Abstract

The present invention pertains to a novel method for the generation of highly diverse RNA expressing vectors and vector libraries for use in targeted gene knock out, knock down and genome modification approaches. The invention pertains to a method for generating such higher order libraries without the need of classical cloning technologies. This is particularly useful for libraries based on large vectors wherein a sequence cannot be easily mutated with classical mutagenesis methods. The vectors and libraries generated according to the methods of the invention are in particular for RNA assisted silencing technologies such as RNA interference, and for targeted genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system or similar RNA/DNA-encoded gene perturbation systems which use small guide RNAs to target the CRISPR complex to a specific genomic sequence. The invention provides also kits comprising the materials for performing the methods of the invention.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
• C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
• C40B 20/04 - Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
• C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cellsLibraries contained in or displayed by vectors, e.g. plasmidsLibraries containing only microorganisms or vectors
• C40B 40/06 - Libraries containing nucleotides or polynucleotides, or derivatives thereof

Abstract

The invention is based on in vitro transcribed or in vitro synthesized RNA compounds for a translation of tumor suppressor proteins in subjects suffering from a proliferative disease such as cancer. The invention provides the RNA compounds, as well as compositions for their delivery or administration to subjects.

IPC Classes  ?

• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61K 31/7115 - Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
• A61P 35/00 - Antineoplastic agents
• A61P 35/04 - Antineoplastic agents specific for metastasis
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans

Abstract

The present invention concerns novel Gram-negative bacteria efflux pump inhibitors. It further relates to the use of Gram-negative bacteria efflux pump inhibitors to prevent and/or treat antibiotic resistance by potentiating the activity of antibiotics. Infections by multidrug resistant (MDR) Gram-negative bacteria are a major threat to global healthcare. The inventors have discovered a novel class of Resistance Nodulation cell Division-efflux pump inhibitors. The inventors tested the effects of these inhibitors on growth inhibition of different bacteria as well as their impact on the boosting of antibiotic activity in different bacteria. Particularly, the inventors tested the effects of these inhibitors on E. coli, A. baumamnii, K. pneumoniae and P. aeruginosa.

IPC Classes  ?

• C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• 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 31/4545 - 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 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• 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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C07D 213/80 - AcidsEsters in position 3
• C07D 215/38 - Nitrogen atoms
• C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
• C07D 241/44 - Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• C07D 295/073 - 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 halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• 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 413/04 - 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 directly linked by a ring-member-to-ring- member bond
• C07D 471/04 - Ortho-condensed systems
• C07D 471/08 - Bridged systems
• C07D 487/08 - Bridged systems

Abstract

b,fb,f][1,4]oxazepine. The compounds of the invention were shown in a comparative study to bind and activate potassium channels, in particular Slack. Based on their activating activity, the compounds of the invention and pharmaceutical compositions containing them can be used in various therapeutic applications for the treatment or prevention of pathologies.

IPC Classes  ?

• A61P 17/04 - Antipruritics
• A61P 29/02 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
• C07D 413/04 - 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 directly linked by a ring-member-to-ring- member bond
• 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
• C07D 417/04 - 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 directly linked by a ring-member-to-ring- member bond
• 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 31/554 - 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 sulfur as ring hetero atoms, e.g. clothiapine, diltiazem

Abstract

Improved SAW-sensor with thin piezoelectric layer and osmotic sensor device including the same The invention refers to a SAW sensor (10) comprising: a substrate (12), a piezoelectric layer (14) deposited on the substrate (12), an input IDT (16, 16a) configured for converting input electric signals into surface acoustic waves, and an output IDT (16, 16b) configured for converting said surface acoustic waves into output electric signals, wherein the input IDT (16, 16a) and the output IDT (16, 16b) are arranged on the piezoelectric layer (14). The invention further refers to an osmotic sensor device (20) for measuring a property of a body fluid comprising a cavity (22) for confining a fluid, a membrane (24) for allowing osmotic diffusion into and/or from the cavity (22), and such SAW sensor (10). The invention also refers to a method of manufacturing such SAW sensor comprising depositing (104) the piezoelectric layer (14) on the substrate (12) by means of a deposition process.

IPC Classes  ?

• G01N 29/02 - Analysing fluids
• A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves
• G01N 29/036 - Analysing fluids by measuring frequency or resonance of acoustic waves
• G01N 29/22 - Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic wavesVisualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object Details
• G01H 1/06 - Frequency

Abstract

12012062072020 alkyl-substituted aryl, R' is selected from among the group consisting of H and R; to a process for producing said compounds, and to the use of the compounds for producing silicones.

IPC Classes  ?

• C07F 7/14 - Preparation thereof from halogenated silanes and hydrocarbons
• C08G 77/04 - Polysiloxanes
• C07F 7/12 - Organo silicon halides
• C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages

Abstract

The present invention relates to a novel type of composition for developing stable synthetic perfluoro-hydrocarbon-based oxygen carriers, the manufacturing thereof, and the use thereof as a synthetic blood and oxygen substitute carrier and as a volume replacement.

IPC Classes  ?

• A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids

Abstract

The invention relates to a measuring system for detecting pressure measurement values in a blood vessel of a patient. The measuring system comprises a multi-arm connection (10), comprising a first connection arm (12), a second connection arm (14) and a third connection arm (16), which are fluidically connected to one another. The first connection arm (12) can be fluidically connected to a pump device (40) in order to allow a fluid to pass through. The second connection arm (14) can be connected to a patient-side cannula (30). Using the third connection arm (16), a measuring catheter (20) can be introduced into the patient-side cannula in a fluid-tight and moveable manner. The measuring catheter (20) is designed to measure pressure measurement values at a patient-side end (22) of the measuring catheter (20). The measuring system allows for the measurement of pressure measurement values in different positions within a blood vessel during operation of a pump device (40). The invention also relates to an extracorporeal membrane oxygenation assembly with a measuring system of this type and a method for detecting pressuring measurement values within a blood vessel (G) of a patient (P) using a measuring system of this type.

IPC Classes  ?

• A61B 5/0215 - Measuring pressure in heart or blood vessels by means inserted into the body
• A61M 1/36 - Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation
• A61M 25/00 - CathetersHollow probes

Abstract

The present invention relates to polypeptides which are galacturonate (GalA) reductase variants comprising at least one amino acid substitution at a position corresponding to K261 and/or R267. The present invention further relates to nucleic acid molecules encoding the polypeptides and to host cells containing said nucleic acid molecules. The present invention further relates to a method for the production of L-galactonate (GalOA) and/or other bio-based compounds, comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention also relates to the use of the polypeptides, nucleic acids molecule or host cells for the production of L-galactonate (GalOA) and/or other bio-based compounds, and/or for the recombinant fermentation of biomaterial containing D-galacturonate (GalA).

IPC Classes  ?

• C12P 17/06 - Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
• C12P 7/58 - Aldonic, ketoaldonic or saccharic acids
• C12N 9/04 - Oxidoreductases (1.), e.g. luciferase acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
• C12N 15/81 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts

Abstract

The present invention pertains to an improved mesenchymal stromal cell (MSC) preparation and a method for producing the same. The invention provides a new strategy to isolate MSC from bone marrow mononuclear cells (BM-MNCs) by pooling BM-MNCs of multiple unrelated (third-party) bone marrow donors. The MSC preparation manufactured in accordance with the methodology of the invention is characterized by a stable proliferative capability and an increased immunosuppressive potential when compared to individual donor MSC preparations or a pool of individual MSCs generated from multiple donors. The MSCs prepared according to the invention are particularly useful for medical applications such as the treatment of graft-versus-host disease (GvHD) in recipients with hematopoietic stem cell transplants, patients with autoimmune disorders and as a cell-based therapy in regenerative medicine.

IPC Classes  ?

• C12N 5/0775 - Mesenchymal stem cellsAdipose-tissue derived stem cells
• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• 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

Abstract

The invention is based on the modulation of cancer-associated fibroblasts (CAFs) in the treatment of proliferative disorders by radiotherapy. By reducing CAF sensitivity to cellular senescence adverse immune reactions upon radiotherapy of solid tumours and subsequent treatment resistance could be avoided. The invention pertains to senolytics or Interleukin 1 (IL1) signalling inhibitors for use in a method of treating solid tumours and in the treatment or prevention of inflammatory adverse effects upon radiation therapy in context of a cancer treatment. The invention optionally also pertains to senolytics or Interleukin 1 (IL1) signalling inhibitors for use in a method of treating solid tumours and in the treatment or prevention of inflammatory adverse effects upon chemotherapy and/or radiation therapy in context of a cancer treatment.

IPC Classes  ?

• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• 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 14/715 - ReceptorsCell surface antigensCell surface determinants for cytokinesReceptorsCell surface antigensCell surface determinants for lymphokinesReceptorsCell surface antigensCell surface determinants for interferons
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

The invention pertains to a compounds or compositions comprising antagonists of miR- 92 which are useful in a method of treatment of a heart disease associated with or caused by a reduced ventricular elasticity and/or a diastolic dysfunction in a subject, which preferably is a subject suffering from Heart Failure with preserved Ejection Fraction (HFpEF). The invention provides such compounds and/or compositions, which are preferably nucleic acid based antagonists of miR-92, preferably oligonucleotide inhibitors, as well as uses and method for treating subjects.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 9/12 - Antihypertensives
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contractionDrugs for heart failure

Abstract

The present invention provides a method for non-invasive quantitative imaging of a heart, the method comprising: obtaining an initial T1 map and a T2 map of the heart, and correcting the initial T1 map using the T2 map in order to obtain a corrected T1 map, wherein the correcting the initial T1 map comprises subtracting from a value in the initial T1 map a weighted value of the T2 map and adding a constant. The present invention also provides further methods and devices for non-invasive quantitative imaging of the heart.

IPC Classes  ?

• 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
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing

Abstract

The present invention refers to a device and method for stereolithograpic three dimensional (3D) printing comprising: a) a container adequate for containing a photopolymerizable polymer, b) at least one laser generator emitting a light beam with a wavelength between 360 nm and 1000 nm, c) modulation means for modulating said light beam into at least two light sheets which are matrices of light, and d) means for irradiating said light sheets in the container containing said photopolymerizable polymer; wherein said at least one laser generator is arranged so that said at least two light sheets are crossed inside said container, leading to polymerization of the photopolymerizable polymer at the crossing of said light sheets.

IPC Classes  ?

• B29C 64/135 - Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified characterised by the energy source therefor, e.g. by global irradiation combined with a mask the energy source being concentrated, e.g. scanning lasers or focused light sources
• B29C 64/282 - Arrangements for irradiation using multiple radiation means, e.g. micromirrors or multiple light-emitting diodes [LED] of the same type, e.g. using different energy levels

Abstract

The invention is based on the finding that a subjects suffering from a viral infection and which is distinguished by a systemic inflammatory complication such as systemic endotheliitis are in particular indicated for a treatment with mesenchymal stromal cell (MSC) compositions. The invention provides treatments in the context of SARS Cov2 infections, in severely affected subjects receiving mechanical ventilation. Provided are MSC compositions for use in treatments, diagnostic stratification methods, and diagnostic kits for such purposes.

IPC Classes  ?

• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• A61P 31/14 - Antivirals for RNA viruses

Abstract

The present invention relates to a method for identifying a pharmaceutically active compound that modulates the function of a frame-shift pseudoknot element and/or modulates the function of a translation initiation-RNA element of an RNA virus in a mammalian cell. Furthermore, the present invention relates to a method to identify a second and further generation candidate compound with improved modulating properties, a screening system for identifying the pharmaceutically active compound, as well as compounds as identified, and methods of treating or preventing a viral infection caused by an RNA virus in a mammalian cell.

IPC Classes  ?

• C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• A61K 31/33 - Heterocyclic compounds

Abstract

The present invention relates to a method of identifying sub-forms of acute myeloid leukemia (AML), said method comprising (a) determining protein expression levels of a plurality of proteins in a cohort of patients suffering from AML; and (b) classifying said patients according to said protein expression levels; thereby obtaining classes of patients which define sub-forms of AML.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention relates to novel beta-lactone inhibitors of hydrolytic enzymes and their medical use, in particular a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in therapy. The present invention further relates to a pharmaceutical composition for use in therapy, comprising the compound of formula (I) as defined herein and a pharmaceutically acceptable excipient. The instant compounds and compositions are useful in the treatment or prevention of cancer, an infectious disease, an inflammatory disease, or an autoimmune disease, and are useful as proteasome inhibitors. The present invention further relates to the use of a composition comprising a compound of formula (I) or an agriculturally acceptable salt thereof as a plant protection composition, and to a method of controlling a plant disease, the method comprising applying a compound or composition according to the invention. The present invention further relates to the non-therapeutic use of a compound of formula (I) as a disinfectant, and to the non-therapeutic use of the instant compounds or disinfectants for disinfecting or sterilizing an inanimate object.

IPC Classes  ?

• A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
• A01N 31/00 - Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
• A01P 1/00 - DisinfectantsAntimicrobial compounds or mixtures thereof
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 33/00 - Antiparasitic agents
• A61P 35/00 - Antineoplastic agents
• A61P 37/00 - Drugs for immunological or allergic disorders
• A61L 2/00 - Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lensesAccessories therefor

Abstract

The present invention relates to a chimeric antigen receptor (CAR) molecule comprising at least one variable NAR (vNAR) antigen binding.domain. The variable NAR-domain specifically binds to a T cell or B cell specific antigen, and the variable NAR-domain binds to a specific idiotype of a B cell receptor (BCR) or T cell receptor (TCR) in a patient. The present invention further relates to uses of the CAR molecule in the treatment of clonal malignancies, such as T-ALL or B-ALL.

IPC Classes  ?

• 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

Abstract

The present invention concerns novel Gram-negative bacteria efflux pump inhibitors. It further relates to the use of Gram-negative bacteria efflux pump inhibitors to prevent and/or treat antibiotic resistance by potentiating the activity of antibiotics. Infections by multidrug resistant (MDR) Gram-negative bacteria are a major threat to global healthcare. The inventors have discovered a novel class of Resistance Nodulation cell Division-efflux pump inhibitors. The inventors tested the effects of these inhibitors on growth inhibition of different bacteria as well as their impact on the boosting of antibiotic activity in different bacteria. Particularly, the inventors tested the effects of these inhibitors on E. coli, A. baumannii, K. pneumoniae and P. aeruginosa.

IPC Classes  ?

• C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• C07D 215/38 - Nitrogen atoms
• C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
• C07D 241/44 - Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• C07D 295/073 - 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 halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• C07D 471/08 - Bridged systems
• C07D 487/04 - Ortho-condensed systems
• C07D 487/08 - Bridged systems
• C07D 498/04 - Ortho-condensed systems
• A61P 31/04 - Antibacterial agents
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin

Abstract

A sanggenon preparation comprising a sanggenon content of at least 5% (w/w), for use in the prophylactic or therapeutic anti-β-coronavirus treatment of a subject in need of anti-β-coronavirus treatment.

IPC Classes  ?

• A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 31/14 - Antivirals for RNA viruses
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

The invention relates to an oligonucleotide molecule having from 10 to 50 nucleotides comprising at least one G-quartet forming motif comprising 10 to 20 nucleotide residues, wherein at least 60% of said G-quartet forming motive forming residues are guanosine or deoxyguanosine residues, and wherein the molecule inhibits tumor growth and/or viral or bacterial replication and/or exerts anti-inflammatory effects in mammalian cells.

IPC Classes  ?

• A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• 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

Abstract

The invention relates to a system for expressing nonribosomal peptide synthetases (NRPSs), polyketide synthases (PKS) or NRPS/PKS hybrid synth(et)ases. NRPS, PKS or hybrids thereof are large multi-domain proteins or multi-domain complexes, the expression of which for the production of peptides often causes difficulties. The invention correspondingly relates to a system for expressing portions of the enzymes which can be assembled post-translationally via protein-protein interactions, introduced in a targeted manner, to form multi-enzyme complexes. The invention discloses protein fragments of such an assembly, and the nucleic acids coding therefor. The invention also relates to a vector system for the protein fragments of the invention and its use for producing functional NRPS/PKS enzyme complexes.

IPC Classes  ?

• C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying enzymes
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof

Abstract

The invention pertains to the use of mesenchymal stromal cells (MSC) in the treatment of bone disorders or injuries. The invention provides MSC and preparations of specifically pooled MSC for use in the manufacturing of bone graft material for implanting into or attaching to bones in order to enhance bone regeneration after surgery or injury, or to treat various bone disorders, such as osteonecrosis. The invention provides bone graft material, a method for its production, bone graft implants, and medical methods and uses of the inventive products.

IPC Classes  ?

• A61K 35/32 - BonesOsteocytesOsteoblastsTendonsTenocytesTeethOdontoblastsCartilageChondrocytesSynovial membrane
• A61L 27/38 - Animal cells
• A61L 27/56 - Porous or cellular materials
• A61L 27/46 - Composite materials, i.e. layered or containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers

Abstract

The present invention relates to using a genetically encoded voltage indicator (GEVI) protein and counteracting optogenetic protein(s) for depolarization and hyperpolarization as an optic voltage clamp with feedback control in a cell. The present invention further relates to cells coexpressing a GEVI protein, and counteracting optogenetic protein(s) for depolarization and hyperpolarization and their uses. The present invention further relates to a method for controlling the membrane voltage of a target cell and to a method for determining the functionality of or modulating ion channels and/or for determining influences on ion channels.

IPC Classes  ?

• A61K 49/00 - Preparations for testing in vivo
• G01N 21/64 - FluorescencePhosphorescence
• G01N 33/487 - Physical analysis of biological material of liquid biological material

Abstract

Bartonella bacilliformisBartonella bacilliformisBartonella bacilliformis.

IPC Classes  ?

• C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
• A61K 39/02 - Bacterial antigens
• G01N 33/558 - ImmunoassayBiospecific binding assayMaterials therefor using diffusion or migration of antigen or antibody
• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• A61P 31/04 - Antibacterial agents

Abstract

The present invention relates to a compound of formula (I), wherein E1to E6independently of each other represent Si or Ge; X1to X43312020 alkyl and halogen; R1to R12120220220320620772012020 alkyl; to a process of preparing those compounds and to their use for producing an Si- and Ge-containing solid.

