Abstract

The Inventors have developed an ELISA of a new molecular marker detecting a neoepitope generated from the cleavage of the α1 chain of type III collagen within its helical domain. Serum levels of this marker were significantly increased in patients with RA and is significantly associated to CRP and ESR levels. Indeed, they demonstrated that the median serum HELIX-III levels were significantly higher in patients with moderate (p=0027) and active RA (p=00004) compared with those in age-matched controls. The present invention relates to an antibody recognizing an epitope having SEQ ID NO:1 of collagen protein and its uses for diagnostic, prognostic and monitoring purposes.

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

Abstract

A scanning dynamic collimator device (SDD) for minibeam production. The SDD includes a single slit collimator being mounted on a support. The SDD is arranged to translate the collimator in a plane perpendicular to a plane whereby the single slit extends and/or in a direction parallel to the plane whereby the single slit extends and/or to rotate the collimator relative to a rotation axis parallel to the plane whereby the single slit extends and to tilt the collimator relative to a predefined reference axis and/or relative to a point comprised in the single slit.

IPC Classes  ?

• A61N 5/10 - X-ray therapyGamma-ray therapyParticle-irradiation therapy

Abstract

The present invention relates to a device (10) for the localised treatment of a tissue, the device comprising: - an endoscopic injection needle (14); - at least one stimulation element (22) arranged around the injection needle (14), comprising at least two electrodes (26) in the form of shape-memory rods; wherein the injection needle (14) and the stimulation element (22) are each electrically connected to a separate electrical conductor (32); - a tube (28) intended to house the injection needle (14) and the stimulation element (22) in a retracted state of the device (10); wherein the injection needle (14) and the stimulation element (22) are movable in the tube (28) such that, in a deployed state of the device (10), the injection needle (14) extends at least partially out of the tube (28) and the electrodes (26) extend out of the tube (28) in a predetermined shape.

IPC Classes  ?

• A61B 18/14 - Probes or electrodes therefor
• A61N 1/32 - Applying electric currents by contact electrodes alternating or intermittent currents
• A61B 18/00 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
• A61N 1/05 - Electrodes for implantation or insertion into the body, e.g. heart electrode
• A61N 1/40 - Applying electric fields by inductive or capacitive coupling

Abstract

The invention relates to a computer implemented method for detecting at least one mutation in the genome of a member of a population and to a method for detecting at least one mutation in the genome of a member of a population.

IPC Classes  ?

• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• C12Q 1/6869 - Methods for sequencing
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids

Abstract

According to the WHO, the population aged 60 and over will have doubled by 2050. Unfortunately, aging comes along with an explosion of aging-associated disorders, such as metabolic and cardiovascular diseases, bone and muscle weakening, cognitive dysfunction, that all contribute to the loss of functional capacities, leading to frailty and dependence. Now, the inventors reveal a premature aging phenotype, associating metabolic defects and muscle weakness, in a mouse model of Noonan Syndrome. Both clinical traits are linked to myeloid cells dysfunction and increased senescence, highlighting the role of SHP2 hyperactivation in the onset of aging-associated diseases. Thus the present invention relates to the use of SHP2 inhibitors for inhibiting senescence.

IPC Classes  ?

• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings

Abstract

Investigating the impact of Tau protein expression in cancer cell lines, Inventors have demonstrated that the Tau expression is associated with an increased resistance to HDAC inhibitors. Briefly in the present invention, inventors report that Tau expression in breast cancer cell lines causes resistance to the anti-cancer effects of histone deacetylase inhibitors, by preventing histone deacetylase inhibitor-inducible gene expression and remodeling of chromatin structure. Inventors identify Tau as a protein recognizing and binding to core histone when H3 and H4 are devoid of any post-translational modifications or acetylated H4 that increases the Tau's affinity. In addition, they demonstrate that the interaction between Tau and histones prevents further histone H3 post-translational modifications induced by histone deacetylase-inhibitor treatment by maintaining a more compact chromatin structure The present invention relates to means to improve the bioavailability of histone deacetylase (HDAC) inhibitor and thereby also improve the efficacy of histone deacetylase (HDAC) inhibitor treatments.

IPC Classes  ?

• A61K 38/15 - DepsipeptidesDerivatives thereof
• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
• A61K 31/4406 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• 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

Metastases increase the risk of bone fracture. Consequently, clinicians need to know if the patient's metastatic bones can withstand the stress of daily activities, in particular femurs and vertebras. Accordingly, it is disclosed a method for determining a probability of fracture of a metastatic bone of a patient in daily activities, that is determined from a numerical simulation of load application performed on a Finite Element model of the bone, and from a determined uncertainty related to the building of the FE model and the numerical simulation. The uncertainty has been elaborated by studies of replicability and sensitivity of models. According to the disclosed method, various probabilities may be computed for different types of daily activities according to the average load represented by each activity on the bone. The method may be applied to metastatic bones or vertebras.

IPC Classes  ?

• G06T 7/00 - Image analysis
• G06T 7/10 - SegmentationEdge detection

Abstract

γγ-PIK3R5/p101 axis blocks AKT signaling, compromises cell fitness, and sensitizes to established AML therapies. Importantly, the inventors find that existing small molecule inhibitors against PIK3CG are insufficient to achieve a sustained longterm anti-leukemic effect. To address this concern, the inventors developed a proteolysis- targeting chimera (PROTAC) heterobifunctional molecule that specifically degrades PIK3CG and potently suppresses AML progression alone and in combination with venetoclax in human AML cell lines, primary AML patient samples, and syngeneic mouse models.

IPC Classes  ?

• A61K 31/427 - Thiazoles 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 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
• 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 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

The present invention relates to a construct comprising a cell-penetrating peptide sequence coupled by a peptide bond to at least one first binding molecule which is coupled by a peptide bond to the N-terminal end of an interfering amino acid sequence selected from the following sequences: SEQ ID NO: 1 which forms the 2104-2206 domain of the human FlnA protein and SEQ ID NO: 2 which defines the 330-350 domain of the UT receptor, the sequences having at least 90% identity, and preferably at least 95% identity, with the aforementioned sequences.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to a population of small extracellular vesicles (sEVs) for use in the treatment of obesity in a subject in need thereof, wherein the sEVs comprise at least one polynucleotide encoding a D168A dominant negative AMP-activated protein kinase alpha 1 (AMPKa1-DN) mutant protein operably linked and under the control of a steroidogenic factor 1 (SF1) promoter, wherein the sEVs are engineered to transiently express in their outer membrane at least one fusion protein comprising the neurotrophic rabies virus (RVG) peptide fused to lysosome-associated membrane protein 2b. Said population is highly safe and effective, as the sEVs, when administered systematically, are capable of exerting their effect in the SF1 expressing neurons located in the ventromedial nucleus of the hypothalamus.

IPC Classes  ?

• A61K 38/45 - Transferases (2)
• A61K 9/50 - Microcapsules
• A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• A61P 3/04 - AnorexiantsAntiobesity agents

Abstract

The present invention relates to hybrid transcription regulatory elements to drive gene expression, in particular hybrid promoters, designed by the fusion of at least two transcription regulatory elements with different tissue selectivity, such as two promoters driving expression in different tissues in a tissue-selective manner.

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

The invention relates to engineered immune cells overexpressing CD74 molecule which have improved properties.

IPC Classes  ?

• C07K 14/74 - Major histocompatibility complex [MHC]
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells

Abstract

The invention concerns new oncolytic viruses and their uses In particular, the invention is a viral particle for its use in the prevention and/or the treatment of a tumor, said viral particle comprising: an inactivated nucleic acid sequence encoding the native envelope glycoprotein of the IROV encoded by said IROV genome; and a nucleic acid sequence encoding a retroviral envelope glycoprotein or a fragment thereof having a native targeting capacity for said host cell surface protein.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 15/86 - Viral vectors
• A61P 35/00 - Antineoplastic agents
• A61K 35/766 - Rhabdovirus, e.g. vesicular stomatitis virus

Abstract

The present invention relates to a treatment of CCHFV infection, in particular CCFHV infection. Here, the inventors showed that antibody blocking LDL-R family at the surface of human cells could reduce CCHFV infection by 80%, such inhibition only occurred when blocking was performed prior to or at the time of infection though not at later time points. Furthermore, they found that incubation of viral particles with a soluble form of LDL-R could impair CCHFV infection. They found that ApoE antibodies could block CCHFV infectivity by up to 10-fold only when the viral particles were produced in cells that express ApoE. Thus, the present invention relates to an LDL-R family and/or an ApoE inhibitor for use in the prevention and/or the treatment of CCHFV infection in subjects in need thereof.

