Abstract

The invention provides compositions and methods for modulating expression of SUV39H1 using inhibitory or activating polynucleotides based on the sequence of a long noncoding RNA or of a short hairpin RNA (shRNA).

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61K 40/31 - Chimeric antigen receptors [CAR]
• A61K 40/32 - T-cell receptors [TCR]
• 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 disclosure provides Nectin-4 antibody drug conjugates (ADCs) comprising exatecan and pharmaceutical compositions thereof, and methods of using the ADCs for the treatment of cancer.

IPC Classes  ?

• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• A61P 35/00 - Antineoplastic agents
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Goods & Services

Formation, organisation de manifestations publiques et d'expositions à but culturel; Services d’éducation et d’instruction, à savoir animation culturelle et éducative de forums de discussions en ligne et animation culturelle et éducative de forums de discussions; publication électronique de revues, de périodiques, de livres en ligne; publication électronique de revues scientifiques; publication de textes (à l'exception de textes publicitaires), de périodiques, de livres; Services d’éducation et d’instruction, à savoir animation de débats dans des lieux privés ou publics, organisation et conduite de colloques, séminaires, symposiums, conférences; tous ces services dans le domaine de la santé et des sciences de la vie à l’exclusion de services d’organisation et de conduite de salons dans le domaine des technologies innovantes dans le secteur de la santé. Services de recherches scientifique, clinique et médicale; conduite d’études cliniques; essais cliniques; fourniture d'informations concernant la recherche scientifique; Services de conseils en matière de recherche scientifique. Services d’informations dans le domaine médical; Services d’informations en ligne dans le domaine de la santé et des sciences de la vie.

Abstract

The present invention relates to a vector for use in the treatment of a polyglutamine repeat spinocerebellar ataxia, which vector comprises cholesterol 24-hydroxylase encoding nucleic acid.

IPC Classes  ?

• A61K 38/44 - Oxidoreductases (1)
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 15/86 - Viral vectors

Abstract

Despite reaching an epidemic status worldwide, metabolic disorders, notably diabetes, still miss efficient and specific therapeutic strategies because of their multifactorial origin. SHP2 is a ubiquitous tyrosine phosphatase that regulates major signalling pathways (e.g. MAPK, PI3K) in response to many growth factors. The inventors evaluate whether chronic inhibition of SHP2 could improve insulin sensitivity in animal models. Obese diabetic mice were thus treated by gavage (50 mg/kg/day). And the inventors note a significant improvement in the glucose tolerance of the treated animals compared to their control, with a decreased fasting blood glucose, without any change in weight or body composition. Accordingly, the present invention relates to use of SHP2 inhibitors for the treatment of insulin resistance.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Abstract

Despite the notion that human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Urocortin 3 was identified as a novel β-cell antigen, which was processed into HLA-A2-and HLA-A3-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from urocortin-3 and uses thereof for the diagnosis and treatment of T1D.

IPC Classes  ?

• C07K 14/575 - Hormones
• C07K 14/74 - Major histocompatibility complex [MHC]
• C07K 16/26 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones
• C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith

Abstract

The present invention relates to a method for determining the methicillin-resistance properties of a Staphylococcus aureus strain present in a biological sample, the method comprising the following steps: •a) incubating the biological sample containing the Staphylococcus aureus strain for at least 15 minutes in the presence of an antibiotic from the class of beta-lactams selected from the following group: cefoxitin and 6-APA (6-aminopenicillanic acid); •b) isolating the bacteria present in the biological sample; •c) lysing the bacteria and hydrolysing the bacterial proteins in order to obtain a mixture of peptides; and •d) analysing this mixture of peptides by targeted mass spectrometry, the detection of at least one peptide originating from the protein PBP2a (SEQ ID NO. 1) or PBP2c (SEQ ID NO. 2) during this analysis step being indicative of the methicillin resistance of the Staphylococcus aureus strain present in the biological sample.

IPC Classes  ?

• C12Q 1/18 - Testing for antimicrobial activity of a material
• C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

The present invention concerns a compound of formula (I), or one of its pharmaceutically acceptable salts, especially for use as inhibitors of the ERK kinase activity, in particular ERK2 activity.

IPC Classes  ?

• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 31/18 - Antivirals for RNA viruses for HIV
• A61P 35/00 - Antineoplastic agents
• C07D 213/64 - One oxygen atom attached in position 2 or 6
• C07D 471/04 - Ortho-condensed systems
• C07F 5/02 - Boron compounds

Abstract

The present inventors have shown that specific benzene sulfonamide thiazole compounds (I) have the ability to induce an early endoplasmic reticulum stress. These compounds also lead to cancerous cells growth inhibition and death.

IPC Classes  ?

• A61K 31/426 - 1,3-Thiazoles
• A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 35/00 - Antineoplastic agents
• C07D 277/46 - Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to improved constructs comprising the short and long Rod-Derived Cone Viability Factors and to methods for treating retinal degenerative diseases.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans

Abstract

in vitroin vitro detection and/or quantification of a biological or chemical substance of interest in a sample by detecting the emission of luminescence emitted by inorganic photoluminescent nanoparticles, comprising at least the steps of: arranging inorganic photoluminescent nanoparticles with a vanadate or vanadate/phosphate matrix of a particular formula coupled to a coupling agent for coupling to the substance of interest; placing the photoluminescent particles in contact with the substance of interest under conditions for coupling the substance of interest with the coupling agent; exciting the matrix of inorganic photoluminescent nanoparticles, by radiation with a wavelength of 240 nm to 330 nm; detecting the emission of luminescence by the inorganic photoluminescent nanoparticles; and determining the presence and/or concentration of the substance of interest by interpreting the measurement of the emission of luminescence by the particles.

IPC Classes  ?

• C09K 11/77 - Luminescent, e.g. electroluminescent, chemiluminescent, materials containing inorganic luminescent materials containing rare earth metals
• C09K 11/02 - Use of particular materials as binders, particle coatings or suspension media therefor
• G01N 21/64 - FluorescencePhosphorescence

Abstract

The present invention relates to SMIFH2 derivative compounds and their use as inhibitor of interferon-γ mediated signaling. In particular, the invention relates to compounds of general formula (I), and their use as inhibitor of interferon-γ mediated signaling, preferably for use for preventing and/or treating diseases associated to the hyper-activation of interferon-γ mediated JAK/STAT signaling.

IPC Classes  ?

• C07D 405/06 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• A61K 31/515 - Barbituric acidsDerivatives thereof, e.g. sodium pentobarbital

Abstract

The invention relates to a progenitor T cell comprising an expression cassette that enables controlled expression of a trans gene of interest based on the stage of maturation of said progenitor T cell. The invention also relates to a cell population enriched in progenitor T cells of this kind, to a process for preparing progenitor T cells, and to the use of said cells in a treatment method.

IPC Classes  ?

• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to methods and pharmaceutical compositions for the treatment of retinal capillary non-perfusion. In particular, the present invention relates to a method of treating retinal capillary non-perfusion in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a ROCK inhibitor.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4409 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
• 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
• A61P 27/02 - Ophthalmic agents

Abstract

The present invention relates to multispecific antibodies that specifically bind an ectodomain of human G6B receptor and an ectodomain of a platelet or megakaryocyte immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor, and their use in the treatment of diseases caused or exacerbated by platelet or megakaryocyte activation mediated by said platelet or megakaryocyte ITAM-containing receptor.

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
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

An adhesive composition including a calcium phosphate ceramic selected from tetracalcium phosphate and alpha-tricalcium phosphate, phosphorylated serine, polydopamine, and an aqueous solvent. Also, a kit for preparing the adhesive composition, which includes the calcium phosphate ceramic, phosphorylated serine, and polydopamine and a method for preparing the adhesive composition, as well as the uses thereof.

