A device for delivery of a drug into cerebrospinal fluid of a brain including a hollow container having a reservoir volume and an outlet, the container having an upper surface and a lower surface; a porous structure having a sintered rigid material that passively regulates diffusion of a drug from the container at a controlled release rate; and a catheter coupled to a lower end of the container, the catheter having a lumen, a proximal end region, and a distal end region, the lumen configured to communicate with the reservoir volume of the container through the porous structure. Related systems and methods are provided.
The invention provides methods of dosing for the treatment of cancers, such as multiple myelomas, with anti-fragment crystallizable receptor-like 5 (FcRH5)/anti-cluster of differentiation 3 (CD3) bispecific antibodies.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present disclosure relates to benzothiazole compounds and to methods of using such compounds. The present disclosure further relates to the use of the compounds described herein, or pharmaceutical compositions thereof, to prevent and/or treat a range of diseases, disorders, and conditions.
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
Recombinant DPO4-type DNA polymerase variants with amino acid substitutions that confer modified properties upon the polymerase for improved single molecule sequencing applications are provided. Such properties may include enhanced binding and accurate incorporation of bulky nucleotide analog substrates into daughter strands and the like. Also provided are compositions comprising such DPO4 variants and nucleotide analogs, as well as nucleic acids which encode the polymerases with the aforementioned phenotypes.
The present invention relates to systems and methods in the field of digital pathology. It is particularly, but not exclusively, concerned with systems and methods for detecting brain lesions, and in particular brain metastases, in brain digital images.
The presently disclosed subject matter relates to retroviral -like particle (RVLP)-reduced Chinese hamster ovary (CHO) cells suitable to produce recombinant proteins, as well as methods of producing and using such RVLP-reduced CHO production cells.
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
7.
TREATMENT OF AUTOIMMUNE ENCEPHALITIS WITH SATRALIZUMAB
All currently available treatment options for autoimmune encephalitis such as anti-NMDAR encephalitis and anti-LGI1 encephalitis carry substantial potential safety risks. Further, no approved therapies exist for anti-NMDAR encephalitis and anti-LGI1 encephalitis. The invention provides a means for a treatment for autoimmune encephalitis (AIE) such as NMDAR encephalitis and anti-LGI1 encephalitis, comprising an IL-6 inhibitor such as anti-IL-6 receptor antibody or antigen binding fragment thereof.
The present invention generally relates to antibodies that bind to HLA-A2/WTI, 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.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
9.
IMIDAZO[4,5-B]PYRIDINE AND PYRAZOLO[1,5-A]PYRIMIDINE DERIVATIVES AS SIK MODULATORS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS
The invention relates to a compound of formula (I)
The invention relates to a compound of formula (I)
wherein L, A1, A2, R1, R2, R3, R4 and R5 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.
The present invention relates to methods of diagnosing whether a subject has endometriosis, to methods of classifying the stage of endometriosis, to methods of determining the therapeutic effect of a treatment regimen for endometriosis, and methods of monitoring endometriosis progression in a subject, by determining the amount or concentration of c-Kit in a sample of the subject, and comparing the determined level to a reference value.
C07K 7/64 - Cyclic peptides containing only normal peptide links
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
12.
METHODS OF TREATING CANCER WITH PI3K INHIBITOR, GDC-0077
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/565 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The invention provides compounds having the general formula (I), wherein R1, R2, X, and Y are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
C07D 205/12 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
C07D 207/06 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
C07D 207/20 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
The invention provides diagnostic methods for identifying individuals having a lung cancer (e.g., NSCLC) suitable for treatment a treatment regimen that includes a PD-1 axis binding antagonist (e.g., atezolizumab) after adjuvant therapy (e.g., after a platinum-based adjuvant therapy) and therapeutic methods for treating lung cancer (e.g., NSCLC) in an individual identified as one who may benefit from treatment with a treatment regimen that includes a PD-1 axis binding antagonist (e.g., atezolizumab) to the individual following an adjuvant therapy (e.g., after a platinum-based adjuvant therapy). Also provided are compositions (e.g., a PD-1 axis binding antagonist (e.g., atezolizumab), pharmaceutical compositions thereof, assays thereof, kits thereof, and articles of manufacture thereof) for use in identifying patients suitable for treatment and for treating lung cancer (e.g., NSCLC) in an identified individual.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The disclosure provides methods of treating HER2-positive cancers, such as breast cancer and gastric cancer, by administering a combination of a heterodimeric protein comprising a first monomer comprising an IL15 protein-Fc domain fusion and a second monomer comprising an IL15Rα protein-Fc domain fusion, such as efbalropendekin alfa, and a HER2xCD3 bispecific antibody, such as runimotamab.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The invention relates to compounds of formula I:
The invention relates to compounds of formula I:
The invention relates to compounds of formula I:
and pharmaceutically acceptable salts thereof wherein A, X, R1, R4 and n are as defined herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61P 11/00 - Drugs for disorders of the respiratory system
IVA test unit (1) comprising: a test strip (2) for detecting an analyte, wherein the test strip comprises at least an application function, a test reaction function and a test detection function; and a housing (3) for storing the test strip (2) wherein the housing (3) comprises an insert tray (4) and an insert hole (5) for inserting the test strip (2) into the insert tray (4), characterized in that the housing (3) is formed as one single piece.
