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: A closure system for closing a container opening is disclosed that includes a stopper member, a cage member and a lock activation formation. The stopper member includes a plug portion to fit into the container opening and a cover portion to abut a boundary surface of the container opening. In the assembled state of the closure system, the plug portion is fitted into the container opening, the cover portion abuts the boundary surface, and the cage member is mounted to the container. The cage member has a locking structure that in a detached position is disengaged from the container, and in a fixed position engages a corresponding structure of the container. The lock activation formation is configured to interact with the cage member such that the cage member changes from the detached position to the fixed position.

Abstract: An inventive drug product filling device for filling a liquid drug product into containers is disclosed. The drug filling device includes a drug product preparer configured for preparing the liquid drug product and a filling station configured for filling the liquid drug product into the containers. The filling station is fluidly coupled to the drug product preparer. A degasser is fluidly interposed between the drug product preparer and the filling station. The degasser has a membrane configured for at least partially separating off gas from the liquid drug product. Methods of (i) filling a liquid drug product into containers, (ii) increasing the accuracy of the filling weight of a liquid drug product in a container, (iii) increasing the stability oxygen-sensitive active pharmaceutical ingredient in a liquid drug product, and (iv) reducing polysorbate aggregate formation in a liquid drug product are also disclosed.

Abstract: The invention relates to a method for predicting the metabolic condition of a cell culture of cells of a specific cell type. The method comprises providing (102) a metabolic model (402) of a cell of the specific cell type and carrying out the following steps at each of a plurality of points in time during the cultivation of the cell culture: receiving (106) measured concentrations of several extracellular metabolites and a measured cell density in the culture medium; inputting (108) the received measured values as input parameter values into a trained machine learning program logic—MLP (218); predicting (110) extracellular flows (408) of the extracellular metabolites at a future point in time by means of the MLP; carrying out (112) a metabolic flow analysis for calculating the intracellular flows at the future point in time on the basis of the predicted extracellular flows and the stoichiometric equations of the metabolic model.

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 relates autonomous VH domains (aVH) with cysteines in positions 52a and 71 or in positions 33 and 52 in order to stabilize the autonomous VH domains. Said cysteines are capable of forming a disulfide bond and/or form a disulfide bond under suitable conditions. The invention further relates to aVH libraries.

Abstract: The present invention relates to methods for the prediction of the progression of chronic kidney disease in a patient. More particularly, the invention relates to the early prediction of the fast progression of chronic kidney disease using specific biomarker signatures in urine sample of patients.

Abstract: The present invention generally relates to antibodies that bind to STEAP-1, including bispecific antigen binding molecules e.g. for activating T cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease.

Abstract: The present invention relates to multispecific antibodies comprising at least three antigen binding sites wherein the third binding site is disulfide stabilized by introduction of cysteine, method for their production, pharmaceutical compositions containing said antibodies and uses thereof.

Abstract: The present invention generally relates to the provision of means and methods for preparing protein compositions. The invention provides a method comprising the steps of (i) contacting a starting composition comprising a protein with a hydrolase inhibitor, wherein the hydrolase inhibitor is immobilized on a solid carrier; (ii) recovering a composition comprising the protein. Furthermore, the invention relates to a method for preparing a protein formulation comprising the steps of (i) contacting a starting composition comprising a protein with a hydrolase inhibitor, wherein the hydrolase inhibitor is immobilized on a solid carrier; (ii) recovering a composition comprising the protein, wherein the method for preparing the protein formulation further comprises adding a surfactant, preferably a fatty acid ester, to the composition comprising the protein.

Abstract: The present invention relates to anti-VEGF antibodies and methods of their production and their use.

