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 nucleic acid molecules that are complementary to both PAP associated domain containing 5 (PAPD5) and PAP associated domain containing 7 (PAPD7), leading to inhibition of the expression of both PAPD5 and PAPD7 when using a single nucleic acid molecule. The invention also provides for PAPD5 and PAPD7 specific nucleic acid molecules for use in treating and/or preventing a HBV infection, in particular a chronic HBV infection. Also comprised in the present invention is a pharmaceutical composition for use in the treatment and/or prevention of a HBV infection.

Abstract: Recent advancements in LNA oligonucleotides include the use of amine linkers to link an LNA antisense oligonucleotide to a conjugate group. For example please see WO2014/118267. The present invention originates from the identification of a problem when de-protecting LNA oligonucleotides which comprise an aliphatic amine group and DMF protected LNA G nucleoside, which results in the production of a +28 Da impurity. This problem is solved by using acyl protection groups on the exocyclic nitrogen of the LNA-G residue, rather than the standard DMF protection group.

Abstract: The invention relates to the field of oligonucleotide therapeutics, and in particular to the use of a cleavable, e.g. a phosphodiester region covalently attached to a conjugate, a targeting group or blocking group to enhance the properties of the oligonucleotides, for example to improve the therapeutic index.

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: 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: 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: 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 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 analog, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analog or a 2-deoxynucleotide, subscript “s” designates a phosphorothioate link between neighboring nucleotides/LNA nucleotide analogs, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighboring nucleotides/LNA nucleotide analogs, 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: 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 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 very short heavily modified oligonucleotides which target and inhibit microRNAs in vivo, and their use in medicaments and pharmaceutical compositions.

Abstract: The present invention is directed to novel double-stranded short interfering (siRNA) analogs 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 analogs comprising a sense strand and an antisense strand, wherein each strand comprises 12-35 nucleotides and wherein the siRNA analogs comprise at least one locked nucleic acid (LNA) monomer.

Abstract: Disclosed are oligonucleotides which target and hybridize to nucleic acid molecules encoding FGFR3, leading to reduced expression of FGFR3. Reduction in the aberrant expression of FGFR3 is beneficial for the treatment of certain medical disorders, such as achondroplasia.

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 invention provides for LNA oligomers, for the treatment of a metabolic or liver disorder, wherein the LNA oligomer is administered orally in a unit dose of less than 50 mgs/kg, wherein the LNA oligomer is administered in the presence of a penetration (permeation) enhancer.

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 invention relates to conjugates of antisense oligonucleotides (oligomers) that target the APOB gene at position 2265 to 2277.

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: 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.