IPC Classes  ?

• A61K 31/4748 - QuinolinesIsoquinolines forming part of bridged ring systems
• 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 31/14 - Antivirals for RNA viruses

Abstract

The present invention is based on the demonstration that bacteria of the Akkermansia genus improve the response to CAR T-cells therapy. According to the invention, Akkermansia bacteria are administered to patients treated with CAR T-cells, especially if their gut microbiome was devoid of such bacteria before administering said CAR T-cells.

IPC Classes  ?

• A61K 35/74 - Bacteria
• A61K 35/741 - Probiotics
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• A61K 40/11 - T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cellsLymphokine-activated killer [LAK] cells
• A61K 40/31 - Chimeric antigen receptors [CAR]
• A61K 40/42 - Cancer antigens

Abstract

Today, more than 40% of acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT) will remain severely disabled at 3 months. The inventors hypothesized that acute microglial inflammation plays a pivotal role in post-AIS brain changes leading to poor functional outcome. Glycoprotein YKL-40 is a biomarker of astrocytic and microglial activation. The inventors thus conducted a monocentric prospective study including 120 patients treated with EVT, for whom 3 blood samples (before, within 1-h, 24-h post-EVT) were drawn to measure plasma YKL-40 concentrations. The inventors found that 3 -month functional outcome was significantly and independently associated with acute plasma YKL-40 levels, the present invention relates to the use of YKL-40 as a biomarker for assessing functional outcome in AIS patients treated with EVT.

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

Abstract

The inventors hypothesized that inhibition of complement activation could reduce the inflammatory period observed even before clinical signs of Alzheimer's disease and thus slow down the onset and progression of AD. In order to validate the hypothesis, the inventors injected Factor H (FH: the main inhibitor of complement activation) into the brain of APP/PS1 AD- mice model at early or late stage of this pathology. The results showed effects of FH brain injection on the AD-onset as well as progression by reducing pro-inflammatory IL6, TNF-α, Il1β, MAC and Aβ levels associated with an increase of VGLUT1 and Psd95 neurotransmitters levels in hippocampal region leading to improvement of cognitive functions even at late stage of the pathology. The results thus prompt the inventors to consider that FH would be suitable for the treatment of dementia, and more particularly for the curative treatment of dementia.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• 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 present invention relates to a non-invasive prognostic method for assessing the prognostic of atrial cardiomyopathy in a subject in need thereof comprising determining a prognostic score based on groove epicardial adipose tissue variables and at least one additional demographic, metabolic or biologic variable. The present invention further relates to a method for preventing atrial cardiomyopathy occurrence in a subject, comprising determining the personalized course of the personalized course of clinical follow-up and/or preventive medical care for the subject based on the obtained prognostic score.

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
• G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
• G16H 30/00 - ICT specially adapted for the handling or processing of medical images

Abstract

Clk1Pak1Clk-4Pak1Pak1 using validated shRNAs and combinations of FRAX597 and TG003, or FRAX597 and ML 167 synergized to reduce the growth and the colony-forming capacity of chemoresistant AML cells and sensitized them to chemotherapy. The combined treatment improved overall mouse survival and reduced disease burden in the chemoresistant AML mouse models. Moreover, AML patient cells that were primarily refractory or from a post chemotherapy relapse (n=21 ) exhibited a higher ex vivo sensitivity to the FRAX597 + TG003 combination in comparison with chemosensitive patients at diagnosis (n=28). Finally, combined PAK1 and CLK inhibition more effectively reduced disease progression in animals transplanted with the relapse sample than in those engrafted with the sample taken at diagnosis. Thus, the present invention relates to combination of PAK1 inhibitors and CLK inhibitors for preventing resistance to chemotherapy in patients suffering from acute myeloid leukemia.

IPC Classes  ?

• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• 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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

OF THE INVENTION LOCAL ADMINISTRATION OF RIPK2 INHIBITORS FOR THE CURATIVE TREATMENT OF ALLERGIC ASTHMA The present invention relates to a method for use in the treatment of Asthma. Here, the inventors identified the receptor-interacting serine/threonione protein kinas 2 (RIPK2) as a novel therapeutic target to improve Asthma-related diseases. They demonstrated that a local preventive administration of the RIPK2 inhibitor reduced AHR, airway eosinophilia, mucus production, Th2 cytokines and the alarmin IL-33. Moreover, they demonstrated the early role of IL-33 in the NOD1-dependent response of the epithelium to HDM. Therefore, the inventors demonstrated that the local interference of the NOD1 signaling pathway through RIPK2 inhibition may represent a new therapeutic approach in asthma. Other pulmonary diseases could also benefit of this treatment. Thus, the present invention relates to a method for use in the curative treatment of HDM-induced asthma comprising administrating to a subject in need thereof a therapeutically effective amount of an inhibitor of RIPK2.

IPC Classes  ?

• A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
• A61K 31/47 - QuinolinesIsoquinolines
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 11/06 - Antiasthmatics
• A61P 37/08 - Antiallergic agents

Abstract

The invention relates to a cell-free method for synthesizing bacteriophages, comprising: (a) in vitro assembling overlapping DNA fragments into a phage genome, in a ligase-free assembling reaction, comprising: (a1) digesting the overlapping DNA fragments by an exonuclease, and (a2) annealing the overlapping DNA fragments to assemble a phage genome, and (b) cell-free transcribing and translating the phage genome. The invention also relates to phages synthesized by the method and to their applications.

IPC Classes  ?

• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• C12P 21/00 - Preparation of peptides or proteins
• C12N 15/70 - Vectors or expression systems specially adapted for E. coli

Abstract

Here, the Inventors show that chronic IL- 1 -induced H2A.X signaling, which mediated DNA DSB response, in hippocampal neurons is a critical driver of cognitive deficits in chronic low grade neuroinflammation. They show that mice chronically infected with the brain- persisting T. gondii parasite display deficits in spatial memory consolidation without general memory loss. Extensive mapping of the neuroinflammatory landscape, beyond a latent T. gondii infection elicited type 1-like neuroinflammation, display elevated production of IL-1α and IL-1β in the hippocampus. Using a mouse model to specifically delete the IL-1 receptor from excitatory neurons, they uncovered that neuronal IL-1 signaling is required for the spatial memory deficits caused by latent T. gondii infection. By singling out a chronic exposure to IL- ip they found that IL-1β signaling in neurons indeed impairs spatial memory. Moreover, they showed that chronic exposure to IL-1β increases DNA DSB levels in neurons, and that neuronal H2A.X-dependent DSB response mediates the IL-1β-induced memory deficits. Importantly, neuronal DSBs were also increased upon T. gondii infection and the deficit in hippocampus- dependent spatial memory caused by T. gondii infection was prevented by the abrogation of neuronal H2A.Xdependent signaling. These results highlight the instrumental role of cytokine- induced DSB-dependent signaling in spatial memory defects elicited by a chronic infectious neuroinflammatory process. Accordingly, the present invention relates to a method of treating a subject suffering from cognitive deficit comprising administering to said subject a therapeutically effective amount of an inhibitor of IL- 1 -induced H2A.X signaling.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 25/00 - Drugs for disorders of the nervous system
• 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 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

1 235621011777 represents a functional group selected among a hydrogen and an aliphatic chain; or a pharmaceutical acceptable derivative thereof, for use as a medicament.

IPC Classes  ?

• C07F 5/02 - Boron compounds
• A61K 31/69 - Boron compounds
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys

Abstract

The present invention relates to a method for determining a risk of having or developing a respiratory condition in a subject, based on the detection of the presence or abundance of bacteria of specific genus in a respiratory sample of said subject.

