Abstract: The present invention relates to a compound of formula (II) or (IIb) Wherein X, Y, Rx, Ry, R5 and Nu are as defined in the description and in the claims. The compound of formula (II) can be used in the manufacture of oligonucleotides.

Abstract: The present invention relates to antisense oligonucleotides that are capable of reducing expression of GSK3B in a target cell. The antisense oligonucleotides hybridize to GSK3B pre-mRNA. The present invention further relates to conjugates of the antisense oligonucleotide, pharmaceutical salts and pharmaceutical compositions and methods for treatment or alleviation of conditions such as cancer, inflammatory diseases, neurological diseases, neurological injury, neuronal degeneration, psychiatric diseases and Type 2 diabetes.

Abstract: The present invention relates to antisense oligonucleotides that are capable of reducing expression of ERC1 in a target cell. The oligonucleotides hybridize to ERC1 pre-mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of disease associated with ERC1 overexpression, such as cancer or Dengue virus infection using the antisense oligonucleotide.

Abstract: The present invention relates to antisense LNA oligonucleotides (oligomers) complementary to SREBF1 pre-mRNA intron and exon sequences, which are capable of inhibiting the expression of SREBP1 protein. Inhibition of SREBF1 expression is beneficial for a range of medical disorders including cardiovascular disease, type 2 diabetes, fatty liver, metabolic diseases, and cancer.

Abstract: The present invention relates to antisense oligonucleotides that are capable of modulating expression of PIAS4 in a target cell. The antisense oligonucleotides hybridize to PIAS4 pre-mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of cancers such as pancreatic cancer, breast cancer and liver fibrosis using the antisense oligonucleotide.

Abstract: The invention relates to methods for predicting the in vivo toxicity of oligonucleotides, such as antisense oligonucleotides using in vitro cell based assays based on gymnotically administering oligonucleotides to primary mammalian hepatocytes and subsequently measuring the levels of toxicity biomarkers such as the release of LDH into the cell culture media and/or intracellular ATP.

Abstract: The invention relates to the field of therapeutic oligonucleotide analytics and discovery, and provides methods for primer based parallel sequencing of modified oligonucleotides which provide sequence based quality information which may be used in oligonucleotide therapeutic discovery, manufacture, quality assurance, therapeutic development, and patient monitoring.

Abstract: The present invention relates to antisense oligonucleotides that are capable of modulating expression of FNDC3B in a target cell. The oligonucleotides hybridize to FNDC3B pre-mRNA or mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of cancers, such as hepatocellular carcinoma or acute myeloid leukemia using the oligonucleotide.

Abstract: The present disclosure relates to antisense oligonucleotides, which target SNCA mRNA (e.g., at an intron exon junction) in a cell, leading to reduced expression of SNCA protein. Reduction of SNCA protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.

Abstract: The present disclosure relates to antisense oligonucleotides, which target SNCA mRNA (e.g., at an intron exon junction) in a cell, leading to reduced expression of SNCA protein. Reduction of SNCA protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.

Abstract: The present invention relates to an oligonucleotide comprising at least one phosphorodithioate internucleoside linkage of formula (I) (I) as defined in the description and in the claim. The oligonucleotide of the invention can be used as a medicament.

Abstract: The invention relates to a method of identifying stereodefined phosphorothioate oligonucleotide variants with reduced toxicity by creating and screening libraries of stereodefined chiral phosphorothioate variants for compounds with reduced toxicity, either in vitro or in vivo.

Abstract: The present invention relates to a gapmer oligonucleotide comprising at phosphorodithioate internucleoside linkage of formula (I) as defined in the description and in the claims. The oligonucleotide of the invention can be used as a medicament.

Abstract: The present invention relates to the field of oligonucleotide conjugates and to methods of synthesis thereof. In the present method a low-water content solvent environment allows a more efficient conjugation, reducing the amount of conjugate moiety needed and increasing the conjugation reaction speed.

Abstract: The present invention relates to antisense oligonucleotides that are capable of modulating expression of NF-?B1 in a target cell. The oligonucleotides are complementary to mammalian NFKB1 pre-mRNA intron sequence. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of cancer, inflammation or autoimmune diseases using the oligonucleotide.

Abstract: The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

Abstract: The present invention relates to compositions and methods for preparing splice variants of TNFalpha receptor (TNFR) in vivo or in vitro, and the resulting TNFR protein variants. Such variants may be prepared by controlling the splicing of pre-mRNA molecules and regulating protein expression with splice switching oligonucleotides or splice switching oligomers (SSOs) The preferred SSOs according to the invention target exon 7 or 8 of TNFR1 (TNFRSF1A) or TNFR2 (TNFRSF1A) pre-MRNA, typically resulting in the production of TNFR variants which comprise a deletion in part or the entire exon 7 or 8 respectfully. SSOs targeting exon 7 are found to result in a soluble form of the TNFR, which has therapeutic benefit for treatment of inflammatory diseases. The SSO's are characterised in that they are substantially incapable or incapable of recruiting RNaseH.

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 present invention relates to oligomeric compounds and conjugates thereof that target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for a range of medical disorders, such as hypercholesterolemia and related disorders.

Abstract: The present invention relates to oligomeric compounds and conjugates thereof that target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for a range of medical disorders, such as hypercholesterolemia and related disorders.