Abstract

The present invention relates to the treatment of the COVID-19, here, the inventors generated potent non-neutralizing pan-SARS-CoV-2 mAb, notably the antibody C10, targeting a conserved region of the virus. Noteworthy, C10 demonstrated remarkable efficacy in recognizing nearly all known variants of the virus and effectively binding infected cells. Leveraging this pan-SARS-CoV-2 mAb, they have engineered CAR-T cells capable of efficiently killing lung epithelial cells infected with the virus. Overall, their work identifies a pan-SARS-Cov-2 able to target bona fide infected cells and provides a proof-of-concept for the potential use of CAR-T cell therapy in combating SARS-CoV-2 infections. Their findings also highlight the potential of non-neutralizing mAbs in mediating immune protection against emerging infectious diseases. Thus, the present invention relates to anti-spike antibodies, particularly in a purified form or in an isolated form and their use to treat SARS-CoV-2. Particularly, the present invention is defined by the claims.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
• A61P 31/14 - Antivirals for RNA viruses
• A61K 40/31 - Chimeric antigen receptors [CAR]

Abstract

The present invention relates to a method of screening for a molecule mimicking interleukin 34 (IL-34) bone regulation activity based on the binding of IL-34 to bone morphogenetic proteins (BMPs), which comprises the steps of: 1) reacting a candidate molecule and BMPs under suitable conditions, 2) detecting the binding of the candidate molecule to BMPs and optionally a bone regulation activity, 3) comparing the binding and optionally the bone regulation activity detected in step 2) to a control, and 4) selecting a molecule capable of binding to BMPs and inducing osteoblast differentiation and activities without activating osteoclast functions. The present invention also relates to a molecule mimicking IL-34 bone regulation activity based on the binding of IL-34 to BMPs, obtained by the method, and to a pharmaceutical composition comprising the molecule and a pharmaceutically acceptable carrier.

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

Herein disclosed are compounds of formula (I), which are metabolized into, or act as, analogues of oncosterone (6-oxo-cholestan-3β,5α-diol), a metabolite produced by tumor cells overexpressing cholesterol-5,6-epoxide hydrolase (ChEH) and/or expressing 11β-hydroxysteroid dehydrogenase type 2 (HSD2) and the glucocorticoid receptor (GR), neutralizing the signaling pathway and tumorigenicity of oncosterone. The compounds of formula (I) herein disclosed are thus useful in preventing and/or treating cancers, in subjects, preferably humans, overexpressing cholesterol-5,6-epoxide hydrolase (ChEH) and/or expressing 11β-hydroxysteroid dehydrogenase type 2 (HSD2) and the glucocorticoid receptor (GR). In addition, being analogues of oncosterone, some of the compounds of formula (I) are also useful in the prevention and/or treatment of cancers expressing the glucocorticoid receptor (GR).

Abstract

uimxxS cc mm) at every point of spatial position (x, z); g) construction of an image from the dynamic confocal signals.

IPC Classes  ?

• G01S 7/52 - Details of systems according to groups , , of systems according to group
• G01N 29/44 - Processing the detected response signal
• G01S 15/89 - Sonar systems specially adapted for specific applications for mapping or imaging

Abstract

The present invention pertains to the provision of conjugates for the detection of target molecules by using mass spectrometry imaging. In particular, disclosed herein a particularly innovative conjugate for the detection of target molecules that is usable in the four following techniques of MSI: MALDI-MSI, DESI-MSI, nano-DESI- MSI and SpiderMass (MSI).

IPC Classes  ?

• G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
• C07D 403/00 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• G01N 33/53 - ImmunoassayBiospecific binding assayMaterials therefor

Abstract

The present invention relates to new specific 6-6 or 5-6 fused bicyclic compounds comprising pyrimidine or pyridine useful in the prevention and/or treatment of infectious diseases. In particular, the present invention relates to a compound of formula (I) wherein: Ar1 is a (C5-C11)arylene or (C5-C11)heteroarylene group, X is —CH—, —S—, —NR5 or —N—, Y is —CH—, —NR5—S— or —NR6—CH2—, T is —CH— and Q is —CH— or T is —N— and Q is —CR10— or —N—, provided that one or two of X, Q and Y comprise a heteroatom, and with the proviso that, at least one of R1, R2, and, if present, R5 or R6, contains a group —NH-Alk-NR3R4. The inventors showed that compounds of formula (I) present an activity against both W2 and 3D7 Plasmodium falciparum strains, an activity against T. brucei brucei but also an activity against SARS-CoV-2 virus, and that they are positive for G4 recognition. The invention also relates to the preparation process and to the therapeutic uses of the compounds of formula (I). The present invention relates to new specific 6-6 or 5-6 fused bicyclic compounds comprising pyrimidine or pyridine useful in the prevention and/or treatment of infectious diseases. In particular, the present invention relates to a compound of formula (I) wherein: Ar1 is a (C5-C11)arylene or (C5-C11)heteroarylene group, X is —CH—, —S—, —NR5 or —N—, Y is —CH—, —NR5—S— or —NR6—CH2—, T is —CH— and Q is —CH— or T is —N— and Q is —CR10— or —N—, provided that one or two of X, Q and Y comprise a heteroatom, and with the proviso that, at least one of R1, R2, and, if present, R5 or R6, contains a group —NH-Alk-NR3R4. The inventors showed that compounds of formula (I) present an activity against both W2 and 3D7 Plasmodium falciparum strains, an activity against T. brucei brucei but also an activity against SARS-CoV-2 virus, and that they are positive for G4 recognition. The invention also relates to the preparation process and to the therapeutic uses of the compounds of formula (I).

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/52 - Purines, e.g. adenine
• A61P 33/02 - Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• C07D 471/04 - Ortho-condensed systems
• C07D 473/00 - Heterocyclic compounds containing purine ring systems
• C07D 473/40 - Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
• C07D 487/04 - Ortho-condensed systems
• C07D 495/04 - Ortho-condensed systems

Abstract

The present invention provides a method for selecting a cancer patient for a cancer treatment or for predicting or monitoring the response of a cancer patient to a cancer treatment, comprising: determining the level of effector regulatory T cells in a biological sample from the patient, wherein said level of effector regulatory T cells correlates with the responsiveness of said patient to the cancer treatment.

IPC Classes  ?

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

Abstract

The present invention pertains to the provision of conjugates for the detection of target molecules using mass spectrometry imaging (MSI).

IPC Classes  ?

• G01N 33/53 - ImmunoassayBiospecific binding assayMaterials therefor
• G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
• C07D 403/00 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group
• 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

Despite the high prevalence and serious clinical implications of metabolic associated steatohepatitis (MASH) in patients with type 2 diabetes (T2D), MASH is usually overlooked in clinical practice, due to the lack of accurate biomarkers. The inventors evaluated the ability of plasma large extracellular vesicles (lEVs) to serve as noninvasive biomarkers for the diagnosis of MASH, in particular in T2D patients. Proteomic analysis identified Transferrinreceptor on lEVs (TFRC-lEVs) as associated with MASH. The inventors thus measured TFRC- lEVs on plasma samples from patients included in the derivation cohort. The proportion of patients with TFRC-lEVs concentration > 61 ng/mL was significantly higher in patients with MASH than in those with steatosis. TFRC-lEVs > 61 ng/mL remained associated with MASH after adjustment on either usual laboratory variables, or on the NASH-Test or on the Fibroscan FAST-score. When combining TFRC-lEVs with available methods the population suspected of having MASH was 32% and 29%, versus 22% and 16% for NASH-test or FAST score alone, without decreasing specificity. In conclusion, TFRC-lEVs, a marker of hepatocyte ballooning, is a promising biomarker for MASH. It could be used for patients' screening to enlarge recruitment of patients with MASH in clinical trials.

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 present invention relates to a composition comprising a probiotic composition comprising a Lactobacillus salivarius strain and a Lactobacillus gasseri strain. The invention further relates to the nutraceutical and therapeutical uses of such compositions in oxytocin-related neuropsychiatric disorders, in particular autism or anxiety related disorders selected from depression and eating disorders.

IPC Classes  ?

• A61K 35/747 - Lactobacilli, e.g. L. acidophilus or L. brevis
• A61K 35/745 - Bifidobacteria
• A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• A61P 25/22 - Anxiolytics
• A61P 25/24 - Antidepressants

Abstract

The present invention concerns new tricyclic spirolactams (TriSLas) compounds and their use as a drug, in particular for the prevention and/or treatment of a mycobacterial infection or for the treatment of a disease caused by infection with a Mycobacterium. The tuberculosis drug development pipeline requires further supplementation with additional candidates, ideally acting on novel targets (to minimize cross-resistance) and impacting on drug-tolerant bacilli to shorten treatment. The inventors of the present invention have identified new tricyclic spirolactams (TriSLas) compounds with particular activity against M. tuberculosis.

IPC Classes  ?