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

Abstract

The invention relates to an in vitro prognosis method of an aggressive multiple sclerosis in a patient afflicted by a multiple sclerosis, the method comprising: - quantifying in a biological sample of the patient the amount of a cell called NK-like cell having a phenotype CD3+, CD8+, CD45RA-, Vα7.2-, CCR7-, and CD94+; - comparing the quantified amount of NK-like cells with a reference, and - concluding that - if the quantified amount of NK-like cells is lower than or equal to the reference, then the patient is not liable to develop an aggressive multiple sclerosis, and - if the quantified amount of NK-like cells higher than the reference, the patient will probably develop an aggressive multiple sclerosis within 24 months or more.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

Lung fibroblast play an important role in lung cancer tumor microenvironment (TME). Senescence is involved in the pathophysiology of tumorogenesis. analyze how sPLA2 influenced lung cancer cell malignant properties. The inventors show that secreted PLA2 XIIA (sPLA2 XIIA) play a key role in lung cancer cell malignant properties. They demonstrate that sPLA2 XIIA increases the proliferation, the migration and organoid growth of both lung cancer cell lines (NCI and A549). Indeed, they shows that sPLA2 XIIA induces notably the epithelial mesenchymal transition (EMT), which is involved in the invasion of cancer cells and in the formation of metastasis. They also demonstrate that the effect of sPLA2 XIIA is mediated in particular by syndecan 1 and 4. Taken altogether, these data define sPLA2 XIIA as a circulating biomarker of poor prognosis in lung cancer and establish a requirement for sPLA2 XIIA inhibition for the treatment or prevention of cancer, especially lung cancer in the COPD patients.

IPC Classes  ?

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

Abstract

The invention relates to a cell-free method for making a library of phage variants comprising the steps of: (a) providing a library of phage genomes in mixture, and (b) subjecting said library of phage genomes to a step of cell-free transcription and translation. The invention also relates to the applications of such method, for instance in phage display or continuous evolution processes.

IPC Classes  ?

• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• C12P 21/00 - Preparation of peptides or proteins
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12P 1/00 - Preparation of compounds or compositions, not provided for in groups , by using microorganisms or enzymesGeneral processes for the preparation of compounds or compositions by using microorganisms or enzymes
• C40B 50/00 - Methods of creating libraries, e.g. combinatorial synthesis
• C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cellsLibraries contained in or displayed by vectors, e.g. plasmidsLibraries containing only microorganisms or vectors
• C12N 15/70 - Vectors or expression systems specially adapted for E. coli

Abstract

A technique for moving various objects such as cells and particles of hydrogel or a compressible material, suspended in a fluid, so as to form a layered structure akin to human organ tissue. A standing sound wave is propagated through the fluid so as to position the cells on a pressure node and the particles on a pressure antinode. As such, the cells have a positive acoustic contrast relative to the fluid, while the particles have a negative acoustic contrast relative to the fluid.

IPC Classes  ?

• C12M 1/00 - Apparatus for enzymology or microbiology
• C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means

Abstract

The human bone marrow (BM) microenvironment involves hematopoietic and non-hematopoietic cell subsets organized in a rather complex architecture. Tremendous efforts have been made to model it in order to analyse normal or pathological hematopoiesis and its stromal counterpart. Herein, the inventors report an original, fully-human in vitro 3D model of the BM microenvironment dedicated to study interactions taking place between mesenchymal stromal cells (MSC) and hematopoietic stem and progenitor cells (HSPC) during the hematopoietic differentiation. This fully-human artificial marrow organoid (AMO) model is highly efficient to recapitulate MSC support to myeloid differentiation and NK cell development from the most immature CD34+ HSPC to the most terminally differentiated CD15+ CD64+ polymorphonuclear neutrophils or NKG2A-KIR2D+CD57+ NK subset. Interestingly, mature NK cell's phenotype showed significant differences after AMO-based culture compared to a conventional 2D co-culture system in the expression of adhesion molecules and immune checkpoint receptors, suggesting that the 3D model is more suitable to study the BM immunosuppressive microenvironment. Thus, the present invention relates to the use of an artificial marrow organoid for generating NK cells and myeloid cells.

IPC Classes  ?

• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells

Abstract

Nowadays, the interest to use ultrasound waves in medical field is well established. Such ultrasound waves may be focused for treating a zone in an organ such as the brain for instance. The focus allows to treat only the zone relative to the disease and avoid treating a healthy zone. Therefore, it is mandatory to use an image guidance system to monitor in real time where the ultrasound waves are focused. The guidance can be performed by Magnetic Resonance Imaging (MRI), Ultrasound Imaging (echography), or Optical Imaging (neuronavigation). However, such systems increase the cost and the complexity of the whole process. The present disclosure overcomes the above drawbacks by proposing a self-positioning acoustic lens allowing to ensure good ultrasound waves transmission in the zone to treat without requiring to the use of a navigation system.

IPC Classes  ?

• A61N 7/02 - Localised ultrasound hyperthermia
• A61N 7/00 - Ultrasound therapy

Abstract

Melanoma cell plasticity plays a key role in the acquisition of resistance to therapy. TRIM24/TIF1α, which encodes for the tripartite RING/B-Box/Coil-coiled transcriptional coactivator, is frequently amplified in human melanomas. The inventors observed a strong correlation between elevated TRIM24 expression and metastatic disease, adverse outcome to immune checkpoint inhibitor therapy and a worse relapse-free survival. shRNA-mediated knock-down of TRIM24 decreased the migratory capacities and increased the sensitivity to BRAF inhibitors in two cellular melanoma models. RNA-sequencing analyses revealed that TRIM24 knock-down significantly represses undifferentiated/invasive transcriptional programs. A protac-based approach for degradation of Trim24 was shown to resensitize resistant melanoma cells to BRAF inhibitors. Thus, the present invention relates to a method for predicting the survival time of a patient suffering from melanoma comprising the step of measuring the level of TRIM24, and the use of TRIM24 inhibitor for treating melanoma, in particular resistant melanoma.

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

Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients. Treatment of residual microscopic disease remains a challenge with new anticancer modalities development. Now, the inventors propose an innovative therapeutic management of peritoneal carcinomatosis (PC) that is bio-inspired and tumor-targeted by combining MSC-derived EVs and at least one chemotherapeutic agent for improved chemotherapy efficiency ty. In this work, the present inventors have shown in two different mice models of PC and with two different chemotherapeutic agents that, while the MSC-derived EVs from mice (mEVs) have no effect on mice suffering from PC, treatment with mEvs combined with chemotherapeutic agent has a superior therapeutic effect i.e. a significant reduction of the Peritonal Carcinomatosis Index (PCI) compared to treatment with chemotherapeutic agent alone. Thus, the present invention relates to the combination of EVs and at least one chemotherapeutic agent and uses thereof for the treatment of cancers such as PC.

IPC Classes  ?

• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• A61K 31/282 - Platinum compounds
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
• 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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention concerns a new tracheal decellularization tissue engineering protocol for circumferential tracheal replacement, to develop a clinical- grade partially tracheal decellularized matrix.

IPC Classes  ?

• A61L 27/36 - Materials for prostheses or for coating prostheses containing ingredients of undetermined constitution or reaction products thereof
• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues

Abstract

mixmixmix)mix), based on a given pathology progression profile (I(t)).

IPC Classes  ?

• G06N 3/045 - Combinations of networks
• G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
• G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
• 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

The present invention relates to a method to capture circulating tumor extracellular vesicles. Here the inventors describe a novel approach inspired by Chimeric Antigen Recognition (CAR)-like strategy, to selectively capture and locally accumulate circulating tumor EVs towards engrafted trapping cells, or endogenous trapping tissues of choice. Focusing on Prostate Cancer (PCa)-derived EVs as a proof of concept, they combined the pHluorin- genetic tagging of tumor EVs with the expression on target cells of the EV-Trap, a chimeric surface mCD8α receptor exposing various nanobodies directed against EVs' surface antigens (synthetic or tumor associated). They demonstrate how the simultaneous presence of PCa- derived CD63-pHluorin+, CD9-pHluorin+ or PSMA+ EVs in a system presenting GFP-TRAP or PSMA-TRAP accessible cell surfaces, results in significant accumulation and rerouting of PCa-derived pHluorin and PSMA EVs towards the EV-TRAP sites, both in vitro and in vivo in the zebrafish embryo. This approach has the potential to shed new lights on the role of EVs in various physiopathological processes, in particular on pre-metastatic niches formation. Thus, the present invention relates to a fusion protein comprising or consisting of an antigen binding compound, the mCD8α and optionally a domain which induce endocytosis (or internalisation).

IPC Classes  ?

• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 35/00 - Antineoplastic agents
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

The present invention relates to antagonist of PDGF-AA protein, for use in the treatment of cancer. Here in the present invention, they show for the first time that targeting PDGF signaling through a ligand trap approach is able to inhibit tumor progression by the reprogramming the activation status of the CAFs (Cancer -Associated Fibroblasts). The inventors found that PDGF-AA bind directly on CD8+T cells by reducing their activation and cytotoxic properties. Furthermore, the use of neutralizing PDGF-AA antibodies in PDAC mouse model, reduced tumor growth by enhancing CD8+ T cell anti-tumoral response. Thus, neutralizing PDGF-AA which acts as a novel immunological check-point target in PDAC therefore allows to restore beneficial anti-tumor immunity in cancer, and especially in PDAC.