IPC Classes  ?

• C07F 7/30 - Germanium compounds
• C23C 16/30 - Deposition of compounds, mixtures or solid solutions, e.g. borides, carbides, nitrides

Abstract

The present invention relates to an intubation bougie for endotracheal intubation, comprising a flexible sealing cuff that is arranged on a distal end and to be inserted into the trachea and that is designed and/or expandable such that it is in sealing contact with the trachea in order to seal it from liquids such as gastric juices.

IPC Classes  ?

• A61M 16/04 - Tracheal tubes

Abstract

The present invention relates to a slow wave structure (1) for transmitting an electromagnetic wave in a travelling wave tube (2), wherein the slow wave structure (1) comprises an electrical conductor (10) formed along a helix, wherein the helix twists around a longitudinal axis (11). In order to provide a slow wave structure and a traveling wave tube amplifier facilitating a simplified amplification of high frequency electromagnetic waves, the electrical conductor (10) comprises at least one coupling section (12), wherein the coupling section (12) is formed in order to generate a non-zero axial electric field outside a space confined by an envelope of the helix of the electrical conductor (10) in a direction parallel to the longitudinal axis (11), when during operation of the slow wave structure (1), the electromagnetic wave is transmitted along the electrical conductor (10), wherein the axial electric field is generated between two ends of the coupling section (20, 20'), wherein the ends of the coupling section (20, 20') are distanced from each other in a direction parallel to the longitudinal axis (11).

IPC Classes  ?

• H01J 23/12 - VesselsContainers
• H01J 23/16 - Circuit elements, having distributed capacitance and inductance, structurally associated with the tube and interacting with the discharge
• H01J 23/18 - Resonators
• H01J 23/27 - Helix-derived slow-wave structures
• H01J 25/36 - Tubes in which an electron stream interacts with a wave travelling along a delay line or equivalent sequence of impedance elements, and without magnet system producing an H-field crossing the E-field

Abstract

The invention is based on the modulation of cancer-associated fibroblasts (CAFs) in the treatment of proliferative disorders by radiotherapy. By reducing CAF sensitivity to cellular senescence adverse immune reactions upon radiotherapy of solid tumours and subsequent treatment resistance could be avoided. The invention pertains to senolytics or Interleukin 1 (IL1) signalling inhibitors for use in a method of treating solid tumours and in the treatment or prevention of inflammatory adverse effects upon radiation therapy in context of a cancer treatment. The invention optionally also pertains to senolytics or Interleukin 1 (IL1) signalling inhibitors for use in a method of treating solid tumours and in the treatment or prevention of inflammatory adverse effects upon chemotherapy and/or radiation therapy in context of a cancer treatment.

IPC Classes  ?

• A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 38/20 - Interleukins
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 35/00 - Antineoplastic agents
• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
• A61N 5/10 - X-ray therapyGamma-ray therapyParticle-irradiation therapy
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The present invention provides a method for non-invasive quantitative imaging of a heart, the method comprising: obtaining an initial T1 map and a T2 map of the heart, and correcting the initial T1 map using the T2 map in order to obtain a corrected T1 map, wherein the correcting the initial T1 map comprises subtracting from a value in the initial T1 map a weighted value of the T2 map and adding a constant. The present invention also provides further methods and devices for non-invasive quantitative imaging of the heart.

IPC Classes  ?

• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G01R 33/50 - NMR imaging systems based on the determination of relaxation times

Abstract

The present invention refers to a device and method for stereolithograpic three dimensional (3D) printing comprising: a) a container adequate for containing a photopolymerizable polymer, b) at least one laser generator emitting a light beam with a wavelength between 360 nm and 1000 nm, c) modulation means for modulating said light beam into at least two light sheets which are matrices of light, and d) means for irradiating said light sheets in the container containing said photopolymerizable polymer; wherein said at least one laser generator is arranged so that said at least two light sheets are crossed inside said container, leading to polymerization of the photopolymerizable polymer at the crossing of said light sheets.

IPC Classes  ?

• G03F 7/20 - ExposureApparatus therefor
• B33Y 30/00 - Apparatus for additive manufacturingDetails thereof or accessories therefor

Abstract

The present invention relates to a method for removing a corrosion product from a metal surface, the method comprising the steps of: - providing an aqueous solution, which comprises a functionalized polyethylene imine; and - bringing the aqueous solution into contact with at least part of the metal surface; wherein the corrosion product is at least partly present on the part of the metal surface that is brought into contact with the aqueous solution; and wherein the functionalized polyethylene imine is represented by formula (I); - n is an integer from 10 to 10,000,000; - X is independently selected from a group of formula (I) and (CR1R2mm Y; - the sum of all n is an integer from 10 to 10,000,000; - R1and R21233R3R433R3R433R333R322R3, R3and R444+, R511010 alkyl.

IPC Classes  ?

• C23G 1/06 - Cleaning or pickling metallic material with solutions or molten salts with acid solutions using inhibitors organic inhibitors
• C23G 1/08 - Iron or steel
• C23G 1/12 - Light metals

Abstract

The present invention relates to proteins involved in fatty acid synthesis, such as fatty acid synthases (FAS) variants, comprising one or more polypeptide chains, wherein said polypeptide chain(s) comprise one or more subunits comprising a malonyl/palmitoyl transferase domain (MPT domain), acetyl transferase domain (AT domain), and ketoacyl synthase domain (KS domain), and at least one amino acid substitution in the MPT domain at a position corresponding to R130, in the AT domain at a position corresponding to 1306, and/or in the KS domain, preferably in the acyl binding channel and/or at KS domain binding site to ACP, to modulate affinities of acyl intermediates, and optionally further amino acid substitution(s). The present invention relates to the respective polypeptide domains. The present invention relates to proteins involved in fatty acid synthesis, such as fatty acid synthases (FAS) variants, comprising one or more polypeptide chains, wherein said polypeptide chain(s) comprise one or more subunits comprising a malonyl/palmitoyl transferase domain (MPT domain), acetyl transferase domain (AT domain), and ketoacyl synthase domain (KS domain), and at least one amino acid substitution in the MPT domain at a position corresponding to R130, in the AT domain at a position corresponding to 1306, and/or in the KS domain, preferably in the acyl binding channel and/or at KS domain binding site to ACP, to modulate affinities of acyl intermediates, and optionally further amino acid substitution(s). The present invention relates to the respective polypeptide domains. The present invention further relates to nucleic acid molecules encoding the proteins (or the polypeptide domains) and to host cells containing said nucleic acid molecules. The present invention further relates to a method for the production of short fatty acids, CoA esters of short fatty acids, ethyl esters of short fatty acids, esters of short fatty acids with other metabolites, and/or enzyme bound short fatty acids (C6 to C12), comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention further relates to a method for the production of biofuels, flavoring compounds and/or fine chemicals, comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention also relates to the use of the proteins, nucleic acids molecule or host cells for the bulk production of short fatty acids (C6 to C12), the specific production of C6 fatty acids and/or C8 fatty acids, the bulk production of CoA esters of short fatty acids (C6 to C12), the specific production of C6-CoA esters and/or C8-CoA esters, the bulk production of ethyl esters of short fatty acids (C6 to C12), the specific production of C6 fatty acid ethyl esters and/or C8 fatty acid ethyl esters, the bulk production of esters of short fatty acids (C6 to C12) with other metabolites, the specific production of C6 fatty acid esters with other metabolites and/or C8 fatty acid esters with other metabolites, the bulk production of enzyme bound short fatty acids (C6 to C12), the specific production of enzyme bound C6 fatty acids and/or enzyme bound C8 fatty acids, the production of biofuels, fine chemicals and/or flavoring substances.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C12P 7/04 - Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic
• C12P 7/64 - FatsFatty oilsEster-type waxesHigher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl groupOxidised oils or fats
• C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells

Abstract

Disclosed herein is an optical system comprising a microscope objective lens (10), a sample holder (12), and an optical pad (20) to be provided in a gap between said microscope objective lens (10) and said sample holder (12). The optical pad (20) is attached or attachable to one of the microscope objective lens (10) and the sample holder (12) and has a dry, free surface (22) configured to be in contact with an abutment surface (24) provided on the other of the microscope objective lens (10) and the sample holder (12) during microscopy, but free to move with respect to it to allow for carrying out microscopy at different relative positions between said free surface (22) and said abutment surface (24). The pad (20) is deformable such that the relative distance between said microscope objective lens (10) and said sample holder (12) can be varied by a working distance while continuously filling the gap between said microscope objective lens (10) and said sample holder (12).

IPC Classes  ?

• G02B 21/33 - Immersion oils
• G02B 21/00 - Microscopes
• G02B 21/34 - Microscope slides, e.g. mounting specimens on microscope slides

Abstract

The present invention relates to a compound of the formula (Ia) or of the formula (Ib), a process for preparing same; and to the use of the compound for producing the Si- and Ge-containing solid.

IPC Classes  ?

