be effective in reducing the growth of cancer cells [see, for example, U.S. Pat. Nos. 5,998,383 and 6,121,000]. [0004] In view of the high incidence of various types of cancer throughout the world, there remains a need for improved therapies for the treatment of cancer. [0005] This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention. SUMMARY OF THE INVENTION [0006] An object of the present invention is to provide antisense oligonucleotides directed to ribonucleotide reductase R2 and uses thereof in the treatment of cancer. In accordance with an aspect of the present invention, there is provided an antisense oligonucleotide of between 7 and 100 nucleotides in length comprising at least 7 consecutive nucleotides from SEQ ID NO:1 for use in the treatment of cancer in a mammal in need of such therapy. [0007] In accordance with another aspect of the present invention, there is provided an antisense oligonucleotide of between 7 and 100 nucleotides in length comprising at least 7 consecutive nucleotides from SEQ ID NO:1 for use in combination with one or more chemotherapeutic agents in the treatment of cancer in a mammal in need of such therapy. [0008] In accordance with another aspect of the present invention, there is provided an antisense oligonucleotide of between 20 and 100 nucleotides in length comprising the sequence as set forth in SEQ ID NO:1 for use in combination with one or more chemotherapeutic agents in the treatment of a human having a cancer selected from the group of: a solid tumour, renal cancer, breast cancer, lung cancer, prostate cancer, colon cancer and leukaemia. [0009] In accordance with another aspect of the present invention, there is provided a use of an antisense oligonucleotide of between 7 and 100 nucleotides in length comprising at least 7 consecutive nucleotides from SEQ ID NO:1 in the manufacture of a medicament for the treatment of cancer. BRIEF DESCRIPTION OF THE FIGURES [0010] FIG. 1 depicts effects of combination therapy on HT-29 colon tumour growth in nude mice; [0011] FIG. 2 depicts effects of combination therapy on HT-29 colon tumour growth in nude mice; [0012] FIG. 3 depicts effects of combination therapy on Caki-1 renal tumour growth in SCID mice; [0013] FIG. 4 depicts effects of combination therapy on prostatic tumour growth in SCID mice; [0014] FIG. 5 depicts effects of combination therapy on prostatic tumour growth in SCID mice; [0015] FIG. 6 depicts effects of combination therapy on A2058 melanoma growth in nude mice; [0016] FIG. 7 depicts effects of combination therapy on breast tumour growth in CD-1 nude mice; [0017] FIG. 8 depicts effects of combination therapy on ovary tumour growth in CD-1 nude mice; [0018] FIG. 9 depicts effects of SEQ ID NO: 1 in the treatment of human pancreatic carcinoma in CD-1 nude mice; [0019] FIG. 10 depicts effects of SEQ ID NO: 1 in the treatment of human cervix epitheloid carcinoma resistant to hydroxyurea (HU) in SCID mice; [0020] FIG. 11 depicts effects of SEQ ID NO: 1 in the treatment of human breast adenocarcinoma resistant to cisplatin in SCID mice; Continue reading... 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