Abrégé

Conventional methods for obtaining phenotype and genotype information from single cells are hampered by the fact that methods cannot (easily) be coupled, in particular when cells are contained in an environment wherein these are desirably studied, i.e. being comprised in a plurality of cells. The present invention can provide individual cells in a plurality of cells with a unique combination and/or expression level of cell surface receptors, of which representative information can be retrieved both in imaging and sequencing methods. This highly advantageously allows for coupling different informations, e.g. imaging information and sequencing information, at the single cell level.

Classes IPC  ?

• C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]

Abrégé

This invention pertains in improved culture methods for culturing and expanding cells, including epithelial and endothelial cells, and obtaining organoids. The invention also pertains to particular integrin-binding peptides and proteins used in such culture methods, carriers coated with such integrin-binding peptides and proteins, and tissue culture systems comprising such carriers.

Classes IPC  ?

• C07K 14/24 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de bactéries provenant d'Entérobacteriaceae (F), p. ex. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet

Abrégé

The present invention relates to paecilomycone compound that may be isolated from a fungus, Aspergillus allahabadii, which inhibit bacterial quorum sensing, biofilm formation and virulence factor production. Paecilomycone may be used as medicament, in particular as medicament for treating and preventing microbial infections, such as infections by multidrug resistant bacteria, by itself or in combination with other antimicrobial agents.

Classes IPC  ?

• A61K 31/122 - Cétones ayant l'atome d'oxygène lié directement à un cycle, p. ex. quinones, vitamine K1, anthraline
• A61K 31/136 - Amines, p. ex. amantadine ayant des cycles aromatiques, p. ex. méthadone ayant le groupe amino lié directement au cycle aromatique, p. ex. benzène-amine
• A61P 31/04 - Agents antibactériens

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/095 - Cellules souchesCellules progénitrices
• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to methods and media for differentiating cells, for example for obtaining enteroendocrine cells, and to uses of the cells and organoids obtained by said methods. The invention also relates to methods for modulating hormone expression in enteroendocrine cells and medical uses relating to such methods.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/38 - EstomacIntestinCellules caliciformesMuqueuse oraleSalive

Abrégé

The present invention relates to a new single-chain variable fragment (scFv) agonist of integrin β-1, that interacts with particular epitopes of the human integrin β1 subunit of SEQ ID NO: 1. The invention discloses particular complementarity-determining regions CDR1 to CDR3 of a variable light and a variable heavy chains. The scFv is proposed as an ingredient of stem cell or organoid culture media, as well as an ingredient in compositions comprising collagen or in extracellular matrix compositions. Methods of culturing stem cells or organoids in the presence of this scFv are also disclosed. The invention also provides several uses of scFv, and kits adapted to carry out these several applications.

Classes IPC  ?

• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
• C12N 5/074 - Cellules souches adultes
• C12N 5/71 -
• A61K 35/12 - Substances provenant de mammifèresCompositions comprenant des tissus ou des cellules non spécifiésCompositions comprenant des cellules souches non embryonnairesCellules génétiquement modifiées
• A61K 35/37 - Appareil digestif

Abrégé

The invention relates to human hepatocyte organoids. In particular, hepatocyte organoids with modified genes involved in lipid homeostasis. The invention also relates to the use of such organoids for modelling diseases involving steatosis. Also included is the use of such organoids as models of fatty liver, such as caused by genetic as well as diet related fatty liver disorders and their use in discovery of novel drugs for treating fatty liver and related disorders. The invention further relates to agents for reducing steatosis in subjects having similar modifications as the hepatocyte organoids of the invention. The invention also relates to methods of reducing or preventing steatosis, treating or preventing cardiovascular disease; treating or preventing NAFLD, and preventing and/or reducing the risk of NASH and/or cirrhosis by increasing FADS2 activity in a subject. Also included is a FADS2 agonist, such as a small molecule, nucleic acid or polypeptide for use in said methods.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
• C12N 9/22 - Ribonucléases
• C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées

Abrégé

The invention relates to methods of treating an individual suffering from a structural cardiac muscle defect, comprising providing cardiomyocytes of at least part of the cardiac muscle of the individual with a high mobility group A (HMGA) protein to thereby promote proliferation of said cardiomyocytes. The invention further relates to an expression construct for functional expression of said HMGA protein, a pharmaceutical composition, comprising HMGA or said expression construct, and to a method of culturing cardiomyocytes in vitro, comprising providing cardiomyocytes with a HMGA protein or the expression construct.

Classes IPC  ?

• C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
• A61K 38/00 - Préparations médicinales contenant des peptides
• A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
• C12N 5/077 - Cellules mésenchymateuses, p. ex. cellules osseuses, cellules de cartilage, cellules stromales médulaires, cellules adipeuses ou cellules musculaires
• C12N 15/86 - Vecteurs viraux

Abrégé

The invention relates to an in vitro method for the production of conjunctiva or limbal organoids. It also encompasses new conjunctiva or limbal organoids and their uses as implants in regenerative medicine, and as conjunctiva model or corneal limbus tissue and/or corneal tissue model for the study of this tissue. Particular cell culture media are also disclosed, which are in particular suitable for the production of the conjunctiva organoids or limbal organoids.

Classes IPC  ?

• C12N 5/079 - Cellules neurales
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to transduction buffers and methods for transducing molecules into cells using said buffers. The invention also relates to pharmaceutical compositions comprising said transduction buffers and methods of treatment involving the use of said buffers or pharmaceutical compositions to treat diseases, in particular genetic diseases.

Classes IPC  ?

• A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
• A61K 38/46 - Hydrolases (3)
• C12N 9/22 - Ribonucléases
• C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
• C12N 15/90 - Introduction stable d'ADN étranger dans le chromosome

Abrégé

The invention pertains to an ex vivo method for increasing expression of at least one of gamma globin 1 (HBG1) and 2 (HBG2). The method can be used for the treatment or prevention of a haemoglobinopathy. The method comprises a step of introducing a first and a second site-specific endonuclease into a cell, wherein the first and second site-specific endonuclease generate a first and a second double stranded break in a chromosome, thereby generating a first, an intervening second and a third chromosomal fragment, wherein i) the first fragment comprises an beta globin locus control region (LCR) a functional fragment thereof; and ii) the third fragment comprises a sequence encoding at least one of HBG1 and HBG2. The length of the second intervening fragment is at least about 5 kb, and wherein joining the first fragment to the third fragment results in operably linking the beta globin LCR to the sequence encoding at least one of HBG1 and HBG2, thereby increasing at least one of HBG1 and HBG2 protein expression. The invention further pertains for compositions for use in the method of the invention.

Classes IPC  ?

• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
• C07K 14/805 - HémoglobinesMyoglobines
• C12N 9/22 - Ribonucléases
• C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées

Abrégé

The invention pertains to method for ribosome profiling at a single cell resolution. The method comprises the steps of i) lysing a single cell; ii) digesting the RNA with a ribonuclease, thereby generating an ribosome footprint containing RNA molecules that are protected against digestion; iii) Inactivating the ribonuclease and releasing the RNA molecules from the ribosomes; iv) end repairing the released RNA; v) constructing an RNA library from the end-repaired RNA molecules; vi) size selecting part of the prepared RNA library for fragments having an insert size of about 20-40 nucleotides; vii) sequencing the size selected RNA library; and viii) determining the translatome of the single cell.

Classes IPC  ?

• C12Q 1/6869 - Méthodes de séquençage
• G16B 5/00 - TIC spécialement adaptées à la modélisation ou aux simulations dans la biologie des systèmes, p. ex. réseaux de régulation génétique, réseaux d’interaction entre protéines ou réseaux métaboliques
• G16B 35/00 - TIC spécialement adaptées aux bibliothèques combinatoires in silico d’acides nucléiques, de protéines ou de peptides

Abrégé

The disclosure relates to methods and tools for studying enteroendocrine cells, including intestinal reporter organoids, methods and media for making said organoids, uses of said organoids, and enteroendocrine cell targets and treatments.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 15/65 - Introduction de matériel génétique étranger utilisant des vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression utilisant des marqueurs
• C40B 30/06 - Procédés de criblage des bibliothèques en mesurant les effets sur des cellules, des tissus ou des organismes vivants

Abrégé

The invention pertains to an ex vivo method for increasing expression of at least one of gamma globin 1 (HBG1) and 2 (HBG2). The method can be used for the treatment or prevention of a haemoglobinopathy. The method comprises a step of introducing a first and a second site-specific endonuclease into a cell, wherein the first and second site-specific endonuclease generate a first and a second double stranded break in a chromosome, thereby generating a first, an intervening second and a third chromosomal fragment, wherein i) the first fragment comprises an beta globin locus control region (LCR) a functional fragment thereof; and ii) the third fragment comprises a sequence encoding at least one of HBG1 and HBG2. The length of the second intervening fragment is at least about 15 kb, and wherein joining the first fragment to the third fragment results in reducing the genomic distance between the beta globin LCR and the closest sequence encoding HBG and operably linking the beta globin LCR to the sequence encoding at least one of HBG1 and HBG2, thereby increasing at least one of HBG1 and HBG2 protein expression. The invention further pertains for compositions for use in the method of the invention.

Classes IPC  ?

• C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens

Abrégé

The invention relates to a high density brain electrode assembly, comprising an elongated main shaft comprising a plurality of guiding lumens, extending to a distal end of the main shaft, a plurality of elongated electrode shanks, each electrode shank comprising a plurality of electrical contacts, extending through one of the plurality of guiding lumens, and being movable from a retracted position in which the electrode shank is retracted within the main shaft to an extended position in which the electrode shank extends distally from the distal end of the main shaft, a plurality of shuttle elements, each shuttle element extending through one of the plurality of guiding lumens, and being movable between a retracted position in which the shuttle element is retracted within the distal end of the main shaft and an extended position in which the shuttle element extends distally from the distal end of the main shaft, wherein the electrode shanks are more flexible than the shuttle elements, wherein each shuttle element is connected with an electrode shank of the plurality of electrode shanks to move the respective electrode shank from the retracted position to the extended position, and wherein the high density brain electrode assembly is arranged to distribute distal ends of the electrode shanks over a surface area in a plane perpendicular to a longitudinal axis of the main shaft which is larger than a largest cross section of the distal end of the main shaft perpendicular to the longitudinal axis of the main shaft.

Classes IPC  ?

• A61N 1/05 - Électrodes à implanter ou à introduire dans le corps, p. ex. électrode cardiaque
• A61N 1/36 - Application de courants électriques par électrodes de contact courants alternatifs ou intermittents pour stimuler, p. ex. stimulateurs cardiaques
• A61B 5/00 - Mesure servant à établir un diagnostic Identification des individus
• A61N 1/372 - Aménagements en relation avec l'implantation des stimulateurs

Abrégé

Aspergillus allahabadiiAspergillus allahabadii, which inhibit bacterial quorum sensing, biofilm formation and virulence factor production. Paecilomycone may be used as medicament, in particular as medicament for treating and preventing microbial infections, such as infections by multidrug resistant bacteria, by itself or in combination with other antimicrobial agents.

Classes IPC  ?

• A61K 31/122 - Cétones ayant l'atome d'oxygène lié directement à un cycle, p. ex. quinones, vitamine K1, anthraline
• A61K 31/136 - Amines, p. ex. amantadine ayant des cycles aromatiques, p. ex. méthadone ayant le groupe amino lié directement au cycle aromatique, p. ex. benzène-amine
• A61P 31/04 - Agents antibactériens

Abrégé

Modular microfluidic devices, systems and methods for total RNA analyses The invention relates to microfluidic methods of preparing a sequencing library for analyses of total RNA. The invention also relates to modular microfluidic systems for carrying out these methods.

Classes IPC  ?

• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
• B01L 3/00 - Récipients ou ustensiles pour laboratoires, p. ex. verrerie de laboratoireCompte-gouttes

Abrégé

The invention relates to differentiation methods for progenitor cells, e.g. mammalian epithelial stem cells, differentiation media for use in said methods, organoids and cells obtainable by said methods and uses, including therapeutic uses, thereof.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The present invention provides a CNS organoid capable of propagation by dissection and culture of the organoid. Further provided is a method of producing, propagating or inducing maturation of an organoid of the present invention. The present invention also provides a maturation medium and an expansion medium and a kit of parts comprising such media and optionally an organoid of the invention.

Classes IPC  ?

• C12N 5/079 - Cellules neurales
• C12N 5/0797 - Cellules souchesCellules progénitrices

Abrégé

The present invention relates to the field of molecular biology and more in particular to DNA technology. The invention relates to strategies for assessing structural integrity of DNA sequences of a genomic region of interest, which has clinical applications in diagnostics and personalized cancer therapy. In particular, the invention provides a method of detecting a chromosomal rearrangement involving a genomic region of interest.

Classes IPC  ?

• G16B 20/00 - TIC spécialement adaptées à la génomique ou protéomique fonctionnelle, p. ex. corrélations génotype-phénotype
• C12Q 1/6827 - Tests d’hybridation pour la détection de mutation ou de polymorphisme

Abrégé

A method for sequencing DNA wherein a sample comprising isolated cell nuclei is contacted with an antibody that forms a covalent conjugate with a first DNA adapter, and wherein the formed antibody-DNA conjugate can bind a protein of interest and ligate to an end of a dephosphorylated DNA fragment, and wherein the sample is then contacted with a second DNA adapter that coheres to the first DNA adapter of the antibody-DNA conjugate to obtain a second DNA adapter- first DNA adapter – DNA fragment product that allows for sequencing of an amplified product.