IPC Classes  ?

• A61L 24/00 - Surgical adhesives or cementsAdhesives for colostomy devices

Abstract

A medical device for penetrating an anatomic structure, e.g., a bone structure, including a processing unit programmed to execute one or more statistical algorithms, e.g., Bayesian-based perforation detection algorithms, with electrical conductivity measured during penetration of an anatomic structure as an input to detect a breach condition, e.g., a spinal canal perforation, based on the measured electrical conductivity. The medical device may include a drill bit having sensing capabilities coupled to the distal end of a robot arm via a power drill unit mounted on the robot arm. The power drill unit may cease transmission of rotary motion to the drill bit upon detection of the breach condition.

IPC Classes  ?

• A61B 17/17 - Guides for drills
• A61B 17/00 - Surgical instruments, devices or methods
• A61B 17/16 - Instruments for performing osteoclasisDrills or chisels for bonesTrepans
• A61B 17/56 - Surgical instruments or methods for treatment of bones or jointsDevices specially adapted therefor
• A61B 34/30 - Surgical robots
• A61B 90/00 - Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups , e.g. for luxation treatment or for protecting wound edges
• G16H 20/40 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
• G16H 40/63 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation

Abstract

The present disclosure provides transmembrane chimeric proteins derived from transposable element (TE)-exon fusion transcripts, as well as nucleic acids, antibodies, CARs, non-HLA restricted TCR and immune cells targeting such chimeric proteins that can be used in cancer therapy.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 14/725 - T-cell receptors
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells

Abstract

The invention relates to a nanoparticle comprising at least one cationic lipid, at least one neutral lipid, and at least one pH sensitive lipid which differs from said cationic lipid, which can be used as a vector for the transport and release of nucleic acids within cells.

IPC Classes  ?

• A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
• A61K 9/51 - Nanocapsules
• 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 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links

Abstract

The present invention relates to regulatory T cell and uses thereof. By their immunosuppressive and anti-inflammatory activities, regulatory T cells play a central role in peripheral tolerance and thus critically prevent the development of autoimmune and inflammatory disorders. The inventors showed that Foxp3+CD4+ Tregs express high levels of LTα, which negatively regulates their immunosuppressive signature. The inventors have demonstrated that the adoptive transfer of Tregs previously incubated with soluble lymphotoxin-β receptor in mice protects from dextran sodium sulfate (DSS)-induced colitis. Thus, the number of cells to be injected in adoptive transfer may be reduced and a transfection or transduction step avoided, which represents a technical facilitation. In particular, the present invention relates to a method of treating or preventing autoimmune disorders and inflammatory-associated cancers in a subject in need thereof comprising the step of administrating to the subject a therapeutically effective amount of regulatory T cells which have been previously incubated with effective amount of soluble lymphotoxin-β receptor.

IPC Classes  ?

• C07K 14/725 - T-cell receptors
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells

Abstract

Methods and pharmaceutical compositions for the treatment of choroidal neovascularisation are provided. In particular, a method of treating choroidal neovascularisation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a mineralocorticoid receptor antagonist is provided.

IPC Classes  ?

• 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 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/16 - AgglomeratesGranulatesMicrobeadlets
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 27/02 - Ophthalmic agents

Abstract

An immunogenic product including a cytokine conjugated with a carrier protein, wherein the cytokine is selected from the group including IL-4, IL-13 and mixtures thereof, and wherein the carrier protein is CRM197. Further, a method for manufacturing the immunogenic product. Also, the therapeutic use of the immunogenic product for treating an inflammatory disorder associated with aberrant IL-4 and/or IL-13 expression or activity.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 17/00 - Drugs for dermatological disorders
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• A61P 37/08 - Antiallergic agents

Abstract

The present invention concerns a micro-utrophin comprising the structure NTDH1R1R2R3H2R22H4CRD and two further rod domains selected from the group consisting of: - the R4 to R10 rod domains of utrophin; - the R16 and R17 rod domains of dystrophin; a nucleic acid sequence encoding such a micro-utrophin, a recombinant adeno-associated virus (rAAV) vector comprising such a sequence, and their use for treating a muscular dystrophy such as Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD).

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals

Abstract

The present invention concerns mididystrophins comprising at least the rod domains R1, R8, R9, R10, R11, R12, R16, R17 and R24 of the dystrophin and their use for treating a muscular dystrophy, in particular a Duchenne muscular dystrophy (DMD).

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 15/864 - Parvoviral vectors
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/62 - DNA sequences coding for fusion proteins
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The present invention relates to a new and specific T-cell therapy strategy based on the use of memory stem T-cells (Tscm), in particular highly functional memory stem T-cells (Tscm) negatively selected on the basis of inhibitory receptor expression. This new cellular immunotherapy may be applied to PML patients but also to other infections or cancers for which the specific memory T cell responses are functionally impaired.

IPC Classes  ?

• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells

Abstract

The present invention relates to antibodies having specificity to Nectin-4 and uses thereof.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Abstract

The present invention concerns endothelin receptor antagonists for use in the treatment or the prevention of muscle fibrosis.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• A61K 38/08 - Peptides having 5 to 11 amino acids
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• G01N 33/74 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving hormones

Abstract

The present invention relates to an engineered immune cell defective for Suv39h1. Preferably, said engineered immune cell further comprises a genetically engineered antigen receptor that specifically hinds a target antigen. The present invention also relates to a method for obtaining a genetically engineered immune cell comprising a step consisting in inhibiting the expression and/or activity of Suv39h1 in the immune cell; and further optionally comprising a step consisting in introducing in the said immune cell a genetically engineered antigen receptor that specifically binds to a target antigen. The invention also encompasses said engineered immune cell for their use in adoptive therapy, notably for the treatment of cancer.

IPC Classes  ?

• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/02 - Antineoplastic agents specific for leukemia
• C07K 14/725 - T-cell receptors
• C12N 5/078 - Cells from blood or from the immune system

Abstract

The present invention relates to a pharmaceutical combination comprising i) cyclic dinucleotides packaged into a virus-like particle (VLP) and ii) an anti-CTLA-4 antibody or a fragment thereof binding a CTLA-4 antigen, and to uses thereof, in particular for the treatment of cancer or of a STING-mediated disease or disorder.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 9/51 - Nanocapsules
• A61K 31/7084 - Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents

Abstract

The invention provides low-molecular-weight non-sulfated or sulfated exopolysaccharide derivatives prepared from a marine native exopolysaccharide excreted by a mesophilic marine bacterium from a deep-sea hydrothermal environment (the HE800 strain, a Vibrio diabolicus species of the Vibrio genus), and relates to the use of such low-molecular-weight exopolysaccharide derivatives for the treatment of cancer.

IPC Classes  ?

• A61K 31/737 - Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
• A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
• A61K 31/726 - Glycosaminoglycans, i.e. mucopolysaccharides
• A61P 35/00 - Antineoplastic agents

Abstract

Ischemic conditions are a leading cause of death for both men and women, Ischemia, a condition characterized by reduced blood flow and oxygen to an organ. Re-establishment of blood flow, or reperfusion, and re-oxygenation of the affected area following an ischemic episode is critical to limit irreversible damage. However, reperfusion also associates potentially damaging consequences. For instance, increased vascular permeability is an important contributor to edema and tissue damage following ischemic events. Here the inventors shows that genetic inhibition of PI3K-C2β reduces cerebral infarction in two ischemic/reperfusion (I/R) models and improves neurological outcome. The genetic inhibition stabilizes the blood-brain barrier (BBB) after ischemic stroke and reduces inflammation. Accordingly, the present invention relates to a method for the preservation of vascular endothelial cell barrier integrity in a patient in need thereof comprising administering to the subject a therapeutically effective amount of a PI3KC2β inhibitor.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The present invention relates to a pharmaceutical combination comprising i) a vector comprising a stimulator of interferon genes (STING) activator and ii) an anti-regulatory T cells (Tregs) agent, and to uses thereof, in particular for the treatment of cancer or of a STING-mediated disease or disorder.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/7084 - Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• 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
• C12N 15/86 - Viral vectors

Abstract

Disclosures herein are directed to methods and compositions for predicting high- and low-risk for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease (NAFLD). Provided herein are methods of identifying the NAFLD as indolent-, progressive, or advanced-NAFLD. Based on the results achieved from the methods and compositions disclosed herein, non-alcoholic fatty liver disease patients can be classified into a prognostic risk group, which enables early diagnosis and prevention of hepatocellular carcinoma and other lethal complications. Methods and compositions disclosed herein substantially improve the poor prognosis of subjects having or at risk for hepatocellular carcinoma.