• C07D 498/20 - Spiro-condensed systems
• A61K 31/438 - 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 being spiro-condensed with carbocyclic or heterocyclic ring systems
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/4747 - QuinolinesIsoquinolines spiro-condensed
• A61K 31/537 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
• A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 31/06 - Antibacterial agents for tuberculosis
• C07D 498/10 - Spiro-condensed systems

Abstract

The present invention relates to the field of the treatment of cancer. In this study, the inventors found that VDAC2 is heterogeneously expressed in MM cells. VDAC2 protein expression correlated with BAK but not with BAX protein levels. Transient silencing of VDAC2, but not VDAC1 or VDAC3, sensitized MM cells to intrinsic mitochondrial apoptosis signals, alongside with the induction of pre-activated BAK and the increase of global, MCL1 and BCL2 mitochondrial priming. They also found a that a VDAC2 compound, efesevin recapitulated the sensitization effect of VDAC2 knock-down on BH3 mimetics apoptotic response. This novel VDAC2 modulator sensitized MM cells to BH3 mimetics targeting MCL1 (S63845) or BCL2 (Venetoclax) without modifying BAK or BAX protein expression. The efficiency of the VDAC2 modulator was directly correlated with the levels of VDAC2 protein. To better understand the VDAC2/BAK interplay, The inventors generated VDAC2 KO myeloma cells. VDAC2 KO cells exhibited an important decrease of BAK protein expression while BAX remained unchanged. Accordingly, VDAC2 KO cells completely lost their mitochondrial priming. Interestingly, they also found that BAK KO myeloma cells displayed decreased levels of VDAC2. The reciprocal regulation between VDAC2 and BAK was dependent on both the proteasome and lysosome degradation pathways. Thus, the present invention relates to a combination of a VDAC2 modulator and a BH3- mimetics compound for use in the treatment of a cancer in a subject in need thereof.

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention concerns the treatment of Fibrotic interstitial lung diseases (Fibrotic ILDs) and particularly Progressive pulmonary fibrosis (PPF) such as idiopathic lung fibrosis (IPF). In particular inventors develop antisense oligonucleotides targeting HSPB5 and study their effects on the development of experimental pulmonary fibrosis. Specific antisense oligonucleotides (ASO) were designed and screened in vitro, based on their ability to inhibit both human and murine HSPB5 expression. One of them, ASO22, was selected by its capacity to inhibit TGF-β1-induced expression of HSPB5 and additional key markers of fibrosis such as PAI-1, collagen, fibronectin and α-SMA in fibroblastic human CCD-19Lu cells as well as PAI- 1 and α-SMA in pulmonary epithelial A549 cells. Intra-tracheal or intravenous administration of ASO22 in bleomycin-induced pulmonary fibrotic mice decreased HSPB5 expression and reduced fibrosis as measured by the decrease in pulmonary remodeling, collagen accumulation and Acta2 and Col1a1 expression. Altogether, these results suggest a real interest of using an antisense oligonucleotide strategy targeting HSPB5 for the treatment of pulmonary fibrosis.

IPC Classes  ?

• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 43/00 - Drugs for specific purposes, not provided for in groups
• 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

Abstract

The present application relates to a method of treating a respiratory viral infection in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an agent that depletes plasmacytoid dendritic cells. Another object of the present application relates to a kit of part comprising said agent and at least one further therapeutic agent as a combined preparation for simultaneous, separate or sequential use in the treatment of a respiratory viral infection in a subject in need thereof.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

The present invention relates to the field of the measuring of temperature of an area inside an object. The gold standard to measure temperature changes during thermal therapies is magnetic resonance imaging but ultrasound scanners seem to be a good alternative because they are portable devices. Several methods have been developed to estimate temperature with ultrasound, by measuring thermal strain, or acoustic attenuation coefficient, or backscatter energy but methods used actually need to be optimized. That's why the inventors worked on a more sensitive method. Thus, the present invention relates to a method for measuring of temperature of an area inside an object implying several ultrasound echoes obtained at different times.

IPC Classes  ?

• A61B 8/08 - Clinical applications
• G01K 11/22 - Measuring temperature based on physical or chemical changes not covered by group , , , or using measurement of acoustic effects
• G01K 11/24 - Measuring temperature based on physical or chemical changes not covered by group , , , or using measurement of acoustic effects of the velocity of propagation of sound

Abstract

The invention relates to a device for trapping at least one cell pair in a solution containing at least one first cell (C1) of a first type and at least one second cell (C2) of a second type, comprising: —a microfluidic channel (3) adapted for a unidirectional flow (F) of the solution; —a first trap (1) comprising a pair of first fingers (10a, 10b) arranged in the microfluidic channel (3), at least one of said first fingers (10a, 10b) being coupled to a respective first actuator (11a, 11b), said first actuator being configured to adjust the first trap (1) along a direction transversal to the flow (F) between an open position allowing passage of the first cell between the first fingers (10a, 10b) and a closed position adapted to a size of the first cell to allow trapping the first cell between the first fingers (10a, 10b); 15—a second trap (2) comprising a pair of second fingers (20a, 20b) arranged in the microfluidic channel (3), at least one of said second fingers (20a, 20b) being coupled to a respective second actuator (21a, 21b), said second actuator being configured to adjust the second trap (2) along a direction transversal to the flow (F) between an open position allowing passage of the second cell between the second fingers (20a, 20b) and a closed position adapted to a size of the second cell to allow trapping the second cell between the second fingers (20a, 20b); wherein the first trap (1) is arranged relative to the second trap (2) so as to form, when the first and second traps are in the closed position, a cell pair comprising the trapped first and second cells such that the second cell is in physical or chemical interaction with the first cell.

IPC Classes  ?

• B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers

Abstract

A process for isolating or extracting rare cells from a biological sample including filtering a biological sample, which may be treated or diluted, through a filter that has a pore size, pore density or other physical properties that retain rare cells, but which permits other kinds of cells to pass through the filter.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• 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
• G01N 33/554 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals the carrier being a biological cell or cell fragment, e.g. bacteria, yeast cells

Abstract

The invention relates to the first hydrolase that specifically digests the archaeal type of a peptidoglycan (PG), the major component of the cell wall of methanogens, named Talosaminidase. The enzyme consists of a signal peptide, several bacterial IG domains, a glycosyl hydrolase, several archaeal PG binding domains and a peptidase domain. The double enzymatic activity for the glycosyl hydrolase and the peptidase maximizes the lysis of archaeal cells with a cell wall of the archaeal PG-type. Engineering the enzyme by removing the signal peptide and bacterial IG domains and keeping only the archaeal PG binding, glycosyl hydrolase and peptidase made the enzyme easier to express and purify, without negatively influencing the enzymatic activity. Therefore, engineered Talosaminidase can be used to regulate populations of archaeal methanogens in the industrial, agricultural and medical settings, and consequently methane production.

IPC Classes  ?

• C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
• A61K 38/00 - Medicinal preparations containing peptides
• A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• A61P 31/04 - Antibacterial agents
• C12N 9/50 - Proteinases
• C12N 9/52 - Proteinases derived from bacteria

Abstract

The present invention relates to a compound of formula (I) for its use in the production of interleukin-10 by immune cells. The invention also relates to induced immune cells capable of producing interleukin 10. The invention also relates to the use of the induced immune cells in the prevention and/or treatment of immune-mediated diseases.

IPC Classes  ?

• A61K 38/20 - Interleukins
• A61K 40/13 - B-cells
• C07D 235/18 - BenzimidazolesHydrogenated benzimidazoles with aryl radicals directly attached in position 2
• C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 471/04 - Ortho-condensed systems
• C07K 14/54 - Interleukins [IL]
• C12N 5/0781 - B cellsProgenitors thereof

Abstract

Inventors have shown evidence of VEGF accumulation in extracellular Aβ plaques in the post-mortem brain of patients with Alzheimer's disease (AD) and of the APP/PS1 mouse model of AD. They identified specific binding domains involved in the direct interaction between A0o and VEGF and engineered a peptide that blocks this interaction. The designed peptide binds to Aβ oligomers with high affinity and inhibits the process of Aβ self-aggregation, leading to the blockade of fibrillar aggregation. Furthermore, the peptide prevents soluble Aβ-derived toxins to target synapses in hippocampal neuron cultures and restores long-term potentiation in the hippocampus of the APP/PS1 mouse model of Alzheimer's disease. Thus, these findings have broad implications for preventing and treating diseases with Aβ neurotoxicity such as Alzheimer's disease. Accordingly, the invention relates to a peptide comprising the amino acid sequence KRKKSRYKSWSVYVG (SEQ ID NO: 1).

IPC Classes  ?

• C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The invention concerns a compound of formula (I) wherein R, R1and R2are independently selected form the group consisting of: a hydrogen atom, a halogen atom, an alkyl group, linear, cyclic or branched, saturated or unsaturated, possibly substituted, comprising from 1 to 10 carbon atoms, an acyl group comprising from 1 to 10 carbon atoms, a carboxyl group, an amido group comprising from 1 to 10 carbon atoms, and an imino group, possibly substituted by an alkyl group, linear, cyclic or branched, saturated or unsaturated, and wherein R3, R4, R5and R6 are independently selected form the group consisting of: a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, linear, cyclic or branched, saturated or unsaturated, possibly substituted, comprising from 1 to 10 carbon atoms, an alkoxy group comprising from 1 to 10 carbon atoms, an acyl group comprising from 1 to 10 carbon atoms, a carbonate group from 1 to 10 carbon atoms, a carboxyl group, and a cyano group, for use as neuroprotectants, or in the treatment of disorders with reduced NAD metabolism.

IPC Classes  ?

• A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
• A61P 3/04 - AnorexiantsAntiobesity agents
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular 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
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

Control tissues and different lesions of either adenomyosis or endometriosis were exposed in vitro during 24 hours either to vehicle (DMSO) or different doses of BYL719 or ST420, a PIK3CA inhibitor. Inventors observed that lesions treated with DMSO had a higher recruitment of the PIK3CA pathway compared to healthy endometrium. Importantly, both inhibitors were able to shut down the phosphorylation of AKT. They concluded that PIK3CA inhibition is a good therapeutic target for patients with endometriosis and adenomyosis. They also investigated the role of the PIK3CA pathway in myoma, another benign uterine condition. They observed that either alpelisib or ST420 were able to inhibit the pathway in myoma. They concluded that myoma demonstrate PIK3CA/AKT pathway activation with somatic mutation and are accessible to targeted treatment. Accordingly, the invention relates to method for treating uterine disease in a subject in need thereof comprising a step of administrating the subject with a therapeutically effective amount of PIK3CA inhibitor such as compound of formula (I), or a deuterated or tritiated form of the compound of formula (I), BYL719.

