Abstract: The present invention relates to isoxazolidines of formula I and their use as receptor-interacting protein kinase 1 inhibitors, for example in the treatment of diseases and disorders mediated by RIP kinase (1) such as rheumatoid arthritis (RA), psoriasis, inflammatory bowel disease (IBD), Crohn's disease or ulcerative colitis.

Abstract: A packaging assembly comprises a case configured to contain at least one injection device for delivering a medicament; a cooling unit configured to lower an internal temperature of the case; a processing arrangement; a device sensor configured to detect at least one injection device contained within the case, and to receive device storage information from the at least one detected injection device; and a data storage device. The processing arrangement is configured to record an injection history on the data storage device. The processor arrangement is configured to control the cooling unit to set an internal temperature of the case according to the received device storage information.

Abstract: The present invention relates to humanized antibodies that specifically bind to CXCR5 and can, for example, inhibit CXCR5 function. The invention also includes uses of the antibodies to treat or prevent CXCR5 related diseases or disorders.

Abstract: The present disclosure concerns antibody-conjugates comprising an anti-CEACAM5-antibody for use for treating cancer in combination with an anti-VEGFR-2 antibody. The disclosure further relates to pharmaceutical compositions and kit-of-parts comprising an anti-CEACAM5-antibody in combination with anti-VEGFR-2 antibody for use for treating cancer.

Abstract: The present technology aims at providing a novel type of drug for treating a subject suffering from an inflammatory disease. Specifically, the present technology provides polypeptides comprising at least four immunoglobulin single variable domains (ISVDs), characterized in that at least two ISVDs bind to IL-13 and at least two ISVDs binds to TSLP. The present technology also provides nucleic acids, vectors and compositions.

Abstract: The invention provides antibodies that specifically bind to Plasminogen Activator inhibitor type-1 (PAI-1), The invention also provides pharmaceutical compositions, as well as nucleic acids encoding anti-PAI-1 antibodies, recombinant expression vectors and host cells for making such antibodies, or fragments thereof. Methods of using antibodies to modulate PAI-1 activity or detect PAI-1, either in vitro or in vivo, are also provided. The disclosure further provides methods of making antibodies that specifically bind to PAI-1 in the active conformational state.

Abstract: The application relates to an aqueous pharmaceutical formulation comprising 200-1000 U/mL [equimolar to 200-1000 IU human insulin] of insulin glargine.

Abstract: A supplementary device configured to be releasably attached to a distal end of a drug delivery device. The supplementary device comprising primary electronics, a non-contact acceleration sensor and a low power processor. The non-contact acceleration sensor is directed towards a proximal end of the drug delivery device and the low power processor is configured to: receive the signals output from the non-contact acceleration sensor; determine based on the signals that an outer needle cap of the drug delivery device has been removed; and in response to determining that an outer needle cap of the drug delivery device has been removed, send a wake-up signal to the primary electronics of the supplementary device.

Abstract: The present disclosure relates to a panel of ER regulated genes and method for using the panel for monitoring the response of an individual having cancer to treatment with amcenestrant, the method comprising determining a first ER activity score from a sample from the individual at a first time point before treatment with amcenestrant using the panel, then determining a second ER activity score from a sample from the individual at a second time point following administration of amcenestrant using the panel, and comparing the first ER activity score with the second ER activity score, wherein a decrease in the second ER activity score relative to the first ER activity score is predictive of target engagement of amcenestrant.

Abstract: An injector device comprising: an outer housing for receiving a medicament container; and a drive mechanism for dispensing a medicament from the medicament container received in the outer housing. The drive mechanism comprises a plunger rod and a displacing member configured to displace a distal end of the plunger rod into said medicament container to dispense said medicament. The device further comprises a brake configured to slow a rate of displacement of the plunger rod under a force of the displacing member.

Abstract: VH domain, in which: (i) the amino acid residue at position 112 is one of K or Q; and/or (ii) the amino acid residue at position 89 is T; and/or (iii) the amino acid residue at position 89 is L and the amino acid residue at position 110 is one of K or Q; and (iv) in each of cases (i) to (iii), the amino acid at position 11 is preferably V; and in which said VH domain contains a C-terminal extension (X)n, in which n is 1 to 10, preferably 1 to 5, such as 1, 2, 3, 4 or 5 (and preferably 1 or 2, such as 1); and each X is an (preferably naturally occurring) amino acid residue that is independently chosen, and preferably independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).

Abstract: The present invention relates to amino acid sequences that can bind to serum albumin. In particular, the present invention relates to immunoglobulin single variable domains, and in particular heavy-chain immunoglobulin single variable domains, that can bind to serum albumin. The invention also relates to proteins, polypeptides and other constructs, compounds, molecules or chemical entities that comprise at least one of the immunoglobulin single variable domains binding to serum albumin that are described herein.