IPC Classes  ?

• C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
• A61P 35/00 - Antineoplastic agents
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum

Abstract

The present invention relates to an ex vivo method for predicting the response to an immunotherapy treatment of hepatocellular carcinoma in a subject, comprising the steps of: 1) determining the energy metabolism status of a liver tissue sample from the subject, said sample containing pathological tissue and optionally non-pathological tissue, 2) detecting the presence or the absence of an energetic shift consisting of a reduction of mitochondrial respiration, in pathological tissue compared to non-pathological tissue from the liver tissue sample of the subject or from a standard non-pathological liver sample, Wherein: - If mitochondrial respiration is reduced in pathological tissue, the subject is unlikely to have a response to the immunotherapy treatment, - If mitochondrial respiration is not reduced in pathological tissue, the subject is likely to have a response to the immunotherapy treatment.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• 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 a treatment of Age-related diseases (ARDs). Here, the inventors identified the AP-1 family of transcription factors (TFs) as a novel actionable therapeutic target to reverse the senescence phenotype and to ameliorate age-related chronic lung and cardiac disease outcomes by repurposing a small molecule AP-1 inhibitor (APli) T- 5224. They demonstrated that AP-1 inhibition induces an improve of ARDs such as Emphysema, lung fibrosis or cardiac function. Other cardiac and pulmonary diseases could also benefit of this treatment. Thus, the present invention relates to an AP-1 inhibitor for use in the treatment of ARDs in subjects in need thereof.

IPC Classes  ?

• A61K 31/423 - Oxazoles condensed with carbocyclic rings
• 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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

A new peptide and its use as a vector for the transport of molecules after conjugation through cellular barriers for the diagnosis, prognosis or treatment of pathologies of the central nervous system (CNS).

IPC Classes  ?

• C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans

Abstract

The present invention relates to an inhibitor of the interaction between the ROCK and PDK1 protein kinases. The present invention also relates to a pharmaceutical composition comprising at least one inhibitor of the interaction between the ROCK and PDK1 protein kinases as an active ingredient and at least one pharmaceutically acceptable excipient and/or support and/or a diluent and/or a pharmaceutically acceptable carrier. The invention also relates to the use of said pharmaceutical composition in the prevention and/or treatment of inflammatory diseases, viral and/or bacterial infections and autoimmune diseases.

IPC Classes  ?

• A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil
• A61K 31/415 - 1,2-Diazoles
• 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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention relates to a device for training a generative model configured to generate at least one synthetic 3D representation of myelin content and to a device and a computer-implemented method for obtaining at least one synthetic 3D image representative of myelin content for a patient using a trained generative model having training parameters obtained using the device for training.

IPC Classes  ?

• G06T 7/00 - Image analysis
• G06T 7/11 - Region-based segmentation

Abstract

The invention relates to the combination of a βig-h3 antagonist and a PDGF-AA antagonist, for use in the prevention or treatment of a patient affected with cancer disease. In particular, the combination restore CD8+ T cell activation and thus anti-tumoral cytotoxic response. The cancer may be pancreatic ductal adenocarcinoma. PDGF-AA antagonist may be an anti-PDGF-AA neutralizing antibody or aptamer. Said βig-h3 antagonist may be an anti-βig-h3 neutralizing antibody or aptamer. The cancer is more particularly a cancer associated with a stroma expressing/secreting PDGF-AA and βig-h3. The invention also relates to methods of treatment of cancer disease with said combination.

IPC Classes  ?

• C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans

Abstract

Jam-3Jam-3Jam-3-deficiency rewired the transcriptional program of leukemia initiating cells (LIC) with upregulation of genes belonging to AP-l/TNF-α pathways. Transposition of results to human allowed to determine a new prognosis score called ATIC for AP-l/TNF-α Initiating Cells, complementary and distinct from the LSC17 score. Thus, the invention relates to a method for predicting the survival time of a patient suffering from an Acute Myeloid Leukemia (AML) based on the determination in a sample obtained from the patient of the expression levels of at least 7 genes selected in the group consisting in: JAM3, DUSP1, JUN, IER2, DUSP2, RGS1, H2BC8, PTGS2, NFKBID, PPP1R15A, NFKBIZ, ZFP36, SNORA28, TPT1, KLF2, BTG2, JUNB, JUNE), ATF3, UBC, SKIL, TAF7, SLFN12L, NR4A1, CHST2, GASS, SNORA31, HES1, EGR3, RPS13, PMAIP1, RHOB, MYL9, ZNF699, ZNF101, FOS, FJX1, RPP25L, HEY1, PTMA, GIMAP4, EFCAB11, FOSE, CD14, CCL4, CCL3, PF4, OSM, CD69, ITGA2B, VWF, MYCN and F2RL2.

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 disclosure relates to methods and pharmaceutical compositions for the treatment of fibrotic related diseases, particularly cancer and immunotherapy-resistant cancer. The inventors investigated the role of new mechanisms and pathways of immunosuppressive microenvironment key factors and the interaction between cancer cells with Cancer-Associated Fibroblasts (CAFs) and immune cells to find alternative curative options for cancer including immunotherapy-resistant cancer. The inventors identified that Invasive Lobular Carcinoma (ILC) have more inflammatory CAF and less myofibroblastic CAF than invasive breast carcinoma of no special type (IBC-NST). The inventors demonstrated that CAF-S1 are among the cells that most frequently interact with ductal tumor cells via the CDH1 pathway through ITGB1, EGFR and IGF1R. The inventors demonstrated that CDH1 inactivation as well as ITGB 1 silencing prevents and reduces iCAF differentiation into ECM-myCAF after co-culture with tumor cells and restores CD8 attraction. Altogether, the present disclosure highlights the role of CDH1 pathway in cancer and the use of CDH1, ITGB1, EGFR and IGFIR antagonists in the treatment of fibrotic related diseases, particularly cancer and immunotherapy-resistant cancer. Thus, the present disclosure relates to CDH1 pathway inhibitor for use in the treatment of fibrotic related disease, particularly cancer and immunotherapy-resistant cancer.

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

This method for analyzing a 3-D image comprises the following steps: i) obtaining at least one 3-D image (2, 4, 6), ii) converting (10) the at least one 3-D image (2, 4, 6) into a 2-D summary image (8) through a projection operation comprising successive convolution operations performed along a depth direction of the 3-D image, and iii) classifying the 2-D summary image (8) by using at least one 2-D neural network (12).

IPC Classes  ?

• G06T 7/00 - Image analysis

Abstract

The present invention relates to an aqueous ophthalmic composition comprising spironolactone, cyclodextrin and trometamol, preferably for topical application to the human eye. The inventors advantageously dissolve spironolactone in HP-γ-cyclodextrin excipient at a concentration of 0.1%, a dose that proved effective in treating ocular surface defects. They also successfully demonstrate that spironolactone eyedrops were stable for up to 9 months at 4°C and dept its efficacy for at least 6 months and that the formulation was well-tolerated after multiple daily instillations over 7 days. Moreover, the inventors show that spironolactone eyedrops according to the invention accelerated rat corneal wound healing, reduced corneal edema and inflammation, enhanced epithelial integrity and improved nerve regeneration, suggesting restoration of corneal homeostasis. Hence, the present invention also relates to the use of aqueous ophthalmic composition for the treatment of eye diseases and conditions.

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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 27/02 - Ophthalmic agents
• A61P 27/04 - Artificial tearsIrrigation solutions
• A61K 9/08 - Solutions
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 47/69 - 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit

Abstract

The present invention concerns at least one modulator of the metabolism and/or mitochondrial activity, in particular at least one inhibitor of the OXPHOS mitochondrial electron transport chain and/or inhibitor of the MVA pathway, for use for the prevention and/or treatment of neurofibroma. Combination of such modulators, in particular of an inhibitor of the OXPHOS mitochondrial electron transport chain with an inhibitor of the MVA pathway, as well as pharmaceutical compositions comprising them are also contemplated.

IPC Classes  ?