IPC Classes  ?

• 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 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 15/00 - Drugs for genital or sexual disordersContraceptives
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to the use of a Lesion Progression Probability Score (LPPS) for predicting the risk of progression of a tumor lesion in a subject suffering from lung cancer when treated by immunotherapy, wherein the tumor lesion comprises a core tumoral region and a peritumoral region referred to as a ring and the LPPS of each lesion comprises 6 specific radiomics features. The invention also relates to the use of a patient progression probability score (PPPS) for predicting the risk of disease progression in a subject suffering from lung cancer when treated by immunotherapy, wherein the PPPS combines the LPPS values of all analyzed tumor lesions of the subject with a volume equal to or higher than a minimum volume Vmin. The invention also relates to therapeutic uses of immunotherapy in subjects with lung cancer with a low or moderate predicted risk of disease progression using the PPPS.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• G06N 3/02 - Neural networks
• G06T 7/00 - Image analysis
• G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
• G16H 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
• 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 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients

Abstract

Translating bacterial-based therapies to clinical success has yet been proven challenging, facing targeting inconsistencies, formulation issues and immune system noncompliance that can lead up to sepsis. To counter these limitations, the invention provides the Smart Polymer Shield (SPS) for the encapsulation of individual live cells.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/107 - Emulsions
• A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
• A61P 35/00 - Antineoplastic agents

Abstract

The inventors have now succeeded in developing arylsulfonium salts, in particular triarylsulfonium salts and dibenzothiophenium salts and a new use of said arylsulfonium salts. These compounds have the advantage of having a thioaryl group as leaving group, which allows all side products to be separated from the radiolabelled product. Said compounds are therefore useful tools in a method for synthesizing iodo- or astatoarryl compounds, in particular radioiodo- or radioastatoaryl compounds. The present invention relates to a method for synthesizing iodo- or astatoaryl compounds comprising the reaction of an arylsulfonium compound with an iodide or astatide salt, respectively. The invention also relates to arylsulfonium compounds as such. The invention also concerns a method of synthesizing an iodo- or astatolabelled biomolecule and/or vector using said iodo- or astatoraryl compound.

IPC Classes  ?

• A61K 51/04 - Organic compounds
• C07B 59/00 - Introduction of isotopes of elements into organic compounds
• C07C 17/093 - Preparation of halogenated hydrocarbons by replacement by halogens
• C07C 45/63 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by introduction of halogenPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by substitution of halogen atoms by other halogen atoms
• C07C 201/12 - Preparation of nitro compounds by reactions not involving the formation of nitro groups
• C07C 247/06 - Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being saturated and containing rings
• C07C 253/30 - Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
• C07C 381/12 - Sulfonium compounds
• C07D 213/61 - Halogen atoms or nitro radicals
• C07D 333/76 - Dibenzothiophenes
• C07D 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond

Abstract

The present invention relates to compositions, and in particular to pharmaceutical compositions, comprising, or even consisting of, a suspension of bacteriophages of the class Caudoviricetes, the bacteriophages having lytic activity against at least one Gram-positive bacterial strain, at a titer of at least 108 PFU/mL, in a dispersing medium comprising, or even consisting of: - at least one non-ionic surfactant, and in particular a single non-ionic surfactant, selected from the polysorbate family, at a molar concentration greater than its critical micelle concentration, but not exceeding 2 mg/mL, and/or the poloxamer family, at a concentration ranging from 0.005% (w/v) to 30% (w/v); - one or more neutral salts formed from a pair of monovalent ions, the total molar concentration of which is in the range from 75 to 160 mM; - a buffer mixture imparting to the composition a pH from 6.0 to 7.9, and preferentially from 7.0 to 7.5, typically selected from hydrogen phosphate ion/dihydrogen phosphate, citric acid/citrate ion and citric acid/hydrogen phosphate ion ion pairs, wherein the molarity of the buffer mixture is in the range from 4 mM to 100 mM; - water, wherein the composition comprises less than 0.9 bacterial endotoxin units per mL and a total protein concentration of less than 0.09 mg/mL, and wherein the bacteriophage suspension in the dispersing medium has an osmolality of between 150 mOsm/kg and 600 mOsm/kg; the invention also relates to associated methods and uses.

IPC Classes  ?

• A61K 35/76 - VirusesSubviral particlesBacteriophages
• A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• A61M 3/00 - Medical syringes, e.g. enemataIrrigators
• A61P 31/04 - Antibacterial agents
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof

Abstract

HDACs are undoubtedly the most extensively studied epigenetic enzymes, and numerous inhibitors have been developed. However, the results of clinical trials with HDAC inhibitors in various cancers remain rather mitigated. To better understand the role of HDACs in melanoma, the inventors analysed the correlation between HDAC expression and patient survival in the TCGA cohort. In particular, the present invention relates to a method for treating melanoma in a subject in need thereof comprising administrating to the subject a therapeutically effective amount of an inhibitor of HDAC4.

IPC Classes  ?

• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/4704 - 2-Quinolinones, e.g. carbostyril
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention is in the field of cancer treatment. It relates to the use of a liver metastasis-specific radiomics-based signature for predicting in a subject suffering from a metastatic cancer with liver metastasis: (a) survival if treated by immunotherapy without preliminary liver focal radiotherapy, (b) response to immunotherapy without preliminary liver focal radiotherapy, (c) survival if treated by liver focal radiotherapy followed by immunotherapy, (d) response to liver focal radiotherapy followed by immunotherapy, or (e) any combination of (a) to (d). It further relates to a method for predicting any one of (a) to (e) based on the same liver metastasis-specific radiomics-based signature, as well as specific therapeutic uses of immunotherapy, with or without previous liver focal radiotherapy, in metastatic cancer subjects with liver metastasis, the selection of the specific treatment being made depending on the same liver metastasis-specific radiomics-based signature.

IPC Classes  ?

• G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
• G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
• G06F 18/00 - Pattern recognition
• G06T 7/00 - Image analysis
• G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
• 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 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• A61B 5/06 - Devices, other than using radiation, for detecting or locating foreign bodies
• A61B 6/03 - Computed tomography [CT]
• A61B 6/00 - Apparatus or devices for radiation diagnosisApparatus or devices for radiation diagnosis combined with radiation therapy equipment

Abstract

T-cell acute lymphoblastic leukemias (T-ALL) are aggressive hematological malignancies associated with poor clinical outcome. TP53 alterations (TP53Alt) were rarely identified in T-ALL at diagnosis and their prognostic impact remains unclear. In a cohort of 476 adults and pediatric T-ALL, TP53Alt were observed in 4% of cases and were associated with chemoresistance and poor prognosis. APR-246, a small compound which restores wild-type configuration to mutated p53, showed efficacy in T-ALL harboring TP53 mutations. More importantly, in TP53 germline T-ALL, Notch 1 pathway gain of function mutations were associated with substantial sensitivity to APR-246. Mechanistically, Notch 1 activation via p53 downregulation and subsequent ferroptosis induction led to preferential APR-246 sensitivity. Given that Notch 1 pathway oncogenic activation is present in more than 70% of T-ALLs, these observations pave the way for promising perspectives in T-ALL treatment which could benefit from the Achilles heel associated with Notch 1 activation sensitizing leukemia cells to APR-246-induced ferroptosis, thus extending the use of APR-246 in T-ALL beyond TP53 alterations.

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 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
• A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
• A61P 35/02 - Antineoplastic agents specific for leukemia
• 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 invention relates to chemically modified adeno-associated (AAV) viruses and their use in gene therapy.

IPC Classes  ?

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

Abstract

The invention is based on the discovery of a novel compound with analgesic properties which could be used as a new tool for the treatment of pain disorders such as visceral pain. Thus, the invention relates to novel lipopeptide compound, derived from gamma-aminobutyric acid. The invention also relates to a lipopeptide compound according to the invention for the treatment of treating pain disorder, such as somatic pain and visceral pain.

IPC Classes  ?

• A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

Hypomelanosis of Ito is a clinical term for patients with mosaic syndromes characterized by skin hypopigmentation and developmental disorders. The genetic causes of these rare diseases remain largely unclear. Here, we report that GNA13 is a new gene that causes Hypomelanosis of Ito. We identified an identical mutation in this gene in four unrelated patients exhibiting pigmentary mosaicism. In depth functional investigations revealed that this is an activatory mutation that alters the cytoskeleton and morphology of melanocytes via a hyperactivation of the RHOA/ROCK signalling pathway. Our results also indicate that this pathology does not necessarily originate from a decreased production of melanin, but can originate from a defect in melanosome transfer to keratinocytes due to cell shape alterations. Thus, our findings suggest for the first time a mechanism by which the clinical symptoms of patients with Hypomelanosis of Ito appear, and pave the path for new therapeutic approaches. Altogether, the present invention relates to a method for treating a patient suffering from hypomelanosis of Ito by administering a ROCK inhibitor and/or RHOA inhibitor.

IPC Classes  ?