• C07F 7/30 - Germanium compounds
• C23C 16/00 - Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
• H01L 21/02 - Manufacture or treatment of semiconductor devices or of parts thereof

Abstract

The invention is based on the finding that ferroptosis mediated cell death results in the local recruitment of immune cells and that a concomitant sensitization of tumour tissue and tumour cells to a cell-mediated immune response results in synergistic therapeutic effects against proliferative diseases. By inducing or supporting ferroptosis, such as inhibition of its key regulators, it could be shown that tumour cells become sensitized to immune checkpoint inhibition, which was even further improved when also myeloid cell recruitment is blocked. Hence, the enhanced recruitment of immune cells via ferroptosis can be harnessed for anti- tumour response by immune checkpoint inhibition and/or suppression of local recruitment of immune suppressive cell fractions. The invention provides such combinatorial approaches to treat proliferative disorders, preferably solid cancers which are characterized by a resistance to immune checkpoint inhibition, which often is observed in hepatocellular carcinoma. The invention pertains to the medical application of ferroptosis induction using ferroptosis agonists in combination with immune checkpoint inhibition – such as inhibition of the PD-1/PD-L1 axis – in the treatment and prevention of proliferative disorders. The invention provides compounds and compositions for use in the indicated medical approaches.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/585 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum

Abstract

The invention is based on the fibrin-derived peptides as therapeutic compounds for the treatment of inflammatory complications of virally caused diseases, such as a diffuse inflammation of the endothelium, also known as systemic endotheliitis or vasculitis and related disorders. The use of fibrin derived peptides and analogues of these compounds resulted in a surprisingly effective patient recovery.

IPC Classes  ?

• A61P 31/14 - Antivirals for RNA viruses
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans

Abstract

The invention is based on the finding that a subjects suffering from a viral infection and which is distinguished by a systemic inflammatory complication such as systemic endotheliitis are in particular indicated for a treatment with mesenchymal stromal cell (MSC) compositions. The invention provides treatments in the context of SARS Cov2 infections, in severely affected subjects receiving mechanical ventilation. Provided are MSC compositions for use in treatments, diagnostic stratification methods, and diagnostic kits for such purposes.

IPC Classes  ?

• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• C12N 5/0775 - Mesenchymal stem cellsAdipose-tissue derived stem cells
• A61P 31/14 - Antivirals for RNA viruses

Abstract

The invention provides a treatment of viral diseases caused by a virus of the family of Coronaviridae by antagonizing downstream components of growth factor (GFR) receptor signalling. The invention provides certain known compounds that are identified as candidates and are repurposed to be useful in viral treatments of the invention. Disclosed is the medical application of the identified repurposed drugs, therapeutic kits and pharmaceutical compositions comprising the compounds.

IPC Classes  ?

• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• 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 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 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 31/14 - Antivirals for RNA viruses

Abstract

555-LOX). The invention pertains to multiple derivatives of the new class of dual inhibitors, their application in medicine, pharmaceutical compositions comprising them as well as to methods for synthesizing the new compounds.

IPC Classes  ?

• C07C 275/20 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
• A61P 19/00 - Drugs for skeletal disorders
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention pertains to a novel method for the generation of a vector construct suitable for gene editing applications which comprises a fixed pair of predetermined expressible guide RNA (gRNA) sequences. The method of the invention allows for an easy construction of such vectors and provides in addition thereto vector libraries for the expression of fixed pairs of gRNAs. The vectors of the invention may be advantageously used to cut out larger genomic DNA sequences, or alternatively, to simultaneously introduce mutations in the genome without a loss or larger genomic sequences. Hence, the system of the invention provides for many molecular genetic approaches for genome alteration.

IPC Classes  ?

• C12N 15/11 - DNA or RNA fragmentsModified forms thereof

Abstract

in vitroin vitro.

IPC Classes  ?

• C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
• C07K 14/35 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Mycobacteriaceae (F)

Abstract

The invention relates to a system for expressing nonribosomal peptide synthetases (NRPSs), polyketide synthases (PKS) or NRPS/PKS hybrid synth(et)ases. NRPS, PKS or hybrids thereof are large multi-domain proteins or multi-domain complexes, the expression of which for the production of peptides often causes difficulties. The invention correspondingly relates to a system for expressing portions of the enzymes which can be assembled post-translationally via protein–protein interactions, introduced in a targeted manner, to form multi-enzyme complexes. The invention discloses protein fragments of such an assembly, and the nucleic acids coding therefor. The invention also relates to a vector system for the protein fragments of the invention and its use for producing functional NRPS/PKS enzyme complexes.

IPC Classes  ?

• C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying enzymes

Abstract

The present invention relates to polypeptides which are galacturonate (GalA) reductase variants comprising at least one amino acid substitution at a position corresponding to K261 and/or R267. The present invention further relates to nucleic acid molecules encoding the polypeptides and to host cells containing said nucleic acid molecules. The present invention further relates to a method for the production of L-galactonate (GalOA) and/or other bio-based compounds, comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention also relates to the use of the polypeptides, nucleic acids molecule or host cells for the production of L-galactonate (GalOA) and/or other bio-based compounds, and/or for the recombinant fermentation of biomaterial containing D-galacturonate (GalA).

IPC Classes  ?

• C12N 15/52 - Genes encoding for enzymes or proenzymes
• C12P 7/00 - Preparation of oxygen-containing organic compounds
• C12N 9/04 - Oxidoreductases (1.), e.g. luciferase acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)

Abstract

The invention is based on a class of dual modulators of soluble epoxide hydrolase (sEH) and farnesoid X receptor (FXR), in particular of compounds having an activity as FXR agonist and sEH inhibitor for the treatment or prevention of kidney diseases and/or fibrotic diseases. The invention provides the compounds for use in such treatments and preventions as well as pharmaceutical compositions comprising the compounds as active ingredients.

IPC Classes  ?

• A61K 31/18 - Sulfonamides
• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
• A61P 17/00 - Drugs for dermatological disorders
• A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• A61P 17/06 - Antipsoriatics

Abstract

Ephrin type receptor tyrosine kinase inhibitors, also known as Eph tyrosine kinase receptor inhibitors, for treating cancer, an inflammatory disease, an autoimmune disease, or a degenerative disease characterized at least in part by the abnormal activity or expression of the Eph receptor tyrosine kinase. The inhibitors are particularly useful for treating colorectal cancer.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• C07D 487/04 - Ortho-condensed systems
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/52 - Purines, e.g. adenine
• A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
• C07D 251/54 - Three nitrogen atoms
• 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 413/04 - 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 directly linked by a ring-member-to-ring- member bond
• C07D 471/04 - Ortho-condensed systems

Abstract

Ephrin type receptor tyrosine kinase inhibitors, also known as Eph tyrosine kinase receptor inhibitors, for treating cancer, an inflammatory disease, an autoimmune disease, or a degenerative disease characterized at least in part by the abnormal activity or expression of the Eph receptor tyrosine kinase. The inhibitors are particularly useful for treating colorectal cancer.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
• A61P 35/00 - Antineoplastic agents
• C07D 251/22 - Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon 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 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 403/04 - 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
• 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
• C07D 471/04 - Ortho-condensed systems

Abstract

The invention pertains to the use of mesenchymal stromal cells (MSC) in the treatment of bone disorders or injuries. The invention provides MSC and preparations of specifically pooled MSC for use in the manufacturing of bone graft material for implanting into or attaching to bones in order to enhance bone regeneration after surgery or injury, or to treat various bone disorders, such as osteonecrosis. The invention provides bone graft material, a method for its production, bone graft implants, and medical methods and uses of the inventive products.

IPC Classes  ?

• A61L 27/42 - Composite materials, i.e. layered or containing one material dispersed in a matrix of the same or different material having an inorganic matrix
• A61L 27/44 - Composite materials, i.e. layered or containing one material dispersed in a matrix of the same or different material having a macromolecular matrix

Abstract

The invention pertains to the use of bone marrow derived cells (BMDC) except mesenchymal stem cells (MSC) in the treatment of bone disorders or injuries. The invention provides BMDC and preparations of specifically pooled BMDC for use in the manufacturing of bone graft material for implanting into or attaching to bones in order to enhance bone regeneration after surgery or injury, or to treat various bone disorders, such as osteonecrosis. The invention provides bone graft material, a method for its production, bone graft implants, and medical methods and uses of the inventive products.

IPC Classes  ?

• A61L 27/42 - Composite materials, i.e. layered or containing one material dispersed in a matrix of the same or different material having an inorganic matrix
• A61L 27/44 - Composite materials, i.e. layered or containing one material dispersed in a matrix of the same or different material having a macromolecular matrix

Abstract

A method is for the detection of SARS-CoV-2 in a plurality of biological samples of living beings and a kit is for carrying out the method. The method includes providing at least one biological sample of a first living being and at least one biological sample of at least a second living being. The samples from the first and second living beings are suspected of containing SARS-CoV-2 and/or SARS-CoV-2 derived material. At least an aliquot of each of the biological samples are pooled to obtain a pool sample. The pool sample is tested for the presence of SARS-CoV-2 and/or SARS-CoV-2 derived material.

IPC Classes  ?