A collaboration platform is provided to analyze one or more biomedical data sets. The collaboration platform may include a project management engine, a data ingestion engine, and a data analysis engine. The project management engine may generate a plurality of project environments for analyzing biomedical data sets of interest, and designate a set of authorized users with access to given project environments. The data ingestion engine may process data sets and store them in a central data storage system for access within the project environments. The data analysis engine may perform analyses and special computing on the ingested data and generate updated output data that may be re-ingested for further analyses in the project environments.
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G06F 21/62 - Protecting access to data via a platform, e.g. using keys or access control rules
20.
ANTI-Ly6E ANTIBODIES, IMMUNOCONJUGATES, AND USES THEREOF
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 51/10 - Antibodies or immunoglobulinsFragments thereof
The invention provides antibodies that bind mixed-topology polyubiquitin and multispecific anti-polyubiquitin antibodies, and methods of using the same.
The present invention is directed to a combination therapy involving an anti-HER2 antibody-drug conjugate and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a HER2-expressing cancer.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
23.
Subcutaneous anti-HER2 Antibody Formulations and Uses Thereof
The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
24.
ELUTION KIT, ANALYTICAL KIT AND METHOD OF ELUTING AND ANALYZING A BIOLOGICAL SAMPLE
An elution kit (1) for eluting a biological sample in a liquid (2) and dispensing the eluted sample liquid (2') onto a test element (102) of an analytical kit (101), the elution kit (1) comprises: a sample collection swab (3) for collecting the biological sample, wherein the sample collection swab (3) comprises a stick portion (4) for being hand-held and a deformable head portion (5) on the stick portion (4) for collecting the biological sample, wherein the head portion (5) is porous for the liquid (2); and an elution liquid tube (6) which comprises: an interior space (7) for housing the liquid (2), receiving the sample collection swab (3) and eluting the biological sample in the liquid (2); an insertion opening (10) on a first side of the interior space (7) for inserting the sample collection swab (3) into the interior space (7); a dispense opening (11) on a second side of the interior space (7) adjacent the first side for dispensing the eluted sample liquid; a first closure element (12) to seal the dispense opening (11) in a water-vapor impermeable manner; a second closure element (13) to seal the insertion opening (10) in a water-vapor impermeable manner, wherein the first closure element (12) and/or the second closure element (13) comprises a foil; and the liquid (2), wherein the elution liquid tube (6) contains the liquid (2), wherein the interior space (7) is defined by an inner surface (8) that comprises an elution zone (16) with at least one elution portion (9) having a smallest side-to-side distance y ranging between approximately 70% and 140% of a largest side-to-side distance x of the head portion (5) of the sample collection swab (3) and defining a gap (14) through which the sample collection swab (3) can be pushed and pulled in a closed state of the dispense opening (11).
The present disclosure provides methods of sequencing one or more target nucleic acid molecules, where each of the one or more target nucleic acid molecules includes one or more modified nucleotides, and wherein the method does not require conversion of any of the one or more modified nucleotides prior to sequencing, and/or does not require any amplification (PCR) cycles prior to sequencing In some embodiments, sequencing is performed with a sequencing-by-tag sequencing device. In other embodiments, sequencing is performed with a Single Molecule Real Time sequencing device.
09 - Scientific and electric apparatus and instruments
Goods & Services
Bio-sensors; Biochip sensors; Bar code readers; Bar code printers; Portable scanners; Radio-frequency identification (RFID) tags; Interfaces for computers; Electronic docking stations; Application software for cloud computing services; Bags adapted for laptops; Cases for tablet computers; Cases for data storage devices; Computer software relating to the medical field; Computer software for use in medical decision support systems; Workflow management system software; Software as a medical device [SaMD], downloadable; Application software for mobile devices.
27.
OLIGONUCLEOTIDES FOR INDUCING PATERNAL UBE3A EXPRESSION
The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.
The invention comprises a process for the preparation of a [Ru(OAc)2(Ligand)] catalysts of the formula I
The invention comprises a process for the preparation of a [Ru(OAc)2(Ligand)] catalysts of the formula I
The invention comprises a process for the preparation of a [Ru(OAc)2(Ligand)] catalysts of the formula I
wherein R1 is C1-6 alkyl and R3 is hydrogen or C1-6 alkyl and R4 is hydrogen or C1-6-alkoxy.
The invention comprises a process for the preparation of a [Ru(OAc)2(Ligand)] catalysts of the formula I
wherein R1 is C1-6 alkyl and R3 is hydrogen or C1-6 alkyl and R4 is hydrogen or C1-6-alkoxy.
[Ru(OAc)2(Ligand)] catalysts are versatile hydrogenation catalysts.
The present invention relates to a composition comprising (i) cesium iodide, (ii) ethylamine and/or formic acid, and (iii) methanol and/or water. The present invention further relates to a method for calibrating a mass spectrometry (MS) device comprising (I) determining a mass spectrum of a composition as specified; and (II) calibrating the MS device based on the mass spectrum determined in step (I). The present invention further relates to devices, kits, uses, and methods related thereto.
The present invention concerns the field of diagnostic assays for prenatal diagnosis of preeclampsia. In particular, it relates to a method for diagnosing whether a pregnant subject is not at risk for preeclampsia within a short window of time comprising a) determining the amount of at least one angiogenesis biomarker selected from the group consisting of sFlt-1, Endoglin and PlGF in a sample of said subject, and b) comparing the amount with a reference, whereby a subject being not at risk for developing preeclampsia within a short period of time is diagnosed if the amount is identical or decreased compared to the reference in the cases of sFlt-1 and Endoglin and identical or increased in the case of PlGF, wherein said reference allows for making the diagnosis with a negative predictive value of at least about 98%. Further contemplates are devices and kits for carrying out said method.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
31.