Classes IPC  ?

• C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
• C12Q 1/6869 - Méthodes de séquençage

Abrégé

The invention relates to human hepatocyte organoids. In particular, hepatocyte organoids with modified genes involved in lipid homeostasis. The invention also relates to the use of such organoids for modelling diseases involving steatosis. Also included is the use of such organoids as models of fatty liver, such as caused by genetic as well as diet related fatty liver disorders and their use in discovery of novel drugs for treating fatty liver and related disorders. The invention further relates to agents for reducing steatosis in subjects having similar modifications as the hepatocyte organoids of the invention. The invention also relates to methods of reducing or preventing steatosis, treating or preventing cardiovascular disease; treating or preventing NAFLD, and preventing and/or reducing the risk of NASH and/or cirrhosis by increasing FADS2 activity in a subject. Also included is a FADS2 agonist, such as a small molecule, nucleic acid or polypeptide for use in said methods.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to methods of treating an individual suffering from a structural cardiac muscle defect, comprising providing cardiomyocytes of at least part of the cardiac muscle of the individual with a high mobility group A (HMGA) protein to thereby promote proliferation of said cardiomyocytes. The invention further relates to an expression construct for functional expression of said HMGA protein, a pharmaceutical composition, comprising HMGA or said expression construct, and to a method of culturing cardiomyocytes in vitro, comprising providing cardiomyocytes with a HMGA protein or the expression construct.

Classes IPC  ?

• A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
• A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
• A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
• A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique

Abrégé

The invention provides a method for suppressing a Striga species (10) in soil (110), wherein the soil (110) has a soil area (115), and wherein the method comprises: a preparation stage comprising (i) providing at least 250 kg of a sulfurous compound (30) per hectare of the soil area (115), wherein the sulfurous compound (30) is selected from the group comprising methionine, methionine sulfoxide, methionine sulfone, S-methyl cysteine, cysteine, elemental sulfur, and hydroxymethionine, and (ii) covering the soil (110); and an incubation stage comprising keeping the soil (110) covered during an incubation time, wherein the incubation time is selected from the range of 1 - 14 days.

Classes IPC  ?

• A01N 37/44 - Biocides, produits repoussant ou attirant les animaux nuisibles, ou régulateurs de croissance des végétaux, contenant des composés organiques comportant un atome de carbone possédant trois liaisons à des hétéro-atomes, avec au plus deux liaisons à un halogène, p. ex. acides carboxyliques contenant au moins un groupe carboxylique ou un thio-analogue, ou un de leurs dérivés, et un atome d'azote lié au même squelette carboné par une liaison simple ou double, cet atome d'azote ne faisant pas partie d'un dérivé ou d'un thio-analogue d'un groupe carboxylique, p. ex. acides aminocarboxyliques
• A01P 13/02 - HerbicidesAlgicides sélectifs
• A01N 63/20 - BactériesSubstances produites par des bactéries ou obtenues à partir de celles-ci
• A01N 63/27 - Pseudomonas

Abrégé

The invention relates to transduction buffers and methods for transducing molecules into cells using said buffers. The invention also relates to pharmaceutical compositions comprising said transduction buffers and methods of treatment involving the use of said buffers or pharmaceutical compositions to treat diseases, in particular genetic diseases.

Classes IPC  ?

• C12N 15/87 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation
• A61K 33/00 - Préparations médicinales contenant des ingrédients actifs inorganiques
• A61K 38/00 - Préparations médicinales contenant des peptides
• A61K 45/00 - Préparations médicinales contenant des ingrédients actifs non prévus dans les groupes
• C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés

Abrégé

The invention relates to improved methods for culturing an epithelial stem cell or an organoid comprising epithelial stem cells. The invention also relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention pertains to an ex vivo method for increasing expression of at least one of gamma globin 1 (HBG1) and 2 (HBG2). The method can be used for the treatment or prevention of a haemoglobinopathy. The method comprises a step of introducing a first and a second site-specific endonuclease into a cell, wherein the first and second site-specific endonuclease generate a first and a second double stranded break in a chromosome, thereby generating a first, an intervening second and a third chromosomal fragment, wherein i) the first fragment comprises an beta globin locus control region (LCR) a functional fragment thereof; and ii) the third fragment comprises a sequence encoding at least one of HBG1 and HBG2. The length of the second intervening fragment is at least about 5 kb, and wherein joining the first fragment to the third fragment results in operably linking the beta globin LCR to the sequence encoding at least one of HBG1 and HBG2, thereby increasing at least one of HBG1 and HBG2 protein expression. The invention further pertains for compositions for use in the method of the invention.

Classes IPC  ?

• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
• C12N 15/63 - Introduction de matériel génétique étranger utilisant des vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression
• C07K 14/805 - HémoglobinesMyoglobines
• C12N 9/22 - Ribonucléases

Abrégé

The invention relates to methods for processing an RNA sample and allows for single cell sequencing of full length total RNA. The method includes labeling the RNA sample with at least one of a barcode and a unique molecular identifier.

Classes IPC  ?

• C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p. ex. séquençage par hybridation [SBH]
• C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
• C12Q 1/6876 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes
• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN

Abrégé

The invention pertains to method for ribosome profiling at a single cell resolution. The method comprises the steps of i) lysing a single cell; ii) digesting the RNA with a ribonuclease, thereby generating an ribosome footprint containing RNA molecules that are protected against digestion; iii) Inactivating the ribonuclease and releasing the RNA molecules from the ribosomes; iv) end repairing the released RNA; v) constructing an RNA library from the end-repaired RNA molecules; vi) size selecting part of the prepared RNA library for fragments having an insert size of about 20 – 40 nucleotides; vii) sequencing the size selected RNA library; and viii) determining the translatome of the single cell.

Classes IPC  ?

• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
• C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques

Abrégé

The invention relates to in vitro cell culture methods for expanding epithelial cells from head and neck tissue, including head and neck tumour tissue, to obtain organoids. The invention relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 5/09 - Cellules tumorales
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/095 - Cellules souchesCellules progénitrices
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/13 - Cellules tumorales, quel que soit le tissu d’origine
• A61K 35/42 - Appareil respiratoire, p. ex. poumons, bronches ou cellules pulmonaires
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The present invention relates to novel treatments for treating cardiac disease involving fibro-fatty replacement, such as arrhythmogenic cardiomyopathy, atrial fibrillation, myocardial infarction and dilated cardiomyopathy. Such cardiac diseases can e.g. be caused by a mutation in a desmosomal protein such as plakophilin-2 (PKP2). The invention provides for agents for use in the prevention or treatment of such cardiac diseases, wherein the agent is at least one of: a) an agent that causes a reduction in expression in at least one TFAP2 subtype; and, b) an agent that causes a reduction in TFAP2-induced transcription. More preferably the agent is at least one of: a) an inhibitor of TFAP2; and, b) an agent that causes an increase in expression of PKP2.

