MDM2-specific antisense oligonucleotides

Details MDM2-specific antisense oligonucleotides MDM2-specific antisense oligonucleotides

2005-09-20

2005-09-20

LeGuyader, John (Department: 1635)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

C435S006120, C435S325000, C435S375000, C536S023100, C536S024500

Reexamination Certificate

active

06946447

ABSTRACT:
The invention provides methods to activate tumor suppressors. The invention further provides antisense oligonucleotides complementary to a portion of the MDM2-encoding RNA and methods for using such antisense oligonucleotides as analytical and diagnostic tools, as potentiators of transgenic animal studies and for gene therapy approaches, and as potential therapeutic agents. The invention also provides methods to augment and synergistically activate a tumor suppressor in conjunction with the use of a DNA-damage inducing agent. The invention further provides in vitro and in vivo models to evaluate the therapeutic effectiveness of a recently identified anti-human-MDM2 antisense oligonucleotide in the treatment of human colorectal cancers.

REFERENCES:
patent: WO-9320238 (1993-04-01), None
Andrea D. Branch, A good antisense molecule is hard to find, TIBS Feb. 23, 1998, pp. 45-50.
W. Clark et al., Systemic and Adjuvant Therapy for Patients with Pancreatic Carcinoma, American Cancer Society, Cancer Supplement, Aug. 1, 1996, vol. 78, No. 3, pp. 688-693.
Seiji Kondo et al., MDM2 protein confers the resistance of a human glioblastoma cell line to cisplatin-induced apoptosis, Oncogene (1995) 10, pp. 2001-2006.
Alan M. Gewirtz et al., Facilitating oligonucleotide delivery: Helping antisense deliver on its promise, Proc. Natl. Acad. Sci. USA, vol. 93, pp. 3161-3163.
Sudhir Agrawal, Antisense oligonucleotides: towards clinical trials, Tibtech Oct. 1996, vol. 14, pp. 376-387.

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