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 utilising 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 invention is directed to novel oligonucleotides with improved antisense properties. The novel oligonucleotides comprise at least one Locked Nucleic Acid (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. The present invention also provides a new class of pharmaceuticals which comprise antisense oligonucleotides and are useful in antisense therapy.

Abstract: The present application discloses locked nucleoside compounds of the Formula I which act as antagonists of adenosine receptors, in particular the adenosine A3 receptor, and the use of such adenosine A3 receptor compounds in medicine, e.g.

Abstract: The present invention is directed to novel oligonucleotides with improved antisense properties. The novel oligonucleotides comprise at least one Locked Nucleic Acid (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. The present invention also provides a new class of pharmaceuticals which comprise antisense oligonucleotides and are useful in antisense therapy.

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 current invention provides oligonucleotides which comprise a dinucleotide consisting of a 5? locked nucleic acid (LNA), a phosphorothioate internucleoside linkage bond to a 3? RNA or RNA analogue. The dinucleotide reduces the strength of hybridization of the oligonucleotide to a complementary nucleic acid target. The modification can be used to modulate hybridisation properties in both single stranded oligonucleotides and in double stranded siRNA complexes, particularly in oligonucleotides where the use of LNA results in excessively strong hybridisation properties.

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 a method of purifying a flow of a gas, in particular an exhaust gas from a Diesel engine, which is contaminated with a particulate material (e.g. nanoparticles) using an apparatus comprising (i) a conduit for passage of the gas flow, (ii) means for applying electromagnetic radiation, e.g. microwaves, and (iii) means for supplying a dipolar liquid, e.g. water, said method comprising the steps of allowing the contaminated gas to flow through the conduit; and applying the electromagnetic radiation to said gas and said liquid. The invention also relates to an apparatus, e.g. a diesel engine exhaust system for purifying a continuous exhaust gas flow contaminated with particulate material(s), e.g. nanoparticles, in order to reduce the content of nanoparticles.

Abstract: The present invention is directed to novel double-stranded short interfering (siRNA) analogues comprising locked nucleic acid (LNA) monomers. Such compounds induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). The compounds disclosed herein has improved properties compared to non-modified siRNAs and may, accordingly, be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the present invention is directed to siRNA analogues comprising a sense strand and an antisense strand, wherein each strand comprises 12-35 nucleotides and wherein the siRNA analogues comprise at least one locked nucleic acid (LNA) monomer.

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: 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: The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as &agr;-L-oxy-LNA, amino-LNA, &agr;-L-amino-LNA, thio-LNA, &agr;-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising 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 invention relates to therapeutic applications of LNA-modified oligonucleotides. In particular, the invention provides methods for treatment of infectious diseases and disorders caused by viruses, bacteria, protozoa or fungi. Preferably, administration of an LNA-modified oligonucleotide modulates expression of a targeted gene associated with the replication or infectivity of a virus, virulence genes, host immune modulating genes and the like. That is, preferred use of LNA-modified oligonucleotide provides an antisense-type therapy with selective modulation of gene expression of predetermined targets.

Abstract: Nucleic acid analogs provide a particularly useful tool for the preparation of complex polymeric structures of defined geometry because they are relatively stable to reaction conditions for the preparation of such structures and provide the opportunity to induce reactive groups which would not be possible with usual nucleic acids.

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 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-&agr;-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-&agr;-D-allofuranose.

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 invention relates to therapeutic applications of LNA-modified oligonucleotides. In particular, the invention provides methods for treatment of undesired cell growth as well as treatment of inflammatory related diseases and disorders. Preferably, administration of an LNA-modified oligonucleotide modulates expression of a targeted gene associated with the undesired cell growth or an inflammatory related disease or disorder.