• A61K 31/015 - Hydrocarbons carbocyclic
• A61K 31/38 - Heterocyclic compounds having sulfur as a ring hetero atom
• A61K 31/415 - 1,2-Diazoles
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 31/4409 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
• 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 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61P 17/00 - Drugs for dermatological disorders

Abstract

Hepcidin is an hyposideremic hormone made primarily by the liver. To address the role of hepcidin made specifically by the intestine in lowering serum iron, the inventors generated transgenic mice overexpressing the peptide specifically in this tissue. These mice exhibit, at one month of age, a severe hyposideremia, along with decreased haematological indices and hair loss. Mechanistically, they showed that intestinal hepcidin made by the transgenic mice had no effect on intestinal ferroportin, but, in contrast, induced a striking down-regulation of Divalent Metal Transporter 1 (DMT1) protein at the apical side of the enterocyte. Intestinal hepcidin can be produced in the apical side suggesting the direct role of apical hepcidin on DMT1. To confirm the therapeutic capacity of hepcidin on regulation of DMT1, the inventors developed probiotics (engineered recombinant lactic acid bacteria), capable of delivering hepcidin directly into the lumen of the intestine. They orally administrated daily these probiotics in hemochromatosis mice model, after 28 days of treatments they observe a decrease of iron overload. Thus, the present invention relates to a method for preventing or treating an iron overload associated disease in a subject in need thereof, comprising administering locally in the gut of the subject hepcidin.

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 3/00 - Drugs for disorders of the metabolism
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61K 35/747 - Lactobacilli, e.g. L. acidophilus or L. brevis
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

in vivoin vivo, showing that Tgfbi can indeed regulate cachexia-associated cytokine production via macrophage integrin signaling. Thus, the present invention relates to an anti-TGFBI antibody and uses thereof.

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 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

The present disclosure relates to a method of treating a cholangiocarcinoma in a human subject in need thereof, comprising administering a therapeutically effective amount of an anti-Claudin-1 antibody to the human subject.

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 31/7068 - 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 containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• A61K 33/243 - PlatinumCompounds thereof
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• A61P 35/04 - Antineoplastic agents specific for metastasis

Abstract

Aortic valve stenosis (AS), is the most frequent valvular heart disease in Europe and affects more than 1 in 4 people over 65 years old. AS progression from fibrotic thickening to valvular leaflets calcification leads to heart failure development and eventually to death within 2 to 5 years after symptoms occurrence. The inventors now show that endothelin receptor type B (ETB) activation with an agonist decreased the calcium content of VIC. Therefore, the present invention relates to the use of endothelin receptor type B (ETB) agonists for the treatment of aortic valve stenosis.

IPC Classes  ?

• A61K 38/22 - Hormones
• A61F 2/24 - Heart valves

Abstract

The present invention relates to serotonin derivatives of general formula (I), and their use in the pharmaceutical field, in particular for preventing or treating metalloptosis associated disorders. The invention also relates to new serotonin derivatives of general formula (I) and their use for preventing or treating iron- and/or copper-associated disorders.

IPC Classes  ?

• A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
• 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
• C07D 209/16 - Tryptamines
• C07D 209/30 - IndolesHydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
• C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 405/14 - 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 three or more hetero rings

Abstract

The present invention concerns monocytes that over-express the cyclin-dependent kinase inhibitor p21 protein and therapeutic compositions comprising thereof, and in particular their use in the treatment of a mammal suffering from a solid cancer, preferably chosen from cancers resistant to radiation therapy and cancers sensitive to radiation therapy.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to a method for generating T cell progenitors from pluripotent stem cells, and to the therapeutic use of the generated T cell progenitors.

IPC Classes  ?

• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C12N 5/0789 - Stem cellsMultipotent progenitor cells

Abstract

ortho44 solution or human and rat microsomes. The present invention relates to astatoaryl compounds, a method for synthesizing astatoaryl compounds comprising the reaction of an aryl compound carrying a leaving group with astatine. The invention also concerns a method of synthesizing an astatolabelled biomolecule and/or vector using said astatoraryl compound.

IPC Classes  ?

• C07B 59/00 - Introduction of isotopes of elements into organic compounds
• C07F 13/00 - Compounds containing elements of Groups 7 or 17 of the Periodic Table
• A61P 35/00 - Antineoplastic agents
• C07C 29/147 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen-containing functional group of C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
• C07C 29/62 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogenPreparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by substitution of halogen atoms by other halogen atoms
• C07C 33/46 - Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic part
• C07C 41/30 - Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
• C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
• C07C 51/16 - Preparation of carboxylic acids or their salts, halides, or anhydrides by oxidation
• C07C 67/08 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
• C07C 231/02 - Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• C07C 231/12 - Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
• C07C 309/30 - Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings of six-membered aromatic rings substituted by alkyl groups
• C07C 63/70 - Monocarboxylic acids
• C07C 63/68 - Compounds having carboxyl groups bound to carbon atoms of six-membered aromatic rings containing halogen
• C07C 69/76 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a six-membered aromatic ring
• C07C 69/157 - Acetic acid esters of monohydroxylic compounds of unsaturated alcohols containing six-membered aromatic rings
• C07C 69/68 - Lactic acid esters
• C07C 69/63 - Halogen-containing esters of saturated acids
• C07C 233/65 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals

Abstract

The present disclosure pertains to a combination of specific benzene sulfonamide thiazole compounds with an anticancer treatment for use in the treatment of cancer in a patient in need thereof. Using several cancer cell models, the present inventors have shown that a combined therapy using specific benzene sulfonamide thiazole compounds and an anticancer treatment such as an 5 immunotherapeutic agent, a chemotherapeutic agent or targeted therapies allows specifically triggering immune cell death markers, thereby potentializing the effects of each compound alone.

IPC Classes  ?

• A61K 31/428 - Thiazoles condensed with carbocyclic rings
• A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
• A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
• 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 33/00 - Antiparasitic agents

Abstract

The present invention relates to GLP-1 receptor agonist compounds having an additional agonist activity over the GIP receptor and/or an agonist activity over the glucagon receptor and/or an antagonist activity over the GIP receptor for use in the treatment of joint diseases and/or joint pain and selected from the group comprising retatrutide, tirzepatide, orforglipron, mazdutide, efinopegdutide, froniglutide, maridebart cafraglutide, survodutide, efpeglenatide, ecnoglutide, efocipegtrutide and UBT251. The invention also relates to a pharmaceutical composition comprising at least one of the above mentioned GLP-1 receptor agonist compound, and a pharmaceutically acceptable excipient, for use in the treatment of joint diseases and/or joint pain.

IPC Classes  ?

• A61K 38/26 - Glucagons
• A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

Here, the inventors have developed a spectral flow cytometry assay to measure heme biosynthesis. By using this new assay on melanoma cell lines, they observed a direct correlation between high PPIX levels in differentiated MITFhighcells and a protection against ferroptosis. Conversely, cell lines with low PPIX levels were associated with a dedifferentiated MITFlow phenotype enriched in stem cell markers and more sensitive to ferroptosis inducers. They also found that inhibition of PPIX biosynthesis in differentiated melanoma cells synergizes with iron overload to induce lipid peroxidation and tumor cell death. Finally, they show that decreased levels of PPIX linked to increased ferroptosis sensitivity can be acquired in vivo in melanoma tumors that relapse after anti-MAPK targeted therapies. The present invention relates to a method of determining whether a subject has or is at risk of having melanoma ferroptosis sensitivity and targeted therapy resistance comprising i) determining the level of protoporphyrin IX (PPIX) in a biological sample obtained from the subject and ii) comparing the level determined at step i) with a predetermined reference value: wherein if the level of the PPIX determined at step (i) is lower than the predetermined reference value is indicative that the said patient is having melanoma ferroptosis sensitivity and targeted therapy resistance or wherein if the level of the PPIX determined at step (i) is higher than the predetermined reference value is indicative that the said patient is having melanoma ferroptosis resistance and targeted therapy sensitivity. The present invention also relates to a method for treating resistant melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of a ferroptosis inducer.

IPC Classes  ?

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

Abstract

The present invention relates to combination of (i) a methionine-depleting composition, of (ii) one or more methionine synthase inhibitors and of (iii) optionally one or more further agent selected from a chemotherapeutic agent, a radiotherapeutic agent or an immunotherapeutic agent against cancer, for its use for treating a cancer, especially in cancers involving the presence of methionine-independent cancer cells

IPC Classes  ?

• A61K 38/51 - Lyases (4)
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• 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 35/00 - Antineoplastic agents
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The present invention relates to FGF10 for use in the treatment of heart diseases.

IPC Classes  ?

• A61K 38/18 - Growth factorsGrowth regulators
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A01K 67/0275 - Genetically modified vertebrates, e.g. transgenic
• C12N 15/86 - Viral vectors

Abstract

Myotonic Dystrophy type 1 (DM1) is an inherited disease characterized by multi-systemic symptoms, particularly in skeletal muscles (progressive weakness and atrophy, myotonia). The inventors screened 7 500 bioactive compounds for their ability to improve the myogenic fusion and reduce the molecular hallmarks of DM1 skeletal muscle cells. The inventors found that five compounds, all inhibiting HDAC6, a cytoplasmic histone deacetylase, were effective at the micromolar range in normalizing the myogenic fusion, reducing the number of nuclear foci of mutant DMPK mRNA, decreasing the expression level of DMPK mRNA, restoring the splicing of several genes, and increasing the acetylation of SMAD3, a transcription factor involved in muscle development. The effects of HDAC6 inhibitors were observed both in immortalized and hiPSC-derived skeletal muscle cells from DM1 patients, and in different stages of differentiation. Thus, the present invention relates to the use of selective HDAC6 inhibitors for the treatment of DM1.

IPC Classes  ?