IPC Classes  ?

• G01N 30/72 - Mass spectrometers
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Disclosed are methods and compositions relating to antisense therapy for treating epilepsy, such as a temporal lobe epilepsy, in a subject in need thereof by targeting Grik2 mRNA. In particular, the disclosure provides inhibitory RNA constructs capable of inhibiting expression of GluK2 protein and inhibiting epileptiform discharges in hyperexcitable neuronal circuits.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 25/08 - AntiepilepticsAnticonvulsants
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to the treatment of inflammatory bowel diseases with a kynurenine aminotransferase, a living recombinant bacterium which has been genetically modified to express and secrete said kynurenine aminotransferase, and/or a product of said kynurenine aminotransferase which is xanthurenic acid, a derivative thereof, or any pharmaceutically acceptable salt or solvate thereof.

IPC Classes  ?

• A61K 38/45 - Transferases (2)
• A61K 31/47 - QuinolinesIsoquinolines
• A61K 31/7084 - Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
• A61K 35/74 - Bacteria
• A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention relates to methods for promoting T cells response. The inventors examined the expression and function of CLEC-1 in human DCs and demonstrated for the first time a cell-surface expression. They investigated its functional role following triggering on orchestration of T-cell responses. The inventors showed in vitro and in vivo with CLEC-1 deficient rats and rat CLEC-1 Fc fusion protein that disruption of CLEC-1 signalling enhances in vitro Th17 activation and in vivo enhances T cell priming and Th17 and Th1 activation. In particular, the present invention relates to CLEC-1 antagonists for promoting T cells response in a subject in need thereof.

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
• A61P 35/00 - Antineoplastic agents
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith

Abstract

The present invention relates to a novel pharmaceutical use of bromide, i.e. the treatment of autism spectral disorder (ASD)).

IPC Classes  ?

• A61K 33/00 - Medicinal preparations containing inorganic active ingredients
• A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

Haloperidol, or a pharmaceutically acceptable salt, ester or solvate thereof, as well as pharmaceutical compositions comprising the same, for use in methods for preventing and/or treating spinal muscular atrophy, are described.

IPC Classes  ?

• A61K 31/4515 - Non-condensed piperidines, e.g. piperocaine having a butyrophenone group in position 1, e.g. haloperidol
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The present invention relates to a targeted chimeric construct, comprising i) an interleukin 2 (IL2) moiety and ii) a targeting moiety which binds to an oxidized protein or oxidized lipid. The targeting moiety is preferably an antibody or scFv binding specific oxidized proteins or oxidized lipids and targets the fusion protein to inflammatory tissues. The chimeric construct preferably further comprises a beta chain of the C4b-binding protein (C4BP), which is capable of forming a dimeric protein.

IPC Classes  ?

• C07K 14/55 - IL-2
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
• C12N 15/86 - Viral vectors

Abstract

The present application relates to a computer-implemented method for identifying at least one class of at least one biological image, notably to predict the genomic signature from biological image(s), in particular to predict Homologous Recombination DNA-repair deficiency (HRD) from biological images of tissues. The present application further proposes a computer-implemented method for visualizing clusters of sub-images or tiles of at least one biological image, in particular to predict the phenotypic feature or combination of phenotypic features (or phenotypic patterns) associated with the genomic signature.

IPC Classes  ?

• G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
• G06V 10/42 - Global feature extraction by analysis of the whole pattern, e.g. using frequency domain transformations or autocorrelation
• G06V 10/774 - Generating sets of training patternsBootstrap methods, e.g. bagging or boosting
• G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
• G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
• G06V 20/70 - Labelling scene content, e.g. deriving syntactic or semantic representations

Abstract

The present results show that KDM1A is a key epigenetic regulator of tissue-specific expression of GIP receptor and possibly of other receptors from the G-protein coupled receptor family in hormone-producing glands, and that its alteration leads to the development of aberrant overexpression of eutopic hormone receptors or expression of ectopic hormone receptors that lead to abnormal steroidogenesis. They also show that loss of expression of KDM1A is likely to be the initiating event that trigger the abnormal cell proliferation leading to the development of tissue lesions in adrenal and possibly in other endocrine tissues (notably in the adrenal glands). The present invention therefore proposes to detect altered expression of KDM1A in the genome of subjects, in order to diagnose a genetic predisposition to an endocrine disease and/or to an endocrine hyperplasia. On another hand, the present results suggest that the physiological eutopic GIP receptor expression in the pancreas may be also epigenetically regulated by KDM1A. This expression could be pharmacologically targeted by KDM1A inhibitors so as to treat patients suffering from diabetes mellitus and other metabolic diseases.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

The present invention relates to the activation of FGF10 signaling pathway for use in the treatment of a heart disease.

IPC Classes  ?

• A61K 38/18 - Growth factorsGrowth regulators

Abstract

This invention relates to the treatment of macular edema. Macular edema is the main cause of vision loss during diabetic macular edema, wet AMD (Age Related Macular Degeneration), retinal vein occlusion and chronic intraocular inflammation. Currently, beyond photocoagulation by laser irradiation, two types of drugs are used, protein molecules that neutralize VEGF family members and glucocorticoids, with different mechanisms of action, but targeting one single symptom: macular edema. The inventors have now found that macular edema may be treated by increasing the oncotic pressure of the vitreous. According to the inventors' understanding, causing an increase in the oncotic pressure of the vitreous induces a liquid flow from the interstitial water accumulated in the retina tissue to the vitreous compartment, so as to reduce or stop macular edema. Increasing the oncotic pressure of the vitreous is preferably performed by intravitreal injection of an oncotic pressure-increasing macromolecule, which macromolecule may be selected in a group comprising protein or non-protein macromolecules, such as albumin, gelatin, alpha2 macroglobulin, fibrinogen, haptoglobin multimers, beta lipoproteins and antibodies, as well as dextran and hydroxyethyl starch.

IPC Classes  ?

• A61K 38/38 - Albumins
• A61K 38/01 - Hydrolysed proteinsDerivatives thereof
• A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• A61P 27/02 - Ophthalmic agents
• A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone

Abstract

The present invention relates to novel hybrid promoters. The invention further relates to expression cassettes and vectors containing said hybrid promoters. Also disclosed herein are methods implementing these hybrid promoters, in particular methods of gene therapy.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/86 - Viral vectors

Abstract

SATSAT domain, that are useful to facilitate and improve the purification yield of fusion proteins, in particular of thermostable fusion proteins by simple heating.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 1/22 - Affinity chromatography or related techniques based upon selective absorption processes
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants

Abstract

The present invention relates to the use of a polyaminated fatty acid compound responding to formula (I), a pharmaceutically acceptable salt and/solvate thereof, as an adjuvant to an antibacterial drug, a pharmaceutical composition comprising at least said polyaminated fatty acid compound and at least one antibacterial drug, said pharmaceutical composition for use as a medicament, said pharmaceutical composition for use in the treatment of bacterial or infectious diseases, in particular caused by Gram-negative bacteria, said pharmaceutical composition for use in killing or inhibiting the growth of persister cells, a kit comprising a composition comprising said polyaminated fatty acid compound, and a separate pharmaceutical composition comprising at least one antibacterial drug, and a polyaminated fatty acid compound responding to formula (I'-a), a pharmaceutically acceptable salt and/solvate thereof.