Abstract: Embodiments disclosed herein generally relate to multi-arm machine learning models for lesion detection. Particularly, aspects of the present disclosure are directed to accessing a three-dimensional magnetic resonance imaging (MRI) images. Each of the three-dimensional MRI images depict a same volume of a brain of a subject. The volume of the brain includes at least part of one or more lesions. Each three-dimensional MRI image of the three-dimensional MRI images is processed using one or more corresponding encoder arms of a machine-learning model to generate an encoding of the three-dimensional MRI image. The encodings of the three-dimensional MRI images are concatenated to generate a concatenated representation. The concatenated representation is processed using a decoder arm of the machine-learning model to generate a prediction that identifies one or more portions of the volume of the brain predicted to depict at least part of a lesion.

Abstract: Methods are provided for the adjuvant treatment of operable HER2-positive primary breast cancer in human patients by administration of pertuzumab in addition to chemotherapy and trastuzumab. The methods reduce the risk of recurrence of invasive breast cancer or death for a patient diagnosed with HER2-positive early breast cancer (eBC) compared to administration of trastuzumab and chemotherapy, without pertuzumab.

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

Abstract: The present invention relates to nucleic acid molecules that are complementary to both PAP associated domain containing 5 (PAPD5) and PAP associated domain containing 7 (PAPD7), leading to inhibition of the expression of both PAPD5 and PAPD7 when using a single nucleic acid molecule. The invention also provides for PAPD5 and PAPD7 specific nucleic acid molecules for use in treating and/or preventing a HBV infection, in particular a chronic HBV infection. Also comprised in the present invention is a pharmaceutical composition for use in the treatment and/or prevention of a HBV infection.

Abstract: The present invention relates to nucleic acid molecules that are complementary to both PAP associated domain containing 5 (PAPD5) and PAP associated domain containing 7 (PAPD7), leading to inhibition of the expression of both PAPD5 and PAPD7 when using a single nucleic acid molecule. The invention also provides for PAPD5 and PAPD7 specific nucleic acid molecules for use in treating and/or preventing a HBV infection, in particular a chronic HBV infection. Also comprised in the present invention is a pharmaceutical composition for use in the treatment and/or prevention of a HBV infection.

Abstract: The invention relates to a method of identifying a biomarker in a tissue sample. The method comprises receiving an acquired image depicting a tissue sample, the pixel intensity values of the acquired image correlating with an autofluorescence signal or of an X-ray induced signal or a signal of a non-biomarker specific stain or a signal of a first biomarker specific stain adapted to selectively stain a first biomarker. The acquired image is input into a trained machine learning logic—MLL which automatically transforms the acquired image into an output image highlighting tissue regions predicted to comprise a second biomarker.

Abstract: Methods and systems disclosed herein relate generally to systems and methods for predicting a future visual acuity of a subject by using machine-learning models. An image of at least part of a retina of a subject can be processed by one or more first machine-learning models to detect a set of retina-related segments. Segment-specific metrics that characterize a retina-related segment of the set of retina-related segments can be generated. The segment-specific metrics can be processed by using a second machine-learning model to generate a result corresponding to a prediction corresponding to a future visual acuity of the subject.

Abstract: A force testing machine (FTM) validation apparatus is disclosed for validating a test process involving a force testing machine to measure forces involved in operation of a syringe arrangement. Particularly a syringe arrangement that includes a staked-in needle prefilled syringe and a needle safety device cooperating with the staked-in needle prefilled syringe. The FTM validation apparatus includes a syringe arrangement surrogate, and a holder arranged to support the syringe arrangement surrogate in a predefined position and orientation in the force testing machine. The syringe arrangement surrogate includes a break loose part arranged to mimic a break loose force of the syringe arrangement and an injection force part arranged to mimic an injection force of the syringe arrangement. Methods are also disclosed for validating a test process that measures forces involved in operation of a syringe arrangement and for measuring forces involved in operation of the syringe arrangement.

Abstract: Genotyping methods and compositions for selecting patients with cardiovascular disease who will benefit from treatment with HDL-raising or HDL mimicking agent, in particular with a CETP inhibitor/modulator.