• A61K 31/17 - Amides, e.g. hydroxamic acids having the group N—C(O)—N or N—C(S)—N, e.g. urea, thiourea, carmustine
• A61K 31/42 - Oxazoles
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

aaaaaaa filtered images.

IPC Classes  ?

• A61B 8/08 - Clinical applications
• G01S 15/89 - Sonar systems specially adapted for specific applications for mapping or imaging
• A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves

Abstract

Circadian rhythms control the diurnal nature of many physiological, metabolic and immune processes. The inventors hypothesized that age-related impairments in circadian rhythms are associated with high susceptibility to bacterial respiratory tract infections. The diurnal control of Streptococcus pneumoniae infection is impaired in elderly mice. A lung circadian transcriptome analysis revealed that aging alters the daily oscillations in the expression of a specific set of genes and that some pathways that are rhythmic in young-adult mice are nonrhythmic or time-shifted in elderly mice. In particular, the circadian expression of the clock components Rev-erb-α, and Rev-erb-β to a lesser extent, altogether with apelin/apelin receptor were altered in elderly mice compared to young mice. In young mice, the inventors discovered that novel interaction between Rev-erb and the apelinergic axis controls host defenses against S. pneumoniae via alveolar macrophages. Pharmacological repression of Rev-erb-α and/or Rev- erb-β in elderly mice resulted in greater resistance to pneumococcal infection. Thus, the present invention relates to the use of Rev-erb antagonists for the treatment of lung infections.

IPC Classes  ?

• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• A61P 31/04 - Antibacterial agents
• A61P 31/10 - Antimycotics
• A61P 31/12 - Antivirals

Abstract

The present invention relates to the field of treat age-related cognitive declines. In this study, the inventors report that GPR158, which localizes at the PC, is required for OCN- dependent autophagy induction in hippocampal neurons. Consistently, the mobilization of key autophagy players by OCN in hippocampal neurons requires core PC-proteins. In aged hippocampi, neuronal PC present an abnormal morphology, correlated with a reduction of the major core ciliary proteins levels. Conversely, restoration of their levels in aged hippocampi is sufficient to improve autophagy and cognitive deficits. Lastly, they show that core PC-proteins are required to integrate the rejuvenating effects of OCN in the hippocampus, thereby ameliorating age-related cognitive deficits. Altogether, these findings demonstrate a new paradigm for the neuron/systemic milieu communication and significantly advance our understanding of the regulatory mechanism mediating the rejuvenating effects of the pro-youth blood factor, OCN, in hippocampal neurons. This study also provides the foundation for novel therapeutic strategies to treat age-related cognitive decline, as well as neurological deficits in ciliopathies. Thus, the present invention relates to an activator of the primary cilia (PC) for use in the restoration and/or improvement of cognitive functions 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 31/365 - Lactones
• A61P 25/00 - Drugs for disorders of the nervous system
• C07K 14/46 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals

Abstract

The present application relates to peptides derived from the transmembrane domain of Plexin-A1 that inhibits Neu-ropilin-1/Plexin-A1 heterodimerization. These peptides neutralize the inhibitory effect of Sema3A on cell migration and angiogenesis, and may be useful for the treatment of diseases associated with Sema3A and/or Neuropilin-1/Plexin-A1 activity, such as demyelinating diseases and diseases associated with abnormal angiogenesis such as cancer.

IPC Classes  ?

• C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The device comprises a substrate comprising a first zone (1) on which is absorbed a protein capable of binding to a first membrane molecule and comprising a second zone (2), on which an antibody is absorbed, targeting a second membrane molecule, the first zone and the second zone extending together in length over a dimension comparable to the length of a cell.

IPC Classes  ?

• G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
• 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 invention relates to a topcially-acting pain-relief pharmaceutical composition for topical use, comprising, as an active ingredient, one or more natural or synthetic peptides from the ω-conotoxin family, or one or more functionally active natural or synthetic variants thereof, the composition being intended for use in a method for treating acute or chronic nociceptive, neuropathic or nociplastic pain, such as intense chronic inflammatory and neuropathic pain, and being characterised in that it is administered locally, via the skin, close to and at the site of the free endings in the skin of the nociceptors that innervate the skin.

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 9/00 - Medicinal preparations characterised by special physical form
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]

Abstract

Here, the inventors use genomics to discover a new family of lanthipeptides from Actinobacteria dedicated to anti-phage defense. They demonstrate that a specific family of metabolic pathways that produce unknown class I lanthipeptides are encoded near known anti-phage defense systems or within mobile genetic elements, indicating their anti-phage function. Furthermore, the inventors show that the heterologous expression of these pathways in Streptomyces albus (a model strain of Actinobacteria) confers anti-phage defense. The experimental results show that different lanthipeptides of this family confer a selective protection against phages, without compromising the cell viability. The inventors also have identified a specific regulatory system that controls the expression of "defensive lanthipeptides" in Actinobacteria and use this to demonstrate their anti-phage function in a native strain. Finally, the inventors explore the anti-phage mechanism of action of these compounds. Thus the present invention relates to a new class of anti-phage natural peptides.

IPC Classes  ?

• C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
• C07K 7/54 - Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring

Abstract

Glycated Hb was measured in reticulocytes (RNA-positive cells) and was correlated to a decrease in RNA fluorescence intensity in a Log-linear dependent manner, with no statistically significant differences in slope or in the ordinate of the origin between individuals. The loss of RNA fluorescence intensity in reticulocytes observed by flow cytometry is directly related to the time they spend in circulation and consequently to their lifespan. By setting the time that reticulocytes spend to mature in the blood circulation and because the relation between the decrease in log RNA fluorescence intensity and the increase in log HbA1c fluorescence intensity is linear, the inventors are able to calculate the increase in HbA1c fluorescence intensity depending on the time and thus to determine the mean half-life of a RBC population. This new tool is noninvasive and requires only one single time point measurement. The present invention relates to a method for in vitro determination of the age of red blood cells of a set of red blood cells by using intracellular glycated hemoglobin measurement by flow cytometry and by using a standard curve generated from glycated hemoglobin measurement in reticulocyes.

IPC Classes  ?

• G01N 33/72 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood pigments, e.g. hemoglobin, bilirubin
• G01N 33/80 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood groups or blood types

Abstract

The present invention provides fusion molecules comprising the extracellular domain of CSF-1R which contains a specific single amino acid mutation. Such fusion molecules are capable of efficiently binding both CSF-1 and IL-34. The present invention also provides the use of such fusion molecules, or pharmaceutical compositions thereof, as therapeutic agents, in particular in the treatment of cancers, neurodegenerative diseases, autoimmune diseases, and allergic diseases, or in the prevention or inhibition of transplant rejection.

IPC Classes  ?

• C07K 14/715 - ReceptorsCell surface antigensCell surface determinants for cytokinesReceptorsCell surface antigensCell surface determinants for lymphokinesReceptorsCell surface antigensCell surface determinants for interferons
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

The invention relates to the field of Bipolar Disorder. In a recent study, the inventors performed the first genome-wide analysis of DNA methylation profiles among individuals with BD type I assessed for their response to long-term treatment with Li and identified differentially methylated regions (DMRs) between GR and NR, selecting only methylation differences that were not impacted by co-prescribed treatments that are -by definition- more frequent in NR (Marie-Claire et al., 2020). They then used MS-HRM to validate 3 DMRs that discriminated GR from NR in an extended sample of 70 individuals with BD-I. They also showed, in an independent sample that combining a few clinical variables with the three DMRs improved the performance of these MS-HRM-based biomarkers to discriminate groups (Marie-Claire et al., 2023). In the present study, they improved the performance of the combination of MS-HRM- based biomarkers and clinical predictors to discriminate individuals that benefited from Li treatment (GR and PaR) from those who did not (NR) in a retrospective sample. Thus, the present invention relates to a method for predicting whether a patient achieves a response with a treatment of Bipolar Disorder (BD) comprising determining, in a biological sample from the patient the epigenetic profile of at least 4 of the differentially methylated regions (DMRs) selected in the list consisting of DMR7291, DMR17107, DMR17978, DMR24332, DMR63769, DMR79888, DMR106540 and DMR81023.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• 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 present invention relates to a newly identified skin-tropic subset of Tscm that expresses the cutaneous homing marker CLA+. The identification of this new cell population of skin homing Tscm opens up new cell therapy strategies to treat cutaneous diseases, in particular cutaneous cancers such as Merkel cell carcinoma.

IPC Classes  ?

• C12N 5/078 - Cells from blood or from the immune system

Abstract

It is disclosed a method processing imaging data of a patient having cancer, for instance lymphoma, comprising:—Providing three-dimensional imaging data of the patient,—computing from said three-dimensional imaging data, at least one two-dimensional Maximum Intensity Projection image. corresponding to the projection of the maximum intensity of the three-dimensional imaging data along one direction onto one plane,—extracting a mask of the MIP image corresponding to cancerous lesions by application of a trained model. Using the extracted mask it is possible to compute one or more cancer prognosis indicators.

IPC Classes  ?