TETRAHYDRO-PYRIDO[3,4-b]INDOLE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
Described herein are tetrahydro-pyrido[3,4-b]indol-1-yl compounds with estrogen receptor modulation activity or function having the Formula I structure:
Described herein are tetrahydro-pyrido[3,4-b]indol-1-yl compounds with estrogen receptor modulation activity or function having the Formula I structure:
and stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such estrogen receptor modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
32.
SULFONIMIDAMIDE COMPOUNDS AS INHIBITORS OF INTERLEUKIN-1 ACTIVITY
The present disclosure relates to novel sulfonimidamide compounds and related compounds and their use in treating a disorder responsive to modulation of cytokines such as IL-1β and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process.
A method for crammed training of a molecular computation model includes receiving the molecular computation model. One or more crammed training constraints may be identified. An modification to the molecular computation model may be determined based on the one or more crammed training constraints. One or more training hyperparameters may be based on the one or more crammed training constraints. The molecular computation model having the architectural modification may be trained, or in some cases, pretrained in accordance with the one or more training hyperparameters. In some cases, the pretrained molecular computation model may undergo finetuning for a specific task such as predicting the function of a protein sequence or classifying a pair of protein sequences as an interacting pair or a non-interacting pair. Related systems and computer program products are also provided.
G06F 30/27 - Design optimisation, verification or simulation using machine learning, e.g. artificial intelligence, neural networks, support vector machines [SVM] or training a model
34.
METHOD FOR SCREENING A BIOLOGICAL FLUID SAMPLE FOR AN ANALYTE ASSOCIATED WITH PROTEINOPATHY USING WHITE LIGHT INTERFEROMETRY OR ATOMIC FORCE MICROSCOPY
Disclosed herein is a device and method for measuring spatial mass distribution profiles to weigh the accumulated-aggregated mass of an analyte in a crowded bioorganic material background by employing a high frequency recognition pattern. The recognition pattern allows for the Fourier filtering of mass sensitive image data for background and noise subtraction. The device and method enables the screening of a biological fluid sample for an analyte associated with proteinopathy.
G01B 9/00 - Measuring instruments characterised by the use of optical techniques
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01Q 60/24 - AFM [Atomic Force Microscopy] or apparatus therefor, e.g. AFM probes
G01N 21/45 - RefractivityPhase-affecting properties, e.g. optical path length using interferometric methodsRefractivityPhase-affecting properties, e.g. optical path length using Schlieren methods
A method may include generating a training dataset including a pair of sample molecules. The sample molecule pair includes a first molecule and a second molecule. A property computation model is trained to determining a sequence difference comprising a difference between an amino acid sequence of the first molecule and an amino acid sequence of the second molecule. The property computation model is further trained to generate a relative embedding representative of the sequence difference and associating the sequence difference with the sample molecule pair. The property computation model is further trained to determine, based on the relative embedding, a property difference corresponding to a difference between a value of the property exhibited by the first molecule and a value of the property exhibited the second molecule. The trained property computation model may be applied to determine a property difference of a pair of input molecules.
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
This invention relates to carbamate compounds of Formula (I), as further detailed herein, which are used for inhibition of SARM1 proteins, as well as compositions comprising these compounds and methods of treatment by their administration.
C07D 413/08 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
37.
STRUCTURED DATA CAPTURE, AGGREGATION, AND ANALYSIS OF CLINICAL CHARACTERISTICS OF PATIENTS IN A LIVER DISEASE DIAGNOSTIC SETTING
A system for managing liver disease including an electronic medical record system comprising a plurality of patient records. The system includes a patient management platform configured to access the electronic medical record (EMR) system to retrieve medical records of one or more patients, analyze the medical records to selectively identify data relating to liver condition(s), interface with one or more data analytics platform(s), the data analytics platform(s) configured to receive and analyze the data relating to liver-conditions. Based on the analyzing by the patient management interface and/or the data analytics platform(s), generating a display including specific liver-related patient attributes and conditions, and at least one of a liver-health prognosis or recommended treatment for addressing the liver condition(s) respective to the one or more patients. The liver conditions may include one or more of: cancer, cirrhosis, liver failure, fatty liver disease, steatosis, ischemia, and/or hepatitis.
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
The invention relates to a compound of formula (I)
The invention relates to a compound of formula (I)
The invention relates to a compound of formula (I)
wherein A1, R1, R2, R3, R4 and R5 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present invention relates to methods for assessing whether or not a patient has aggressive prostate cancer by determining the levels of particular glycoforms attached to prostate specific antigen (PSA) protein in a biofluid sample of a subject, and comparing the determined level or concentration to a reference. The methods are particularly useful for assessing subjects that have 2-10 ng/ml total PSA in the subject's serum.
The invention provides a compound of formula (I):
The invention provides a compound of formula (I):
The invention provides a compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein the variables Y1-Y6, X, Z, Z1, Z2, R2-R3, and R6 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
41.
TECHNIQUES FOR EVALUATING ARTIFICIAL INTELLIGENCE SYSTEMS WITHOUT GROUND-TRUTH ANNOTATIONS
Disclosed systems and methods provide a framework for evaluating AI systems without ground-truth annotations. The disclosed embodiments may assign temporary labels to data points in sets of working data and use the temporarily labeled data to train one or more distinct models. These models may be evaluated to determine which has the highest performance and is thus indicative of the temporary labels most likely to be correct.