IPC Classes  ?

• A61K 31/16 - Amides, e.g. hydroxamic acids
• A61L 2/00 - Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lensesAccessories therefor
• C07C 233/38 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms 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 having the carbon atom of the carboxamide group bound to a carbon atom of an acyclic unsaturated carbon skeleton
• A61P 31/04 - Antibacterial agents

Abstract

The present invention relates to methods for diagnosing hematological cancers. In particular, the present invention relates to a method for diagnosing a hematological cancer in a patient comprising i) detecting the presence of CD45RARO NK cells in a sample obtained from the patient and ii) and concluding that the patient suffers from a hematological cancer when the presence of CD45RARO NK cells is detected in the sample and the presence of at least one phenotypic marker indicates the nature of the haematological cancer.

IPC Classes  ?

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

Abstract

The invention provides a spray system comprising a reservoir, a two-fluid spray nozzle, a dispenser mounted on the reservoir, and a wet gas source designed to inject a controlled wet gas into the reservoir.

IPC Classes  ?

• A61M 11/00 - Sprayers or atomisers specially adapted for therapeutic purposes
• A61M 11/02 - Sprayers or atomisers specially adapted for therapeutic purposes operated by air pressure applied to the liquid to be sprayed or atomised
• A61M 11/06 - Sprayers or atomisers specially adapted for therapeutic purposes of the injector type
• A61M 16/16 - Devices to humidify the respiration air
• G01L 27/00 - Testing or calibrating of apparatus for measuring fluid pressure
• G01N 33/00 - Investigating or analysing materials by specific methods not covered by groups

Abstract

The invention relates to a recombinant adeno-associated virus (AAV) capsid protein, which is a hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins, wherein said recombinant hybrid AAV capsid protein has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins. The invention relates also to the derived hybrid AAV serotype vector particles packaging a gene of interest and their use in gene therapy, in particular for treating neuromuscular genetic diseases.

IPC Classes  ?

• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• C07K 14/075 - Adenoviridae
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 9/22 - Ribonucleases
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/86 - Viral vectors

Abstract

A method of diagnosing an MSI cancer in a patient including extracting and sequencing DNA from a tumoral sample and if available from a normal sample and operate an analyse of MNRs. The method is based on the demonstration that the FDA-approved NGS-based diagnostic test for identifying MSI in mCRC and nmCRC gave inaccurate results when compared with the gold standard reference methods. Consequently, whole exome sequencing (WES) data from all samples was further analyzed to improve detection of the MSI genomic signal in CRC and other primary tumor types. This allowed identification of weaknesses and limits of MSISensor and the design and validation of a newly optimized algorithm, namely MSICare. The high accuracy of MSICare for the detection of MSI in CRC and non-CRC tumors should allow it to become a future reference test for assessing MSI in pan-cancer.

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 invention relates to an immune cell comprising at least one Fc receptor on its surface, characterised in that a hybrid molecule is grafted onto the Fc receptor, said hybrid molecule comprising at least one antibody Fc fragment covalently bound to at least one fibrin-derived peptide comprising one or more citrullyl residue(s). The present invention also relates to the uses of such a grafted cell, as well as its method of production.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/735 - Fc receptors
• C07K 14/75 - Fibrinogen
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C12N 5/0786 - MonocytesMacrophages

Abstract

A metabolomic signature of acute mesenteric ischemia (AMI) and the determination thereof in a method for identifying a subject suffering or being at risk of suffering from AMI. Also, a kit that includes elements for determining the metabolomic signature of AMI and implementing the method for identifying a subject suffering or being at risk of suffering from AMI.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• G01N 33/53 - ImmunoassayBiospecific binding assayMaterials therefor
• 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 relates to methods and compositions for the diagnostic and for the treatment of nasal intestinal type adenocarcinomas (ITAC). The inventors used a non-invasive brushing technique, which permits to identify transcriptomic and methylation modifications that are consistent with phenotypic profiles and ITACs natural history. Thus, they identified CACNA1C as a new predictive marker of ITAC. In particular, the invention relates to a method of determining whether a subject has or is at risk of having nasal intestinal type adenocarcinoma (ITAC) comprising determining the expression level of CACNA1C in a sample wherein said expression level indicates whether the subject has or is at risk of having a nasal intestinal type adenocarcinoma (ITAC).

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
• A61B 10/02 - Instruments for taking cell samples or for biopsy

Abstract

Natalizumab a monoclonal antibody is associated with the risk of progressive multifocal leukoencephalopathy (PML), an infection caused by the John Cunningham (JC) virus. The inventors explored the hypothesis that bacteria should be involved in the onset of PML in connection to the HLA-DR haplotype in multiple sclerosis (MS) patients. Thus 625 MS patients starting Natalizumab therapy from the BIONAT study were followed prospectively. Among those patients, 12 developed a PML. Outside the BIONAT cohort, we included nine additional MS patients with PML who had been referred to our center. For each patient, blood metagenomics sequencing and sequencing-based typing for HLA-DRB1*15:01 ancestral haplotype were determined. HLA-DRB1*15:01 haplotype carriers show a protection against PML (p=0.03). Among blood taxa, at genus level, Phyllobacterium was only significantly associated in HLA-DRB1*15:01 haplotype carriers with an inflammatory marker (p<0.0001) as opposed to HLA-DRB1*15:01 haplotype negative where no significant correlation was observed. Among the patients with no HLA-DRB1*15:01 haplotype, we showed a positive association (p=0.02) between the abundance of Phyllobacterium and PML whereas no significant association was observed in patients with HLA-DRB1*15:01 haplotype. JC positive virus patients with no HLA-DRB1*15:01 haplotype and a level of Phylobacterium in blood >2% have an odds ratio of 4.55 (95% confidence intervals 1.82-11.37; p=0.001) of developing or having PML under NTZ treatment. In conclusion, the inventors showed a relation between the HLA-DRB1*15:01 haplotype, the circulating microbiota and the risk of PML. The interaction between blood microbiota and the HLA-DRB1*15:01 haplotype may play a role in the virulence of the viruses.

IPC Classes  ?

• C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
• 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
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

Cytotoxic anti-LAG-3 monoclonal antibodies or fragments thereof causing depletion of LAG-3+ activated T cells are described, as are related pharmaceuticals and methods of treating. Also described are related nucleic acid and protein sequences.

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
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The present invention relates to a synergistic combination of Vonafexor with PEG-INFα for the treatment of hepatitis D, especially the treatment of chronic hepatitis D.

IPC Classes  ?

• A61K 38/21 - Interferons
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61P 31/14 - Antivirals for RNA viruses

Abstract

The invention relates to a hybrid molecule comprising a fibrin-derived citrullinated peptide and an antibody or antibody fragment which binds to CD38 and/or CD138, the uses of such a hybrid molecule and its method of production.

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
• A61K 38/00 - Medicinal preparations containing peptides
• C07K 14/745 - Blood coagulation or fibrinolysis factors

Abstract

The invention provides a clonal cell line derived from a liver cancer cell line, preferably derived from a Huh7 hepatocarcinoma cell line, engineered to produce and secrete viral particles containing pregenomic RNA of the hepatitis B virus (HBV), predominantly over DNA of HBV, to calibrate quantitative HBV RNA assays.

IPC Classes  ?

