Abstract: Provided herein are solid forms, salts, and formulations of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol, processes and synthesis thereof, and methods of their use in the treatment of cancer.

Abstract: Assays to analyze quality and quantity attributes of fixed dose combinations are provided. In particular, assays for fixed dose combinations of two anti-HER2 antibodies, and for subcutaneous formulations comprising pertuzumab and trastuzumab are described herein.

Abstract: The present invention relates to antibodies against human CD19 (anti-human CD19 antibodies), methods for their production, pharmaceutical compositions containing these antibodies, and methods of using the same.

Abstract: Disclosed herein are novel copolymers of poly(?-caprolactone) (PCL) and polydopamine (PDA), optionally further comprising a PEG chain, methods for making them as well as their use in pharmaceutical preparations, especially implants or in situ gelling depots, for the treatment of ocular disorders or eye diseases.

Abstract: Provided are combination therapies comprising inavolisib (a.k.a. GDC-0077) and other HER2-targeted therapies (e.g., pertuzumab and trastuzumab) for the treatment of HER2-positive cancers; and methods of treating HER2 positive (HER2+) cancers in a patient (preferably a patient with a PIK3CA mutant breast cancer) comprising administering a therapeutically effective amount of inavolisib and a HER2-targeted therapy (e.g., trastuzumab, pertuzumab, or a combination of trastuzumab and pertuzumab).

Abstract: The present invention relates to a modified antibody comprising a heavy chain and a light chain, wherein the heavy chain or/and the light chain comprises one or more first recognition site(s) for the transglutaminase from Kutzneria albida (KalbTG) or a functionally active variant thereof. The one or more first recognition site(s) are introduced at one or more selected position(s) within the antibody's heavy chain and/or light chain. The invention further relates to one or more nucleic acids encoding the modified antibody according to the invention as well as a covalent conjugate comprising (i) the modified antibody according to the invention and (ii) one or more non-antibody moieties (payload(s)) covalently conjugated to the one or more first recognition site(s) either directly or via a first linker. In certain embodiments, the non-antibody moiety comprises a therapeutic entity and optionally a second linker.

Abstract: Processes for preparing biheteroaryl compounds are provided, including the biheteroaryl compound 3-(difluoromethoxy)-5-[2-(3,3-difluoropyrrolidin-1-yl)-6-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrimidin-4-yl]pyridin-2-amine. Among other advantages, the processes provide for: the use of solvents that are relatively non-toxic and inexpensive; reduced usage of expensive precious metal catalysts; reaction temperature reduction in certain steps; the use of relatively non-toxic oxidation agents; the use of inexpensive transition metal catalysts; a reduction of molar ratios of certain reactants thereby improving process efficiency while reducing cost and waste; significantly higher reactant concentrations in certain steps; elimination of the need for multiple chromatographic purification steps; elimination of the need for certain extraction steps using organic solvent; and provide for higher yield and improved purity.

Abstract: A method for predicting the metabolic state of a cell culture of cells of a specific cell type includes providing a metabolic model of a cell of the specific cell type, and performing at each of a plurality of points in time during cultivation of the cell culture, receiving measured concentrations of a plurality of extracellular metabolites and a measured cell density in the culture medium; inputting the received measurements as input parameter values to a trained machine learning program logic—MLP; predicting extracellular fluxes of the extracellular metabolites at a future point in time by the MLP; performing metabolic flux analysis to calculate the intracellular fluxes at the future point in time based on the predicted extracellular fluxes and the stoichiometric equations of the metabolic model.

Abstract: The present invention provides novel compounds having the general formula (I): wherein R1 to R3 are as described herein, or a pharmaceutically acceptable salt thereof, compositions including the compounds and methods of using the compounds.