• C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage

Abstract

The present invention pertains to a system for the assembly and modification of non-ribosomal peptide synthases (NRPS). The system uses novel well defined building blocks (units) comprising condensation subdomains. This strategy allows for the efficient combination of assembly units referred to as eXchange Units (XU2.0) independent on their natural occurring specificity for the subsequent NRPS adenylation domain. The system of the invention allows for the easy assembly of NRPS having any amino acid sequence of choice, without any restrictions due to natural occurring NRPS units. The system also allows the exchange of natural NRPS building blocks with the inventive XU2.0 leading to the production of modified peptides. The invention provides the system, their individual exchange units, nucleic acids encoding these units, as well as methods and uses thereof.

IPC Classes  ?

• C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
• C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying enzymes

Abstract

The invention is based on the surprising finding of the ability of gene editing nucleases to be automatically packaged into viral particles. The invention provides viral particles, such as viral capsids, containing a high amount of the gene editing nuclease that efficiently transduce target cells with either components for gene editing or alternatively any other cargo attached to the gene editing nuclease. Since the viral particles of the invention do not need to contain any components of the viral genome, they can both efficiently and safely transduce mammalian cells for editing genome sequences or other purposes. The invention provides the viral particles, compositions comprising them, methods for their generation, and medical and laboratory applications of the new transduction methods and tools.

IPC Classes  ?

• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 9/22 - Ribonucleases
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA

Abstract

The present invention relates to a product comprising a metal surface onto which a corrosion protection layer is applied, the corrosion protection layer comprising at least one amino acid amide composed of a linear or branched fatty acid and an amino acid which are bonded to one another by means of an amide bond. The invention also relates to a method for producing said product and the use of amino acid amides in corrosion protection.

IPC Classes  ?

• C23F 11/14 - Nitrogen-containing compounds

Abstract

The invention relates to a compound produced by one of the following formulae (I) to (VII), wherein E is selected from B and Al; Kat+is a monovalent cation; and R1and R2independently represent a functional group or R1is CI and R2 is a functional group. The invention also relates to a method for reacting and/or producing same and to their use for producing silicones.

IPC Classes  ?

• C07F 7/12 - Organo silicon halides
• C07F 5/02 - Boron compounds
• C07F 5/06 - Aluminium compounds

Abstract

Attachment (10) for an immersion objective (14) for performing an inverse immersion microscopy is provided. The attachment (10) comprises an attachment portion (12) for receiving an end portion of an immersion objective (14), wherein the attachment portion (12) defines a detecting axis (20) coinciding with the optical axis (22) of the immersion objective (14), when the immersion objective (14) is received in the attachment portion (12), and a container portion (16). The container portion (16) defines, when the immersion objective (14) is received in the attachment portion (12) and oriented in an inverse orientation, together with a front surface of the received immersion objective (14) a container (34) for retaining an immersion fluid (38), comprises a transparent wall portion (50) defining an intended illumination direction (52) being orthogonal to the transparent wall portion (50) and tilted to the detecting axis (20), and is arranged, such that when the immersion objective (14) is in the inverse orientation and received in the attachment portion (12) a sample (54) being located on the detecting axis (20) can be illuminated through the transparent wall portion (50) and through an immersion fluid (38) being retained by the container (34).

IPC Classes  ?

• G02B 21/00 - Microscopes
• G02B 21/33 - Immersion oils

Abstract

The present invention pertains to a novel architecture of non-ribosomal peptide synthases (NRPS). The invention provides artificial NRPS wherein the naturally occurring terminal condensation or thioesterase-domain is replaced by internal condensation or dual condensation/epimerization domains. Moreover, the present invention enables the portability of terminal condensation domains to unrelated NRPS in respect of peptide release of linear peptides. The replacement results in a product independent release of the synthesized product and therefore enables the rational design of NRPS. The invention provides the new NRPS, nucleic acids encoding them, methods for artificial NRPS generation, and methods for producing non-ribosomal peptides.

IPC Classes  ?

• C12N 9/88 - Lyases (4.)
• C12N 15/70 - Vectors or expression systems specially adapted for E. coli
• C12P 21/00 - Preparation of peptides or proteins

Abstract

Disclosed herein are a device and a method for synthesizing diamond. The device comprises an inner capsule containing a buffer medium for stabilizing a hydrogen fugacity, the inner capsule consisting of a hydrogen-permeable material; an outer capsule enclosing the inner capsule, wherein the outer capsule contains a reaction medium containing reactants for a chemical reaction yielding diamond; and a pressure medium surrounding the outer capsule, wherein the pressure medium is configured to transfer a pressure applied to an outer surface of the pressure medium to an outer surface of the outer capsule and wherein the pressure medium is further configured to inhibit hydrogen exchange through the pressure medium at a temperature of the pressure medium and a pressure applied to the pressure medium that are required to transform the reaction medium to a supercritical phase.

IPC Classes  ?

• B01J 3/06 - Processes using ultra-high pressure, e.g. for the formation of diamondsApparatus therefor, e.g. moulds or dies

Abstract

The present invention pertains to a method for detecting whether a cancer disease in a subject is susceptible to a treatment with a Spleen Tyrosine Kinase (SYK) inhibitor by determining the amount or level of a biomarker selected from Hoxa9/Meis1, PU.1 and miR146a in a biological sample from the subject. The invention provides novel treatment approaches based on the detection of the differential expression of the above biomarkers using SYK inhibitors. Also provided are diagnostic kits, and combined therapeutic and diagnostic kits for use in the inventive methods.

IPC Classes  ?

• 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
• 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
• G16B 40/10 - Signal processing, e.g. from mass spectrometry [MS] or from PCR

Abstract

The present invention pertains to a novel method for the generation of a vector construct suitable for gene editing applications which comprises a fixed pair of predetermined ex- pressible guide RNA (gRNA) sequences. The method of the invention allows for an easy construction of such vectors and provides in addition thereto vector libraries for the expres- sion of fixed pairs of gRNAs. The vectors of the invention may be advantageously used to cut out larger genomic DNA sequences, or alternatively, to simultaneously introduce muta- tions in the genome without a loss or larger genomic sequences. Hence, the system of the invention provides for many molecular genetic approaches for genome alteration.

IPC Classes  ?

• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The present invention pertains to a system for the assembly and modification of non- ribosomal peptide synthases (NRPS). The system uses novel well defined building blocks (units) comprising condensation subdomains. This strategy allows for the efficient combination of assembly units referred to as eXchange Units (XU2.0) independent on their natural occurring specificity for the subsequent NRPS adenylation domain. The system of the invention allows for the easy assembly of NRPS having any amino acid sequence of choice, without any restrictions due to natural occurring NRPS units. The system also allows the exchange of natural NRPS building blocks with the inventive XU2.0 leading to the production of modified peptides. The invention provides the system, their individual exchange units, nucleic acids encoding these units, as well as methods and uses thereof.

IPC Classes  ?

• C40B 40/00 - Libraries per se, e.g. arrays, mixtures
• C12P 21/00 - Preparation of peptides or proteins
• C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying enzymes

Abstract

The present invention relates to small molecule compounds and their use as agonists of farnesoid X receptor (FXR) and/or peroxisome proliferator activated receptor delta (PPARδ). The present invention also relates to the use of said compounds in the treatment of metabolic diseases and respective methods of treatment.

IPC Classes  ?

• C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4
• C07D 215/48 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• C07D 333/24 - 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
• C07D 249/04 - 1,2,3-TriazolesHydrogenated 1,2,3-triazoles
• C07D 261/08 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07D 263/32 - Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• C07C 237/42 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
• C07C 237/44 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
• C07D 307/54 - 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
• A61P 3/06 - Antihyperlipidemics
• A61P 3/04 - AnorexiantsAntiobesity agents
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine

Abstract

Diploid transgenic animals are either hemizygous or homozygous. Genetic assays are, therefore, necessary to identify the genotype. Herein disclosed is a novel vector system, referred to as the"AGameOfClones" vector concept, which uses two transformation markers embedded in interweaved, but incompatible Lox site pairs. Cre-mediated recombination leads to heterozygous progeny that is identifiable by both markers. In the following generation, the omission of one marker indicates homozygous individuals. The inventors prove this concept in Tribolium castaneumby systematically creating multiple homozygous transgenic lines suitable for long-term fluorescence live imaging. Since this approach relies on the universal Cre-Lox system, it should work in most diploid model organisms, e.g. rodents, zebrafish, insects and plants. It saves resources, simplifies transgenic animal handling and contributes to the ethically motivated endeavor to minimize the number of wasted animals.

IPC Classes  ?

• C12N 15/79 - Vectors or expression systems specially adapted for eukaryotic hosts

Abstract

The present invention provides a cellular system for the detection of the presence of one or more antibody species in sample, preferably a serum or plasma sample. The method is in particular useful for the analysis of patients who have been sensitized against blood group antigens expressed on erythrocytes, platelets or granulocytes. The system uses fluorescence labeled cells specific for each antigen and hence, for each antibody species. Provided are the methods, system and diagnostic kits for performing the methods of the invention. In addition, the present invention discloses a method for removing antibodies from a sample such as a serum sample. Such a method is useful for absorbing antibodies from poly-agglutinating sera.

IPC Classes  ?

