Abstract: The invention relates to novel TNF family ligand trimer-containing antigen binding molecules comprising (a) at least one moiety capable of specific binding to a target cell antigen, (b) a polypeptide comprising three ectodomains of a TNF ligand family member or fragments thereof that are connected to each other by peptide linkers and (c) a Fc domain composed of a first and a second subunit capable of stable association, and to methods of producing these molecules and to methods of using the same.

Abstract: The present invention relates to oligonucleotides which up-regulate or restore the expression of progranulin in cells, and their use in the treatment of neurological disorders, and disorders associated with progranulin haploinsufficiency.

Abstract: Disclosed is a method for assessing a cognition and movement disease or disorder in a subject. In the method, a qualimetric activity parameter for cognition and/or fine motoric activity measurements is determined from a dataset of measurements obtained from the subject using a mobile device. The qualimetric activity parameter is compared to a reference and the disease or disorder is thereby assessed. A method identifying whether a subject will benefit from a therapy for a cognition and movement disease or disorder is also disclosed. The method can be carried out with a mobile device having a processor, a sensor and a database as well as software that carries out the method. Also disclosed is a system having a mobile device with a sensor and a remote device having a processor and a database and software that carries out the method for assessing a cognition and movement disease or disorder.

Abstract: This invention relates to a new medical use for certain chemical compounds and pharmaceutical compositions containing them. The invention relates to compounds which are mGlu2/3 negative allosteric modulators for use in the treatment of intellectual disabilities. In another aspect, the invention relates to a pharmaceutical composition for use in the treatment of intellectual disabilities comprising a compound according to the invention and a pharmaceutically acceptable carrier.

Abstract: The present invention relates to the treatment of subjects having CD20-positive cell proliferative disorders (e.g., B cell proliferative disorders, such as non-Hodgkin's lymphomas). More specifically, the invention pertains to the treatment of subjects having a CD20-positive cell proliferative disorder (e.g., B cell proliferative disorder) by administering a combination of an anti-CD20/anti-CD3 bispecific antibody and an anti-CD79b antibody drug conjugate.

Abstract: The present invention relates to ethynyl derivatives of formula I with variables as defined herein, or to a pharmaceutically acceptable acid addition salt thereof Compounds of formula I are metabotropic glutamate receptor antagonists (negative allosteric modulators) for use in the treatment of, e.g., anxiety and pain, depression, Fragile-X syndrome, autism spectrum disorders, Parkinson's disease, and gastroesophageal reflux disease (GERD).

Abstract: The invention provides 7-phenoxy-N-(3-azabicyclo[3.2.1]octan-8-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-amine derivatives and related compounds of the general formula (I) wherein R1, Ar, n and m are as described herein, compositions including the compounds, processes of manufacturing the compounds and the compounds for use in methods of medical treatment. The present compounds are as gamma-secretase modulators for the treatment of diseases associated with the deposition of ?-amyloid in the brain, such as Alzheimer's disease, cerebral amyloid angiopathy, cochlear synaptopathy, hearing loss, hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), multi-infarct dementia, dementia pugilistica and Down syndrome. The present description discloses the preparation of exemplary compounds as well as pharmacological data thereof (e.g. pages 54 to 74; examples 1 to 64; table). An exemplary compound is e.g. (R)-7-(3,5-difluorophenoxy)-N-((1R,5S,8s)-3-(6-methoxypyridazin-4-yl)-3-azabicyclo[3.2.

Abstract: The present invention relates to compounds of formula (I), wherein R1, R2, R3, Y, Q1, Q2, Q3, Q4 and Q5 are as described herein, and their pharmaceutically acceptable salt thereof, and compositions including the compounds and methods of using the compounds.

Abstract: The present invention is directed to the combination therapy of an anti-CD20 antibody with a BTK inhibitor for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with a type I anti-CD20 antibody or an afucosylated humanized B-Ly1 antibody and a BTK inhibitor.

Abstract: The present disclosure relates generally to rapid-release pharmaceutical dosage unit tablets containing small molecule API medicines. In some instances the API is an inhibitor of Ras proteins, such as K-Ras, H-Ras, and N-Ras, that have a G12C mutation. Such tablets also contain a disintegrant and an excipient. More specifically, the present disclosure relates to pharmaceutical dosage unit tablets containing divarasib, or a pharmaceutically acceptable salt thereof, an extragranular disintegrant, and an extragranular excipient, and to processes for preparing the tablets from granules formed by dry granulation.