Abstract: A syringe (18) has a longitudinal body (28) with an interior (228) in which a pharmaceutical substance is arranged, a needle connected to one longitudinal end of the body (228) and a rigid needle shield (38) encasing the needle. The rigid needle shield (38) is essentially water vapour tight. The syringe (18) according to the invention allows for preventing needle clogging and, thus, proper provision of pharmaceuticals, particularly by subcutaneous, intramuscular or ocular injection.

Abstract: The present invention is directed to compositions and methods for treating hepatitis B virus infection. In particular, the present invention is directed to a combination therapy comprising administration of a TLR7 agonist and an HBV capsid assembly inhibitor for use in the treatment of chronic hepatitis B patient.

Abstract: The problem to be solved is to provide a humanized anti-IL-6 receptor antibody AMA-containing formulation which is suitable for subcutaneous administration, wherein dimerization or deamidation is prevented during long-term storage. The present application is directed to a stable antibody-containing liquid formulation characterized by containing arginine and histidine buffer. A method of inhibiting deamidation or dimerization of such an antibody in a concentrated liquid formulation includes histidine buffer in the liquid formulation.

Abstract: Herein is reported a method for the enzymatic production of an antibody with a modified glycosylation in the Fc-region comprising the steps of incubating the antibody light chain affinity ligand-bound monoclonal antibody with a glycosylation in the Fc-region with a first enzyme for a time sufficient and under conditions suitable to modify the glycosylation of the Fc-region, recovering the antibody from the antibody light chain affinity ligand, incubating the recovered antibody in solution with a second enzyme for a time sufficient and under conditions suitable to modify the glycosylation of the Fc-region to a defined form, separating the antibody with the modified glycosylation in the Fc-region from the second enzyme in a cation exchange chromatography, and thereby producing the antibody with a modified glycosylation in the Fc-region.

Abstract: The present invention relates to compounds of formula (I), (I), wherein R1, R2, R3, R4 and A are as described herein, and their pharmaceutically acceptable salt thereof, and compositions including the compounds and methods of using the compounds.

Abstract: Separating apparatus, comprising a sedimentation settler and a collection vessel disposed underneath and being in fluid communication with the sedimentation settler, the collection vessel forming a receiving chamber having an outlet at or adjacent to the chamber bottom and having an inlet opening, wherein the collection vessel is arranged such the flow direction of the fluid in the area underneath the sedimentation settler is substantially in line with the direction of the channels of the sedimentation settler.

Abstract: The invention provides novel imidazole pyrazole derivatives having the general formula (I), and pharmaceutically acceptable salts thereof, wherein R1-R7 are as described herein: Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and resulting diseases.

Abstract: The invention relates to a process for the production of a mixed P?O/P?S backbone oligonucleotide comprising a selective oxidation of an intermediary phosphite triester compound of formula I into a phosphodiester compound of formula II according to the scheme with an oxidation solution obtained by mixing iodine, an organic solvent and water, characterized in that the oxidation solution has been aged for a time period that is sufficient to selectively oxidize the phosphite triester compound of formula I into the phosphodiester compound of formula II without oxidizing the phosphorothioate intenucleotide linkages.

Abstract: The present invention provides a pharmaceutical composition comprising an effective dosage of at least one anti miR-134 oligonucleotide for administration to a mammal suffering from a disease wherein lowering of the activity of miR-134 is beneficial, wherein single administration of the pharmaceutical composition time interval between each administration is at least 50 days and methods using such composition.

Abstract: The present invention generally relates to novel protease-activatable T cell activating bispecific molecules and idiotype-specific polypeptides. The present invention also relates to polynucleotides encoding such protease-activatable T cell activating bispecific molecules and idiotype-specific polypeptides, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the protease-activatable T cell activating bispecific molecules and idiotype-specific polypeptides of the invention, and to methods of using these protease-activatable T cell activating bispecific molecules and idiotype-specific polypeptides in the treatment of disease.

Abstract: The present invention provides novel compounds having the general formula: wherein A1 to A4, L1, L2, R1 and R2 are as described herein, compositions including the compounds and methods of using the compounds.