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 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 provides LNA therapeutics oligonucleotide carbohydrate conjugates with considerably enhanced potency, extended therapeutic index and reduced toxicity.

Abstract: The present invention relates to conjugates of LNA antisense oligonucleotides (oligomers) that target ApoB.

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 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: A system and method for determining the integrity of a sealed container closure assembly wherein the closure is secured to the container by a force applying member and the integrity is determined by converting the force used to secure the closure into a force signal and comparing the force signal to a reference signal, which is reflective of the force used during a closure operation which resulted in seal integrity. The force signal which comprises a series of electrical signals is compared to a series of corresponding reference signals or is a single signal compared to a reference signal at a plurality of points during the closure operation. An indicator is used to indicate when a preselected number of acceptable or non-acceptable comparisons are reached.

Abstract: A method, apparatus and system for determining the integrity of a container sealed by means of a closure comprising a resilient sealing element and a cup-like cap having a top and a depending skirt compressing the resilient sealing element over the discharge opening in the container. The invention consists of verifying seal integrity by applying an external force to the cap and measuring the force required to effect initial movement thereof to overcome the residual static force in the resilient sealing element and by comparing the measured force which is essentially equal to the residual static force in the resilient sealing element to a predetermined standard known to provide an acceptable seal. It is known that when the force between the crimped edge of the cap and the container is zero which occurs upon initial displacement of the cap relative to the container, the externally applied force is essentially equal to the residual static force in the resilient sealing element.

Abstract: A container-closure assembly. The container has a discharge opening, a locking flange of generally circular opening with a frusto conical side face diverging downwardly from the axial end face of the opening. A shaping surface is formed below the locking flange of non-circular cross section and has a maximum cross section less than the cross section of the locking flange and at least one cam member extends axially downwardly from the locking flange. The cap of the assembly has a top and a peripheral skirt portion engaging under the locking flange and extending at least to the juncture of the locking flange and shaping surface. The cap is of a deformable material whereby the skirt is shaped to a generally circular shape by the cam member upon relative rotation of the cap and container.