• G01N 33/53 - ImmunoassayBiospecific binding assayMaterials therefor
• G01N 33/80 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood groups or blood types
• C07K 16/34 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood group antigens
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography

Abstract

The present invention pertains to novel dual modulators of farnesoid X receptor (FXR) and soluble epoxide hydrolase (sEH). The modulators of the invention were designed to provide compounds which harbor a dual activity as agonists of FXR and inhibitors (antagonists) of sEH. The invention also provides methods for treating subjects suffering from diseases associated with FXR and sEH, such as metabolic disorders, in particular non-alcoholic fatty liver or nonalcoholic steatohepatitis (NASH).

IPC Classes  ?

• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• C07C 255/60 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
• C07C 311/08 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• C07C 311/46 - Y being a hydrogen or a carbon atom
• C07C 311/51 - Y being a hydrogen or a carbon atom
• C07C 317/32 - SulfonesSulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
• C07C 321/28 - Sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings
• C07D 257/04 - Five-membered rings
• C07C 233/73 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
• C07C 233/76 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
• C07C 233/78 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
• C07C 233/87 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
• C07C 235/52 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• C07C 237/30 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
• C07C 237/36 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• A61P 3/06 - Antihyperlipidemics
• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• A61K 31/18 - Sulfonamides
• A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil
• A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole

Abstract

The present invention pertains to novel dual modulators of farnesoid X receptor (FXR) and soluble epoxide hydrolase (sEH). The modulators of the invention were designed to provide compounds which harbor a dual activity as agonists of FXR and inhibitors (antagonists) of sEH. The invention also provides methods for treating subjects suffering from diseases associated with FXR and sEH, such as metabolic disorders, in particular non-alcoholic fatty liver or non-alcoholic steatohepatitis (NASH).

IPC Classes  ?

• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• C07C 255/60 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
• C07C 311/08 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• C07C 311/46 - Y being a hydrogen or a carbon atom
• C07C 311/51 - Y being a hydrogen or a carbon atom
• C07C 317/32 - SulfonesSulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
• C07C 321/28 - Sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings
• C07D 257/04 - Five-membered rings
• C07C 233/73 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
• C07C 233/76 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
• C07C 233/78 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
• C07C 233/87 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
• C07C 235/52 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• C07C 237/30 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
• C07C 237/36 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• A61P 3/06 - Antihyperlipidemics
• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• A61K 31/18 - Sulfonamides
• A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil
• A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole

Abstract

A cover lid collector (10) for a sample carrier (40) for cell cultivation, wherein the cover lid collector (10) comprises a connecting portion (12) for engaging with the sample carrier (40) for closing the same, wherein the connecting portion (12) defines a first plane (11). The cover lid collector (10) further comprises a cavity (14), which when the cover lid collector is engaged with the sample carrier (40), has a cross-section that decreases in a direction perpendicular to the first plane (11) and pointing away from said sample carrier (40) between a near end (16) of the cavity (14) and a far end (18) of the cavity (14), wherein the near end (16) is closer to the sample carrier (40) than the far end (18).

IPC Classes  ?

• C12M 1/32 - Inoculator or sampler multiple field or continuous type
• B04B 7/02 - CasingsLids
• C12M 1/00 - Apparatus for enzymology or microbiology
• C12M 1/26 - Inoculator or sampler

Abstract

The present invention relates to the field of diagnostic methods. Specifically, the present invention relates to a method for diagnosing neuropathic pain in a subject, a method for predicting whether a subject is at risk of developing neuropathic pain or a method for determining whether a neuropathic pain therapy is successful. The invention also relates to tools for carrying out the aforementioned methods, such as diagnostic devices and to an oxidized lipid, preferably an epoxylipid, for use in the aforementioned methods.

IPC Classes  ?

• G01N 33/92 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving lipids, e.g. cholesterol

Abstract

The present invention pertains to novel treatments for cancer diseases. Treatment of cancers with nucleoside analogs (NA), which specifically inhibit rapidly dividing cells, may face preexisting NA resistance or development of resistant cancer cells resulting in poor clinical prognosis. Treatment of cancers with oncolytic herpes simplex viruses (HSV) may face preexisting resistance or development of resistant cancer cells resulting in poor clinical prognosis. The invention overcomes chemotherapy resistance or resistance to oncolytic HSV by providing methods for detecting the resistance in a cancer disease based on the expression of SAM domain and HD domain-containing protein 1 (SAMHD1) in cancer cells. Furthermore provided are treatment options addressing the chemotherapy resistance such as a combination of a SAMHD1 inhibitor with a NA. Moreover, provided are treatment options addressing the resistance to oncolytic HSV such as a combination of a SAMHD1 inhibitor or depletion of SAMHD1 with an oncolytic HSV. The combination in some embodiments may furthermore include an inhibitor of CTP-synthetase. The invention provides new medicines and companion diagnostics supporting clinical treatment decisions.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• A61K 35/763 - Herpes virus
• A61K 35/76 - VirusesSubviral particlesBacteriophages
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention pertains to a method for detecting whether a cancer disease in a subject is susceptible to a treatment with a Spleen Tyrosine Kinase (SYK) inhibitor by determining the amount or level of a biomarker selected from Hoxa9/Meis1, PU.1 and miR146a in a biological sample from the subject. The invention provides novel treatment approaches based on the detection of the differential expression of the above biomarkers using SYK inhibitors. Also provided are diagnostic kits, and combined therapeutic and diagnostic kits for use in the inventive methods.

IPC Classes  ?

• 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

Abstract

The present invention pertains to a novel method for the generation of highly diverse RNA expressing vectors and vector libraries for use in targeted gene knock out, knock down and genome modification approaches. The invention pertains to a method for generating such higher order libraries without the need of classical cloning technologies. This is particularly useful for libraries based on large vectors wherein a sequence cannot be easily mutated with classical mutagenesis methods. The vectors and libraries generated according to the methods of the invention are in particular for RNA assisted silencing technologies such as RNA interference, and for targeted genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system or similar RNA/DNA-encoded gene perturbation systems which use small guide RNAs to target the CRISPR complex to a specific genomic sequence. The invention provides also kits comprising the materials for performing the methods of the invention.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA

Abstract

The present invention relates to a compound of general formula A, where X1 and X2 are selected independently of each other from the group consisting of H, F, Cl, Br and I, electron-rich aromatic compounds, preferably substituted or unsubstituted thiophene; R1 and R2 are selected independently of each other from OH, alkyl-substituted phenyl groups, Br or a group of the following formulas (a) to (f); wherein the bond indicated with the wavy line is the bond of the group to a boron atom, and the dashed line together with the phenyl group connected to the ends of the dashed line is an annulated aromatic group which is optionally substituted. The invention also relates to a method for the production of the compound, to an organic light-emitting diode comprising the compound according to the invention and to the use of the compound.

IPC Classes  ?

• C07F 5/05 - Cyclic compounds having at least one ring containing boron but no carbon in the ring
• C07F 7/08 - Compounds having one or more C—Si linkages
• C08K 5/55 - Boron-containing compounds
• H01L 51/00 - Solid state devices using organic materials as the active part, or using a combination of organic materials with other materials as the active part; Processes or apparatus specially adapted for the manufacture or treatment of such devices, or of parts thereof

Abstract

The present invention pertains to the modification of the eukaryotic ubiquitin system by using the bacterial virulence factor SdeA and variants and mutants thereof. The invention is based on the phosphodiesterase activity of SdeA, which catalyzes a phospho-ribosylation (or simply "ribosylation") event of ubiquitin and ubiquitin-like proteins. The invention provides SdeA proteins and mutants without said phosphodiesterase activity, as well as medical applications of these recombinant proteins, their encoding nucleic acids, ribosylated ubiquitin proteins, and compounds which may act as selective or non-selective phosphodiesterase inhibitors.

IPC Classes  ?

• C12N 15/09 - Recombinant DNA-technology
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
• C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying enzymes

Abstract

8 fatty acids, the production of biofuels, fine chemicals and/or flavoring substances.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C12P 7/64 - FatsFatty oilsEster-type waxesHigher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl groupOxidised oils or fats
• C12P 7/04 - Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic
• C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells

Abstract

The present invention pertains to antagonists and inhibitors of soluble epoxide hydrolase (sEH) and 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) for use as a therapeutic in the treatment of eye disorders that are characterized by pericyte loss and motility. The invention is useful for treating the non-proliferative form of diabetic retinopathy. Furthermore provided are methods for monitoring or diagnosing diabetic retinopathy, in particular in subjects at risk of developing the disorder, for example diabetic patients.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/17 - Amides, e.g. hydroxamic acids having the group N—C(O)—N or N—C(S)—N, e.g. urea, thiourea, carmustine
• A61K 31/4468 - Non-condensed piperidines, e.g. piperocaine having a nitrogen atom directly attached in position 4, e.g. clebopride, fentanyl
• A61P 27/02 - Ophthalmic agents

Abstract

The present application provides antisense oligonucleotides for spatially controlled activation of micro RNA silencing via local irradiation after administration of the molecule. The anti- sense design of the invention uses photo labile protecting groups attached to the oligonucleo¬ tides which impair antisense binding to its target. The antisense molecules of the invention are useful for in vivo applications and hence will be useful as therapeutics in medicine to activate micro RNA silencing spatially confined, which will result in reduced antisense toxicity. The invention also provides a light inducible miR-92a antisense oligonucleotide for use in aiding tissue generation and wound healing, as well as pharmaceutical compositions comprising the light inducible miR-92a antisense oligonucleotide of the invention.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
• A61K 47/50 - 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
• A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

The present invention pertains to a novel architecture of non-ribosomal peptide synthases (NRPS). The invention provides artificial NRPS wherein the naturally occurring terminal condensation or thioesterase-domain is replaced by internal condensation or dual condensation/epimerization domains. Moreover, the present invention enables the portability of terminal condensation domains to unrelated NRPS in respect of peptide release of linear peptides. The replacement results in a product independent release of the synthesized product and therefore enables the rational design of NRPS. The invention provides the new NRPS, nucleic acids encoding them, methods for artificial NRPS generation, and methods for producing non-ribosomal peptides.