• A61K 31/155 - Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (HN=C(OH)NH2), isothiourea (HN=C(SH)—NH2)
• A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
• A61K 31/40 - 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
• A61K 31/404 - Indoles, e.g. pindolol
• A61K 31/4418 - Non-condensed pyridinesHydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
• A61K 31/451 - Non-condensed piperidines, e.g. piperocaine having a carbocyclic ring directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• A61K 31/47 - QuinolinesIsoquinolines
• A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim
• A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to the field of the treatment and/or prevention of viral infection caused by SARS-CoV-2. The inventor found that N-(2(quinolyl)-valyl-O-methylaspartyl-(2,6-difluorophenoxy)methyl ketone was able to inhibit SARS-CoV-2 replication both in vitro and in vivo and that this inhibition was more important compared to the one obtained with the non-O-methylated form of this compound (quinolyl-valyl-aspartyl-[-2,6-difluorophenoxy]-methyl ketone). Thus the present invention concerns the N-(2(quinolyl)-valyl-O-methylaspartyl-(2,6-difluorophenoxy)methyl ketone or a pharmaceutically acceptable salt or solvate thereof for use in preventing and/or treating a viral infection caused by SARS-CoV-2. The present invention also concerns a pharmaceutical composition and a kit of parts comprising such a compound for the same use.

IPC Classes  ?

• A61K 38/05 - Dipeptides
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 31/14 - Antivirals for RNA viruses

Abstract

Using a Burkitt's lymphoma (BL) cell model, the present inventors have shown that it is possible to suppress the synthesis of c-Myc by using specific compounds that bind to MDM2. The present inventors have shown that under low-cell proliferation conditions, MDM2 binds to the 5' untranslated region (UTR) of the c-Myc mRNA and suppresses its synthesis in a p53-independent manner, but 5 that this interaction does not take place under under medium/high cell proliferation conditions due to a conformational change in MDM2. The inventors have shown that under such conditions, it is possible to use specific MDM2-binding agents that induce an allosteric transition of MDM2 to promote its ability to interact with c-Myc mRNA, thereby suppressing its expression. The present invention therefore pertains to an MDM2-binding agent for use in the treatment of a proliferative disorder, 10 wherein said agent restores the c-Myc binding conformation of MDM2 and wherein said proliferative disorder is a p53-mutated disorder.

IPC Classes  ?

• 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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/706 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to the treatment of ciliopathies and manifestations of ciliopathies, comprising the use of 2-(3-(3',4-difluoro-[1,1'-biphenyl]-3- ylcarboxamido)phenoxy)acetic acid (compound 1), or a pharmaceutically acceptable salt and/or solvate thereof.

IPC Classes  ?

• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

As epigenetic regulators of gene expression, circulating microRNAs (miRNAs) have been described in several bone diseases as potential prognostic markers. The aim of the inventors was to identify circulating miRNAs potentially associated with the severity of Osteogenesis Imperfecta (OI), in 3 steps. They have screened by RNA sequencing for the microRNAs (miRNAs) that were differentially expressed in sera of a small group of OI patients versus controls and then conducted a validation phase by RT-qPCR analysis of sera of a larger patient population. In the first phase of miROI, the inventors found 79 miRNAs that were significantly differentially expressed. They therefore selected 19 of them as the most relevant. In the second phase, the inventors were able to validate the significant overexpression of 8 miRNAs in the larger OI group (miR-106b-3p, miR-191-5p, miR-363-3p, miR-451a, miR-93-3p, miR-93-5p, let-7g-5p, miR-15b-5p). Finally, the inventors looked for a relationship between the level of variation of the validated miRNAs and the clinical characteristics of OI. The inventors found a significant difference in the expression of two microRNAs in those patients with Dentinogenesis Imperfecta. After reviewing the literature, the inventors found 6 of the 8 miRNAs already known to have a direct action on bone homeostasis. Furthermore, the use of a miRNA-gene interaction prediction model revealed a 100% probability of interaction between 2 of the 8 confirmed miRNAs and COL1A1 and/or COL1A2 (miR93 and miR-106b). This is the first study to establish the miRNA signature in OI, showing a significant modification of miRNAs expression potentially involved in the regulation of genes involved in the physiopathology of OI.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease

Abstract

The invention relates to a method for monitoring at least one substance which may be produced or consumed by at least one living entity, and to an assembly for implementing the method. The method comprises flowing liquid medium having a controlled concentration of a dissolved gas and a controlled flow rate to a culture system and taking at least one measurement within the culture system so as to determine the presence, concentration or amount of the at least one substance in the liquid medium in the culture system; and/or taking at least a first measurement upstream of the culture system and a second measurement downstream of the culture system, and determining a concentration or amount of the substance consumed or produced by the at least one living entity based on the difference between the second measurement and the first measurement.

IPC Classes  ?

• C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters

Abstract

Method for imaging vascular activity dynamically at a microscopic scale in a vascular network of a human or animal, the method including: (a) performing a temporal series of Ultrasound Localization Microscopy images of a region of the vascular network, to obtain values of a vascular dynamics parameter in an area of interest in the region, a recording period of the temporal series of ULM images corresponding to a dynamical event, due to a cause other than cardiac pulsatily, which activates the vascular network in the region; (b) computing, based on the values of the vascular dynamics parameter, a measure of an evolution of the vascular dynamics parameter in response to the dynamical event.

IPC Classes  ?

• A61B 8/08 - Clinical applications
• A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves
• A61B 8/04 - Measuring blood pressure
• A61B 8/06 - Measuring blood flow

Abstract

The present invention is defined by the claims. In particular, the present invention relates to the use of TCR-deficient CAR-Tregs in combination with anti-TCR complex monoclonal antibodies for inducing durable tolerance.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• C12N 9/22 - Ribonucleases
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

The present invention relates to anti-ACE2 peptidase domain single domain antibodies. Further, the present invention relates to anti-ACE2 single domain antibodies comprising the CDR regions of the present single domain antibodies, polypeptides comprising thereof such as multimers thereof, and fusion proteins comprising thereof, as well as pharmaceutical compositions comprising the single domain antibodies, the polypeptides comprising thereof such as the multimeric single domain antibodies thereof, or the fusion proteins comprising thereof, and their use for treating diseases caused by a virus having ACE2 as receptor.

IPC Classes  ?

• C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 11/00 - Drugs for disorders of the respiratory system

Abstract

The present invention relates to an ophthalmic composition, comprising a nonionic oil-in-water emulsion with: • an aqueous phase Aq, • a lipid phase L, in the form of droplets dispersed in the aqueous phase, • an interface between said lipid phase L and said aqueous phase Aq, and • a particulate surface-active agent for stabilizing the emulsion, located at the interface between the lipid phase and the aqueous phase, said surface-active agent comprising or consisting of organic particles with an average size of less than or equal to 1 μm, said composition being free of non-particulate surfactant, and advantageously free of preservative. These compositions are useful as a medicament, in particular for administration by ocular instillation. The invention also relates to a method for preparing said compositions.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/107 - Emulsions

Abstract

The present invention relates to compounds of formula (I) as deoxycytidine kinase inhibitors and pharmaceutical compositions comprising the same. The present invention further relates to the use of such compounds of formula (I) for use for treating a cancer.

IPC Classes  ?

• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• 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
• A61P 35/02 - Antineoplastic agents specific for leukemia
• C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 487/10 - Spiro-condensed systems

Abstract

At least one embodiment of an ultrasonic periodontal probe, the ultrasonic periodontal probe comprising a grip portion having a longitudinal axis, a support member comprising a part having a longitudinal axis different from the longitudinal axis of the grip portion, and an ultrasonic device fastened to the grip portion via the support member, wherein the ultrasonic device is configured for emitting ultrasound signals within at least two emitting cones and for receiving corresponding echoed ultrasound signals, the at least two emitting cones extending in opposite directions with regard to a plane comprising the longitudinal axis of the grip portion.

IPC Classes  ?

• A61B 8/12 - Diagnosis using ultrasonic, sonic or infrasonic waves in body cavities or body tracts, e.g. by using catheters
• A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves
• A61B 8/08 - Clinical applications
• A61B 8/14 - Echo-tomography
• A61C 19/04 - Measuring instruments specially adapted for dentistry

Abstract

The invention deals with the crucial issue of obtaining reliable measurement of the fetus's physiological values during labour. For this, the inventors has found that maintaining a good position of the probe during measurement is very important and has developed a specific contact surface for the probe with a principal portion surrounded by two lateral wings. This drastically improves the quality of the measurement, resulting in a better prevention of hypoxia.

IPC Classes  ?

