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.

Abstract: The present invention relates to a polynucleotide that comprises at least one phosphorothioate internucleoside linkage and at least one guanosine analogue comprising a guanine nucleobase analogue selected from the group consisting of: formula (I) and formula (II). Polynucleotides comprising such guanosine analogues show a relative reduced neurotoxicity compared to polynucleotides with natural guanosine.

Abstract: This invention generally relates to the field of phosphoramidite derivatives. In particular, the invention relates to N-Acetylgalactosamine phosphoramidite molecules and to conjugates of nucleic acid molecules with N-Acetylgalactosamine containing molecules. Also provided are methods for preparation of these molecules and possible uses thereof, in particular in medicine.

Abstract: The present invention relates to an optimized method for preparing a P(V) monomer of formula (IIIa) or (IIIb) from a nucleoside using DBU as a base at about 0.8 equivalent to nucleoside.

Abstract: Stereodefined phosphorothioate oligonucleotides, related nucleoside monomers and methods of synthesis of both are described. The disclosed isobutyryl protected L-LNA-G monomers have following Formula 50 or 51 where R3 is independently CH2ODMTr or CH2OMMTr and R8, when present, is cyanoethyl. The monomers have improved solubility and stability characteristics, resulting in improved efficacy in oligonucleotide synthesis.

Abstract: This invention generally relates to the field of phosphoramidite derivatives. In particular, the invention relates to N-Acetylgalactosamine (GalNAc) compounds, in particular phosphoramidite or phosphonoamidite molecules of formula (I) with only one GalNAc moiety (formula II) and to conjugates of nucleic acid molecules with such N-Acetylgalactosamine containing molecules. Also provided are methods for preparation of these molecules and possible uses thereof, in particular in medicine. Wherein R1 is H or C1-6alkyl; R2 is a triphenylmethyl-based hydroxyl protecting group R3 is a phosphorus-containing group, particularly a phosphoramidite or a phosphonoamidite group, and K is represented by the general formula (II).

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 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: 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 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: This invention generally relates to the field of phosphoramidite derivatives. In particular, the invention relates to N-Acetylgalactosamine phosphoramidite molecules and to conjugates of nucleic acid molecules with N-Acetylgalactosamine containing molecules. Also provided are methods for preparation of these molecules and possible uses thereof, in particular in medicine.

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 methods for identifying improved stereodefined phosphorothioate oligonucleotide variants of antisense oligonucleotides utilising sub-libraries of partially stereodefined oligonucleotides. The methods allow for the efficient identification of stereodefined variants with improved properties, such as enhanced in vitro or in vivo activity, enhanced efficacy, enhanced specific activity, reduced toxicity, altered biodistribution, enhanced cellular or tissue uptake, and/or enhanced target specificity (reduced off-target effects).

Abstract: The present invention relates to the field of stereodefined phosphorothioate oligonucleotidess and to nucleoside monomers and methods of synthesis thereof. Herein are disclosed acyl protected L-LNA-G monomers which have improved solubility and stability characteristics, and result in improved efficacy in oligonucleotide synthesis.

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.

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.

Abstract: The invention relates to the field of oligonucleotide therapeutics, and in particular to poly oligo oligonucleotides conjugates where two or more antisense oligonucleotides are covalently linked by physiologically labile linkers, and to a biocleavable functional group such as a conjugate group.