POTENT LNA OLIGONUCLEOTIDES FOR THE INHIBITION OF HIF-1a EXPRESSION
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Accused Products
Abstract
The present disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5′-(Tx)GxGxcsasasgscsastscscsTxGxT-3′ and 5-(Gx)TxTxascstsgscscststscsTxTxA-3′, wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analogue or a 2-deoxynucleotide, subscript “s” designates a phosphorothioate link between neighbouring nucleotides/LNA nucleotide analogues, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighbouring nucleotides/LNA nucleotide analogues, and wherein the sequence is optionally extended by up to five 2-deoxynucleotide units. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-1a (HIF-1a), e.g. in the treatment of cancer diseases, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, or treating an angiogenic disease, e.g. diabetic retinopathy, macular degeneration (ARMD), psoriasis, rheumatoid arthritis and other inflammatory diseases.
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Citations
26 Claims
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1-16. -16. (canceled)
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17. A method for treating cancer, said method comprising administering a therapeutically effective amount of an LNA oligonucleotide consisting of the sequence:
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5′
-TsGsGscsasasgscsastscscsTsGsTsa-3′
(SEQ ID NO.
1)wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, lower case letters designate a 2-deoxynucleotide, and subscript “
s”
designates a phosphorothioate link between neighboring nucleotides/LNA nucleotide analogues to a patient in need thereof. - View Dependent Claims (18, 19)
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20-23. -23. (canceled)
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24. A method of inducing apoptosis in a cell comprising contacting the cell with an effective amount of an LNA oligonucleotide consisting of the sequence:
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5′
-TsGsGscsasasgscsastscscsTsGsTsa-3′
(SEQ ID NO.
1)wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, lower case letters designate a 2-deoxynucleotide, and subscript “
s”
designates a phosphorothioate link between neighboring nucleotides/LNA nucleotide analogues.
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25. A method of preventing proliferation of a cell comprising contacting the cell with an effective amount of an LNA oligonucleotide consisting of the sequence:
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5′
-TsGsGscsasasgscsastscscsTsGsTsa-3′
(SEQ ID NO.
1)wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, lower case letters designate a 2-deoxynucleotide, and subscript “
s”
designates a phosphorothioate link between neighboring nucleotides/LNA nucleotide analogues.
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26-30. -30. (canceled)
Specification