IPC Classes  ?

• C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying enzymes

Abstract

The present invention pertains to novel treatments for cancer diseases. Treatment of cancers with nucleoside analogs (NA), which specifically inhibit rapidly dividing cells, may face preexisting NA resistance or development of resistant cancer cells resulting in poor clinical prognosis. Treatment of cancers with oncolytic herpes simplex viruses (HSV) may face preexisting resistance or development of resistant cancer cells resulting in poor clinical prognosis. The invention overcomes chemotherapy resistance or resistance to oncolytic HSV by providing methods for detecting the resistance in a cancer disease based on the expression of SAM domain and HD domain-containing protein 1 (SAMHD1) in cancer cells. Furthermore provided are treatment options addressing the chemotherapy resistance such as a combination of a SAMHD1 inhibitor with a NA. Moreover, provided are treatment options addressing the resistance to oncolytic HSV such as a combination of a SAMHD1 inhibitor or depletion of SAMHD1 with an oncolytic HSV. The combination in some embodiments may furthermore include an inhibitor of CTP-synthetase. The invention provides new medicines and companion diagnostics supporting clinical treatment decisions.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention concerns a novel method for the modification and/or custom-made design of artificial non-ribosomal peptide synthetases (NRPSs) from naturally available NRPSs. The artificial NRPSs are of predetermined length and amino acid composition and sequence. Via fusion of well-defined NRPS units (so-called "exchange units") in a certain manner, using a specific sequence motif in the linker areas it is possible to construct artificial and/or modified NRPS assembly lines, which have the ability of synthesizing peptides of a desired structure.

IPC Classes  ?

• C12N 9/00 - Enzymes, e.g. ligases (6.)ProenzymesCompositions thereofProcesses for preparing, activating, inhibiting, separating, or purifying enzymes
• C12N 15/62 - DNA sequences coding for fusion proteins
• C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione

Abstract

The present invention relates to proteins involved in fatty acid synthesis, such as fatty acid synthases (FAS) variants, comprising one or more polypeptide chains, wherein said polypeptide chain(s) comprise one or more subunits comprising a malonyl/palmitoyl transferase domain (MPT domain), acetyl transferase domain (AT domain), and/or ketoacyl synthase domain (KS domain), and at least one amino acid substitution in the MPT domain at a position corresponding to R90, in the AT domain at a position corresponding to I151, and/or in the KS domain, preferably in the acyl binding channel, to modulate affinities of acyl intermediates, and optionally further amino acid substitution(s). The present invention relates to the respective polypeptide domains. The present invention further relates to nucleic acid molecules encoding the proteins (or the polypeptide domains) and to host cells containing said nucleic acid molecules. The present invention further relates to a method for the production of short fatty acids, CoA esters of short fatty acids, ethyl esters of short fatty acids, esters of short fatty acids with other metabolites, and/or enzyme bound short fatty acids (C6 to C12), comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention further relates to a method for the production of biofuels, flavoring compounds and/or fine chemicals, comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention also relates to the use of the proteins, nucleic acids molecule or host cells for the production of short fatty acids (C6 to C12), the production of CoA esters of short fatty acids (C6 to C12), the production of ethyl esters of short fatty acids (C6 to C12), the production of esters of short fatty acids (C6 to C12) with other metabolites, the production of enzyme bound short fatty acids (C6 to C12), the production of biofuels, fine chemicals and/or flavoring substances.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C07K 14/34 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Corynebacterium (G)
• C07K 14/345 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Brevibacterium (G)

Abstract

The invention relates to the use of protein body (PB)-inducing sequences and/or PB-inducing sequence-containing fusion protein(s) in combination with membrane-type transport protein(s) for forming artificial membrane-bound compartments or organelles in a eukaryotic host cell. The invention further relates to methods for forming artificial membrane-bound compartments or organelles in a eukaryotic host cell, to eukaryotic host cells containing at least one artificial membrane-bound compartment or an organelle, to the uses thereof, and to methods for synthesizing compounds and/or for degrading substrates.

IPC Classes  ?

• C12N 15/62 - DNA sequences coding for fusion proteins
• C07K 14/425 - Zeins
• C12N 15/79 - Vectors or expression systems specially adapted for eukaryotic hosts
• C12N 15/81 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts

Abstract

The present invention pertains to novel diagnostic procedures for the prognosis, diagnosis and monitoring of liver diseases such as hepatocellular carcinoma (HCC). The present invention provides sphingolipids and especially long chain ceramides as significant and highly prognostic serum biomarkers in HCC compared to liver cirrhosis. Therefore the invention in particular provides a method for detecting the presence or absence of a HCC in a liver cirrhosis patient using the disclosed biomarkers. Also provided is a method for monitoring the treatment success of a HCC treatment by monitoring the disclosed serum biomarkers. Finally the invention pertains to diagnostic kits for performing the disclosed methods of the invention.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• G01N 33/92 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving lipids, e.g. cholesterol

Abstract

The invention relates to silyl compounds comprising an anion and a cation, to a method for the production thereof and to the use thereof for producing silicones and silicon carbides.

IPC Classes  ?

• C01B 33/08 - Compounds containing halogen
• C07F 9/00 - Compounds containing elements of Groups 5 or 15 of the Periodic Table

Abstract

The present invention relates to proteins involved in fatty acid synthesis, such as fatty acid synthases (FAS) variants, comprising one or more polypeptide chains, wherein said polypeptide chain(s) comprise one or more subunits comprising a malonyl/palmitoyl transferase domain (MPT domain), acetyl transferase domain (AT domain), and ketoacyl synthase domain (KS domain), and at least one amino acid substitution in the MPT domain at a position corresponding to R130, in the AT domain at a position corresponding to I306, and/or in the KS domain, preferably in the acyl binding channel and/or at KS domain binding site to ACP, to modulate affinities of acyl intermediates, and optionally further amino acid substitution(s). The present invention relates to the respective polypeptide domains. The present invention further relates to nucleic acid molecules encoding the proteins (or the polypeptide domains) and to host cells containing said nucleic acid molecules. The present invention further relates to a method for the production of short fatty acids, CoA esters of short fatty acids, ethyl esters of short fatty acids, esters of short fatty acids with other metabolites, and/or enzyme bound short fatty acids (C6 to C12), comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention further relates to a method for the production of biofuels, flavoring compounds and/or fine chemicals, comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention also relates to the use of the proteins, nucleic acids molecule or host cells for the bulk production of short fatty acids (C6 to C12), the specific production of C6 fatty acids and/or C8 fatty acids, the bulk production of CoA esters of short fatty acids (C6 to C12), the specific production of C6-CoA esters and/or C8-CoA esters, the bulk production of ethyl esters of short fatty acids (C6 to C12), the specific production of C6 fatty acid ethyl esters and/or C8 fatty acid ethyl esters, the bulk production of esters of short fatty acids (C6 to C12) with other metabolites, the specific production of C6 fatty acid esters with other metabolites and/or C8 fatty acid esters with other metabolites, the bulk production of enzyme bound short fatty acids (C6 to C12), the specific production of enzyme bound C6 fatty acids and/or enzyme bound C8 fatty acids, the production of biofuels, fine chemicals and/or flavoring substances.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells

Abstract

The present invention provides novel non-coding RNAs (lncRNA) that were identified to be expressed in pericytes upon hypoxia. The lncRNA of the invention positively affect Platelet-derived Growth Factor Receptor (PDGFR) beta expression, pericytes proliferation and pericyte recruitment to endothelial cells. The invention provides inhibitors of the lncRNA for use in the treatment of diseases mediated by PDGFR expression. For example the invention described antisense approaches to target the lncRNA of the invention. Furthermore, the invention provides lncRNA inhibitors as amplifier of therapeutic PDGFR inhibitors such as imatinib or other tyrosine kinase inhibitors. lncRNA inhibitors and methods for screening modulators of lncRNA expression and/or function are provided.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids

Abstract

The present invention provides a cellular system for the detection of the presence of one or more antibody species in sample, preferably a serum or plasma sample. The method is in particular useful for the analysis of patients who have been sensitized against blood group antigens expressed on erythrocytes, platelets or granulocytes. The system uses fluorescence labeled cells specific for each antigen and hence, for each antibody species. Provided are the methods, system and diagnostic kits for performing the methods of the invention. In addition, the present invention discloses a method for removing antibodies from a sample such as a serum sample. Such a method is useful for absorbing antibodies from poly-agglutinating sera.