• C12N 5/09 - Tumour cells
• C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
• C12R 1/91 - Cell lines

Abstract

The present invention relates to the field of anticancer immunotherapy. In particular, the present invention concerns the role of the MAdCAM-1/α4β7 axis the gut microbiota in the efficacy of cancer treatments and provides methods for determining if a patient is likely to benefit from a cancer treatment, more precisely, and immuno-oncology (I-O) therapy, such as a treatment comprising administration of an antibody directed against immune checkpoint blockers PD1, PD-L1 or PD-L2 alone or together with CTLA4 and/or chemotherapy. The present invention also provides methods to improve the efficacy of such a treatment in patients in need thereof.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

FGFR3 gain-of-function mutations are responsible for a family of chondrodysplasias namely, achondroplasia (ACH) the most common form of dwarfism, a lethal form of dwarfism thanatophoric dysplasia (TD) as well as and hypochondroplasia. Recent data demonstrate that Infigratinib (NVP-BGJ398) corrects pathological hallmarks of ACH and support it as a 10 potential therapeutic approach for FGFR3-related skeletal diseases. Now the inventors has investigated the feasibility to treat the defective growth of the skeleton during the pregnancy with the drug. They treated pregnant female Fgfr3Nco/Y67C mice with the drug (4 mg/kg) that was injected subcutaneously at day E14.5 continuing daily through day 1 (after birth). The data indicated that BGJ398 treatment during 5 days in pregnant mice successfully repressed skeletal 15 anomalies that occurred during embryonic stages. Accordingly, the present invention relates to methods for treatment of FGFR3-related skeletal diseases during pregnancy with Infigratinib.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 19/00 - Drugs for skeletal disorders

Abstract

A prodrug formed by a compound including a pharmaceutically active antioxidant molecule which is covalently coupled, via a bond comprising at least one carboxylic ester group, to a nucleoside devoid of free hydroxyl and primary amine functions, comprising a ribose or deoxyribose unit covalently bonded to a nucleic base, this nucleoside bearing at least one lipidising group. A pharmaceutical composition which is particularly useful for therapeutic uses contains this prodrug in a nanoemulsion, in which the prodrug is contained in the lipophilic phase.

IPC Classes  ?

• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61P 17/00 - Drugs for dermatological disorders

Abstract

Rheumatic heart disease (RHD) ranks as one of the most serious cardiovascular scourges of the past century and remains a force to be reckoned with in the developing world. Using the B-HOT panel, developed in part by our team, and based on heatmap analysis, we show two distinct transcriptomic profiles between inflammatory burden region of RHD valves patients (n=13) and control valves (without lesions, n=10). Our differential gene expression analysis between those 2 groups show several genes overexpressed in RHD group compared to control valves. Interestingly, and as potential therapeutic targets, genes related to CD20 (MS4A1. MS4A2) are among genes that are differentially expressed. Taken together, these results suggest a potential role for CD20 in inflammatory responses of RHD valves lesions. Anti-CD20 antibodies, like Rituximab (CD20), would be potential therapeutic molecules to be used on RHD patients.

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
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

A portable imaging system for visualizing a biological target structure by a tracking element introduced therein, including: a control unit with a memory for storing at least one ultrasound image of the target structure, a probe to be removably fixed to a biological fixing structure surrounding at least partially the target structure, the probe being connected to the control unit, and a positioning assistance module of the probe. The probe is capable of detecting the tracking element by means of ultrasound, the control unit being able to locate it, in real time, inside the target structure, so as to characterize it geometrically and create the ultrasound image. The control unit can also display it on a display device. The ultrasound image allows rapid diagnosis to be made independently of any location and environment.

IPC Classes  ?

• A61B 8/08 - Clinical applications
• A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves

Abstract

The present invention pertains to a method for the prognosis or clear cell renal cell carcinoma (ccRCC) based on cell clusters identified by deconvolution of a single-cell malignancy atlas. The present inventors have designed and validated a scRNA-seq protocol to characterize the malignant cells (MC) in ccRCC tumors from ccRCC patients. By applying an in silico deconvolution approach 5 to a bulk RNA-seq dataset of ccRCCs, the present inventors have shown that the predicted proportion of specific cells clusters were strongly associated with specific prognoses and notably allow for the accurate stratification of patients. The markers identified by the present inventors particularly allow identifying high-grade patients who would have erroneously been classified as low- grade according to the current classification system.

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 relates to anti-mesothelin constructs, such as antigen binding fragments and single-domain antibodies, that specifically bind to mesothelin, irrespective of the presence of MUC16. The invention further relates to the use of anti-mesothelin constructs in diagnostics and in therapeutic field.

IPC Classes  ?

• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• G01N 33/53 - ImmunoassayBiospecific binding assayMaterials therefor
• A61K 49/00 - Preparations for testing in vivo

Abstract

The invention relates to methods and pharmaceutical compositions for the treatment and diagnosis of cancer. The invention also relates to methods and pharmaceutical compositions for the treatment of inflammatory diseases and autoimmune diseases. The inventors investigate the role and specific contribution of extracellular vesicles (EVs) in cancer environment. The inventors demonstrate that CSF1-associated EVs induce macrophage signature associated with T cell infiltration and extended patient survival. The inventors demonstrate that via specific extracellular vesicles, these tumors promote pro-inflammatory macrophages correlated with better clinical outcome and a better prognosis in TNBC patients. In the present invention, the inventors provide in vitro evidences towards a direct role of CSF1-associated EVs as tools, alone or with other immuno-therapies, to promote anti-tumor immune responses. Thus, the present invention relates to CSF1-associated EVs, their use in the treatment and diagnosis of cancer, and their targeting in the treatment of inflammatory diseases and autoimmune diseases.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 9/50 - Microcapsules
• A61P 35/00 - Antineoplastic agents
• C07K 14/725 - T-cell receptors
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• C12N 5/0786 - MonocytesMacrophages

Abstract

A laser device for treating a target region of biological tissue comprises: a sheath; at least two optical fibers in the sheath, each configured to guide a laser beam to the target region, distal ends of at least two of the optical fibers configured so that each emits a laser beam in a different direction; a system of laser sources configured to generate at least two laser beams, the two laser beams having different or identical wavelengths with adjustable power; and a laser-beam control unit configured to control the system of laser sources so as to select the wavelength, the power, the duration of the deposition of laser energy, and the moment of emission of each of the laser beams in the direction of the target region so as to dynamically generate and adjust a 3D thermal distribution having a geometric shape matching a geometric shape of the target region.

IPC Classes  ?

• A61B 18/22 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibreHand-pieces therefor
• A61B 5/01 - Measuring temperature of body parts
• 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
• A61B 18/00 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
• A61B 18/20 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
• A61N 5/00 - Radiation therapy
• A61N 5/06 - Radiation therapy using light
• A61N 5/067 - Radiation therapy using light using laser light
• G01K 11/32 - Measuring temperature based on physical or chemical changes not covered by group , , , or using changes in transmittance, scattering or luminescence in optical fibres

Abstract

The invention relates to methods for detecting inactivation of the DNA Homologous Recombination pathway in a patient, and in particular for detecting BRCA1 inactivation.