• A61B 5/291 - Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
• A61B 5/369 - Electroencephalography [EEG]
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons

Abstract

The present invention relates to a method of predicting assessing or monitoring the sensitivity of a subject having a cancer to a combination therapy, preferably to a therapy combining an immunotherapeutic agent and an anti-angiogenic agent, and to corresponding kits and uses thereof. The method of predicting, assessing or monitoring the sensitivity of a subject having a cancer or malignant tumor to a proposed combination therapy typically comprises a step a) of determining, in a biological sample from said subject, the presence, absence or expression level or proportion of at least one biomarker, for example at least two biomarkers, and when the expression level or proportion is determined a step b) of comparing said expression level or proportion to reference expression level(s) or to reference expression ratio(s), thereby predicting, assessing or monitoring whether the subject having a tumor is responsive or resistant to the proposed combination therapy.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• 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

It was previously demonstrated that the RAC2 G12R mutation rapidly induced HSPCs cell death and hematopoiesis regulation. Now, the invention evaluated the impact of said mutation on three tumor cell lines: MDA-MB-231 (mammary gland adeno-carcinoma), HT29 (colorectal adenocarcinoma) and HepG2 (hepatocellular carcinoma). Briefly, cells were transduced with a lentiviral vector containing the green fluorescent protein (GFP) reporter cDNA (WPI) or a wild type form of RAC2 cDNA (WT) or a RAC2 mutated cDNA form (G12R). The inventors showed that the number of GFP+ cells is drastically lower in the G12R condition as compared to the WT and WPI conditions. The cell morphology and content are particularly disrupted. These observations were confirmed in a time-course proliferation assay performed on MDA-MB-231 and HT29 cell lines. Altogether, these data underlie the deleterious impact of the RAC2 G12R mutation on tumor cell lines proliferation.

IPC Classes  ?

• C12N 9/14 - Hydrolases (3.)
• A61K 38/00 - Medicinal preparations containing peptides
• C12N 15/86 - Viral vectors

Abstract

This invention relates to recombinant lentiviral vectors, compositions thereof, the use of the vectors or the compositions thereof, kits of parts comprising said vectors or compositions thereof and a catalytically active Cas9 or Cpf1 protein, methods for modifying the genome of a hematopoietic stem/progenitor cell (HSPC), and the HSPC obtainable by such methods.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 38/42 - HaemoglobinsMyoglobins
• C12N 5/074 - Adult stem cells
• C12N 9/22 - Ribonucleases

Abstract

The disclosure is related to a method of treating chronic kidney disease in a subject with a melanocortin-4 receptor (MC4R) agonist, e.g., a compound of any one of Formulas (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (X), or (XI), or a pharmaceutically acceptable salt thereof (e.g., as described herein).

IPC Classes  ?

• A61K 38/12 - Cyclic peptides
• A61P 3/04 - AnorexiantsAntiobesity agents
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys

Abstract

Using NLRP3-deficient U937 cells reconstituted with doxycycline-inducible NLRP3 variants in response to NLRP3 induction, the present inventors have developed a novel functional cell-based assay to screen for NLRP3 variants that uncouples NLRP3 induction, priming and activation. The inventors studied and characterized 38 NLRP3 variants by assessing pyroptosis and IL-1β/18 5 secretion in, priming and/or activation. The results were confirmed in primary monocytes from patients carrying different variants. The present invention pertains to a method for characterizing NLRP3 mutations that allows discriminating gain-of-function mutants from polymorphism without any impact on NLRP3 activity. The invention also relates to methods for the diagnosis of NLRP3- associated autoinflammatory diseases and for predicting a response to NLRP3 inhibitors based on 10 the detection of specific NLRP3 mutations in a sample obtained from a patient. The invention also relates to new NLRP3 inhibitors.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• 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
• G01N 33/564 - ImmunoassayBiospecific binding assayMaterials therefor for pre-existing immune complex or autoimmune disease

Abstract

The present patent application relates to the field of skin tissue engineering and aims to generate a reconstructed skin model. The present invention more particularly provides processes to create a three-dimensional construct possessing key features reminiscent of native skin tissue, including capillaries, skin appendages and immune cells. The present invention further relates to this three-dimensional skin construct, and applications thereof.

IPC Classes  ?

• C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues

Abstract

The present invention concerns a pharmaceutical composition for use in the prevention or treatment of cerebral cavernous malformations (CCM) comprising a transient receptor potential vanilloid 4 (TRPV4) inhibitor.

IPC Classes  ?

• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61P 43/00 - Drugs for specific purposes, not provided for in groups
• A61K 31/18 - Sulfonamides
• A61K 31/196 - Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Identification of small organic molecules capable of stimulating aerobic glycolysis and cone survival would lead to the conception of new therapies of the retinal degenerative diseases. Now the inventors identified Geralexin, an acetogenin, extracted from Uvaria chamae a medicinal plant and showed that the molecule can stimulate aerobic glycolysis and cone survival. Geralexin would be suitable for the treatment of retinal degenerative diseases in particular for Age-Related Macular Degeneration (AMD) by preventing cone outer segment shortening and maintaining central vision.

IPC Classes  ?

• C07D 405/04 - 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 directly linked by a ring-member-to-ring- member bond
• A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• A61K 36/185 - Magnoliopsida (dicotyledons)

Abstract

RNA interferent (RNAi) molecules that inhibit a PMP22 protein expression and/or activity by targeting exon 5 of a nucleic acid sequence encoding the PMP22 protein, and the prevention and treatment of the Charcot-Marie-Tooth type 1A or 1E diseases in which an adeno-associated virus (AAV) vector including an RNAi molecule is administered.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 25/02 - Drugs for disorders of the nervous system for peripheral neuropathies
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to a method for preparing insects or insect larvae rich in vitamin D, comprising raising insects or their larvae on an ergosterol-rich food substrate, for example fungi, in order to obtain ergosterol-rich insects or larvae and then exposing them to UV radiation. The present invention also relates to insects and insect larvae rich in vitamin D, and to compositions comprising same, in particular intended for human and/or animal food or for cosmetic use.

IPC Classes  ?

• A23K 10/30 - Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hayAnimal feeding-stuffs from material of fungal origin, e.g. mushrooms
• A01K 67/033 - Rearing or breeding invertebrates; New breeds of invertebrates
• A23K 50/90 - Feeding-stuffs specially adapted for particular animals for insects, e.g. bees or silkworms
• A23L 33/155 - Vitamins A or D

Abstract

The present invention relates to the use of KMT inhibitors and in particular of Suv39h1 inhibitors to increase immune response, and in particular immune cell mediated response, notably elicited by a vaccine or immunogenic composition.

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 35/00 - Antineoplastic agents

Abstract

The present disclosure relates to pyrazolo[1,5-a][1,3,5]triazine derivatives and uses thereof. In particular the present disclosure relates to compounds of formula (I) which are 2- substituted 8-halogeno-N4-(4-(pyridin-2-yl) benzyl) pyrazolo[1,5-a][1,3,5] triazine-2,4-diamine, pharmaceutical compositions comprising these compounds, the preparation of these compounds 5 and uses thereof, in particular as a molecular glue degrader.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention describes the identification of a soluble glomerular permeability factor, anti-Vasorin (or anti-VASN) autoantibodies synthesized by immune system cells, which opens up new perspectives for pathophysiological understanding, monitoring, and therapy of nephrotic syndrome. Clinical applications can include strategies for preventing the action of autoantibodies against said podocyte protein, inhibiting the production of antibodies against this protein, or eliminating these autoantibodies. Although the exact role of anti-VASN autoantibodies and VASN in nephrotic syndrome is still not well understood, the presence of circulating autoantibodies against VASN is highly specific to nephrotic syndrome. Up to now, no anti-VASN autoantibodies have been described in healthy individuals. Thus, the present invention relates to methods and kits for determining whether a subject has or is at risk of having a nephrotic syndrome associated with anti-VASN auto-antibodies or not.

IPC Classes  ?

• G01N 33/52 - Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper
• 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 disclosure relates to antibody-drug conjugates, wherein the drug is a pyrazolo[1,5-a][1,3,5]triazine derivative or a pyrazolo[1,5-a]pyrimidine derivative. In particular the drug can be a 2-substituted 8-halogeno-N4-(4-(pyridin-2-yl) benzyl) pyrazolo[1,5-a][1,3,5] triazine-2,4-diamine. Such antibody-drug conjugates are useful in particular in treating proliferative diseases including cancers.