• G06T 7/00 - Image analysis
• G06N 3/0455 - Auto-encoder networksEncoder-decoder networks
• G06N 3/0464 - Convolutional networks [CNN, ConvNet]
• G06T 3/06 - Topological mapping of higher dimensional structures onto lower dimensional surfaces
• G06V 10/75 - Organisation of the matching processes, e.g. simultaneous or sequential comparisons of image or video featuresCoarse-fine approaches, e.g. multi-scale approachesImage or video pattern matchingProximity measures in feature spaces using context analysisSelection of dictionaries
• G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
• 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

Abstract

Inventors demonstrated that an epigenetic regulator CBX3 antagonizes IFNγ signalling via directly repressing the transcription of two key interferon-stimulated immune genes, STAT1 and PD-L1. The key role of CBX3 in repressing STAT1 and PD-L1 transcription suggests that CBX3 is an important checkpoint to control immune genes' activation in response to different ligands' stimulation, such as the important immune modulator IFNγ, which placed CBX3 in a key position to keep colon immune homeostasis. This role placed also CBX3 in a key position to keep colon immune homeostasis. These studies have started to reveal a new role of CBX3 in controlling the colon epithelium inflammatory response, in addition to its classical role in the formation and stabilization of heterochromatin. Particularly, low CBX3 expression is associated with better CRC patients' overall survival. Corresponding to this result, CBX3 depletion makes IFNγ-insensitive CRC cells dramatically regain IFNγ sensitivity, which significantly increases CRC cells' chemosensitivity under IFNγ stimulation. Accordingly, the invention relates to a Chromobox protein homolog 3(CBX3) inhibitor for use in the treatment of cancer in a subject in need thereof.

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
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• A61K 38/21 - Interferons
• 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

Abstract

The invention relates to the human protein Family with sequence similarity 118 member B (FAM118B). In particular, the present invention relates to the activation, or the inhibition of the activity or effect provided by FAM118B, for modulating the inflammatory response. In particular, it is provided the use of activator of FAM118B, or an activator of the biological effects provided by FAM118, for inducing, sustaining, or enhancing an inflammatory process, in particular an inflammatory process associated with a cancer, a bacterial infection, or a viral infection. In particular, it is also provided the use of an inhibitor of FAM118B, or an inhibitor of the biological effects provided by FAM118B, for inhibiting, or reducing an inflammatory process, more particularly for inducing the resolution of an inflammatory process.

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 1/00 - Drugs for disorders of the alimentary tract or the digestive system
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 35/00 - Antineoplastic agents
• A61P 37/00 - Drugs for immunological or allergic disorders

Abstract

The present invention relates to aptamers that specifically bind to the extra-cellular domain of alpha7/beta1 integrin dimers, conjugates or particles comprising said aptamers, in muscles cells such as skeletal muscle fibres and satellite cells, or in cells aberrantly expressing said domain e.g. tumour cells such as rhabdomyosarcoma (muscle-derived tumours), or glioblastoma cancer stem cells, as well as conjugates comprising said aptamers, therapeutic or diagnostic compositions comprising said conjugates or said aptamers, and their use as a medicament and in diagnostic methods.

IPC Classes  ?

• C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith

Abstract

A tracking system and a method for 3D tracking of a medical device, equipped of at least one ultrasound sensor, inside an anatomical region of a subject having at least one layer of a first tissue type at least partially surrounding a volume having at least one second tissue type, wherein the properties of ultrasounds propagation in the first and second tissue type are different.

IPC Classes  ?

• A61B 8/08 - Clinical applications
• A61B 34/20 - Surgical navigation systemsDevices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
• A61B 90/00 - Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups , e.g. for luxation treatment or for protecting wound edges

Abstract

EVs are being recognized as vectors for drug delivery. In particular. EV loading with targeting and therapeutic agents brings along an interesting opportunity to translate EVs into a bio-mimetic selective delivery system. Indeed. EVs constitute a physiological carrier being potentially less immunogenic than artificial delivery vehicles. The inventors now developed a novel method to control the loading of a cargo into EVs on demand. These EVs are equipped, if necessary, with non-viral fusogen, therefore enhancing EV-cargo delivery into acceptor cells. To acutely measure this process, they follow the fate of a luciferase-tagged cargo. Cargo loading was enabled through a drug-reversible inducible dimerization system. Briefly, donor cells were transfected with plasmids encoding for FKBP-tagged CD63, a classical membrane EV marker, and FRB-Nanoluciferase (NLuc) that is normally cytosolic. Upon addition of the dimerizing drug. FRB-Nluc interacts with FKBP-CD63 and is recruited into secreted EVs. This is accompanied by an enhanced delivery into acceptor cells. This phenomenon can be further enhanced when EVs are equipped with syncitin1, a mammalian fusogenic protein that trigger fusion between EV membrane and the plasma membrane of acceptor cells. Using this novel process, the inventors further demonstrated that the catalytic domain of the Diphteria toxin (DTA), that is responsible for protein synthesis inhibition and ultimately cell death, can be delivered to acceptor cells via functionalized EVs. This led to protein synthesis inhibition and death of acceptor cells. This novel method and the derived applications promise to open new doors in precision care medicine, especially when EVs will be equipped with antibodies raised against cell specific antigens.

IPC Classes  ?

• A61K 9/50 - Microcapsules
• A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
• 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
• C12N 9/22 - Ribonucleases
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof

Abstract

An elastography apparatus is described that is designed to assist in magnetic resonance elastography of the head of an examination object. The elastography apparatus comprises a first support element which is designed to be positioned within a radiofrequency receiving coil unit and a vibration generator which is designed to generate mechanical waves. The first support element has a first recess for receiving the vibration generator, the first support element has a second recess for receiving the head, and the first recess is so shaped as to at least partially enclose the vibration generator in a custom-fit manner and the vibration generator is arranged at least partially within the first recess.

IPC Classes  ?

• G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging

Abstract

The present invention relates to lipid nanoparticle loaded with antitumoral agent and functionalized to target immunosuppressive cells. Inventors developpe valrubicin-loaded immunoliposomes (Val-ILs). A small amount of valrubicin incorporated into Val-ILs induces leukemia cell death in vivo, suggesting that Val-ILs could be used to treat acute leukemia cells. Inventors also demonstrated that Val-ILs could reduce the risk of contamination of CD34+ hematopoietic stem cells by acute leukemia cells during autologous peripheral blood stem cell transplantation. They also highlighted the potential of Val-ILs to target immunosuppressive cell populations in the spleen. The most efficient Val-ILs were found to be those loaded with CD11b,CD223, CD64, TIM1, CD200R3, CD204, CD49b, VEGFR2 and SIGLECF antibodies. This study provides the effectiveness and ease of preparation of Val-ILs as a novel nanoparticle technology. In the context of cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.

IPC Classes  ?

• 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
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• A61K 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
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to the use of Melanoma Differentiation-Associated protein (MDA5) inhibitors for enhancing the number of p16highin vitroin vitro or in a patient in need thereof, in particular to extend health span and protect tissues against aging. It is moreover herein reported that p16highimmune cells surprisingly play a key role in establishing disease tolerance, and can be useful for counteracting different lethal conditions, including LPS-induced sepsis, acute lethal SARS-CoV-2 infection, cancer and ionizing irradiation. Mechanistically, it is shown that inhibition of MDA5 induces an increase in p16high immune cells subsets that, in turn, establishes a low adenosine environment and disease tolerance. The present invention also relates to a pharmaceutical composition comprising immune cells such as CAR-T cells in which the MDA5 expression and/or activity is inhibited, and its use for various therapeutic purposes.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
• C12N 9/14 - Hydrolases (3.)
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

22 ratio, improving metabolic adaptation to the HFD challenge. Our results highlight the role of mitochondrial daily rhythms in the pathophysiology of obesity and open avenues for chronopharmacological treatments targeting these rhythms. Thus, the present invention pertains to a method for treating or preventing obesity in a subject in need thereof. This method includes administering to the subject, at a specific time of the circadian rhythm, a therapeutically effective amount of a dihydroorotate dehydrogenase inhibitor that exhibits an inhibitory duration of less than 24 hours, and more specifically, a short half-life of less than 24 hours.

IPC Classes  ?

• A61K 31/4196 - 1,2,4-Triazoles
• A61P 3/00 - Drugs for disorders of the metabolism
• A61P 3/04 - AnorexiantsAntiobesity agents

Abstract

The present invention relates to a CXCR4 inhibitor compound for use in the treatment of a severe acute respiratory distress syndrome (sARDS), wherein the sARDS is characterized by a dysregulation of NETosis which may be measured by the plasmatic levels of cDNA, citrullinated histone H3, neutrophil elastase, interleukin-8, myeloperoxidase-DNA complexes and/or calprotectin. The present invention also relates to a method of prognostic of severe ARDS, a pharmaceutical composition for use in the treatment of severe acute respiratory distress syndrome (ARDS), a kit of prognostic of severe ARDS in a subject and the use of NETosis biomarkers.

IPC Classes  ?

• A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• A61K 31/4402 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61K 31/4427 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems
• A61K 38/10 - Peptides having 12 to 20 amino acids
• G01N 33/00 - Investigating or analysing materials by specific methods not covered by groups

Abstract

The present invention relates to the use of a STING agonist, of a TLR5 agonist or of a TLR7 agonist for enhancing the number of p16highin vitroin vitro or in a patient in need thereof, in particular to extend health span and protect tissues against aging. It is also herein reported that p16highimmune cells surprisingly play a key role in establishing disease tolerance, and can be useful for counteracting different lethal conditions, including LPS-induced sepsis, acute lethal SARS-CoV-2 infection, cancer and ionizing irradiation. The present invention thus relates to a pharmaceutical composition comprising autologous or heterologous p16highimmune cells such as p16high CAR-T cells, and its use for various therapeutic purposes. These cells are preferably obtained by contacting them with a STING agonist, a TLR5 agonist and/or a TLR7 agonist.

IPC Classes  ?