The invention relates to a novel process for making baloxavir marboxil (1) and baloxavir (1a), as well as to an integrated continuous manufacturing (ICM) implementation thereof. Formulae (1) and (1a), (1) and (1a).
Methods of screening drug combinations are described. The methods comprise obtaining, for a first drug and a second drug, the values of a plurality of features associated with the drug combination; and predicting, using the values of said plurality of features, the effect of the drug combination using a machine learning model that has been trained to predict whether a drug combination is likely synergistic. The plurality of features comprises at least one feature that characterises the similarity between one or more indications or diseases associated with one or more targets of the first drug and one or more indications or diseases associated with one or more targets of the second drug. Related methods, products and systems are also described.
This invention relates to lactam compounds of Formula (I), as further detailed herein, which are used for inhibition of SARM1 proteins, as well as compositions comprising these compounds and methods of treatment by their administration.
C07D 401/08 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing alicyclic rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/08 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing alicyclic rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
The invention provides a novel process for manufacturing a compound of formula (I), or a salt thereof,
The invention provides a novel process for manufacturing a compound of formula (I), or a salt thereof,
The invention provides a novel process for manufacturing a compound of formula (I), or a salt thereof,
wherein PG1, PG2 and PG3 are amino protective groups. The process according to the invention is particularly suitable for large-scale manufacturing under GMP conditions.
C07K 5/09 - Tripeptides the side chain of the first amino acid containing more amino groups than carboxyl groups, or derivatives thereof, e.g. Lys, Arg
C07D 209/20 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
C07D 209/26 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07K 1/107 - General processes for the preparation of peptides by chemical modification of precursor peptides
46.
METHODS FOR VIRAL INACTIVATION AND OTHER ADVENTITIOUS AGENTS
The invention provides for methods of viral inactivation using high temperature short time (HTST) treatment and adjustment of various parameters such that generation of precipitate and depositions of precipitate are reduced and/or minimized.
The invention provides dual specific antibodies and methods of making and using such antibodies. In general, the dual specific antibodies are generated by identification of a monospecific antibody having light chain variable region VL residues that are electrostatic or hydrophobic and altering the nucleic acid sequence encoding one or more solvent accessible residues in the VH of the antibody either alone or in combination with alteration of the nucleic acid sequence encoding the VL of the antibody. The altered VH and the VL are expressed and dual specific antibodies, or antigen-binding fragments thereof, are selected. Exemplary dual specific antibodies are also provided as well as methods of using the antibodies.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The invention relates generally crystalline mesylate salts, crystalline chloride salts and crystalline sulfate salts of the compound(S)-2-(3′-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino) -6-oxo-1,6-dihydro-[3,4′-bipyridin]-2′-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one that is an inhibitor of Bruton's tyrosine kinase. In some aspects, the crystalline salts are single polymorphs.
A computer-implemented method for performance verification of a thermal block cycler unit for automated thermal treatment of at least one sample is described. The thermal block cycler unit includes at least one thermal block configured for receiving at least one sample vessel, and a plurality of hardware modules. The hardware modules include a plurality of heating and/or cooling elements and at least one temperature sensor. The method includes consecutively functional testing the hardware modules, and defining the order of tests by using a thermal energy of its preceding test and/or a status of the thermal block cycler unit of its preceding test, and balancing energy consumption between the steps to minimize a difference between an input temperature before consecutively testing the hardware modules and an output temperature after consecutively testing the hardware modules.
The application relates to compounds of formula (I) which act as antagonists of STING useful for the treatment of autoimmune diseases, inflammatory diseases, neurological disorders, metabolic diseases, cardiovascular diseases, ocular diseases, or selective types of cancer where overexpression or activation of STING is implicated.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present invention relates to a splice variant of an ICA1 protein that acts as a biomarker for a TDP-43 pathology. In particular, the present invention relates to methods for identifying a splice variant of ICA1 comprising a cryptic peptide sequence, and to related methods of identifying a TDP-43 pathology and/or reduced TDP-43 function in a subject.
A federated analytics (FA)/federated learning (FL) system configured to implement a federated learning pipeline or a federated analytics pipeline comprises: a centralized FA/FL platform comprising a client environment interface module; and a plurality of local environments, each local environment comprising a respective local memory configured to store local raw data and/or local pre-processed data. The local environments are configured to obtain data from data sources, and to generate local statistical models which are aggregated at the centralized platform to generate a global statistical model, thereby fulfilling a client request.
An apparatus (200) includes a pair of rigid legs (210) extending parallel with each other along a plane. Each leg of the pair of legs has a sharp tip (215). The apparatus also includes head (210), including a top surface (222), a bottom surface (224), a pair of end surfaces (226), a pair of side surfaces (227), and a guide notch (230) extending upwardly from the bottom surface. The guide notch is configured to cooperate with a surface of a sclera of a patient's eye to define a guide opening that is oriented transversely relative to the plane associated with the legs and that is sized to receive a cannula having a generally flat profile. The head further includes a pair of receptacles (240) extending laterally inwardly from respective side surfaces of the pair of side surfaces. Each receptacle of the pair of receptacles is configured to engage a deployment instrument.
