Abstract: The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as ?-L-oxy-LNA, amino-LNA, ?-L-amino-LNA, thio-LNA, ?-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilizing intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues.

Abstract: The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5?-(MeCx)(Tx)MeCxAsAstscscsastsgsgsMeCxAx)(Gx)(c)-3?, and preferably of the general formula 5?-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3?, wherein capital letters designate an LNA nucleotide analogue selected from ?-D-oxy-LNA, ?-D-thio-LNA, ?-D-amino-LNA and ?-L-oxy-LNA, small letters designate a deoxynucleotide, 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.

Abstract: The present invention relates to very short heavily modified oligonucleotides which target and inhibit microRNAs in vivo, and their use in medicaments and pharmaceutical compositions.

Abstract: The invention relates to oligomer compounds (oligomers), which target beta-catenin mRNA in a cell, leading to reduced expression of beta-catenin. Reduction of beta-catenin expression is beneficial for a range of medical disorders, such as hyperproliferative disorders, such as cancer. The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of beta-catenin using said oligomers, including methods of treatment.

Abstract: The invention relates to oligomer compounds (oligomers), which target HER3 mRNA in a cell, leading to reduced expression of HER3 and/or HER2 and/or EGFR. Reduction of HER3 and/or HER2 and/or EGFR expression is beneficial for a range of medical disorders, such hyperproliferative disorders (e.g., cancer). The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of HER3 and/or HER2 and/or EGFR using said oligomers, including methods of treatment.

Abstract: The present invention is directed to modified siRNA which are significantly impaired in their ability to support cleavage of mRNA when incorporated into a RISC complex. Such modified siRNA may be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the modified siRNA comprises a sense strand and an antisense strand, wherein the sense strand contains a modified RNA nucleotide in at least one of positions 8-14, calculated from the 5?-end.

Abstract: The present invention relates to large scale preparation of LNA phosphoramidites using a 2-cyanoethyl-N,N,N?,N?-tetra-substituted phosphoramidite and a nucleophilic activator, e.g. 2-cyanoethyl-N,N,N?,N?-tetraisopropylphosphoramidite and 4,5-dicyanoimidazole. The method is faster and more cost efficient that previously known methods.

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.

Abstract: The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5?-(MeCx)(Tx)MeCxAsAstscscsastsgsgsMeCxAx(Gx)(c)-3?, and preferably of the general formula 5?-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3?, wherein capital letters designate an LNA nucleotide analogue selected from ?-D-oxy-LNA, ?-D-thio-LNA, ?-D-amino-LNA and ?-L-oxy-LNA, small letters designate a deoxynucleotide, 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.

Abstract: A novel class of pharmaceuticals which comprises a Locked Nucleic Acid (LNA) which can be used in antisense therapy. These novel oligonucleotides have improved antisense properties. The novel oligonucleotides are composed of at least one LNA selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides.

Abstract: The present invention relates to a new method for the synthesis of purine LNA (Locked Nucleic Acid) analogues which provides a higher overall yield. The method comprising a regioselective 9-N purine glycosylation reaction followed by a one-pot nucleophilic aromatic substitution reaction of the 6-substituent in the purine ring and simultaneous nucleophile-induced intramolecular ring closure of the C-branched carbohydrate to form novel purine LNA analogues. The novel strategy is illustrated by the synthesis of the novel compound (1S,3R,4R,7S)-7-benzyloxy-1-methanesulfonylmethyl-3-(guanin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane which is easily converted into (1S,3R,4R,7S)-7-hydroxy-1-hydroxymethyl-3-((2-N-isobutyrylguanin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane after isobutyryl protection of the 2-amino purine group and subsequent substitution of 1-methanesulfonyl with benzoate, debenzoylation and debenzylation.

Abstract: The present invention provides a novel strategy for the synthesis of allofuranose using glucofuranose as starting material in a one-pot reaction. The novel finding is that it is possible to carry out the oxidation of 1,2:5,6-di-O-isopropylidene-?-D-glucofuranose with DMSO/acetic anhydride and a reduction reaction in one pot obtaining high yields of recrystallised and analytical pure 1,2:5,6-di-O-isopropylidene-?-D-allofuranose.

Abstract: Oligonucleotides directed against the Ha-ras gene are provided for modulating the expression of Ha-ras. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the Ha-ras. Methods of using these compounds for modulation of Ha-ras expression and for the treatment of diseases associated with either overexpression of Ha-ras, expression of mutated Ha-ras or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.

Abstract: Oligonucleotides directed against the TRX gene are provided for modulating the expression of TRX. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the TRX. Methods of using these compounds for modulation of TRX expression and for the treatment of diseases associated with either overexpression of TRX, expression of mutated TRX or both are provided. Examples of diseases are cancer such as lung, breast, colon, prostate, pancreas, lung, liver, thyroid, kidney, brain, testes, stomach, intestine, bowel, spinal cord, sinuses, bladder, urinary tract or ovaries cancers. The oligonucleotides may be composed of deoxyribonucleosides or a nucleic acid analogue such as for example locked nucleic acid or a combination thereof.