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

Abstract

The Inventors hypothesized that the PIK3CA/AKT/mTOR pathway was abnormally affected in patients with HFMH. They identified a somatic gain-of-function mutation of PIK3CA in 5 pediatric patients with hemifacial myohyperplasia, a rare cause of facial asymmetry exclusively involving facial muscles. To understand the physiopathology of muscle hypertrophy, they created a mouse model carrying specifically a PIK3CA mutation in skeletal muscles. PIK3CA gain-of-function mutation led to striated muscle cell hypertrophy, mitochondria dysfunction and hypoglycemia with low circulating insulin levels. A PIK3CA inhibitor, namely Alpelisib, was able to prevent and to reduce muscle hypertrophy in the mouse model. They then concluded that PIK3CA is a relevant target to induce skeletal muscle hypertrophy. The present invention relates to a PIK3CA protein or fragment thereof and/or an agent for PIK3CA protein expression for use in promoting skeletal muscle hypertrophy in a subject in need thereof.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 38/45 - Transferases (2)
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines

Abstract

T-cell lymphomas are a heterogeneous group of malignancies involving T lymphocytes and generally characterized by a poor prognosis. Among them, cutaneous T-cell lymphomas involve primarily the skin. Mycosis fungoides and Sézary syndrome are the most frequent cutaneous T-cell lymphomas. Now the inventors showed the expression of CD38 by Sézary cells and in CD4+ blood cells of patients with Sezary syndrome. CD38 therefore appears as a useful diagnostic, prognostic and follow-up marker, and as a potential therapeutic target in T-cell lymphomas. Therapeutic depletion of CD38-expressing cancer cells would eliminate tumor cells.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• 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

There is an interest to develop anti-ROBO4 antibodies that can be suitable for the treatment of cancer. The inventors produced new human antibodies directed against ROBO4 were by a phage display strategy and the antibody selection was performed by using HEK and HEK stably expressing ROBO4 (HEK-ROBO4) cell lines. As a first step, a batch of 6 different antibodies named D3, H3, H9, E11, H11 and G12 was tested for their binding properties. The antibodies were then tested for their ability to inhibit the attachment of tumor cells to osteoblastic cells in monolayers. Finally the inventors showed that the anti-ROBO4 antibodies E11 and G12 inhibits significantly the formation of the tumor spheroid. The present invention thus relates to anti-ROBO4 human monoclonal antibodies and uses thereof for the treatment of cancer.

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

Abstract

in vitroin vitro method for predicting cognitive decline in a subject comprising the step of determining the level of at least one metabolite selected in the group consisting of 3-hydroxybutyrate, acetone, triglyceride 48:3, glucose, citrate, succinate, methionine, serine, sphingomyelin d18:1/C26:0 in a biological sample obtained from the subject.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• G01N 33/66 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood sugars, e.g. galactose
• 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 33/92 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving lipids, e.g. cholesterol

Abstract

in vitroin vitro method for sperm epigenome editing comprising the steps of: (i) obtaining a sample comprising sperm, (ii) permeabilizing at least one sperm from the sperm sample, (iii) exposing the at least one permeabilized sperm to the activity of at least one chromatin modifier, thereby obtaining at least one epigenetically modified sperm suitable for the generation of an embryo.

IPC Classes  ?

• C12N 5/076 - Sperm cellsSpermatogonia
• C12N 9/02 - Oxidoreductases (1.), e.g. luciferase
• C12N 9/22 - Ribonucleases
• C12N 9/48 - Hydrolases (3.) acting on peptide bonds, e.g. thromboplastin, leucine aminopeptidase (3.4)

Abstract

The present invention relates to the production of a valve leaflet implant and to the use thereof in the treatment of congenital heart disease, cardiac, venous and lymphatic valvulopathies, in particular the tetralogy of Fallot.

IPC Classes  ?

• A61F 2/24 - Heart valves
• A61L 27/36 - Materials for prostheses or for coating prostheses containing ingredients of undetermined constitution or reaction products thereof
• A61L 27/50 - Materials characterised by their function or physical properties

Abstract

jijij2n-11n1nn).

IPC Classes  ?

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

Abstract

This disclosure pertains to the field of tissue regeneration to repair damaged tissue and in particular brain tissue. The scaffold (1) of the present disclosure comprises a set of horizontal layers (11, 12, 13, 14), each layer extending in a horizontal plane orthogonal to the vertical direction (Z), each layer (11, 12, 13, 14) comprising a plurality of openings (15), each opening (15) of one layer (11, 12, 13, 14) being connected to one opening (15) of the directly adjacent layer (11, 12, 13, 14) by at least one first pillar (16) extending along the vertical direction (Z). Thus, the scaffold (1) of the present disclosure is designed to promote a cell growth radially along each layer (11, 12, 13, 14) to reconstruct the grey matter portion of the damaged area and the white matter along the vertical pillars (16) extending through the different layer (11, 12, 13, 14).

IPC Classes  ?

• A61F 2/02 - Prostheses implantable into the body
• A61L 27/18 - Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• A61L 27/22 - Polypeptides or derivatives thereof
• A61L 27/56 - Porous or cellular materials
• A61L 27/58 - Materials at least partially resorbable by the body
• B33Y 80/00 - Products made by additive manufacturing

Abstract

Pediatric liver cancers (PLC) are rare tumors. In particular, hepatoblastomas are usually treated with cisplatin-based neoadjuvant chemotherapy followed by surgical removal of the tumor and adjuvant chemotherapy. However, some hepatoblastomas develop resistance to chemotherapy during the initial neoadjuvant chemotherapy or after tumor recurrence, and the molecular determinants of cisplatin resistance are yet to be discovered. In contrast to hepatoblastomas, pediatric HCCs respond poorly to chemotherapy, and as in adults, they have a poor prognosis if not completely removed by surgery. There is thus an urgent need for new therapeutic strategies to overcome this resistance. Now the inventors demonstrate that Elimusertib and Cisplatin combination shows synergistic efficacy on tumor cell viability inhibition in pediatric liver cancer cell lines. The present invention thus relates to the combination of cisplatin and Elimusertib for the treatment of pediatric liver cancers.

IPC Classes  ?

• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 33/243 - PlatinumCompounds thereof
• A61P 35/00 - Antineoplastic agents

Abstract

Myocardial infarction (MI), the most prevalent manifestation of cardiovascular diseases, is associated with high mortality and morbidity. In particular, long term effects of ischemia-related cardiac damage continue to be a clinical and social burden, due to increased risk of arrhythmias, heart failure and repetitive hospitalizations. Therefore, there is a medical need for the development of therapeutic approaches targeting pathophysiological pathways involved in post-ischemic cardiac remodeling. Now, the inventors obtained several evidences confirming that NK cells promote deleterious post-ischemic cardiac remodeling. In particular, the inventors showed that i) NK cells are recruited in the ischemic heart tissue in mouse, ii) NK cells are detected in human ischemic heart tissue, and iii) NK deficiency protects against deleterious post-ischemic cardiac remodeling, and iiii) NK cell depletion using monoclonal antibody in mice protects against deleterious post-ischemic cardiac remodelling and consecutive ischemic heart failure.

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
• 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 9/04 - Inotropic agents, i.e. stimulants of cardiac contractionDrugs for heart failure

Abstract

Augmenting the portfolio of therapeutics for type 2-driven diseases is crucial to address unmet clinical needs and to design personalized treatment schemes. An attractive therapy for such diseases would consist in targeting the recruitment of T helper 2 (Th2) lymphocytes to inflammatory sites. In the present study, the Inventors unraveled the degradation of filamins (FLN) A and B by the ASB2α E3 ubiquitin ligase as a mechanism sustaining Th2 lymphocyte functions. They showed that low levels of FLNa and FLNb confer an elongated shape to Th2 lymphocytes associated with efficient αVβ3 integrin-dependent cell migration. Genes encoding the αVβ3 integrin and ASB2α belong to the core of Th2-specific genes. Using genetically modified mice and the small molecule thiostrepton, they found that increasing the levels of FLNa and FLNb in Th2 lymphocytes reduces airway inflammation. Collectively, their results highlight ASB2α and its substrates FLNa and FLNb to rewire Th2 lymphocyte mediated responses.

IPC Classes  ?