Classes IPC  ?

• A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
• A61K 31/165 - Amides, p. ex. acides hydroxamiques ayant des cycles aromatiques, p. ex. colchicine, aténolol, progabide
• A61K 31/055 - Phénols le noyau aromatique étant substitué par un halogène
• A61K 31/609 - Amides, p. ex. salicylamide

Abrégé

Modular microfluidic devices, systems and methods for total RNA analyses The invention relates to microfluidic methods of preparing a sequencing library for analyses of total RNA. The invention also relates to modular microfluidic systems for carrying out these methods.

Classes IPC  ?

• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
• C40B 40/06 - Bibliothèques comprenant des nucléotides ou des polynucléotides ou leurs dérivés
• C40B 70/00 - Étiquettes ["tags"] ou marqueurs ["labels"] spécialement adaptés à la chimie combinatoire ou aux chimiothèques, p. ex. "tags" fluorescents ou codes-barres

Abrégé

This invention relates to culture methods and media for in vitro expansion of hepatocytes, particularly primary hepatocytes; hepatocyte cultures and organoids obtainable and obtained by said methods; and uses of said hepatocyte cultures and organoids.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes
• A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques

Abrégé

The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.

Classes IPC  ?

• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The present invention relates to the field of molecular biology and more in particular to DNA technology. The invention relates to strategies for assessing structural integrity of DNA sequences of a genomic region of interest, which has clinical applications in diagnostics and personalized cancer therapy. In particular, the invention provides a method of detecting a chromosomal rearrangement involving a genomic region of interest.

Classes IPC  ?

• C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
• G16B 20/10 - Ploïdie ou détection du nombre de copies
• G16B 20/20 - Détection d’allèles ou de variantes, p. ex. détection de polymorphisme d’un seul nucléotide
• G16B 30/00 - TIC spécialement adaptées à l’analyse de séquences impliquant des nucléotides ou des aminoacides
• C12Q 1/6827 - Tests d’hybridation pour la détection de mutation ou de polymorphisme
• G16B 25/10 - Profilage de l’expression de gènes ou de protéinesEstimation ou normalisation de ratio d’expression

Abrégé

The invention relates to a liver organoid, uses thereof and method for obtaining them.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes

Abrégé

The disclosure relates to methods and tools for studying enteroendocrine cells, including intestinal reporter organoids, methods and media for making said organoids, uses of said organoids, and enteroendocrine cell targets and treatments.

Classes IPC  ?

• C07K 14/605 - Glucagons
• C07K 14/63 - Motilines
• C07K 14/645 - Secrétines
• C07K 14/655 - Somatostatines
• C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 15/65 - Introduction de matériel génétique étranger utilisant des vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression utilisant des marqueurs
• C12N 15/867 - Vecteurs rétroviraux
• C12Q 1/02 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des micro-organismes viables
• G01N 33/569 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour micro-organismes, p. ex. protozoaires, bactéries, virus

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/095 - Cellules souchesCellules progénitrices
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

Provided are methods for generating 2D and 3D differentiated airway organoids, 2D and 3D differentiated airway organoids which are generated by the methods and uses for the 2D and 3D differentiated airway organoids.

Classes IPC  ?

• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
• C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The invention relates to transduction compounds, buffers and methods for introducing molecules into cells. The invention also relates to methods of treatment, pharmaceutical compositions and other uses of the transduction compounds and buffers. The invention also relates to modified cells obtainable by the transduction compounds, buffers and methods of the invention.

Classes IPC  ?

• C12N 15/86 - Vecteurs viraux
• A61K 35/545 - Cellules souches embryonnairesCellules souches pluripotentesCellules souches pluripotentes induitesCellules souches non caractérisées
• C12N 15/87 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation
• A61K 35/30 - NerfsCerveauYeuxCellules cornéennesLiquide céphalorachidienCellules souches neuronalesCellules précurseurs neuronalesCellules glialesOligodendrocytesCellules de SchwannAstrogliesAstrocytesPlexus choroïdeTissu de moelle épinière
• A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
• A61K 38/45 - Transférases (2)
• A61K 38/46 - Hydrolases (3)
• A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
• A61K 47/12 - Acides carboxyliquesLeurs sels ou anhydrides
• A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
• A61K 47/20 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite contenant du soufre, p. ex. sulfoxyde de diméthyle [DMSO], docusate, laurylsulfate de sodium ou acides aminosulfoniques
• A61K 47/22 - Composés hétérocycliques, p. ex. acide ascorbique, tocophérol ou pyrrolidones
• C07K 14/32 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de bactéries provenant de Bacillus (G)
• C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
• C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification
• C12N 9/12 - Transférases (2.) transférant des groupes contenant du phosphore, p. ex. kinases (2.7)
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)

Abrégé

The invention relates to methods and media for differentiating cells, for example for obtaining enteroendocrine cells, and to uses of the cells and organoids obtained by said methods. The invention also relates to methods for modulating hormone expression in enteroendocrine cells and medical uses relating to such methods.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/38 - EstomacIntestinCellules caliciformesMuqueuse oraleSalive

Abrégé

The invention relates to differentiation methods for progenitor cells, e.g. mammalian epithelial stem cells, differentiation media for use in said methods, organoids and cells obtainable by said methods and uses, including therapeutic uses, thereof.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The invention relates to improved methods for culturing an epithelial stem cell or an organoid comprising epithelial stem cells. The invention also relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/39 - PancréasÎlots de Langerhans
• A61K 35/407 - FoieHépatocytes

Abrégé

The invention relates to in vitro cell culture methods for expanding epithelial cells from head and neck tissue, including head and neck tumour tissue, to obtain organoids. The invention relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 5/09 - Cellules tumorales
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The present invention relates to novel treatments for treating cardiac disease involving fibro-fatty replacement, such as arrhythmogenic cardiomyopathy, atrial fibrillation, myocardial infarction and dilated cardiomyopathy. Such cardiac diseases can e.g. be caused by a mutation in a desmosomal protein such as plakophilin-2 (PKP2). The invention provides for agents for use in the prevention or treatment of such cardiac diseases, wherein the agent is at least one of: a) an agent that causes a reduction in expression in at least one TFAP2 subtype; and, b) an agent that causes a reduction in TFAP2-induced transcription. More preferably the agent is at least one of: a) an inhibitor of TFAP2; and, b) an agent that causes an increase in expression of PKP2.

Classes IPC  ?

