Abstract: The invention describes anti-cancer therapies comprising using an LRP5 antagonist in combination with an anti-PD1 antibody, each as described herein.

Abstract: This invention relates to thienopyrimidinones and their use as inhibitors of TRPA1 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of fibrotic diseases, inflammatory and auto-immune diseases and CNS-related diseases.

Abstract: It is disclosed an improved multi-step process for the preparation of a highly concentrated liquid formulation containing biomolecules comprising the steps of (a) a first ultrafiltration UF1; (b) a first diafiltration DF1; (c) a second diafiltration DF2; and (d) a second ultrafiltration UF2; wherein an aqueous solution of one or more salts, as liquid medium B, is used for step (b) and water or an aqueous solution of one or more salts, as liquid medium C, is used for step (c), wherein the one or more salts used for step (b) are the same or different from the one or more salts used for step (c) and wherein the liquid medium B has an ionic strength which is higher than the ionic strength of the liquid medium C. The process according to the present invention allows the preparation of well-defined highly concentrated formulations containing biomolecules, particularly proteins, intended for pharmaceutical or non-pharmaceutical use.

Abstract: The present invention relates to anti-SIRP? (Signal regulatory protein alpha) antibodies and antigen-binding fragments thereof for therapeutic and diagnostic methods and compositions using them.

Abstract: The present invention relates to pharmaceutical compositions comprising fixed dose combinations of a DPP-4 inhibitor drug and/or a SGLT-2 inhibitor drug, and metformin XR, processes for the preparation thereof, and their use to treat certain diseases.

Abstract: The present invention relates to the identification of a genomic integration site for heterologous polynucleotides in Chinese Hamster Ovary (CHO) cells resulting in high RNA and/or protein production. More specifically it relates to CHO cells comprising at least one heterologous polynucleotide stably integrated into the S100A gene cluster of the CHO genome and to methods for the production of said CHO cells. Further, the invention relates to a method for the production of a protein of interest using said CHO cell and to the use of said CHO cell for producing a protein of interest at high yield. Integration within these specific target regions leads to reliable, stable and high yielding production of an RNA and/or protein of interest, encoded by the heterologous polynucleotide.

Abstract: The invention relates to the field of cell culture technology. It concerns the knockdown, using RNA interference, or gene knockout, of activating transcription factor 6 beta (ATF6B), or the combination of ceramide synthase 2 (CERS2) and TBC1 domain family member 20 (TBC1D20) proteins, which play central roles in the cellular secretion pathway. This downregulation leads to improved secretion of biopharmaceutically relevant products produced in mammalian cells. The invention specifically relates to mammalian cells having enhanced secretion of a recombinant therapeutic protein compared to a control cell, a method of producing said mammalian cell, a method for the production of a recombinant secreted therapeutic protein and the use of said mammalian cell for increasing the yield of a recombinant secreted therapeutic protein.

Abstract: This invention relates to a novel process for making alkyl 7-amino-5-methyl-[1,2,5]-oxadiazolo[3,4-b]pyridine-carboxylate.

Abstract: The present invention provides a basal cell culture medium and a feed medium with novel amino acid ratios and/or iron choline citrate as iron carrier that result in improved performance of mammalian cell culture processes, such as CHO cultivation and protein production processes, in particular in increased product titer (e.g. of monoclonal antibodies). Also provided are methods for culturing mammalian cells and producing a protein of interest using said basal cell culture medium and optionally feed medium. The invention also provides for a medium platform that comprises (i) the basal cell culture medium and (ii) the feed medium.

Abstract: The invention relates to substituted 3-phenoxyazetidin-1-yl-pyrazines of general formula (I) which are agonists of GPR52, useful in treating central nervous system diseases and other diseases. In addition, the invention relates to the 3-phenoxyazetidin-1-yl-pyrazines of general formula (I) for use as a medicament, pharmaceutical compositions comprising the 3-phenoxyazetidin-1-yl-pyrazines of general formula (I) and processes for preparing pharmaceutical compositions as well as processes for manufacture the compounds according to the invention.

Abstract: The present invention relates to a method for producing the anti-IL36R antibody spesolimab. More specifically, the present invention relates to a method of producing spesolimab with a serum-free cell culture medium in a fed-batch culture in the presence of reduced copper and increased iron concentrations. In addition, the present invention relates to a composition comprising low levels of basic species of spesolimab and/or low levels of spesolimab species with high mannose structures.

Abstract: The present invention relates to novel pyridazines, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment and/or prevention of diseases and disorders mediated by autotaxin.

Abstract: The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts therefore, wherein R1 to R6, A, U, V, W, X, Y, and Z are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Abstract: A method for determining water content of a preferably solid pharmaceutical preparation/sample, wherein at least two electrodes are brought into direct contact with the pharmaceutical preparation/sample in a measurement chamber such that the electrodes are electrically connected to one another via the pharmaceutical preparation/sample, and wherein a resistance of the pharmaceutical preparation/sample is determined by means of the electrodes and the water content and/or the sample quality of the pharmaceutical preparation/sample is determined with the ohmic resistance.

Abstract: The present invention relates to novel pyridazines of the below formula (I), processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment and/or prevention of diseases and disorders mediated by autotaxin:

Abstract: Disclosed are solid forms of an inhibitor of glycine transporter-1 (GlyT1). The invention also relates to methods of making these solid forms, pharmaceutical compositions comprising these solid forms, and their use for medical conditions responsive to treatment with an inhibitor of glycine transporter-1.

Abstract: Methods for continuously inactivating a virus during manufacture of a protein are provided. Steps include (1) combining, at a single predetermined volumetric ratio, a composition including the protein, and a composition including a virus-inactivation reagent, to obtain a treatment composition having a predetermined property for inactivation of a virus; (2) transferring the treatment composition to a treatment vessel; (3) incubating the treatment composition in the treatment vessel at predetermined conditions; and (4) subjecting the treatment composition to a post-treatment processing operation. The single predetermined volumetric ratio has been selected to ensure that the predetermined property of the treatment composition is maintained across a range of concentrations predicted for the protein in the composition including the protein.

Abstract: The present invention relates to new anti-angiopoietin 2 (ANGPT2) neutralizing antibodies for therapeutic and diagnostic methods and composition using them.

Abstract: The present invention relates to a novel mechanism to control RNA virus replication and gene expression using a conditional protease approach using a specific protease inhibitor for regulation. More specifically it relates to a single-stranded RNA virus, preferably of the order Mononegavirales, comprising a polynucleotide sequence encoding at least one protein essential for viral transcription and/or replication, a protease and a cleavage site for said protease. The protease can be inhibited using a protease inhibitor and hence the protease and the cleavage site for said protease form a regulatable switch. By changing the insertion site of the regulatable switch from an INTRA- to an INTER-molecular location in the at least one protein essential for viral transcription and/or replication, the effect of the protease inhibitor can be altered from an ON switch to an OFF switch. RNA virus may further encode a heterologous protein, the expression of which is then regulated by regulating viral activity.

Abstract: The present invention relates to novel purines of general formula A processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment or prevention of conditions having an association with NR2B negative allosteric modulating properties.