Abstract: High concentration antibody formulations capable of stable long-term storage are disclosed.

Abstract: Binding polypeptides (e.g., antibodies and antigen-binding fragments thereof) that specifically bind one or more species of soluble, AD brain-derived synaptotoxic amyloid beta (A?) without binding to classical monomeric, protofibrillar or fibrillar A?, are provided. Pharmaceutical compositions comprising binding polypeptides that specifically bind one or more species of soluble, synaptotoxic A? are provided. Methods of making binding polypeptides that specifically bind one or more species of soluble, synaptotoxic A? are provided. Methods of treating Alzheimer's disease using binding polypeptides that specifically bind one or more species of soluble, synaptotoxic A? are provided. Methods of reducing one or more symptoms of Alzheimer's disease using binding polypeptides that specifically bind one or more species of soluble, synaptotoxic A? are provided.

Abstract: This invention provides, and in certain specific but non-limiting aspects relates to: assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay).

Abstract: A drug delivery device is proposed, the drug delivery device comprising: a housing; a drive mechanism; a cartridge containing a drug, the cartridge being retained in a defined position relative to the housing, wherein the drive mechanism is configured to dispense the drug from the cartridge; a cartridge bias system, which comprises at least one resilient member and at least one rigid force transfer body, wherein the at least one rigid force transfer body is movably located within the housing, wherein the cartridge bias system is arranged and configured to exert a force on the cartridge to maintain the cartridge in the defined position, wherein the force is provided by the at least one resilient member, and wherein the at least one rigid force transfer body is operatively connected to the at least one resilient member such that the force is reacted by the at least one rigid force transfer body. Further, a method to modify a drug delivery device is disclosed.

Abstract: Provided herein are methods for monitoring production of a multispecific binding protein and one or more mispaired species by a cell line, as well as methods of production and screening related thereto. In some embodiments, the methods comprise detecting an amount (e.g., a relative amount) of a multispecific binding protein and one or more mispaired species in a cell culture medium by size-exclusion ultra-performance liquid chromatography and mass spectrometry (SE-UPLC-MS). In some embodiments, the multispecific binding protein is a multispecific antibody, antibody fragment, or Fc fusion protein.

Abstract: A drug delivery device comprises a housing adapted to receive a medicament container, a plunger and a plunger release mechanism that comprises a first plunger boss arranged on the plunger, a profiled slot arranged on the housing and adapted to be engaged by the first plunger boss so as to inhibit movement of the plunger in a distal direction. The plunger is rotatable about a longitudinal axis to release the first plunger boss from the profiled slot so as to allow movement of the plunger in the distal direction. A sleeve is coupled to the housing to permit movement of the sleeve relative to the housing. A sleeve ramp is arranged on the sleeve and adapted to engage a rib or boss on the plunger to rotate the plunger to release the first plunger boss from the profiled slot when the sleeve is moved in a proximal direction.

Abstract: The present application relates to compounds of formula (I), or pharmaceutically acceptable salts thereof: wherein R1 and R2 represent hydrogen or deuterium; R3 represents hydrogen, —COOH or —OH; R3? and R3? represent hydrogen, methyl, methoxy, chlorine, fluorine or cyano; R4 and R41 represent hydrogen or fluorine; R5 represents hydrogen, fluorine or (C1-C3)alkyl; R6 represents phenyl, fused phenyl, bicyclic group comprising 5 to 12 carbon atoms, heteroaryl group comprising 2 to 9 carbon atoms and comprising from 1 to 3 heteroatoms, cycloalkyl group comprising 3 to 7 carbon atoms, (C3-C6)cycloalkyl(C1-C3)alkyl group, 3 to 8 membered-heterocycloalkyl group comprising 1 or 2 heteroatoms, (C1-C6)alkyl, and phenyl(C1-C2)alkyl group; X represents —CH2—, —O— or —S—; Y represents —CH?, —N? or —CR??, wherein R? represents (C1-C3)alkyl, halogen, cyano, or (C1-C3)fluoroalkyl; R7 represents (C1-C3)alkyl, halogen atom, cyano, or (C1-C3)fluoroalkyl; R8 represents hydrogen or fluorine; R9 represents hydrogen, (C1-C3)alkyl

Abstract: An injection device for expelling a number of preset or user-selectable doses of a medicament. The injection device includes: an elongated housing extending along a longitudinal axis, and a rotatable member and a counterpart member each comprising a first mechanical code and a second mechanical code, respectively. For setting a dose, the rotatable member is rotatable relative to the housing and relative to the counterpart member. During the setting of the dose, the rotatable member is constrained along the longitudinal axis relative to the housing or relative to the counterpart member. For expelling a dose, one of the rotatable member and the counterpart member is displaceable along the longitudinal axis into an expelling position relative to the other one of the rotatable member and the counterpart member only when the first mechanical code is aligned with the second mechanical code.