A61F 9/00 - Methods or devices for treatment of the eyesDevices for putting in contact-lensesDevices to correct squintingApparatus to guide the blindProtective devices for the eyes, carried on the body or in the hand
A61F 9/013 - Methods or devices for eye surgery for compensation of ocular refraction
A61B 17/10 - Surgical instruments, devices or methods for closing wounds or holding wounds closedAccessories for use therewith for applying or removing wound clampsWound clamp magazines
The present invention relates to a process for the preparation of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one useful as pharmaceutically active compounds.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
56.
METHODS OF TREATING CANCER USING TIGIT INHIBITORS AND ANTI-CANCER AGENTS
The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
A method includes determining, within an image of a biological sample from an intestine of a patient, a plurality of image patches depicting a portion of the biological sample. A plurality of bowel disease indication groups corresponding to a subset of the plurality of image patches may be determined based at least on the plurality of image patches. A group-level histological score for each bowel disease indication group of the plurality of bowel disease indication groups may be generated based at least on the subset of the plurality of image patches contained in each respective group. An aggregated histological score indicative of a disease burden in the intestine of the patient may be generated based on the generated group-level histological score for each bowel disease indication group. Related systems and computer program products are also provided.
G06V 10/762 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using clustering, e.g. of similar faces in social networks
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
58.
DETECTING LONGITUDINAL PROGRESSION OF ALZHEIMER'S DISEASE (AD) BASED ON SPEECH ANALYSES
A method implemented by one or more computer device includes detecting longitudinal progression of Alzheimer's disease (AD) in a patient. The method includes receiving speech data including a patient's description of one or more previous or current experiences of the patient, in which the speech data was captured at a plurality of moments during a period of time. The method further includes analyzing the speech data to quantify a plurality of speech variables, in which the plurality of speech variables includes a word-length variable and a use-of-particles variable. The method includes determining a composite score based on a standardization and a substantive weighting assigned to each of the quantified plurality of speech variables. The method thus includes detecting, based on the composite score, a predicted longitudinal change in the quantified speech variables, and further estimating, based on the predicted longitudinal change, a progression of AD for the patient.
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
G16H 10/20 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for electronic clinical trials or questionnaires
The invention provides a compound of formula (I):
The invention provides a compound of formula (I):
The invention provides a compound of formula (I):
or a prodrug thereof, or a pharmaceutically acceptable salt thereof, wherein R1 and R2 have any of the values described in the specification, as well as compositions comprising a compound of formula (I) or a prodrug thereof, or a pharmaceutically acceptable salt thereof. The compounds are agonists of glycolytic enzyme phosphofructokinase-1 liver type and are useful for treating diseases associated with the activity of glycolytic enzyme phosphofructokinase-1 liver type, such as cancer, diabetes, sepsis, and septic shock.
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Methods are disclosed for producing a molecule comprising a polypeptide complex formed by interaction between a first polypeptide comprising a CH3 region comprising a knob modification and a second polypeptide comprising a CH3 region comprising a hole modification.
The present invention relates to a method for stabilizing the C3bBb complex, a rapidly decaying component of the alternative pathway of the complement system, and stabilized C3bBb complexes and uses thereof.
The invention provides new heterocyclic compounds having the general formula (I) wherein A, B, U, V, X, Y, L1, R1, and R2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Systems and methods of prediction of future tumor data. A tumor embedding at a neural ordinary differential equations (ODE) system is received. The tumor embedding is generated using a tumor encoder and observed tumor data that is observed over a selected period of time after a reference point in time. A graph embedding at the neural ODE is received. The graph embedding fuses drug information, disease information, and gene relationship information. The graph embedding is generated using a heterogenous graph encoder that fuses together at least two or more embeddings generated using bipartite graph convolution attention networks. A predicted tumor size at a future point in time is generated using the tumor embedding, the graph embedding, and the neural ODE system. A candidate tumor treatment is administered to a subject in response to the predicted tumor size being less than a selected threshold.
G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/50 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
Goods & Services
Chemical, biological and biochemical preparations for the analysis of biological samples for medical purposes; medical diagnostic assays and reagents for the analysis of biological samples for clinical or medical purposes; diagnostic reagents and preparations for medical purposes; in vitro diagnostic agents for the analysis of biological samples for medical purposes; all of the foregoing excluding active pharmaceutical ingredients, isotopes and radioisotopes Analyzers for the analysis of biological samples for medical diagnostic purposes; in vitro diagnostic devices in the nature of biosensors for the detection and analysis of medically significant analytes in biological samples for medical purposes
65.
COMBINATION THERAPY OF ANTI-TYRP1/ANTI-CD3 BISPECIFIC ANTIBODIES AND TYRP1-SPECIFIC ANTIBODIES
The present invention relates to the combination therapy of a bispecific antibody which binds human TYRP1 and CD3 and a second TYRP1-specific antibody.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
66.
ANTIGEN BINDING MOLECULES COMPRISING A TNF FAMILY LIGAND TRIMER
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 and (b) a first and a second polypeptide that are linked to each other by a disulfide bond, characterized in that the first polypeptide comprises two ectodomains of a TNF ligand family member or fragments thereof that are connected to each other by a peptide linker and in that the second polypeptide comprises only one ectodomain of said TNF ligand family member or a fragment thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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.
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.