Abstract: Provided are methods for the treatment of a Tau associated disease, comprising administering to a subject an effective amount of a compound modulating a protein-protein interaction between a protein comprising a NTF2-like domain having the amino acid sequence set forth as SEQ ID NO: 3 and Tau protein.

Abstract: Herein is reported a method for the generation of multispecific antibodies directly on the cell-surface at the site of action by a half-antibody exchange reaction between two 2/3-IgGs or two 2/3-BiFabs destabilized in one half by asymmetric perturbing mutations fostering the generation of correctly assembled full length bi- or multispecific antibodies. The method is performed in the absence hinge region disulfide bonds in the starting 2/3-IgGs or 2/3-BiFabs.

Abstract: A time-pressure-filling system for filling liquid drug product into containers is disclosed. The time-pressure-filling system has a storage vessel for storing the liquid drug product and a surge vessel. The surge vessel is configured for single use and is at least partially made of a rigid plastic material. A supply line feeds the liquid drug product from the storage vessel into the surge vessel in a pressurized fashion. A pressure control line is provided for applying a control pressure to the surge vessel, a dispenser is provided for dispensing the liquid drug product into the containers, and a dispensing line connects the surge vessel to the dispenser. A pressure sensor determines pressure in the dispensing line and a valve controls flow of the liquid drug product through the dispensing line. A surge vessel for use in the time-pressure-filling system and a time-pressure-filling method are also disclosed.

Abstract: The invention relates to a compound of formula (I) wherein A1 and R1-R4 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

Abstract: Provided are mutant interleukin-7 polypeptides, immunoconjugates, particularly immunoconjugates comprising a mutant interleukin-7 polypeptide and an antibody that binds to PD-1. In addition, provided are polynucleotide molecules encoding the mutant interleukin-7 polypeptides or the immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. Also provided are methods for producing the mutant interleukin-7 polypeptides, immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

Abstract: Herein is reported a composition comprising a pair of a first nucleic acid and a second nucleic acid, wherein the first nucleic acid comprises in the order a first part of a stem nucleic acid sequence, a cleavage site, a first stem loop nucleic acid sequences which 5?- and 3?-parts form a duplex, a first part of a catalytic core sequence, a second stem loop nucleic acid sequences which 5?- and 3?-parts form a duplex, a second part of the catalytic core sequence, and a second part of the stem nucleic acid sequence, which is complementary to the first part of the stem nucleic acid sequence and, thus, form a duplex therewith, wherein the second nucleic acid is complementary to at least a part of the first or the second part of the stem nucleic acid sequence, wherein binding of the second nucleic acid to the first nucleic acid results in a conformational change of the first nucleic acid, which is at least one of the dissociation of the first part of the first stem sequence from the second part of the stem sequenc

Abstract: The present invention generally relates to humanized antigen binding receptors capable of specific binding to an Fc domain comprising the amino acid mutation P329G according to EU numbering. The present invention also relates to T cells, transduced with an antigen binding receptor which is recruited by specifically binding to/interacting with the mutated Fc domain of therapeutic antibodies.

Abstract: Provided herein are methods of synthesizing quinazoline compounds comprising at least one atropisomeric center.

Abstract: Herein is reported an immunoassay for quantifying the amount of anti-drug antibody, which anti-drug antibody can specifically bind to a drug antibody, which drug antibody can specifically bind to a therapeutic target, in a serum or plasma sample comprising the steps of a) incubating the serum or plasma sample at a pH value that is about the pI value of the target, and optionally removing formed precipitate after the incubation, b) incubating the serum or plasma sample obtained in step a) at a pH value of about 2, and optionally centrifuging the incubated sample to remove formed precipitate, c) adjusting the pH value to about 7.

Abstract: It is disclosed crystalline forms of (R)-N-(4-([1, 2, 4]triazolo [1, 5-c]pyrimidin-7-yloxy)-3-methylphenyl)-5-((3, 3-difluoro-1-methylpiperidin-4-yl)oxy)-6-methoxyquinazolin-4-amine, methods for the preparation thereof, pharmaceutical compositions comprising one or more of the crystalline forms as an active ingredient, and use of the crystalline forms in the treatment of hyperproliferative diseases.