• A61K 31/055 - Phénols le noyau aromatique étant substitué par un halogène
• A61K 31/165 - Amides, p. ex. acides hydroxamiques ayant des cycles aromatiques, p. ex. colchicine, aténolol, progabide
• A61K 31/609 - Amides, p. ex. salicylamide
• A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides
• A61P 9/06 - Antiarythmiques

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes
• A61K 35/39 - PancréasÎlots de Langerhans

Abrégé

in vitroin vitro expansion of hepatocytes, particularly primary hepatocytes; hepatocyte cultures and organoids obtainable and obtained by said methods;and uses of said hepatocyte cultures and organoids.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes
• A61P 1/16 - Médicaments pour le traitement des troubles du tractus alimentaire ou de l'appareil digestif des troubles de la vésicule biliaire ou du foie, p. ex. protecteurs hépatiques, cholagogues, cholélitholytiques

Abrégé

The invention relates to methods for determining the cellular composition of a tumor based on bulk mRNA sequencing, and to methods for constructing a reference library comprising single-cell sequencing data for use in the method for determining the cellular composition, as well as methods for predicting recurrence free survival or optimal treatment strategy based on the cellular composition of a tumor.

Classes IPC  ?

• C12Q 1/6809 - Méthodes de détermination ou d’identification des acides nucléiques faisant intervenir la détection différentielle
• C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer

Abrégé

The invention relates to methods for processing an RNA sample and allows for single cell sequencing of full length total RNA. The method includes labeling the RNA sample with at least one of a barcode and a unique molecular identifier.

Classes IPC  ?

• C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN

Abrégé

The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.

Classes IPC  ?

• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

Provided are methods for generating 2D and 3D differentiated airway organoids, 2D and 3D differentiated airway organoids which are generated by the methods and uses for the 2D and 3D differentiated airway organoids.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/36 - PeauSystème pileuxOnglesGlandes sébacéesCérumenÉpidermeCellules épithélialesKératinocytesCellules de LangerhansCellules ectodermiques
• C12Q 1/70 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des virus ou des bactériophages
• C12R 1/93 - Virus des animaux

Abrégé

The present invention provides co-cultures of organoids and immune cells, and methods of using these to identify agents for treating diseases.

Classes IPC  ?

• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
• C12N 5/09 - Cellules tumorales

Abrégé

The invention relates to a method for culturing epithelial stem cells, isolated tissue fragments comprising the epithelial stem cells, or adenoma cells, and culturing the cells or fragments in the presence of a Bone Morphogenetic Protein (BMP) inhibitor, a mitogenic growth factor, and a Wnt agonist when culturing epithelial stem cells and isolated tissue fragments. The invention further relates to a cell culture medium comprising a BMP inhibitor, a mitogenic growth factor, and a Wnt agonist, to the use of the culture medium, and to crypt-villus organoids, gastric organoids and pancreatic organoids that are formed in the culture medium.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The present invention provides fusion proteins and related compounds for use in improving the regenerative capacity of tissues.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 38/18 - Facteurs de croissanceRégulateurs de croissance
• C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
• C07K 14/475 - Facteurs de croissanceRégulateurs de croissance
• C12N 15/62 - Séquences d'ADN codant pour des protéines de fusion

Abrégé

The invention relates to transduction compounds, buffers and methods for introducing molecules into cells. The invention also relates to methods of treatment, pharmaceutical compositions and other uses of the transduction compounds and buffers. The invention also relates to modified cells obtainable by the transduction compounds, buffers and methods of the invention.

Classes IPC  ?

• C12N 15/87 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation
• A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
• A61K 33/14 - Chlorures des métaux alcalinsChlorures des métaux alcalino-terreux
• A61K 38/18 - Facteurs de croissanceRégulateurs de croissance
• A61K 38/45 - Transférases (2)
• A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
• A61K 47/02 - Composés inorganiques
• A61K 47/06 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite
• A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
• A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
• A61K 47/22 - Composés hétérocycliques, p. ex. acide ascorbique, tocophérol ou pyrrolidones
• A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
• A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
• A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
• C12N 5/0735 - Cellules souches embryonnairesCellules germinales embryonnaires
• C12N 9/22 - Ribonucléases
• C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées

Abrégé

The invention relates to the fields of biochemistry, pharmacy and oncology. The invention particularly relates to the use of novel stem cell markers for the isolation of stem cells. The invention further relates to the obtained stem cells and their use in for example research or treatment, for example, for the preparation of a medicament for the treatment of damaged or diseased tissue. In one of the embodiments, the invention provides a method for obtaining (or isolating) stem cells comprising optionally preparing a cell suspension from a tissue or organ sample, contacting said cell suspension with an Lgr 6 or 5 binding compound, identify the cells bound to said binding compound, and optionally isolating the stem cells from said binding compound. The invention further relates to means suitable for cancer treatment and even more specific for the treatment of cancer by eradicating cancer stem cells.

Classes IPC  ?

• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
• A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur

Abrégé

The invention relates to a method for culturing epithelial stem cells, isolated tissue fragments comprising the epithelial stem cells, or adenoma cells, and culturing the cells or fragments in the presence of a Bone Morphogenetic Protein (BMP) inhibitor, a mitogenic growth factor, and a Wnt agonist when culturing epithelial stem cells and isolated tissue fragments. The invention further relates to a cell culture medium comprising a BMP inhibitor, a mitogenic growth factor, and a Wnt agonist, to the use of the culture medium, and to crypt-villus organoids, gastric organoids, pancreatic organoids, liver organoids, colon organoids, Barrett's Esophagus organoids, adenocarcinoma organoids and colon carcinoma organoids that are formed in the culture medium.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to a liver organoid, uses thereof and method for obtaining them.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes

Abrégé

The invention relates to methods and media for differentiating cells, for example for obtaining enteroendocrine cells, and to uses of the cells and organoids obtained by said methods. The invention also relates to methods for modulating hormone expression in enteroendocrine cells and medical uses relating to such methods.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 31/4427 - Pyridines non condenséesLeurs dérivés hydrogénés contenant d'autres systèmes hétérocycliques

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/095 - Cellules souchesCellules progénitrices
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/13 - Cellules tumorales, quel que soit le tissu d’origine
• A61K 35/42 - Appareil respiratoire, p. ex. poumons, bronches ou cellules pulmonaires
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The invention relates to differentiation methods for progenitor cells, e.g. mammalian epithelial stem cells, differentiation media for use in said methods, organoids and cells obtainable by said methods and uses, including therapeutic uses, thereof.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes

Abrégé

The invention relates to transduction compounds, buffers and methods for introducing molecules into cells. The invention also relates to methods of treatment, pharmaceutical compositions and other uses of the transduction compounds and buffers. The invention also relates to modified cells obtainable by the transduction compounds, buffers and methods of the invention.

Classes IPC  ?