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A method of verifying a program code of a synthesis computer program is disclosed. The synthesis computer program is configured for computer-controlling an automatic synthesizer (114) to automatically synthesize at least one oligonucleotide, the synthesis computer program having a plurality of program cycles for computer-controlling the automatic synthesizer (114) to sequentially synthesize the oligonucleotide by using at least one sequence of synthesis cycles. The method comprises:
i. applying an automatic parsing procedure to the program code of the synthesis computer program, the automatic parsing procedure comprising automatically searching for parameter values of parameters of at least one predetermined list of parameters of interest in the program cycles of the synthesis computer program; and
ii. automatically assembling a matrix of parameters comprising, for the program cycles of the synthesis computer program, the parameters of interest and the corresponding parameter values of the parameters of interest.
A method of verifying a program code of a synthesis computer program is disclosed. The synthesis computer program is configured for computer-controlling an automatic synthesizer (114) to automatically synthesize at least one oligonucleotide, the synthesis computer program having a plurality of program cycles for computer-controlling the automatic synthesizer (114) to sequentially synthesize the oligonucleotide by using at least one sequence of synthesis cycles. The method comprises:
i. applying an automatic parsing procedure to the program code of the synthesis computer program, the automatic parsing procedure comprising automatically searching for parameter values of parameters of at least one predetermined list of parameters of interest in the program cycles of the synthesis computer program; and
ii. automatically assembling a matrix of parameters comprising, for the program cycles of the synthesis computer program, the parameters of interest and the corresponding parameter values of the parameters of interest.
Further disclosed is a computer program and a computer-readable storage medium for performing the method of verifying a program code of a synthesis computer program, a system (110) for verifying a program code of a synthesis computer program and a method of synthesizing at least one oligonucleotide.
This disclosure relates to methods, uses, and compositions (e.g., articles of manufacture and kits) comprising an anti-OSMRβ antibody, such as vixarelimab, for the treatment of inflammatory gastrointestinal diseases associated with the oncostatin M (OSM) pathway (e.g., inflammatory bowel disease (IBD) (e.g., ulcerative colitis (UC (e.g., moderate to severe UC)) and Crohn's disease (CD)).
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A computer-implemented method is provided, which determines at a prediction time tp, a likelihood of kidney failure of a patient within an amount of time Δt. The method comprises receiving input data, the input data comprising a recent creatinine level cR or recent eGFR eGFRR, and one or more of the following: (a) an initial creatinine level c0 and either: a time t0 at which the initial creatinine level c0 was measured, or a time interval ΔT0=tp−t0; (b) an initial estimated glomerular filtration rate (eGFR) eGFR0 and either: a time t0 at which the initial eGFR was determined, or a time interval ΔT0=tp−t0; (c) for a plurality of past creatinine level measurements ci measured at a respective times ti, a statistical parameter derived from a linear regression of the plurality of past creatinine level measurements; and (d) for a plurality of past eGFR values eGFRi determined at respective times ti, a statistical parameter derived from a linear regression of the plurality of past eGFR values; and applying a machine-learning model to the input data to generate an output indicating the likelihood of kidney failure within the given amount of time Δt. Corresponding training methods and systems are also provided.
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
71.
ESTIMATION OF QUANTITATIVE SYSTEMS PHARMACOLOGY (QSP) TREATMENT EFFECT PARAMETERS USING DEEP LEARNING
A method and system for evaluating a treatment using one or more model parameters associated with a quantitative systems pharmacology (QSP) system. Input data corresponding to a treatment is received. The input data is sent to a machine learning system that has been trained, the machine learning system representing at least a portion of the QSP model. The machine learning system is used to generate a set of values for a set of treatment effect parameters associated with the QSP model. A final output is generated based on an evaluation of the treatment on a subject using the set of values for the set of treatment effect parameters.
G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 50/50 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
The present disclosure relates to methods, cells, and compositions for producing a product of interest, e.g., a recombinant protein. In particular, the present disclosure provides improved mammalian cells expressing the product of interest, where the cells (e.g., Chinese Hamster Ovary (CHO) cells) have reduced or eliminated activity, e.g., expression, of certain host cell proteins, e.g., enzymes including, but not limited to, certain lipases, esterases, and/or hydrolases.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
73.
THERMAL CONTROL DEVICE FOR TEMPERATURE CYCLING, METHOD FOR CONTROLLING TEMPERATURE CYCLING USING A THERMAL CONTROL DEVICE, AND SYSTEM FOR CONTROLLING TEMPERATURE OF A SAMPLE USING A THERMAL CONTROL DEVICE
In one embodiment, a thermal control device (110) adapted for temperature cycling is provided. The thermal control device (110) comprises a thermally conductive heat spreader layer (118) comprising a first side surface and a second side surface. A heater circuit (120) is disposed adjacent to and in thermal contact with at least one of the first side surface and the second side surface of the thermally conductive heat spreader layer (118). At least one thermal interface material layer (114) is disposed adjacent to and in thermal contact with one of the first side surface and the second side surface of the thermally conductive heat spreader layer (118). A cooling block (116) is disposed adjacent to and in thermal contact with the thermal interface material layer (114). The cooling block (116) is adapted to conduct heat energy away from the thermally conductive heat spreader layer (118). A controller is coupled to and adapted to control the heater circuit (120). In another embodiment, a diagnostic test device is provided.
