Abstract: The invention provides new heterocyclic compounds having the general formula (I) wherein A and R1 to R4 are as described heroin, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

Abstract: The invention relates to a blood treatment device configured to dephosphorylate extracellular adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and/or lipopolysaccharide (LPS) in the blood of a patient in need thereof in an extracorporeal blood circuit, wherein the device comprises a matrix having alkaline phosphatase (AP) immobilized thereon. The invention further relates to an extracorporeal blood circuit comprising a blood treatment device of the invention and to the blood treatment device for use as a medicament or to methods of treating an infection, preferably a blood or systemic infection, such as sepsis, and/or for the treatment of sepsis-associated acute kidney injury (AKI).

Abstract: The present invention provides compounds which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and their use for the treatment of abnormal cellular proliferation. The present invention also provides compounds that may be used as synthetic intermediates in the synthesis of bifunctional compounds used for targeted protein degradation.

Abstract: Disclosed herein are polypeptides, and methods of making and using such polypeptides, that comprise a bispecific antibody construct covalently linked to an extended recombinant polypeptide comprising a barcode fragment releasable from said polypeptide upon digestion by a protease, and a Release Segment that can be proteolytically cleaved wherein said cleavage releases the bispecific antibody construct from the extended recombinant polypeptide.

Abstract: A peritoneal dialysis (“PD”) system (10) including a PD machine (20); a patient line (50) extending from the PD machine (20); and a filter set (100) in fluid communication with the patient line (50), the filter set (100) including a filter body (110, 150, 190) housing first and second filter membranes (112a, 112b, such as a sterilizing grade or bacteria reduction filter membranes), the filter body (110, 150, 190) configured to be placed in different arrangements such that fresh PD fluid (i) flows through the first filter membrane (112a) and then through the second filter membrane (112b) or (ii) splits and flows through first and second filter membranes (112a, 112b) in parallel.

Abstract: A peritoneal dialysis (“PD”) system (10) includes a PD machine (20); a patient line (50) extending from the PD machine (20); and a filter set (100) in fluid communication with the patient line (50), the filter set (100) including a filter membrane (120, e.g., a sterilizing grade filter membrane or a bacteria reduction filter membrane) positioned and arranged such that fresh PD fluid flows through the filter membrane (120) into a filtered fluid compartment (106f), wherein the filtered fluid compartment (106f) includes an outlet (1060) to a port (106p), and wherein the port (106p) is in fluid communication with a circumferential used PD fluid channel (106c) positioned and arranged to carry used PD fluid around the filter membrane (120) without contacting the filter membrane (120). A method for priming filter set (100) is also disclosed.

Abstract: The invention relates to a blood treatment device configured to dephosphorylate extracellular adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and/or lipopolysaccharide (LPS) in the blood of a patient in need thereof in an extracorporeal blood circuit, wherein the device comprises a matrix having alkaline phosphatase (AP) immobilized thereon. The invention further relates to an extracorporeal blood circuit comprising a blood treatment device of the invention and to the blood treatment device for use as a medicament or to methods of treating an infection, preferably a blood or systemic infection, such as sepsis, and/or for the treatment of sepsis-associated acute kidney injury (AKI).

Abstract: Disclosed herein are antibodies and antibody fragments capable of binding to claudin 18.2.

Abstract: Provided herein are, inter alia, antibody binding domains for cluster of differentiation 3 T cell receptor (CD3), antibody binding domains for epidermal growth factor receptor (EGFR), cleavable linker sequences, and protease-activatable bispecific fusion proteins such as protease-activatable T cell engagers, as well as uses and methods of treatment.

Abstract: Disclosed herein are polypeptides, and methods of making and using such polypeptides, that comprise a bispecific antibody construct covalently linked to an extended recombinant polypeptide comprising a barcode fragment releasable from said polypeptide upon digestion by a protease, and a Release Segment that can be proteolytically cleaved wherein said cleavage releases the bispecific antibody construct from the extended recombinant polypeptide.

Abstract: The present invention is related to antibodies and antigen-binding fragments of antibodies that specifically bind the SARS-CoV-2 glycoprotein S (spike) as well as diagnostic and therapeutic methods of using those antibodies.

Abstract: Disclosed herein are polypeptides, and methods of making and using such polypeptides, that comprise a bispecific antibody construct covalently linked to an extended recombinant polypeptide comprising a barcode fragment releasable from said polypeptide upon digestion by a protease, and a Release Segment that can be proteolytically cleaved wherein said cleavage releases the bispecific antibody construct from the extended recombinant polypeptide.

Abstract: The invention relates to a blood treatment device configured to dephosphorylate extracellular adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and/or lipopolysaccharide (LPS) in the blood of a patient in need thereof in an extracorporeal blood circuit, wherein the device comprises a matrix having alkaline phosphatase (AP) immobilized thereon. The invention further relates to an extracorporeal blood circuit comprising a blood treatment device of the invention and to the blood treatment device for use as a medicament or to methods of treating an infection, preferably a blood or systemic infection, such as sepsis, and/or for the treatment of sepsis-associated acute kidney injury (AKI).

Abstract: The invention is based on the surprising finding of antibodies that bind to IGSF11 (VSIG3) can also inhibit the interaction between IGSF11 and IGSF11 receptors such as VSIR(VISTA), the inhibition of such interaction can sensitise tumour cells to anti-tumour immune responses. In particular, the invention provides products, compositions and methods for treating diseases using modulators of IGSF11, especially antigen binding proteins targeting IGSF11, including those being inhibitors of IGSF11-interaction with VSIR. Also provided are methods of sensitising cells involved with a proliferative disorder against the cytotoxic effect of cell-mediated immune responses, and/or to kill such cells and/or methods for treating proliferative diseases, using an IGSF11 inhibitor such as an IGSF11-binding antibody, as well as certain related aspects including detection, diagnostic and screening methods.

Abstract: This disclosure relates to compositions having an antibody binding fragment that specifically binds to CD3 or an epitope thereof. Some embodiments include compositions and antibody binding fragments with increased stability. Bispecific fusion proteins including such antibody-binding fragments are also disclosed.

Abstract: A Paleo Event Table creator tool box is described which is induced and/or allows a user to spatially join a selected area of interest of the earth crust to one selected tectonic plate in a tectonic plate model, which selected tectonic plate has an overlap with the area of interest, and to sample a paleogeographic dataset relevant to the area of interest for a series of paleogeographic time steps. A graphical user interface is induced and/or allows the user to create a Paleo Event Table that displays the sampled paleogeographic dataset. The Paleo Event Table creator tool box is used for paleogeographic reconstruction of the earth crust in the area of interest and identifying information relevant for the area of interest.

Abstract: A Paleo Event Table creator tool box is described which is induced and/or allows a user to spatially join a selected area of interest of the earth crust to one selected tectonic plate in a tectonic plate model, which selected tectonic plate has an overlap with the area of interest, and to sample a paleogeographic dataset relevant to the area of interest for a series of paleogeographic time steps. A graphical user interface is induced and/or allows the user to create a Paleo Event Table that displays the sampled paleogeographic dataset. The Paleo Event Table creator tool box is used for paleogeographic reconstruction of the earth crust in the area of interest and identifying information relevant for the area of interest.