• A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
• A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
• A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
• A61K 47/02 - Composés inorganiques
• C12N 15/87 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation
• A61K 31/205 - Sels d'addition d'acides organiques avec des aminesSels d'ammonium quaternaire internes, p. ex. bétaïne, carnitine

Abrégé

The invention relates to the fields of biochemistry, pharmacy and oncology. The invention particularly relates to the use of novel stem cell markers for the isolation of stem cells. The invention further relates to the obtained stem cells and their use in for example research or treatment, for example, for the preparation of a medicament for the treatment of damaged or diseased tissue. In one of the embodiments, the invention provides a method for obtaining (or isolating) stem cells comprising optionally preparing a cell suspension from a tissue or organ sample, contacting said cell suspension with an Lgr 6 or 5 binding compound, identify the cells bound to said binding compound, and optionally isolating the stem cells from said binding compound. The invention further relates to means suitable for cancer treatment and even more specific for the treatment of cancer by eradicating cancer stem cells.

Classes IPC  ?

• G01N 33/53 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet
• G01N 33/567 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet utilisant un support spécifique ou des protéines réceptrices comme réactifs pour la formation de liaisons par ligand utilisant un extrait de tissu ou d'organe comme agent de liaison
• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
• C12N 5/02 - Propagation de cellules individuelles ou de cellules en suspensionLeur conservationMilieux de culture à cet effet
• A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
• A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur

Abrégé

The invention provides means and methods for inhibiting growth of a cancer. The means in some embodiments comprise proteins and antibodies that binds an extracellular part of a membrane associated member of the epidermal growth factor (EGF) receptor family and an extracellular part of a membrane associated member of a WNT signaling pathway. Further provided are various cells and assays that are helpful in the production of the proteins, antibodies and cells.

Classes IPC  ?

• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
• C07K 16/40 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre des enzymes

Abrégé

The current invention relates to strategies for selection and amplification of genomic regions of interest. The strategy involves an amplification step in a host cell. A target nucleotide sequence associated with the genomic region of interest is used to selectively providea DNA circles derived from the genomic region of interest with an origin of replication and a selection gene. This is in particular useful i.a. for determining DNA sequences of a genomic region of interest, for use in building contiguous sequences and/or for DNA mapping.

Classes IPC  ?

• C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
• C12N 15/64 - Méthodes générales pour la préparation du vecteur, pour son introduction dans la cellule ou pour la sélection de l'hôte contenant le vecteur
• C12N 15/66 - Méthodes générales pour insérer un gène dans un vecteur pour former un vecteur recombinant, utilisant le clivage et la ligatureUtilisation de linkers non fonctionnels ou d'adaptateurs, p. ex. linkers contenant la séquence pour une endonucléase de restriction

Abrégé

The invention relates to transduction compounds, buffers and methods for introducing molecules into cells. The invention also relates to methods of treatment, pharmaceutical compositions and other uses of the transduction compounds and buffers. The invention also relates to modified cells obtainable by the transduction compounds, buffers and methods of the invention.

Classes IPC  ?

• A61K 38/00 - Préparations médicinales contenant des peptides
• A61K 47/02 - Composés inorganiques
• A61K 47/20 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite contenant du soufre, p. ex. sulfoxyde de diméthyle [DMSO], docusate, laurylsulfate de sodium ou acides aminosulfoniques
• A61K 47/12 - Acides carboxyliquesLeurs sels ou anhydrides
• A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
• C12N 15/86 - Vecteurs viraux
• A61K 35/545 - Cellules souches embryonnairesCellules souches pluripotentesCellules souches pluripotentes induitesCellules souches non caractérisées
• C12N 15/87 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation
• A61K 35/30 - NerfsCerveauYeuxCellules cornéennesLiquide céphalorachidienCellules souches neuronalesCellules précurseurs neuronalesCellules glialesOligodendrocytesCellules de SchwannAstrogliesAstrocytesPlexus choroïdeTissu de moelle épinière
• A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
• A61K 38/45 - Transférases (2)
• A61K 38/46 - Hydrolases (3)
• A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
• A61K 47/22 - Composés hétérocycliques, p. ex. acide ascorbique, tocophérol ou pyrrolidones
• C07K 14/32 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de bactéries provenant de Bacillus (G)
• C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
• C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification
• C12N 9/12 - Transférases (2.) transférant des groupes contenant du phosphore, p. ex. kinases (2.7)
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/095 - Cellules souchesCellules progénitrices
• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods,and to uses of said organoids.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 5/095 - Cellules souchesCellules progénitrices

Abrégé

The invention relates among others to a protein comprising a fragment of 30-240 amino acids of Collagen and calcium-binding EGF domain-containing protein 1 (CCBE1) having 0-10 amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 1, wherein said fragment comprises at least a collagen domain of CCBE1, or a variant thereof comprising 1, 2 or 3 amino acid substitutions. The invention further describes means and methods for the treatment of individuals with the protein or protein binding thereto.

Classes IPC  ?

• C07K 14/475 - Facteurs de croissanceRégulateurs de croissance

Abrégé

The present invention relates to novel compounds, comprising an 8-or 9- membered cyclic structure, wherein an (E)-1,4-dioxo-but-2-ene moiety is embedded in said cyclic structure and to pharmaceutical compositions comprising these compounds. The compounds may be used as medicaments, in particular as medicaments for treating and preventing microbial infections, such as infections by multidrug resistant and/or Gram-positive bacteria. The invention further relates to fermentation processes wherein fungi of the genus Ulocladium are used for producing the novel compounds.

Classes IPC  ?

• C07D 313/18 - Cycles à huit chaînons non condensés avec d'autres cycles
• A61K 31/365 - Lactones
• A61P 31/04 - Agents antibactériens

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods,and to uses of said organoids.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes
• A61K 35/38 - EstomacIntestinCellules caliciformesMuqueuse oraleSalive

Abrégé

The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.

Classes IPC  ?

• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The invention relates to transduction compounds, buffers and methods for introducing molecules into cells. The invention also relates to methods of treatment, pharmaceutical compositions and other uses of the transduction compounds and buffers. The invention also relates to modified cells obtainable by the transduction compounds, buffers and methods of the invention.

Classes IPC  ?

• C12N 15/88 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation utilisant la micro-encapsulation, p. ex. utilisant des vésicules liposomiques
• A61K 31/00 - Préparations médicinales contenant des ingrédients actifs organiques
• A61K 31/205 - Sels d'addition d'acides organiques avec des aminesSels d'ammonium quaternaire internes, p. ex. bétaïne, carnitine

Abrégé

The invention relates to a method for making an at least double layered cell aggregate and/or an artificial blastocyst, and/or a further-developed blastoid termed blastoid, by forming a double layered cell aggregate from at least one trophoblast cell and at least one pluripotent and/or totipotent cell, and culturing said aggregate to obtain an artificial blastocyst. This artificial blastocyst has a trophectoderm-like tissue that surrounds a blastocoel and an inner cell mass-like tissue. The cell aggregate can be formed from toti- or pluripotent stem cell types, or induced pluripotent stem cell types, in combination with trophoblast stem cells. Formation of a blastoid can be achieved by culturing the cell aggregate in a medium preferably comprising one or more of a Rho/ROCK inhibitor, a Wnt pathway modulator, a PKA pathway modulator, a PKC pathway modulator, a MAPK pathway modulator, a STAT pathway modulator, an Akt pathway modulator, a Tgf pathway modulator and a Hippo pathway modulator. The invention further relates to a method for growing an at least double layered cell aggregate into an artificial blastocyst, and into a further-developed blastoid, a fetus or a live animal. The invention further pertains to an in vitro cell culture comprising the mentioned compounds and/or cell aggregates.