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
• A61K 31/131 - Amines, e.g. amantadine acyclic
• 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 31/282 - Platinum compounds
• A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• 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 33/243 - PlatinumCompounds thereof
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism

Abstract

Methods of diagnosing subclinical rejection, based on the level, amount or concentration of two genes, TCL1A and AKR1C3, whether independently from each other or in combination. When in combination, the level, amount or concentration of the two genes can further be combined with clinical parameters in the form of a composite score. Also, methods for treating subclinical rejection in a subject if/when the subject was diagnosed with subclinical rejection using the method of the invention; as well as a computer system and a kit-of-parts for implementing the method of diagnosing subclinical rejection.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

Alzheimer disease (also termed Alzheimer's disease or AD) is a progressive and devastating neurodegenerative disorder with a poor prognosis, and for which no curative treatment is available yet With respect to diagnosis, a huge amount of work has been performed with the aim to identify relevant markers for diagnosing AD, ideally the different stages of progression thereof. It is admitted in the art that development of AD involves both genetic factors and non- genetic factors. This explains why the search for biomarkers includes identification of genetic and non-genetic biomarkers. Further, even though the field of Alzheimer disease research has rapidly developed over the last decade, there is still a lack of disease-modifying therapies. Thus, it remains a great need for methods allowing a diagnosis of the Alzheimer disease. The present disclosure relates to methods relating to the diagnosis of AD, including the development stage of AD, as well as methods for monitoring the efficiency of a (candidate) therapeutic treatment of AD, which methods take benefit from the inventors' findings that AD nucleated cells, especially AD skin fibroblasts, show one or more perinuclear crowns of the auto-phosphorylated form of the ATM protein.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• A61N 5/10 - X-ray therapyGamma-ray therapyParticle-irradiation therapy
• A61P 39/06 - Free radical scavengers or antioxidants
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound

Abstract

in vitroin vitro method for chemically-modifying the surface of a cell, which comprises incubating said cell with N-substituted luminol moiety or a N-substituted phenylurazole in conditions conducive for reacting said chemical reagent with a cell surface component so as to form a covalent bound. The Invention also relates to a cell obtainable or obtained by such a process and its use in therapeutic, diagnostic or research field.

IPC Classes  ?

• C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
• A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
• C12N 1/20 - BacteriaCulture media therefor

Abstract

The invention relates to a chemically modified adeno-associated (AAV) virus, a method for preparing it and its use in gene therapy. The chemically modified AAV is preferably prepared by incubating the AAV with a chemical reagent bearing a N-substituted luminol moiety in conditions conducive for reacting said chemical reagent with the surface exposed tyrosine residues of AAV capsid, preferably by electrochemistry.

IPC Classes  ?

• C12N 15/86 - Viral vectors

Abstract

The present invention relates to the field of personalized medicine. In particular, the invention relates to a formulation comprising (i) a calcium phosphate cement or a magnesium phosphate cement and (ii) an hydrogel of polysaccharides, for 3D printing bone implants; characterized in that the polysaccharides comprise at least one selected from: silylated hyaluronic acid and silylated chitosan.

IPC Classes  ?

• A61L 27/38 - Animal cells
• 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
• A61L 27/54 - Biologically active materials, e.g. therapeutic substances
• B33Y 70/10 - Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials
• B33Y 80/00 - Products made by additive manufacturing
• B33Y 10/00 - Processes of additive manufacturing

Abstract

A combination of retinoic acid, an anti-O-acetylated disialoganglioside (OAcGD2) compound and an anti-PD1/PD-L1 compound for treating a cancer, particularly neuroblastoma, in a subject in need thereof. The inventors focused on immunotherapeutic strategies targeting OAcGD2, believing they could address critical neuropathic pain side effects associated with anti-GD2 mAb infusions. They reported mAb 8B6 targeting OAcGD2 displays antitumor activity in NB tumor models, with induction of ADCC similarly to anti-GD2 mAbs. From this, the inventors interrogated whether 13-cis-RA and retinoic acid generally, may augment anti-NB efficiency of mAb 8B6 therapy. They found cooperative interaction of 13-cis-RA and mAb 8B6 treatment in inhibiting the NB growth in vivo. However, this combination regimen also coordinates PD-1/PD-L1 upregulation, which hinders a long-term activation of NK cells and allows tumor cell to relapse. Importantly this counter therapeutic effect can be leveraged with PD1 blockade to improve the therapeutic response of the mAb 8B6+13-cis-RA regimen.

IPC Classes  ?

• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• A61K 31/203 - Retinoic acids
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents
• 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

Described herein is a composition and method of preventing COVID-19 with lipid-peptide fusion antiviral therapy.

IPC Classes  ?

• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 31/14 - Antivirals for RNA viruses
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses

Abstract

The invention relates to compounds capable of inducing autophagy and metabolic reprogramming and to the use thereof as cardioprotectors, in particular in the context of anticancer therapy.

IPC Classes  ?

• A61K 31/4174 - Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
• A61K 31/15 - Oximes (C=N—O—)Hydrazines (N—N)Hydrazones (N—N=)
• A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• A61P 9/14 - VasoprotectivesAntihaemorrhoidalsDrugs for varicose therapyCapillary stabilisers

Abstract

The present invention relates to methods and pharmaceutical compositions for the treatment of post-operative cognitive dysfunction. In particular, the present invention relates to a method of treating post-operative cognitive dysfunction in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an APJ receptor agonist.

IPC Classes  ?

• A61K 38/22 - Hormones
• A61K 31/015 - Hydrocarbons carbocyclic
• A61K 31/02 - Halogenated hydrocarbons
• A61K 31/08 - Ethers or acetals acyclic, e.g. paraformaldehyde
• A61K 33/00 - Medicinal preparations containing inorganic active ingredients
• A61P 23/00 - Anaesthetics
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

An allele specific siRNA able to silence the expression of only one allele of a heterozygous DNM2 gene is provided. The siRNA is useful for treating diseases caused by heterozygous mutation and/or overexpression of Dynamin 2.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The inventors previously demonstrated that mitochondrial VDAC1 directly induces Schwann cell demyelination via MAPK and c-jun activation after sciatic nerve injury and diabetic neuropathy and CMT1A. They found that reduction of mitochondrial calcium release by VDAC1 blocking strongly reduces the number of demyelinating Schwann cell in vivo and improve nerve conduction and neuromuscular activity in diabetic, Guillain-Barre syndrome and Charcot-Marie Tooth disease models. Herein, the inventors precisely map the binding region of the N-terminal HK-1 helix through an ala scan completed by a deletion study. Furthermore, they optimized the HK-derived peptide through stabilization of the helix by replacement of non-essential amino acids by the a-aminoisobutyric acid (Aib) known as a helix inducer. Additionally, they described an in-house cellular screening assay based on the ability of MJ to detach HK from VDAC that allows to determine the peptide potency. Overall, their data confirm that N-terminal HK derived peptides acting on VDAC are promising tools for the study of the demyelination process. Thus, the present invention refers to optimized HK-derived peptide and its use for treating peripheral demyelinating disease, myocardium diseases10 11, cancer12,13-15, diabetes14 14-16, lupus-like diseases17, non-alcoholic fatty liver disease24,25, chemoinduced neuropathy9 Alzheimer disease18 19, Parkinson disease20, Huntington disease21, ALS22,23 and more generally all neurodegenerative diseases linked to a protein aggregation28.

IPC Classes  ?

• C12N 9/12 - Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The invention relates to a method for imaging a living biological tissue, comprising: obtaining (S1) a plurality of successive colour images of said biological tissue, the processing method comprising a calibration phase (S2) in which at least one zonal time-dependent vector representative of the time evolution of spatial averages of intensity values of each of the colours in an area of the images is determined (S21), a bandpass filter centred on a heartbeat frequency is applied (S24), then a projection basis is determined (S26) by principal component analysis of the filtered zonal time-dependent vector, the method comprising deriving (S33) colour data representative of the time evolution of luminous intensities of the living biological tissue in the tissue images, and projecting (S35) colour data onto the projection basis.

IPC Classes  ?

• G06T 7/80 - Analysis of captured images to determine intrinsic or extrinsic camera parameters, i.e. camera calibration
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• G06T 7/00 - Image analysis
• G06T 7/90 - Determination of colour characteristics

Abstract

The present invention relates to an inhibitor of H3K9 histone methyl transferase SUV39H1 for use in combination with at least one immune checkpoint modulator in the treatment of cancer.

