LNA oligonucleotides and the treatment of cancer

An oligonucleotide and nucleotide technology, applied in the field of cancer treatment, can solve problems such as the good performance of LNA oligonucleotides that have not been described
CN101065485AInactive Publication Date: 2007-10-31SANTARIS PHARMA AS +1
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
SANTARIS PHARMA AS
Publication Date
2007-10-31
Estimated Expiration
Not applicable · inactive patent

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Abstract

The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5'- ( Me Cx )(Tx,) Me CXAs Astscscsastsgsgs MeCXAX (G x) (c)-3',and preferably of the general formula 5'- Me C XTX), MeCXAsastscscsastsgsgs Me CxAx G x c-3', wherein capital letters designate a n LNA nucleotide analogue selected from .beta. -D-oxy-LNA, .beta. -D-thio-LNA, .beta.-D-amino-LNA and a-L-oxy-LNA, small letters designate a deoxynucleotid e, and underline designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumour development in vivo. The LNA oligonucleotides are superior to other L NA oligonucletides targeting Surviving mRNA measured by functional read outs such as apoptosis induction and proliferation inhibition, and is potent in down- regulating Survivin mRNA and protein in transfected cancer cell lines, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides.
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Description

field of invention

[0001] The present invention provides pharmaceutical compositions for treating cancer. The composition comprises specific LNA oligonucleotides which have superior properties in inhibiting the expression of survivin. The invention also provides methods and various kits for treating cancer. Background of the invention

[0002] Survivin is one of the most attractive new cancer targets. High levels of Survivin were detected in nearly all tumor types, underscoring the protein's clinical role in cancer. Elevated expression of survivin in tumors is often associated with poor prognosis, increased cancer recurrence and resistance to treatments (radiation and chemotherapy). The fact that survivin is not expressed in normal adult tissues (with a few exceptions) makes survivin a key oncogene.

[0003] Inhibitor of apoptosis protein (IAP) Survival proteins are involved in 2 key biological events: (i) control of cell proliferation (mitosis), and (ii) regulation of p...

Claims

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