• A61K 31/352 - 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 condensed with carbocyclic rings, e.g. cannabinols, methantheline
• 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
• 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]
• G01N 33/00 - Investigating or analysing materials by specific methods not covered by groups
• 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

Abstract

Monitoring active disease or progressive disease under therapy in chronic lymphocytic leukemia (CLL) represents a challenge to earlier and better adapt therapeutic strategy, notably in the era of targeted therapies in which minimal residual detection or mutations are sometimes not associated to poor clinical outcome. By following CLL patients before treatment (Binet stages A and B/C) or during targeted therapy, the Inventors developed a new flow cytometric method, based on CD69, CD49d, CD20 and CD279 expression at the surface of CD19+/CD5+ B leukemic cells. Analyses of these markers alone or in combination show that CD69/CD49d/CD20/CD279 co-expression (quadruple population, QP) > 0.5% is the best criterion predicting CLL active disease or progression under therapy. This new flow cytometry immunophenotyping could help clinicians to monitor CLL evolution and quickly adapt their therapeutic strategy. Accordingly, the present invention relates to an ex vivo method for predicting active Chronic Lymphocytic Leukemia (CLL) or progressive CLL under therapy in a subject suffering from CLL, comprising the step of quantifying a population of CD69+/CD49d+/CD20+/CD279+ cells in a sample obtained from the subject.

IPC Classes  ?

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

Abstract

The invention relates to a modified myeloid cell comprising a cytokine chimeric receptor (CCR), wherein said CCR comprises an extracellular domain comprising an extracellular domain of a cytokine receptor which binds soluble molecules present in the tumor microenvironment (TME); a transmembrane domain; and an intracellular signaling domain comprising CD40 cytotail, CD3zeta intracellular domain and/or STING or one of its fragments. The invention also relates to a modified cell comprising a CCR and a transgene coding for a cytokine. The invention also relates to therapeutic uses thereof and to methods and pharmaceutical compositions for the treatment of cancer.

IPC Classes  ?

• A61K 40/00 - Cellular immunotherapy

Abstract

The present invention relates to a disposable sensor (1) for measuring at least one of the quinolinate concentration and the tryptophan concentration in real time in human urine: - a molecularly imprinted polymer, MIP, support (11) comprising a polymer matrix (110), at least one of a first set of cavities (112) adapted to measure the quinolinate concentration and a second set of cavities (113) adapted to measure the tryptophan concentration within the polymer matrix (110); and - an optical fibre (12) coated with the MIP support (11). It also relates to a system (3) comprising same, a method for making same, and a method for measuring at least one of the quinolinate concentration and the tryptophan concentration using same.

IPC Classes  ?

• G01N 21/64 - FluorescencePhosphorescence
• G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
• G01N 33/493 - Physical analysis of biological material of liquid biological material urine

Abstract

Developing an effective HIV-1 vaccine is contingent on generating protective antibodies (Abs). Novel antigen delivery methods are needed to enhance immune responses. One promising approach involves directing antigens to dendritic cells (DC) through fused monoclonal antibodies (mAbs) to amplify both cellular and humoral responses. Here, the inventors aimed to refine Langerhans cells (EC) targeting by designing three Env monochains instead of 2 (EC3. Env3) mimicking natural Env conformation. The inventors demonstrated that EC3. Env3 construct (i) elicited a rapid and potent Env-IgG response, (ii) enhanced the avidity of anti-Env IgG that was accompanied by a marked expansion of Tfh and GC B cells and (iii) swiftly induced the formation of structured germinal centers in dLN, indicative of a robust immune response. Finally, significant Tier-1 NeutAb induction was observed in rabbits immunized with the construct. In conclusion, HIV Env antigen can be adaptively targeted to LC as a timer, intensifying both the magnitude and quality of humoral responses. The present invention thus relates to the use of such a construct as LC targeting HIV-1 vaccines.

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 39/12 - Viral antigens
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C07K 14/16 - HIV-1
• A61P 31/18 - Antivirals for RNA viruses for HIV

Abstract

The invention relates to an in vitro method for classifying a subject afflicted with a cancer as suffering from a cancer with (at risk of) a metabolic reprograming towards fatty acids oxidation including a step of assaying the activation of RelB in a tumor sample form said cancer. The inventor indeed identified the pivotal role of RelB in energy metabolism and more particularly mitochondrial respiration and fatty acid oxidation. Accordingly, the invention also relates to inhibitors of RelB activity or expression, as well as of lipid metabolism for use in the treatment of cancers showing an activated RelB.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

Early diagnosis of cardiovascular diseases can potentially cure subjects and save innumerable lives. Diagnosis and treatment of subjects at early stages by cardiologists remain a challenge. Here, the inventors have measured baseline sTREM-1 (triggering receptor expressed on myeloid cells-1) in 10,000 initially healthy participants without prevalent cardiovascular disease (CVD) from the Paris Prospective Study 3 (PPS3). They have quantified the association and predictive value of baseline sTREM-1 for incident CVD events over 10 years of follow-up. The analysis reveals strong, significant and independent association with incident CVD events combined and its subtypes (coronary heart disease, stroke, peripheral artery diseases, and heart failure). Furthermore, adding sTREM-1 to existing risk prediction algorithms such as SCORE2 or the US pooled risk equation improved the discrimination capacity of these models in a significant and more importantly in a clinically meaningful manner, including among those at moderate CVD risk. Furthermore, the inventors have examined CVD events such as aneurysm, arrythmias and thromboembolic events. Given the ongoing development of pharmacological molecules blocking blood sTREM-1, the inventors believe these findings support future intervention trials testing to which extent sTREM-1 could be a relevant target for the primary prevention of CVD in the general population.

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 invention pertains to the field of cancer treatment by Immune Checkpoint Inhibitors (ICIs) and to the risk stratification and personalized treatment of patients having ICI-induced myotoxicity.

IPC Classes  ?

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

Abstract

The invention concerns a carbon monoxide-releasing molecule (CORM) or composition thereof for use in the treatment or the prevention of an intestinal dysbiosis in a subject. More particularly, the invention concerns a carbon monoxide-releasing molecule (CORM) or composition thereof for use in the treatment or the prevention of an intestinal dysbiosis, preferably a caecum and/or colon dysbiosis in a subject, wherein the carbon monoxide-releasing molecule or composition thereof is administered orally.

IPC Classes  ?

• A61K 31/28 - Compounds containing heavy metals
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

The present disclosure relates to a method of performing 3D Magnetic Resonance Imaging including applying a magnetic gradient field that causes a concomitant field Bc. A further step of the method includes determining phase accruals due to the self-squared terms of the concomitant field Bc and phase accruals φxz, φyz due to the cross terms of the concomitant field Bc based on an encoding matrix that accounts for the different possible sign combinations of the applied magnetic gradients.

IPC Classes  ?

• G01R 33/565 - Correction of image distortions, e.g. due to magnetic field inhomogeneities
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G01R 33/385 - Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field using gradient magnetic field coils

Abstract

MYCC-MYCC-MYC. The present invention also relates to a nucleic acid encoding said TCR, a vector comprising the nucleic acid, and a cell, preferably a T cell, comprising the same. Another aspect of the present invention is a cell, preferably a T cell, comprising said TCR for use as a medicament or for treating cancer.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 14/725 - T-cell receptors
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes

Abstract

The invention relates to methods of diagnosing kidney cancer and to kits for diagnosing kidney cancer.

IPC Classes  ?

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

Abstract

In the present invention, inventors demonstrate that prenatal excess of anti-Müllerian hormone triggers PCOS-like impairment in female sexual behavior in mice. Sexual dysfunction in PCOS-like mice is associated with decreased expression of neuronal nitric oxide synthase (nNOS) neurons in different hypothalamic regions known to be involved in female sexual behavior: rostral periventricular area of the third ventricle (RP3V), ventromedial nucleus of the hypothalamus (VMH), and arcuate nucleus (ARN) during estrus. Chemogenetic inhibition of nNOS neuronal activity in the ventromedial nucleus of the hypothalamus of control adult females recapitulates PCOS-like sexual dysfunction. Of clinical relevance, administration of nitric oxide (NO) donor rescues normal sexual behavior in PCOS-like mice. Accordingly, the present invention relates to invention relates to Nitric Oxyde (NO) agent for use in the prevention or the treatment of sexual dysfunction associated with Polycystic Ovary Syndrome (PCOS) or with Hypoactive Sexual Desire Disorder (HSDD) in a subject in need thereof.

IPC Classes  ?

• A61K 33/00 - Medicinal preparations containing inorganic active ingredients
• A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 15/00 - Drugs for genital or sexual disordersContraceptives

Abstract

The present invention generally relates to the field of genome engineering (gene editing), and more specifically to ex vivo gene therapy for the treatment of Activated PI3kinase Delta Syndrome type 1 (APDS1) related to PIK3CD gene. Particularly, the present invention pertains to the treatment of PIK3CD deficiency in hematopoietic stem cells (HSCs) and/or T-cells. The present invention provides means and methods for genetically modifying HSCs and/or T-cells involving gene editing reagents, such as TALE-nucleases, that specifically target an endogenous PIK3CD locus, at least in the PIK3CD allele comprising at least one APDS1-associated mutation, thereby allowing the restoration of the normal cellular phenotype. The present invention also provides engineered PIK3CD-edited HSCs and engineered PIK3CD-edited T-cells comprising at least one exogenous sequence comprising a nucleic acid sequence encoding a functional PI3Kδ protein which is integrated in said HSCs' or T-cells' genome into a PIK3CD locus, in a non-functional PIK3CD allele, resulting in the expression of a functional PI3Kδ polypeptide. The present invention further provides populations of cells comprising said engineered HSCs or T-cells, pharmaceutical compositions comprising said engineered cells or populations of cells, as well as their use in gene therapy for the treatment of APDS1.