IPC Classes  ?

• A61K 31/546 - Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula , e.g. cephalosporins, cefaclor, cephalexine containing further heterocyclic rings, e.g. cephalothin
• A61K 38/00 - Medicinal preparations containing peptides
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/02 - Antineoplastic agents specific for leukemia
• 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
• C12N 9/10 - Transferases (2.)
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

CMCMC CPCPC , , the bolus being equal to a predetermined first quantity of the compound when the sum of the first and second fuzzy logic variables is strictly greater than 1, the bolus otherwise being equal to zero.

IPC Classes  ?

• A61B 5/024 - Measuring pulse rate or heart rate
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons

Abstract

There is a dire need for innovative nanomedicine-based solutions for safe and efficient thrombolysis with a non-toxic, biocompatible, and biodegradable thrombus-targeted carrier. In the present invention, polysaccharide hydrogel submicroparticles with remarkable biocompatibility were elaborated by the inverse miniemulsion/crosslinking method. They were functionalized with a fucoidan which has a nanomolar affinity for the P-selectin overexpressed on activated platelets and endothelial cells in vascular diseases. Surprisingly, the inventors show that rtPA (i.e. Alteplase) can be loaded onto the submicroparticles by adsorption, and its amidolytic and fibrinolytic activities were maintained in vitro and in vivo. Thrombus targeting potential of these particles was validated in microfluidic assay under arterial and venous blood shear rates on recombinant P-selectin and activated platelet aggregates. The thrombolytic efficacy of the nanomedicine-based product was tested in a murine model of acute ischemic stroke, revealing faster middle cerebral artery recanalization and reduction in the brain infarct volume and blood-brain barrier permeability post-stroke, evidenced by laser speckle contrast imaging and MRI. Collectively, this proof of concept study demonstrates the potential of these particles for the precise treatment of acute thrombotic events.

IPC Classes  ?

• A61K 9/16 - AgglomeratesGranulatesMicrobeadlets
• A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors

Abstract

The invention relates to a computer-implemented diagnostic method learning for determining clinical interpretation of renal graft alterations by applying a trained machine-learning model and a method for training a model for determining clinical categories based on renal transplant lesions, clinical signs and routine laboratory test results.

IPC Classes  ?

• G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons

Abstract

The invention is in the field of therapy of antibody deficiencies. Inventors demonstrate for the first time in both controls and IgA-deficient patients. systemic anti-microbiota IgG responses correlate with reduced inflammation suggesting that systemic IgG responses contribute to the gut microbiota confinement. Furthermore. SIgAd-associated inflammation is inversely correlated with systemic anti-commensal IgG responses, which may thus serve as a second line of defense. Altogether, these data suggest that systemic IgG and intestinal IgA cooperate in different body compartments to limit systemic pro-inflammatory pathways. As selective IgA deficient patients harbour elevated seric anti-commensal IgG levels. these findings suggest that in selective IgA deficiency, microbiota confinement is obtained at the price of a strong inflammatory response. Accordingly. the invention relates to a composition containing immunoglobulins A (IgA). more particularly secretory IgA. for use by oral administration in the prevention or treatment of antibody deficiencies such as SIgAd (Selective IgA deficiency) or common variable immunodeficiency (CVID) and associated inflammatory diseases.

IPC Classes  ?

• C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
• A61P 37/04 - Immunostimulants

Abstract

The present invention relates to the combination of a nucleic acid encoding a short isoform of rod-derived cone viability factor (RdCVF), a nucleic acid encoding a long isoform of rod-derived cone viability factor (RdCVFL) and a nucleic acid encoding a G protein-activated Inward Rectifier potassium channel 2 (GIRK2), expressed through one, two or three viral vectors, said vectors may be within a single pharmaceutical composition or within several different pharmaceutical compositions (two or three). It also deals with the treatment of a retinal degenerative disease, in particular the retinitis pigmentosa, with said viral vectors or pharmaceutical compositions.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to a human macrophage for use in cancer therapy, said human macrophage comprising at least one mutation in both alleles of a chromosomal gene, wherein said macrophage is resistant to tumor-induced reprogramming and/or shows anti-tumor activity. The human macrophage of the invention demonstrates typical markers of an M1 macrophage, such as the presence of MHC class II proteins, even after having been cultured in an environment which promotes M2-polarization, such as in the presence of M-CSF and/or IL4 and/or IL13. The invention also relates to a collection of human macrophages of the invention, to their use in medicine, and in particular to their use in cancer therapy such as the treatment of solid tumors as a preferred example.

IPC Classes  ?

• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
• A61P 35/00 - Antineoplastic agents

Abstract

The pigmentation disorders alter people's quality of life, the effectiveness of treatments is limited resulting in unsatisfactory outcomes, and there is a high therapeutic demand. The inventors tested BCH and JPH203 on a more physiological model, using reconstructed human epidermis and confirmed a strong inhibition of pigmentation demonstrating the clinical potential of SLC7A5 inhibition and positioning BCH and JPH203 as depigmenting agents suitable for cosmetic or dermatologic intervention in hyperpigmentation diseases. Thus, the invention relates to a method for treating hyperpigmentation disorder in a subject in need thereof comprising administering said subject with a therapeutically effective amount of JPH203.

IPC Classes  ?

• A61K 8/49 - Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
• A61K 31/423 - Oxazoles condensed with carbocyclic rings
• A61P 17/00 - Drugs for dermatological disorders
• A61Q 19/02 - Preparations for care of the skin for chemically bleaching or whitening the skin

Abstract

Cation chloride cotransporters (CCC) play a critical role in neuronal chloride homeostasis. Altered CCC expression and function has emerged as a hallmark of wide range of psychiatric and neurological conditions, including various forms of epilepsy. Elevated intraneuronal chloride concentration is thought to result in depolarizing GABA signaling that may contribute to pathological activities and seizures. Compensating for the dysregulation of CCC function in the pathology therefore appears as a promising therapeutic strategy. Bumetanide, an antagonist of the Na/K/Cl co-transporter NKCC1 failed to prevent acute neonatal seizures in the NEMO trial. Here, instead, the inventors tested the effects of novel candidate KCC2 enhancers on epileptiform activity in vitro and in vivo. The inventors show that FDA-approved prochlorperazine (PCPZ) as well as CLP257 potentiate KCC2 function by promoting its membrane clustering, through a mechanism/pathway that does not involve phosphorylation of canonical residues. Both PCPZ and CLP257 reduce interictal activity recorded in vitro in epileptogenic postoperative brain samples from mesial temporal lobe epilepsy patients. In addition, chronic PCPZ administration strongly reduces seizure occurrence in a mouse model of temporal lobe epilepsy. Their results demonstrate for the first time the antiepileptic potential of a KCC2 enhancer and suggest PCPZ may be used in adjunctive therapy in pharmaco-resistant epilepsy.

IPC Classes  ?