IPC Classes  ?

• G01N 33/80 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood groups or blood types
• C07K 16/34 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood group antigens
• B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The invention relates to a method for influencing the miR-92 expression in a cell, comprising the following steps: (a) providing a cell; and (b1) reducing the miR-92 expression in the cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or (b2) increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct into the cell, wherein said construct includes an expressible miR-92 sequence. Furthermore, the invention relates to a pharmaceutical composition, comprising an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92.

IPC Classes  ?

• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical

Abstract

The present invention associates multiplelong non-coding RNA (lncRNA) with key functions of endothelial cells. The lncRNA of the present invention are therefore useful as novel drug targets for the manufacturing of medicines for the treatment of cardiovascular diseases or pathological angiogenesis in context of proliferative diseases such as cancer. Modulation of the function or expression of the lncRNA of invention can induce or repress angiogenesis and vessel growth or repair in endothelial cells. Provided are further methods for the modulation of endothelial cell functions in vitro, for example, in the context of tissue engineering.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention associates multiple circular (circRNA) with key functions of endothelial cells. The present invention provides circRNA transcripts that are correlated with cardiovascular diseases, in particular acute myocardial infarction. The circRNA of the invention therefore serve as biomarkers in the diagnosis of cardiovascular disorders. The invention provides the new nucleic acid molecules as well as diagnostic kits and compositions comprising the nucleic acids. Modulation of the expression of the circRNA of the invention further leads to endothelial cell sprouting, and therefore is applied as a treatment for cardiovascular diseases or pathological angiogenesis. The invention provides therapeutic agents modulating circRNA expression or function. Further aspects of the invention provide novel circRNA for the treatment of inflammatory diseases.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The present invention discloses functionalized nanomembranes, a method for preparation and their use. The functionalized nanomembrane comprises a) a first layer comprising a nanomaterial, b) a second layer comprising a biorepulsive material, the second layer being attached to at least one side of the first layer, and c) affinity groups, attached to the second layer.

IPC Classes  ?

• B01J 20/32 - Impregnating or coating
• B01J 20/28 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof characterised by their form or physical properties
• G01N 1/28 - Preparing specimens for investigation
• H01J 37/20 - Means for supporting or positioning the object or the materialMeans for adjusting diaphragms or lenses associated with the support

Abstract

The invention relates to a method for producing perhalogenated hexasilane anion by reaction of halogenated monosilane in the presence of organo-substituted ammonium halide and/or organo-substituted phosphonium halide at temperatures in a range of 100 to 120°C, without using solvent, and to method for producing a cyclic silane compound of the formula Si6R12 by reaction of [X]2[Si6Cl14] with ALR3 in at least one organic solvent, with R being chlorine or methyl and X being the same or different and a counter-cation and being preferably selected from organo-substituted ammonium, organo-substituted phosphonium, alkali metal ions and [(PEDETA)(H2SiCl)]+.

IPC Classes  ?

• C01B 33/107 - Halogenated silanes

Abstract

The present invention pertains to a method for the in-vitro or ex-vivo expansion of immune cells using a histone acetyl transferase (HAT) modulator as additive in the cell culture medium during the expansion procedure. Immune cells such as natural killer (NK) cells, T cells or cytokine induced killer (CIK) cells are used in adoptive cell therapies for the injection into patients suffering from malignant cancer diseases such as leukemia. Cells expanded using the method of the invention were superior proliferative and viable. Further provided by the invention is a cell culture medium comprising the HAT modulator of the invention as well as cell populations obtained using the method of the invention.

IPC Classes  ?

• C12N 5/078 - Cells from blood or from the immune system
• A61K 35/14 - BloodArtificial blood
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells

Abstract

Provided is a method for analyzing a polymerization reaction in a sample. The method comprises the steps of providing for fluorescent particles in the sample, exciting the fluorescence of the fluorescent particles, disturbing the sample for making the fluorescent particles move within the sample, taking images of the fluorescent particles within the sample, determining, for each of at least some of the images taken, a measure being indicative of the movement of the particles within the time period during which the respective image has been taken, and analyzing the polymerization reaction based on the determined measure.

IPC Classes  ?

• G01N 21/64 - FluorescencePhosphorescence
• G01N 33/49 - Physical analysis of biological material of liquid biological material blood
• G01N 21/82 - 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 producing a precipitate or turbidity

Abstract

The present invention pertains to an improved mesenchymal stromal cell (MSC) preparation and a method for producing the same. The invention provides a new strategy to isolate MSC from bone marrow mononuclear cells (BM-MNCs) by pooling BM-MNCs of multiple unrelated (third-party) bone marrow donors. The MSC preparation manufactured in accordance with the methodology of the invention is characterized by a stable proliferative capability and an increased immunosuppressive potential when compared to individual donor MSC preparations or a pool of individual MSCs generated from multiple donors. The MSCs prepared ac- cording to the invention are particularly useful for medical applications such as the treatment of graft-versus-host disesase (GvHD) in recipients with hematopoietic stem cell transplants, patients with autoimmune disorders and as a cell-based therapy in regenerative medicine.

IPC Classes  ?

• C12N 5/0775 - Mesenchymal stem cellsAdipose-tissue derived stem cells

Abstract

The invention relates to aryl borane compounds, to methods for the production thereof and to the use thereof in semi-conductive organic materials.

IPC Classes  ?

• C07F 5/02 - Boron compounds
• C07F 7/08 - Compounds having one or more C—Si linkages
• C09K 11/06 - Luminescent, e.g. electroluminescent, chemiluminescent, materials containing organic luminescent materials
• H01L 51/50 - Solid state devices using organic materials as the active part, or using a combination of organic materials with other materials as the active part; Processes or apparatus specially adapted for the manufacture or treatment of such devices, or of parts thereof specially adapted for light emission, e.g. organic light emitting diodes (OLED) or polymer light emitting devices (PLED)

Abstract

The invention relates to a method for producing linear, cyclic and/or cage-type perhalogenated oligosilyl and polysilyl anions by reacting perhalogenated monosilanes, oligosilanes or polysilanes with organo-substituted ammonium and/or phosphonium halides at temperatures ranging from -80°C to 85°C, preferably from -80°C to 60°C. The invention also relates to oligosilyl and polysilyl anions produced according to said method.

IPC Classes  ?

• C01B 33/00 - SiliconCompounds thereof
• C08G 77/60 - Macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon, with or without sulfur, nitrogen, oxygen, or carbon in which all the silicon atoms are connected by linkages other than oxygen atoms

Abstract

The present invention relates to a cuvette (110) for receiving a sample and for positioning the sample for analysis by means of inverted fluorescence microscopy, in particular inverted light sheet fluorescence microscopy. The cuvette comprises an opening (12) which is arranged at an upper end of the cuvette (110) and a first and a second transparent bottom section (20, 22) which are arranged relative to each other in such a way that their surface normals are inclined relative each other at an angle between 70° and 110°, preferably between 80° and 100°, particularly between 85° and 90° and most particularly at least approximately 90°.

IPC Classes  ?

• G01N 21/03 - Cuvette constructions
• G01N 21/64 - FluorescencePhosphorescence
• G02B 21/00 - Microscopes

Abstract

The invention relates to a compound of general formula (I), in which R1 and R2 independently of one another are selected from the group consisting of H, C6-C24-aryl, C5-C30-heteroaryl and C6H4-R'; and R' is selected from the group consisting of H, C1-C20-alkyl, C1-C20-alkoxy, C6-C24-aryl and C5-C30-heteroaryl. The invention also relates to the use of said compound as a fluorescent dye.

IPC Classes  ?

• C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• A61B 1/04 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopesIlluminating arrangements therefor combined with photographic or television appliances
• A61K 49/00 - Preparations for testing in vivo
• C08K 5/00 - Use of organic ingredients
• H01L 51/50 - Solid state devices using organic materials as the active part, or using a combination of organic materials with other materials as the active part; Processes or apparatus specially adapted for the manufacture or treatment of such devices, or of parts thereof specially adapted for light emission, e.g. organic light emitting diodes (OLED) or polymer light emitting devices (PLED)

Abstract

The invention relates to a method for influencing the miR-92 expression in a cell, comprising the following steps: (a) providing a cell; and (b1) reducing the miR-92 expression in the cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or (b2) increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct into the cell, wherein said construct includes an expressible miR-92 sequence. Furthermore, the invention relates to a pharmaceutical composition, comprising an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92.

IPC Classes  ?

• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical

Abstract

The present invention relates to a method for storing gaseous hydrogen, comprising the steps of producing methanoate (formate) through contacting gaseous hydrogen with carbon dioxide in the presence of a hydrogen dependent carbondioxide reductase (HDCR), and thereby storing of said gaseous hydrogen. The HDCR and/or its complex is preferably derived from Acetobacterium woodii.

IPC Classes  ?

• C12P 7/40 - Preparation of oxygen-containing organic compounds containing a carboxyl group