Classes IPC  ?

• C12N 5/073 - Cellules ou tissus embryonnairesCellules fœtales ou tissus fœtaux
• C12N 5/0735 - Cellules souches embryonnairesCellules germinales embryonnaires
• A01K 67/027 - Nouvelles races ou races modifiées de vertébrés

Abrégé

The invention relates to a method for culturing epithelial stem cells, isolated tissue fragments comprising said epithelial stem cells, or adenoma cells, and culturing the cells or fragments in the presence of a Bone Morphogenetic Protein (BMP) inhibitor, a mitogenic growth factor, and a Wnt agonist when culturing epithelial stem cells and isolated tissue fragments. The invention further relates to a cell culture medium comprising a BMP inhibitor, a mitogenic growth factor, and a Wnt agonist, to the use of said culture medium, and to crypt-villus organoids, gastric organoids and pancreatic organoids that are formed in said culture medium.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

Culture media and methods for expanding and differentiating populations of stem cells and for obtaining organoids. Expanded cell populations and organoids obtainable by methods of the invention and their use in drug screening, toxicity assays and regenerative medicine.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 5/09 - Cellules tumorales
• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

The invention relates to a liver organoid, uses thereof and method for obtaining them.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• A61K 35/407 - FoieHépatocytes

Abrégé

The invention relates to an assay for diagnosing a disease or affliction that affects fluid uptake or secretion or for studying the effectiveness of one or more drugs for treating the disease or affliction, wherein the assay comprises measuring swelling of one or more organoids.

Classes IPC  ?

• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet

Abrégé

The present invention relates to compounds that act as agonists of the Wnt signalling pathway, compositions comprising these compounds and the uses of these compounds, both therapeutic and in research. The invention also provides methods of identifying compounds that act as agonists of the Wnt signalling pathway.

Classes IPC  ?

• C07K 14/475 - Facteurs de croissanceRégulateurs de croissance
• C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire

Abrégé

The invention relates to a method for culturing epithelial stem cells, isolated tissue fragments comprising the epithelial stem cells, or adenoma cells, and culturing the cells or fragments in the presence of a Bone Morphogenetic Protein (BMP) inhibitor, a mitogenic growth factor, and a Wnt agonist when culturing epithelial stem cells and isolated tissue fragments. The invention further relates to a cell culture medium comprising a BMP inhibitor, a mitogenic growth factor, and a Wnt agonist, to the use of the culture medium, and to crypt-villus organoids, gastric organoids, pancreatic organoids, liver organoids, colon organoids, Barrett's Esophagus organoids, adenocarcinoma organoids and colon carcinoma organoids that are formed in the culture medium.

Classes IPC  ?

• C12Q 1/02 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des micro-organismes viables
• C12N 5/02 - Propagation de cellules individuelles ou de cellules en suspensionLeur conservationMilieux de culture à cet effet
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to a method for culturing epithelial stem cells, isolated tissue fragments comprising the epithelial stem cells, or adenoma cells, and culturing the cells or fragments in the presence of a Bone Morphogenetic Protein (BMP) inhibitor, a mitogenic growth factor, and a Wnt agonist when culturing epithelial stem cells and isolated tissue fragments. The invention further relates to a cell culture medium comprising a BMP inhibitor, a mitogenic growth factor, and a Wnt agonist, to the use of the culture medium, and to crypt-villus organoids, gastric organoids and pancreatic organoids that are formed in the culture medium.

Classes IPC  ?

• C12N 5/02 - Propagation de cellules individuelles ou de cellules en suspensionLeur conservationMilieux de culture à cet effet

Abrégé

The invention relates to a liver organoid, uses thereof and method for obtaining them.

Classes IPC  ?

• C12N 5/074 - Cellules souches adultes

Abrégé

The invention relates to the diagnostic and therapeutic uses of a miRNA molecule, an equivalent or a source thereof in a disease and condition associated with melanoma or a disease or a condition associated with activated BRAF pathway.

Classes IPC  ?

• C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
• A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
• C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
• A61P 35/00 - Agents anticancéreux

Abrégé

Described are the use of stem cell markers for the isolation of stem cells and the use of the obtained stem cells in, for example, research or treatment, such as for the preparation of a medicament for the treatment of damaged or diseased tissue. In one aspect, provided is a method for obtaining or isolating stem cells that comprises preparing a cell suspension from a tissue or organ sample, contacting the cell suspension with an Lgr 6 or 5 binding compound, identifying the cells bound to the binding compound, and isolating the stem cells from the binding compound. Further described are methods and compositions for cancer treatment, for example, by eradicating cancer stem cells.

Classes IPC  ?

• G01N 33/53 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet
• G01N 33/567 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet utilisant un support spécifique ou des protéines réceptrices comme réactifs pour la formation de liaisons par ligand utilisant un extrait de tissu ou d'organe comme agent de liaison
• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
• C12N 5/02 - Propagation de cellules individuelles ou de cellules en suspensionLeur conservationMilieux de culture à cet effet
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to a method for culturing epithelial stem cells, isolated tissue fragments comprising said epithelial stem cells, or adenoma cells, and culturing the cells or fragments in the presence of a Bone Morphogenetic Protein (BMP) inhibitor, a mitogenic growth factor, and a Wnt agonist when culturing epithelial stem cells and isolated tissue fragments. The invention further relates to a cell culture medium comprising a BMP inhibitor, a mitogenic growth factor, and a Wnt agonist, to the use of said culture medium, and to crypt-villus organoids, gastric organoids and pancreatic organoids that are formed in said culture medium.

Classes IPC  ?

• C12N 5/073 - Cellules ou tissus embryonnairesCellules fœtales ou tissus fœtaux

Abrégé

The invention relates to a method for testing whether a compound is capable of inhibiting the development of lymphatic channels or lymphangiogenesis and/or the migration of lymphangioblasts in an non-human animal, a non-human embryo or a cell culture, comprising steps of contacting a compound capable of interacting with a Ccbe1 gene, a transcript thereof or a ccbe1 protein with a non-human animal, a non-human embryo or a cell culture; determining whether said compound inhibits the development of lymphatic channels, lymphangiogenesis and/or migration of lymphangioblasts in said non-human animal, a non-human embryo or a cell culture. The invention further related to a method of determining whether an individual is a carrier of, or is suffering from, or at risk of suffering from, a lymph vessel disorder, and to a medicament comprising Ccbe1, or comprising a nucleic acid encoding Ccbe1, for the treatment of a lymph vessel disorder.