• A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61K 31/5415 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• A61P 25/08 - AntiepilepticsAnticonvulsants

Abstract

The present invention relates to the predicting a response to immune checkpoint inhibitors (ICI). In this study, the inventors addressed the issue of response to ICIs based on two independent prospective cohorts of 44 and 73 patients with dMMR/MSI mCRC, respectively the multicentric NIPICOL clinical trial and the prospective ImmunoMSI cohort. Following central reassessment for dMMR/MSI status using gold standard methods to discard misdiagnosed mCRC cases, combined DNA and RNA sequencing of the tumor tissues from these patients was performed. Following supervised analysis of the molecular profiles data which failed to confirm previously proposed DNA/RNA indicators for response to treatment, the use of innovative methods allowed them to identify robust independent DNA and RNA signatures for predicting resistance to ICI. Testing of several retrospective and prospective cohorts regrouping 446 patients with metastatic or nonmetastatic MSI CRC untreated with ICI was also performed to evaluate the specificity of the predictive nature of these indicators, i.e., in the context of immune checkpoint blockade therapy. Thus, the present invention relates to a method of predicting a response to immune checkpoint inhibitors (ICI) in a patient with an MSI cancer comprising determining the microsatellite (MS) variation status of a set of selected genes and using a machine learning algorithm.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 40/20 - Supervised data analysis
• 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

Abstract

An assembly for heat-treatment of biological tissue comprises: a thermal energy generator; an energy applicator; an MRI image acquisition device for generating anatomical images and phase images; a planning unit comprising an MRI image processing means for defining a target region, a region to be preserved, and a neutral region in the tissue, and for assigning a heat treatment setpoint and an acceptable temperature measurement uncertainty to the three regions; a unit for monitoring evolution of the status of the heat treatment and for receiving data from the planning unit and from the MRI image acquisition device during a heat treatment, the monitoring unit comprising a means for generating temperature images from the phase images, a means for calculating a reliability indicator from the temperature variation indicated on the temperature image, and a means for calculating an indicator of the status of the heat treatment in the three regions.

IPC Classes  ?

• A61B 34/10 - Computer-aided planning, simulation or modelling of surgical operations
• A61B 18/02 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by cooling, e.g. cryogenic techniques
• A61B 18/12 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
• A61B 18/18 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
• A61B 34/00 - Computer-aided surgeryManipulators or robots specially adapted for use in surgery

Abstract

in vitro in vivo in vivo use of the anti-SLC1A4 monoclonal antibodies disclosed therein for diagnosis purpose.

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
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/04 - Antineoplastic agents specific for metastasis

Abstract

The treatment of cancer and particularly the neuroblastoma, and a combination of an anti-O-acetylated disialoganglioside (OAcGD2) compound and an anti-SIRP-alpha/CD47 compound for treating a cancer in a subject in need thereof. The inventors hypothesized that CD47 expression would interfere with the contribution of macrophage to the therapeutic effect of anti-OAcGD2 mAbs. They found that NB cells up-regulate CD47 expression upon 8B6 mAb immunotherapy in vivo, allowing them to escape mAb 8B6-mediated ADP. Next, they demonstrate that an anti-SIRPα antibody that blocks the binding of CD47 to SIRPα enables macrophages to phagocyte anti-OAcGD2-opsonised CD47-expressing NB cells in vitro. As a result, the combination of CD47 blocking with the targeting of OAcGD2-positive NB cells greatly reduces tumor growth in syngeneic mice. These results suggest that the combination of anti-OAcGD2 mAbs with phagocytosis checkpoints inhibitors may represent a very effective regimen to achieve for lasting responses in a greater number of patients.

IPC Classes  ?

• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• A61K 31/203 - Retinoic acids
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 14/55 - IL-2
• 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

Intracerebral hemorrhage (ICH), defined as spontaneous bleeding into the brain, is the deadliest, most disabling, and least treatable form of stroke. The aim of the present invention is to generate large amount of hemostatic mEVs to be used as hemostatic patches in different preclinical models of ICH. Indeed, the exogenous mEVs pf the present invention bearing TF and PSGL-1 improve outcome after collagenase-induced ICH by acting as intravascular hemostatic patches. The present invention thus relates to monocyte extracellular vesicles (mEVs) functionalized with tissue factor (TF) and P-Selectin Glycoprotein Ligand 1 (PSGL-1).

IPC Classes  ?

• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
• A61K 38/36 - Blood coagulation or fibrinolysis factors
• A61P 7/04 - AntihaemorrhagicsProcoagulantsHaemostatic agentsAntifibrinolytic agents
• C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor

Abstract

in vivoin vivo uptake and transport of oxygen to tissues, in particular tumor tissues, in order to overcome hypoxia to treat and/or prevent cancer in a subject, and potentiate radiotherapy.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/107 - Emulsions
• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
• A61K 51/04 - Organic compounds
• A61K 51/12 - Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes
• C07C 323/52 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• A61K 47/10 - AlcoholsPhenolsSalts thereof, e.g. glycerolPolyethylene glycols [PEG]PoloxamersPEG/POE alkyl ethers
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• C08G 65/333 - Polymers modified by chemical after-treatment with organic compounds containing nitrogen
• C08G 65/334 - Polymers modified by chemical after-treatment with organic compounds containing sulfur
• C08G 65/337 - Polymers modified by chemical after-treatment with organic compounds containing other elements

Abstract

A method of treatment or prevention of myeloproliferative disorders and other hematopoietic malignancies is described. A carbonic Anhydrase 1 (CA1) inhibitor is used in a method for treating or preventing a myeloproliferative disorder, an acute myeloid leukemia (AML) and/or a primary or secondary myelofibrosis. The carbonic Anhydrase 1 is also used as a biomarker for myeloproliferative disorders and other hematopoietic malignancies, and as a biomarker of the efficacy of compounds for treating or preventing these conditions.

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 31/433 - Thiadiazoles
• A61P 35/02 - Antineoplastic agents specific for leukemia
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

An ultrasound probe includes a connector and a probe head that includes a mount located in a tip part of the probe head, various linear matrices of transducers that emit acoustic waves with a given central wavelength and detect backscattered acoustic waves. The linear matrices are electrically connected to the connector, wherein each linear matrix from the linear matrices of transducers includes a first side along a first direction and a second side along a second direction. The second side is smaller than the first side. The linear matrices are fixed to the mount and juxtaposed on the mount with the first sides adjacent. Each linear matrix from the linear matrices of transducers is covered with a single cylindrical acoustic lens that focuses the acoustic waves emitted by the linear matrix. Each cylindrical acoustic lens includes a cylindrical axis substantially parallel to the first direction.

IPC Classes  ?

• G01N 29/06 - Visualisation of the interior, e.g. acoustic microscopy
• G01N 29/26 - Arrangements for orientation or scanning
• G01N 33/483 - Physical analysis of biological material

Abstract

The Inventors herein demonstrate that CD39 is a relevant therapeutic target in B-cell lymphoma, in particular Follicular Lymphoma (FL), Diffuse Large B-Cell Lymphoma (DLBCL) and Mantle Cell Lymphoma (MCL). They also demonstrate that CD39 potentiate anti-CD20 monoclonal antibody therapy and/or anti-PD1 monoclonal antibody therapy, and that ENTPD1 overexpression is correlated with poor prognosis in FL patients. Accordingly, the present invention relates to a method of treating a B-cell lymphoma in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a CD39 inhibitor.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• 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

While 3D ultrasound imaging is becoming a powerful tool in medical field. the main drawback is the difficulty to image large 3D volume. mainly related to the dimensions of the 2D array of transducers. In order to not lose in spatial resolution, it is necessary to use an array of transducers. wherein the size of the transducers does not exceed the wavelength of the ultrasound wave. Such requirement leads to dimensions of array for imaging large 3D volume which are not reachable or at too high cost with the current technology. The present disclosure overcomes the above technology limitation by using greater transducers, and where each transducer has a reception surface with a curved shape or is fitted with an acoustic lens. Such configuration of transducers leads to 2D array of transducers suitable for imaging large 3D volume, as a brain or a heart. with high resolution and high sensitivity.

IPC Classes  ?

• A61B 8/08 - Clinical applications
• A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves
• B06B 1/06 - Processes or apparatus for generating mechanical vibrations of infrasonic, sonic or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction
• G01S 7/52 - Details of systems according to groups , , of systems according to group
• G01S 15/89 - Sonar systems specially adapted for specific applications for mapping or imaging

Abstract

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IPC Classes  ?

• A61P 27/02 - Ophthalmic agents
• C12N 5/079 - Neural cells
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• C12N 15/86 - Viral vectors