• A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
• A61P 11/06 - Antiasthmatics
• C12N 15/09 - Recombinant DNA-technology
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• A61K 38/00 - Medicinal preparations containing peptides
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C07K 7/50 - Cyclic peptides containing at least one abnormal peptide link
• C07K 14/36 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from ActinomycesPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Streptomyces (G)

Abstract

The present invention relates to the treatment of Tauopathies. In this study, the inventors worked on an optimized treatment of Tauopathies, including AD and primary Tauopathies. Previously, the inventors evidenced that Tau pathology is associated with deleterious T-cell-mediated processes that contribute to promote Tau-related detrimental neuroinflammation and cognitive deficits. Considering the unique capacity of immunosuppressive Tregs to inhibit both CD4+ and CD8+ T cell responses, the inventors raise the hypothesis that amplifying Tregs may allow controlling Tau-driven T-cell-mediated detrimental processes in the course of AD and other Tauopathies. They thus evaluated preclinically the impact on disease progression of an optimized IL-2-based Treg-targeting immunomodulatory treatment in the THY-Tau22 mouse model of Tauopathy. They chronically treated THY-Tau22 mice with an optimized IL-2-based treatment, i.e. complexes of IL-2 and anti-IL-2 antibodies (termed herein IL-2C) in order to modulate Tau-associated detrimental T cell responses. Their data supports that this treatment amplifies Tregs more efficiently and selectively than "regular" low dose IL-2 treatment. Furthermore, they hereby showed that IL-2C has a beneficial effect on cognitive deficits since treated THY-Tau22 mice tend to acquire and retain spatial information more potently than untreated littermates. Thus, the invention relates to an IL-2/anti-IL-2 complex (IL-2C) for use in the treatment of Tauopathies.

IPC Classes  ?

• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• A61K 38/20 - Interleukins
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• 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

Insults to vital organs have serious and even life-threatening consequences. Organ insults have different etiologies and typically include drugs, toxins and ischemic insults. Acyl-CoA binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular feedback regulator of autophagy. Here, the inventors report that injection of a monoclonal antibody neutralizing ACBP/DBI (α-DBI) protects the murine liver against ischemia/reperfusion damage, acute intoxication by acetaminophen and concanavalin A, as well as against liver fibrosis induced by bile duct ligation or carbon tetrachloride. Of note, the results support the contention that α-DBI mediates broad organ-protective effects against multiple insults. Thus, the present invention relates to methods and pharmaceutical composition of protecting organs from injuries comprising neutralization of Acyl-CoA Binding Protein.

IPC Classes  ?

• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Abstract

A medical device for the delivery of a therapeutic agent by bioprinting including a rod body including a bioprinting cartridge arranged near the distal end of the rod body including a top layer including a solution containing a therapeutic agent; and an absorbent compound capable of converting light energy from laser radiation into thermal energy and arranged to cause heating of the solution including a therapeutic agent to cause a jet of the solution; an optical fiber extending longitudinally within a lumen of the rod body to deliver laser flow onto the absorbing compound.

IPC Classes  ?

• A61M 25/00 - CathetersHollow probes

Abstract

The present invention relates to a method for the treatment of FGFR-related bone repair and bone formation and quality impairment. The inventors provide data confirming that abnormal activation of the FGFR3 signaling impairs the bone formation and repair process in HCH mandible characterized by the presence of pseudarthrosis in many calluses and bone structure similar to osteoporotic bones. Interestingly, the treatment with catechin partially restore the defective bone formation and repair. The present invention thus relates to a method for the treatment of FGFR-related bone repair and bone formation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of at least one catechin.

IPC Classes  ?

• A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease

Abstract

The present invention relates to a dialysate composition having a composition having a composition allowing for a balance with blood comprising mineral salts and a pH buffer, and comprising at least one iron oxide nanoparticle (Fe2+and/or Fe3+) coated with at least one polymeric compound.

IPC Classes  ?

• A61K 31/7024 - Esters of saccharides
• A61K 33/26 - IronCompounds thereof
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/51 - Nanocapsules
• A61P 7/08 - Plasma substitutesPerfusion solutionsDialytics or haemodialyticsDrugs for electrolytic or acid-base disorders, e.g. hypovolemic shock

Abstract

A method is disclosed for detecting if a subject is at risk of a fibroblast associated disease progression or for determining the clinical outcome of subjects suffering of such a disease, wherein the method comprises detecting SFRP1 positive, SFRP4 negative, FAP negative and RAMP1 negative fibroblasts (CXCL-iFibro) and, optionally, CD68 positive, CD206 positive and FOLR2 positive macrophages in a biological sample from said subject. The presence of CXCL-iFibro is indicative of disease progression and of a poor prognosis.

IPC Classes  ?

• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses

Abstract

(XRCC6, PRKCD, TEK,CLU)CLU) that predicted kidney survival better than histological-based classifications. Thus, the invention relates to a method for predicting the development of a kidney failure in a patient suffering from an ANCA-associated vasculitis-associated GN (AAV-GN).

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

The invention relates to a nucleic acid construct for gene therapy of FGF-23 related hypophosphatemic diseases, in particular gene therapy directed to muscle, liver or hematopoietic tissue, more particularly liver tissue. The invention relates also to a vector comprising the nucleic acid construct, and their use for the treatment of FGF-23 related hypophosphatemic diseases, in particular XLH, by 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
• A61K 38/18 - Growth factorsGrowth regulators
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• C12N 15/86 - Viral vectors

Abstract

The inventors provide strong evidence that FGFR3 gain of function mutation expressed in the brain induces cognitive and behavior deficit. To provide evidence that the constitutive activation of FGFR3 and its downstream signalling pathways are responsible for these behavioral impairments, the inventors treated the Fgfr3A385E/+ mice using subcutaneous injection of catechin isomers for at least seven days. In addition the inventors treated the Fgfr3N534K/+ mice with bottle treatments. The treatment rescues the anomalies in short-term learning and in coping strategy. The present invention thus relates to a method of treating a FGFR3-related cognitive deficit in a subject in need thereof comprising administering to the subject a therapeutically effective amount of at least one catechin.

IPC Classes  ?

• A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin

Abstract

Inventors have shown that salinomycin and its derivatives such as AM23, through lysosomal iron accumulation, reduced proliferation/survival of uveal melanoma cells harboring different genetic background. Accordingly, salinomycin and its derivates ironomycin represent valuable therapeutic strategies to treat melanoma and uveal melanoma. The present invention relates to a method for treating melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of an iron metabolism disruptor.

IPC Classes  ?

• A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

The invention relates to the detection of the risk for a patient with a congenital Long QT (LQT) condition for having a torsades-de-pointes event, and the mechanisms underlying such risk, in particular via the use of neural networks.

IPC Classes  ?

• A61B 5/346 - Analysis of electrocardiograms

Abstract

The invention relates to a nucleic acid sequence encoding a Cyclic GMP-AMP synthase (cGAS), a nanoparticle vector comprising it and uses thereof.

IPC Classes  ?

• C12N 9/12 - Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
• A61P 35/00 - Antineoplastic agents
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

A method for purifying a protein of interest includes the preparation of a fusion protein in which this protein of interest is fused to a protein tag having the protein Mmi1 of a microorganism of the genus Schizosaccharomyces or a fragment thereof, the bringing into contact of this fusion protein with a ribonucleic acid molecule containing at least one motif of UNAAAC nucleotide sequence, so as to allow the affinity binding of the protein tag with this ribonucleic acid molecule, and the recovery of the protein of interest.

IPC Classes  ?

• C07K 1/22 - Affinity chromatography or related techniques based upon selective absorption processes
• C07K 14/39 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from fungi from yeasts

Abstract

A mutated Bordetella strain comprising at least a mutated ptx gene, a deleted or mutated dnt gene and a heterologous ampG gene is provided. The attenuated mutated Bordetella strain can be used in an immunogenic composition or a vaccine for the treatment or prevention of a Bordetella infection. Use of the attenuated Bordetella strain for the manufacture of a vaccine or immunogenic composition, as well as methods for protecting mammals against infection by Bordetella are also provided.

IPC Classes  ?

• A61K 39/02 - Bacterial antigens
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 31/04 - Antibacterial agents
• C07K 14/235 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Bordetella (G)
• C12R 1/01 - Bacteria or actinomycetales

Abstract

The present invention relates to methods for predicting response to an immunotherapeutic treatment in a patient with a cancer.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• 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 use of a chimeric promoter having a promoter activity in AII amacrine cells. The present invention also relates to expression cassettes or vectors comprising said promoter operably linked to a coding sequence of interest as well as viral particles or host cells comprising said expression cassette or vector. The present invention also relates to the use of said expression cassettes, vectors, viral particles or cells in the treatment of ocular disease, in particular ocular disease associated with photoreceptor cell degeneration.

IPC Classes  ?

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