Classes IPC  ?

• G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique

Abrégé

Method of and arrangement (4) for monitoring sleep in a subject by measuring within a prescribed interval skin temperature of a predetermined region of the subject's body and a motion sensor for sensing motion of the subject, comparing the measured skin temperature of the predetermined region with a predetermined temperature threshold, and classifying the subject as being asleep or awake based on whether the skin temperature of the predetermined region is above or below the temperature threshold and on the motion data. In alternative aspects the invention relates to methods of and arrangements for manipulating sleep, as well as monitoring or manipulating alertness.

Classes IPC  ?

• G01K 13/00 - Thermomètres spécialement adaptés à des fins spécifiques

Abrégé

The invention provides a method for characterising a sample comprising nucleic acid derived from a cell. The method comprises determining whether a sample comprises at least a minimal sequence of at least one new microRNA (miRNA) according to the invention or a mammalian ortholog thereof and characterizing the sample on the basis of the presence or absence of the miRNA. The invention further provides nucleic acid molecules and collections thereof and their use in therapeutic and diagnostic applications. The invention furthermore provides a method for identifying a miRNA molecule or a precursor molecule thereof.

Classes IPC  ?

• C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le désoxyribosyle comme radical saccharide

Abrégé

The present invention provides novel antibodies that bind human Leucine-rich-repeat- containing G-protein-coupled Receptor 5 (Lgr5) and/or Lgr6. More specifically, the invention provides antibodies that recognize endogenous Lgr5 and/or Lgr6. The invention further provides methods for generating the antibodies and uses of the antibodies.

Classes IPC  ?

• C07K 14/72 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire pour des hormones
• A61K 38/00 - Préparations médicinales contenant des peptides
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

The invention relates to methods for producing an animal of the genus rattus having a functionally reduced mshϑ expression in a germ line cell with a mutagen induced mutation in said germ line cell. The invention further relates to specific uses of an animal of the genus rattus in which mshϑ expression is functionally decreased and to an animal with a mutagen induced mutation and a collection of germ-line cells or derivatives thereof of said animal.

Classes IPC  ?

• C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
• A61K 49/00 - Préparations pour examen in vivo
• A01K 67/027 - Nouvelles races ou races modifiées de vertébrés

Abrégé

The invention relates to the fieldsof biochemistry, pharmacyand oncology. The invention particularly relates to the use of novel stem cell markers for the isolation of stem cells. The invention further relates to the obtained stem cells and their use in for example research or treatment, for example, for the preparation of a medicament for the treatment of damaged or diseased tissue. In one of the embodiments, the invention provides a method for obtaining (or isolating) stem cells comprising optionally preparing a cell suspension from a tissue or organ sample, contacting said cell suspension with an Lgr 6or 5 binding compound, identify the cells bound to said binding compound, and optionally isolating the stem cells from said binding compound. The invention further relates to means suitable for cancer treatment and even more specific for the treatment of cancer by eradicating cancer stem cells.

Classes IPC  ?

• A61K 38/00 - Préparations médicinales contenant des peptides
• C07K 14/72 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire pour des hormones
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 5/074 - Cellules souches adultes

Abrégé

The invention is related to small RNA molecules, precursors thereof and methods for detecting such molecules. The invention is in particular concerned with differentially expressed small RNA molecules and precursors thereof. Various collections of small RNA molecules, precursors thereof and collections of probe and primers that can be used to detect small RNA molecules, precursors thereof are provided. Further provided are diagnostic test based on this differential expression. Also provided are therapeutic applications using one or more of the members of the presented collections.

Classes IPC  ?

• C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques

Abrégé

The invention provides a method for characterising a sample comprising nucleic acid derived from a cell. The method comprises determining whether a sample comprises at least a minimal sequence of at least one new microRNA (miRNA) according to the invention or a mammalian ortholog thereof and characterizing the sample on the basis of the presence or absence of the miRNA. The invention further provides new nucleic acid molecules and collections thereof and their use in therapeutic and diagnostic applications. The invention furthermore provides a method for identifying a miRNA molecule or a precursor molecule thereof.

Classes IPC  ?

• C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques

Abrégé

The invention provides a method for characterising a sample comprising nucleic acid derived from a cell. The method comprises determining whether a sample comprises at least a minimal sequence of at least one new microRNA (miRNA) according to the invention or a mammalian ortholog thereof and characterizing the sample on the basis of the presence or absence of the miRNA. The invention further provides nucleic acid molecules and collections thereof and their use in therapeutic and diagnostic applications. The invention furthermore provides a method for identifying a miRNA molecule or a precursor molecule thereof.

Classes IPC  ?

• C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
• C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods,and to uses of said organoids.

Classes IPC  ?

• A61K 35/36 - PeauSystème pileuxOnglesGlandes sébacéesCérumenÉpidermeCellules épithélialesKératinocytesCellules de LangerhansCellules ectodermiques
• A61K 35/407 - FoieHépatocytes
• A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
• C12N 5/02 - Propagation de cellules individuelles ou de cellules en suspensionLeur conservationMilieux de culture à cet effet
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

TECHNICAL FIELD The invention is in the field of epithelial stem cell culture media and methods, in particular culture media and methods for expanding populations of epithelial stem cells, e.g. human epithelial stem cells. BACKGROUND There is great interest in culture media and methods for expanding populations of stem cells. Populations of stem cells have many uses. For example, stem cells and their differentiated progeny can be used in cellular assays, drug screening, and toxicity assays. Stem cells also show promise for cell-based therapies, such as in regenerative medicine for the treatment of damaged tissue. Furthermore, efficient cell culture media are important for providing and maintaining populations of cells for research purposes. Methods for the long-term culture of epithelial stem cells or tissue fragments derived from several tissues (e.g. pancreas, colon, intestinal crypts, stomach, liver and prostate) have been described (see WO 2010/090513, WO2012/014076 and WO2012/168930). There is a need for improved culture media and methods that result in a higher efficiency of successful organoid formation. SUMMARY OF THE INVENTION The invention provides a method for expanding epithelial stem cells comprising: providing a population of epithelial stem cells; providing a culture medium comprising an ErbB3/4 ligand, a receptor tyrosine kinase ligand and a BMP inhibitor; contacting the stem cells with the culture medium; and culturing the cells under appropriate conditions. The invention further provides a culture medium comprising a receptor tyrosine kinase ligand and a BMP inhibitor, characterised in that the culture medium further comprises an ErbB3/4 ligand. The invention further provides an organoid that is obtained or obtainable from a method of the invention.

Classes IPC  ?

• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 5/095 - Cellules souchesCellules progénitrices

Abrégé

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

Classes IPC  ?

• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains
• C12N 5/095 - Cellules souchesCellules progénitrices