Abstract: The invention relates to novel compounds having the general formula I wherein R1, R2, X1, X2, X3 and W are as described herein, composition including the compounds and methods of using the compounds.

Abstract: Provided are oligonucleotides that increase the expression of glucocerebrosidase (GBA) in cells; conjugates, salts and pharmaceutical compositions thereof; and methods for treatment of diseases associated with reduced expression of GBA, including Gaucher's disease and/or Parkinson's disease. The oligonucleotides may comprise a contiguous sequence complementary to contiguous bases in the 3? untranslated region (UTR) of the GBA mRNA transcript.

Abstract: The invention provides compounds having the general formula (I) wherein A, L, R1 and R2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

Abstract: A computer-implemented method of identifying a tissue type in digital histological images of human or animal tissue comprises training a convolutional neural network (CNN) to identify a particular target tissue type in a plurality of training data sets of digital histological images, inputting a test data set of digital histological images into the trained CNN, and receiving as an output result of the CNN a probability value that the inputted test data set corresponds to the target tissue type. A training procedure of the CNN comprises performing with training data sets: selecting a target tissue area of the training data set, dividing the target tissue area into different sets of tiles of constant size but having different image magnifications, and inputting the sets of tiles into a multi-headed CNN, wherein the sets of tiles having different image magnifications are processed in parallel and the features of the sets of tiles are concatenated.

Abstract: The invention relates to a compound of formula (I) wherein A1, A2, X and R1-R3 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

Abstract: Provided herein are methods of treating and/or managing non-Hodgkin lymphoma, which comprise administering to a patient 2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione (“Compound A, A-S, or A-R”), or an enantiomer or mixture of enantiomers, a tautomer, an isotopolog, a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, in combination with glofitamab or mosunetuzumab.

Abstract: Herein is reported a method for determining the presence of hydrolase activity in a sample by incubating the sample in a buffered solution, which comprises an artificial hydrolase substrate that comprises an ester bond covalently linking an alcohol residue, which is conjugated to a label for removal, and a carboxylic acid residue, which is conjugated to a capture and detection label, as well as bovine serum albumin, and thereafter determining or quantifying, respectively, the released carboxylic acid in the free alcohol depleted incubation mixture.

Abstract: The present invention relates to a set of heterodimeric polypeptides and its uses, e.g. for generating multispecific antigen binders by polypeptide chain exchange.

Abstract: Herein are reported antibody Fc-region conjugates useful for the treatment of disease and methods for producing the same comprising incubating under conditions that allow for sortase mediated transpeptidation: (i) a dimeric antibody heavy chain Fc region polypeptide comprising the amino acid sequence GGCPX4C, wherein X4 is either S or P (SEQ ID NO: 08) at its N terminus (ii) an antigen binding polypeptide comprising within its 20 C-terminal amino acid residues the amino acid sequence GnSLPX1TG, wherein X1 is any amino acid residue, with n=1, 2, or 3 (SEQ ID NO:2); and (iii) a Sortase A enzyme; and thereby producing the antibody Fc-region conjugate, wherein the antibody Fc-region conjugate comprises two polypeptide chains, and at least one polypeptide chain comprises the amino acid sequence GnSLPX1TGGCPX4C, wherein n=1, 2 or 3, X1 is any amino acid residue, and X4 is either S or P (SEQ ID NO 9).

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: Herein is reported a method for co-cultivating B-cells in the presence of phorbol myristate acetate, IL-1beta, TNFalpha, IL-2, IL-10 and IL-6.

Abstract: The present invention relates to compounds of formula (I), wherein R1 to R8, Y, A, Q, X and M are as described herein, and their pharmaceutically acceptable salt thereof, and compositions including the compounds and methods of using the compounds.

Abstract: Described herein are amorphous and crystalline forms of pharmaceutically acceptable salts of the TAAR1 agonist 5-ethyl-4-methyl-N-[4-[(2S) morpholin-2-yl]phenyl]-1H-pyrazole-3-carboxamide. Also described are pharmaceutical compositions suitable for administration to a mammal that include the TAAR1 agonist, and methods of using the TAAR1 agonist, alone and in combination with other compounds, for treating diseases or conditions that are associated with TAAR1 activity.

Abstract: Herein is reported a method for the determination of a bispecific antibody in a serum-containing sample comprising the steps of first incubating a solid phase to which a capture antibody specifically binding to the bispecific antibody has been immobilized with the sample to form an immobilized capture antibody-bispecific antibody-complex, thereafter incubating the solid phase with a replacement antibody that competes with the capture antibody for binding to the bispecific antibody and thereby forming a solution comprising a replacement antibody-bispecific antibody-complex, and determining in the solution the replacement antibody-bispecific antibody-complex.

Abstract: Compounds having the general formula (I) wherein R1, R2, R3, R4, R5 and X are as described herein, compositions including the compounds and methods of using the compounds.

Abstract: A method includes accessing a digital pathology image that depicts tumor cells sampled from a subject. A plurality of patches may be selected from the digital pathology image, wherein each of the patches depicts tumor cells. A mutation prediction may be generated for each of the patches, wherein the mutation prediction represents a prediction of a likelihood that an actionable mutation appears in the patch. Based on the plurality of mutation predictions, a prognostic prediction related to one or more treatment regimens for the subject may be generated. The prognostic prediction may be based on determining one or more mutational contexts of the digital pathology image as an unknown driver or a tumor suppressor, an oncogene driver mutation, or a gene fusion.

Abstract: The present invention generally relates to the treatment of inflammatory lung disease, particularly chronic obstructive pulmonary disease (COPD), and to therapeutic agents useful therefor. In particular, the present invention relates to antibodies, including bispecific antibodies, useful for the treatment of inflammatory lung disease. In addition, the invention relates to polynucleotides encoding such antibodies, vectors and host cells comprising such polynucleotides, as well as methods for producing such antibodies.

Abstract: The present invention relates to intermediates and processes useful for preparing 1-ethyl-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)piperidine-4-sulfonamide 5 and salts thereof. The present invention further relates to 1-ethyl-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)piperidine-4-sulfonamide and salts thereof when prepared by such processes and to associated pharmaceutical compositions and uses for the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition.

Abstract: Provided herein are combination therapies comprising a BRAF inhibitor (e.g., a compound of formula (I), or a pharmaceutically acceptable salt thereof) and an EGRF inhibitor (EGRFi), as well as pharmaceutical compositions, methods and uses thereof.

Abstract: The present invention relates to multispecific antibodies, their manufacture and use.