The present invention concerns the field of diagnostics. Specifically, it relates to a method for assessing congestion in a subject comprising the steps of determining in a sample of the subject the amount of a BMP 10-type peptide (Bone Morphogenic Protein 10-type peptide) and comparing the amount of the BMP 10-type peptide to a reference for the BMP 10-type peptide, whereby congestion is to be assessed. The present invention also contemplates a method of differentiating between precapillary pulmonary hypertension and postcapillary pulmonary hypertension. Further, the invention concerns computer-implemented methods of the aforementioned methods as well as devices and kits for carrying out said methods. Yet, the invention in general relates to the use of a BMP 10-type peptide or a detection agent therefor in a sample of a subject for assessing congestion or the use of a BMP 10-type peptide or a detection agent therefor in a sample of a subject for differentiating between precapillary pulmonary hypertension and postcapillary pulmonary hypertension.
The current invention is directed to a method for determining homodimeric avid-binding side-products of a bispecific antibody in a sample comprising the correctly assemble heterodimeric affine-binding bispecific antibody and the mis-assembled homodimeric avid-binding side-product of the bispecific antibody using surface plasmon resonance, wherein the correctly assembled heterodimeric affine-binding bispecific antibody comprises one or more binding site for a first antigen and one or more binding sites for a second antigen, wherein the mis-assembled homodimeric avid-binding side-product of the bispecific antibody comprises two or more binding sites to the first antigen but at least more than the correctly assembled bispecific antibody, wherein the correctly assembled bispecific antibody is a heterodimer and the mis-assembled bispecific antibody is a homodimer, wherein the presence of the homodimeric avid-binding side-product is determined if residual binding, i.e. an increased SPR signal, can be determined in the dissolution phase of the SPR analysis.
The present invention generally relates to antibodies that bind to CD3, including multispecific antibodies 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.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
79.
FOLR1 PROTEASE-ACTIVATABLE T CELL BISPECIFIC ANTIBODIES
The present invention generally relates to improved Protease-activatable antigen-binding molecules that comprise an anti-idiotype-binding moiety which reversibly masks a CD3 antigen binding moiety of the molecule. Furthermore, the invention relates to novel Protease-cleavable peptide linkers and their used in such Protease-activatable antigen-binding molecules. In addition, the present invention relates to polynucleotides encoding such Protease-activated T cell binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the Protease-activated T cell binding molecules of the invention, and to methods of using the same, e.g., in the treatment of disease.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
Methods for facilitating selection of cell lines for production of recombinant proteins are disclosed. In particular, disclosed is the use of machine learning models trained on multiomics data to predict one or more values indicative of the titre and/or quality of a recombinant protein expressed by different cell lines, enabling ranking the cell lines based on the predicted values and selecting those predicted to produce the recombinant protein with higher titre and/or higher quality.
A computer-implemented training method (110) of training at least one trainable model is disclosed for classifying a patient's health condition into a systemic inflammatory state (168, 170, 172) selected from a predetermined group of at least three systemic inflammatory states (168, 170, 172). The method comprises: a. providing the trainable model; b. retrieving labeled training patient data, the training patient data comprising gene expression data of patients having known systemic inflammatory states (168, 170, 172); and c. training the trainable model on the labeled training patient data. Further disclosed is a computer-implemented classification method (112) of classifying a patient's health condition into a systemic inflammatory state (168, 170, 172) selected from a predetermined group of at least three systemic inflammatory states (168, 170, 172) and systems, computer programs and computer-readable storage media for performing the methods.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
The present invention relates to the field of diagnostics. In particular, it relates to a method for assessing systemic inflammation in a subject exhibiting symptoms thereof comprising a) determining in a sample of said subject the amounts of biomarkers from a group of biomarkers selected from i) a first group of biomarkers comprising: POMK, NEK6, KCNA5, LARGE2, ZNF425, NACA2, CFAP57, SPINT1, ZNF492, and S100A6, ii) a second group of biomarkers comprising: NEK6, SRPK3, TNFSF8, S100A6, NMUR1, DHFR, HIST1H4D, ZDHHC4, TRAF3, and SGMSlor iii) a third group of biomarkers comprising: C9orfl35, ZNF425, ACOT4, SPDYA, DAPP1, LY86, ZPBP2, RPL3L, UPK1B, and APBB3, b) comparing said determined amounts of biomarkers from said group of biomarkers to a reference, and c) assessing systemic inflammation in the subject. Further, the present invention, in general, relates to the use of the amounts of said biomarkers in a sample of a subject exhibiting symptoms of systemic inflammation for assessing systemic inflammation. Moreover, contemplated are a device and a kit for assessing systemic inflammation.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
Provided herein are biomarkers for the treatment of pathological conditions, such as cancer, and method of using PD-1/PD-L1 pathway antagonists. In particular, provided are biomarkers for patient selection and prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Methods for selecting cell pools for production of recombinant proteins are disclosed. In particular, disclosed is the use of one or more genes whose expression level can be used as a biomarker to predict which cell pool, among a plurality of cell pools, produces a recombinant protein with higher titre and/or higher quality.
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
88.
PROCESS FOR THE PREPARATION OF 7-(4,7-DIAZASPIRO[2.5]OCTAN-7-YL)-2-(2,8-DIMETHYLIMIDAZO[1,2-B]PYRIDAZIN-6-YL)PYRIDO[1,2-A]PYRIMIDIN-4-ONE DERIVATIVES
The present invention relates to a process for the preparation of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one derivatives useful as pharmaceutically active compounds.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The invention provides methods and compositions for treating cancer and for enhancing immune function in an individual having cancer. The methods comprise administering a PD-1 axis binding antagonist and a taxane.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
90.
LOW CONCENTRATION SINGLE PASS TANGENTIAL FLOW FILTRATION TO DE-BOTTLENECK CONNECTED AND/OR HIGH TITER FED BATCH PROCESSES
Exemplary systems and methods are provided for receiving a feed flow at a feed flow inlet of a single pass tangential flow filtration unit, wherein the single pass tangential flow filtration unit includes one or more membranes or membrane devices in a one-or two-stage configuration, and wherein a pressure drop across the one or more membranes or membrane devices is less than or equal to 30 psi. The systems and methods are configured to separate, using the one or more membranes or membrane devices in a one-or two-stage configuration, the feed stream into a permeate stream and a retentate stream and output the permeate stream through one or more permeate outlets and the retentate stream through one or more retentate outlets.
The present application discloses variants of Pertuzumab. In particular, it discloses: an unpaired cysteine variant comprising Cys23/Cys88 unpaired cysteines in one or both variable light domains of Pertuzumab, an afucosylated variant of Pertuzumab, a low-molecular-weight-species (LMWS) of Pertuzumab, and a high-molecular-weight-species (HMWS) or Pertuzumab. The application further discloses the isolated variants, compositions, pharmaceutical compositions, and articles of manufacture comprising the variants, as well as methods of making and characterizing the variants and compositions thereof.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
92.
LOW CONCENTRATION SINGLE PASS TANGENTIAL FLOW FILTRATION TO DE-BOTTLENECK CONNECTED AND/OR HIGH TITER FED BATCH PROCESSES
Exemplary systems and methods are provided for receiving a feed flow at a feed flow inlet of a single pass tangential flow filtration unit, wherein the single pass tangential flow filtration unit includes one or more membranes or membrane devices in a one- or two-stage configuration, and wherein a pressure drop across the one or more membranes or membrane devices is less than or equal to 3Opsi. The systems and methods are configured to separate, using the one or more membranes or membrane devices in a one- or two-stage configuration, the feed stream into a permeate stream and a retentate stream and output the permeate stream through one or more permeate outlets and the retentate stream through one or more retentate outlets.
Methods for preparing the Bruton's Tyrosine Kinase (“BTK”) inhibitor compound 2-{3′-hydroxymethyl-1-methyl-5-[5-((S)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4′]bipyridinyl-2′-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one are provided.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
The present invention relates to systems and methods to detect liver cirrhosis in digital images. Various embodiments of the present invention relate to systems and methods to detect liver cirrhosis in computed tomography (CT) scans and, more specifically but not limited, to systems and methods to detect liver cirrhosis via a model trained on highly-interpretable features.
Methods for facilitating selection of cell lines for production of recombinant proteins are disclosed. In particular, disclosed is the use of machine learning models trained on multiomics data to predict one or more values indicative of the titre and/or quality of a recombinant protein expressed by different cell lines, enabling ranking the cell lines based on the predicted values and selecting those predicted to produce the recombinant protein with higher titre and/or higher quality.
The present invention generally relates to chimeric receptors comprising an extracellular domain comprising a mutated Fc domain. The invention also relates to transduced immune cells expressing the chimeric receptors of the invention and/or nucleic acid molecules encoding the chimeric receptors of the present invention. Further provided are kits comprising such cells and/or nucleic acid molecules encoding the chimeric receptors, and antibodies capable of binding to the chimeric receptors.
In one aspect, a method for identifying residues in a particular conformation of a protein molecule capable of forming a stable binding between a compound and the protein molecule is provided. The method can include identifying, for inclusion in a perturbation set, one or more residues from the conformation of the protein molecule that exhibit a protection factor satisfying one or more thresholds. One or more residues may be excluded from the perturbation set based at least on a spatial arrangement and/or an orientation of the one or more residues. One or more rounds of molecular dynamics simulations whose result is indicative of an interaction between the compound and the residues in the perturbation set may be performed. The residues in the perturbation set may be identified as forming a stable binding between the compound and the protein molecule based at least on the result of the molecular dynamics simulation
The present disclosure provides high viscosity ultrafiltration/diafiltration (UF/DF) and single-pass tangential flow filtration (SPTFF) processes used in the purification of polypeptides. A method for purifying a polypeptide from a polypeptide preparation may include the following steps in order: a) subjecting the polypeptide preparation to one or more purification processes and recovering a first resulting pool having a viscosity of about 5-40 cP; and b) subjecting the pool recovered from step a) to a SPTFF operation comprising use of membranes in either or both a serial membrane and/or a parallel membrane configuration and recovering a second resulting pool having an operating viscosity of about 41-400 cP, wherein, i) the operating temperature is about 15-55° C., and ii) the feed flux is about 5-50 L/m2/hr (LMH).
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or propertiesManufacturing processes specially adapted therefor characterised by their properties
99.
TERT-BUTYL (S)-2-(4-(PHENYL)-6H-THIENO[3, 2-F][1, 2, 4]TRIAZOLO[4, 3-A] [1,4]DIAZEPIN-6-YL) ACETATE DERIVATIVES AND RELATED COMPOUNDS AS BROMODOMAIN BRD4 INHIBITORS FOR TREATING CANCER
The present disclosure relates to compounds and salts thereof that are useful for inhibiting target polypeptides and proteins, in particular, bromodomain (e.g., BRD4) proteins. Also disclosed are pharmaceutical compositions comprising the compounds, or a salt (e.g., a pharmaceutically acceptable salt) thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated diseases or disorders.
C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
C07C 233/05 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
C07D 205/02 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
C07D 211/14 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
C07D 295/10 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulfur atoms
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