IPC Classes  ?

• A61K 40/41 - Vertebrate antigens
• A61K 40/11 - T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cellsLymphokine-activated killer [LAK] cells
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

In a method for performing Magnetic Resonance Elastography (MRE) more efficiently may include providing a periodical vibration signal for exciting mechanical vibrations within an object to be examined with a vibration period, sampling the vibration signal with a sampling period corresponding to a natural number including zero of vibration periods plus a fixed time delay, and performing three motion encoding gradients for magnetic resonance acquisition in each sampling period. The fixed time delay multiplied with a sampling number may be equal to the vibration period. The sampling number may be a natural number greater than two.

IPC Classes  ?

• G01R 33/563 - Image enhancement or correction, e.g. subtraction or averaging techniques of moving material, e.g. flow-contrast angiography
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons
• A61B 5/055 - Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fieldsMeasuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• G01R 33/56 - Image enhancement or correction, e.g. subtraction or averaging techniques

Abstract

The invention relates to a method for the temporal calibration of a phylogenetic tree by means of digital processing, and comprises: - receiving, in digital format, a set of dated events involving the isolation or transmission of a pathogen, and a set of events to be dated involving the isolation or transmission of the pathogen, organised in the form of a phylogenetic tree following a traversal order from the root to the leaves. A plurality of events have a date to be determined; - forming a Hessian matrix of a logarithmic objective function F of a molecular clock model of the pathogen, defining the relationship between the genetic distances, the dates, and the durations between the events, wherein the Hessian matrix H comprises what is referred to as a local block T defining the branches between the events on the phylogenetic tree. The block T has a size proportional to the number of events on the phylogenetic tree for which the date is to be determined; - identifying the dates to be determined by means of Newton's optimisation method.

IPC Classes  ?

• G16B 10/00 - ICT specially adapted for evolutionary bioinformatics, e.g. phylogenetic tree construction or analysis

Abstract

Host protection against infectious diseases involves complex cross-regulation between the immune system and the nervous system. However, the molecular mechanisms behind this regulation remain poorly understood, particularly in the context of viral infections. Using a mouse model of herpes simplex virus 1 (HSV-1) infection, the inventors demonstrate a role of primary sensory neurons in regulating the antiviral innate and adaptive immune response in the skin and the skin draining lymph node. The inventors show that an excess of neutrophil myeloperoxidase (MPO) activity in the skin inhibits the dendritic cell response, thereby limiting the priming of HSV-1-specific CD8+T cells in the skin draining lymph node. This study reveals novel site-specific neuroimmune regulatory mechanisms controlling antiviral host defense, opening up novel therapeutic perspectives. Thus, the present invention relates to a method of promoting CD8+ T-cell responses in a subject in need thereof comprising administering to the patient a therapeutically effective amount of a myeloperoxidase inhibitor.

IPC Classes  ?

• A61K 31/136 - Amines, e.g. amantadine having aromatic rings, e.g. methadone having the amino group directly attached to the aromatic ring, e.g. benzeneamine
• A61K 31/15 - Oximes (C=N—O—)Hydrazines (N—N)Hydrazones (N—N=)
• A61P 31/04 - Antibacterial agents
• A61P 31/12 - Antivirals
• A61P 31/22 - Antivirals for DNA viruses for herpes viruses
• A61P 35/00 - Antineoplastic agents

Abstract

The invention relates to an in vitro method for establishing the prognosis of a subject diagnosed as suffering or having suffered from a diffuse large B-cell lymphoma and including: - an identification step of at least two markers comprising 2-aminobutyrate or its acid derivative thereof and LDL-1 lipoprotein optionally in combination with at least one marker selected from : 2-hydroxybutyrate or its acid derivative thereof, 3-hydroxybutyrate or its acid derivative thereof, LDL-2 lipoprotein, LDL-1-CH lipoprotein, LDL-1 lipoprotein phospholipids, the Apo-B subfraction of LDL-1 lipoprotein, LDL-1 lipoprotein triglycerides, LDL-2 lipoprotein triglycerides, LDL-3 lipoprotein triglycerides, formic acid and acetyl acetic acid, identifying said at least two markers being the prognosis of, or a risk of, a bad clinical course of the diffuse large B-cell lymphoma in the subject.

IPC Classes  ?

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

Abstract

The present invention relates to the treatment of inflammation. Here, the inventors generated a mouse model able to trace the expression of MrgprE and to interrogate its function, in vivo. They identified the cells expressing MrgprE notably among leukocytes. The MrgprEMutmice do not present any abnormality especially in the immune and peripheral nervous systems. Interestingly, the ablation of MrgprE expression decrease significantly asthma associated airway hyperresponsiveness and inflammation; symptoms that are restored when MrgprE is expressed by Nav1.8+ sensory fibers. In the context of asthma, an inhibitor of MrgprE could have a dual mode of action preventing both airway hyperresponsiveness and inflammation. Thus, the present invention relates to a MRGPRE binding agent for use in the treatment of inflammatory disorders 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
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 11/06 - Antiasthmatics
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• C07K 16/08 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses

Abstract

Netherton syndrome (NS) is a rare recessive skin disorder caused by loss-of-function mutations in SPINK5 encoding the protease inhibitor LEKTI. NS patients present with typical ichthyosis linearis circumflexa (NS-ILC) or scaly erythroderma (NS-SE). Here the inventors employed a combination of several molecular profiling methods to comprehensively characterize the skin, immune cells and allergic phenotypes of NS-ILC and NS-SE patients. In particular, they studied a cohort of 13 NS patients comprising 9 NS-ILC and 4 NS-SE. Integrated multi-omics revealed abnormal epidermal proliferation and differentiation and IL-17/IL-36 signatures in lesion skin and in blood in both NS endotypes. This study thus identifies IL-17/IL-36 as predominant signaling axes in both NS endotypes and unveils molecular features distinguishing NS-ILC and NS-SE. In particular, blocking of IL36 signaling would therefore represent a novel therapeutic strategy for NS, in particular in NS-SE patients.

IPC Classes  ?

• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 17/00 - Drugs for dermatological disorders
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Abstract

The invention relates to a microfluidic device (1) comprising a frame (32) and two opposite walls (16a,b), the two opposite walls (16a,b) and the frame (32) delimiting together a chamber (2): —the chamber (2) comprising a first zone (4) and a second zone (5), —the second zone (5) comprising a porous member (3) extending in the chamber (2) and comprising a first surface (9) and a second surface (10) opposite to the first surface (9), the first surface (9) separating the chamber (2) in the first zone (4) and in the second zone (5), —the frame (32) comprising at least a first and a second sets of ports (11, 12, 13, 14), the first set of port comprising at least two ports (11, 12) arranged in the frame (32) for fluid circulation within in the first zone (4) and the second set of ports comprising at least two ports (13, 14) arranged in the frame (32) for fluid circulation within the second zone (5), and—the two ports (13, 14) of the second set of ports being open (i) in a microchannel (15) extending through the porous member (3), or (ii) in a cavity (19) arranged between the second surface (10) of the porous member (3) and the frame (32) of the chamber (2). The invention relates to microphysiological systems comprising a microfluidic device and cultured cells on the top surface of the hydrogel matrix. The microphysiological systems may be used to model biological surface or biological tissue at physiological interface comprising a luminal and a stromal compartments, such as colon, pancreas or skin tissue.

IPC Classes  ?

• C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
• C12M 1/00 - Apparatus for enzymology or microbiology
• C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means

Abstract

The invention pertains to a new computer-implemented method for processing an EEG signal, that makes it possible to extract information about cerebral damage in full-term babies, born in asphyxia context, for help in an indication for treatment of hypoxic-ischemic encephalopathy (HIE), by computing a power spectral density (PSD) of an EEG signal, transforming the PSD by a mathematical function, processing the transformed values by data binning, and creating a probability distribution of the durations of the binned values.

IPC Classes  ?

• A61B 5/374 - Detecting the frequency distribution of signals, e.g. detecting delta, theta, alpha, beta or gamma waves
• A61B 5/00 - Measuring for diagnostic purposes Identification of persons

Abstract

The present application concerns the use of endoprothesis covalently grafted with a fucoidan for treating aneurysms, in particular cerebral aneurysms, and their process for manufacturing the same. Improved healing of cerebral aneurysms was established in vivo on a rabbit model.

IPC Classes  ?

• A61L 31/16 - Biologically active materials, e.g. therapeutic substances
• A61L 31/02 - Inorganic materials
• A61L 31/10 - Macromolecular materials
• C08L 5/00 - Compositions of polysaccharides or of their derivatives not provided for in group or

Abstract

The invention relates compound of formula (I), enantiomers, mixture of enantiomers, diastereoisomers and mixture of diastereoisomers thereof: The invention relates compound of formula (I), enantiomers, mixture of enantiomers, diastereoisomers and mixture of diastereoisomers thereof: The invention relates compound of formula (I), enantiomers, mixture of enantiomers, diastereoisomers and mixture of diastereoisomers thereof: wherein W, X, Y and Z are as defined, for use in the treatment of Multiple Myeloma (MM). A pharmaceutical composition including a pharmaceutical acceptable vehicle and at least a compound of formula (I) is also included.

IPC Classes  ?

• A61K 31/351 - 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 not condensed with another ring
• A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• A61K 31/4162 - 1,2-Diazoles condensed with heterocyclic ring systems
• A61K 31/4433 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• A61K 38/07 - Tetrapeptides
• A61P 35/00 - Antineoplastic agents
• 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
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention relates to the combination of a miR-17mimic and a miR-340 mimic for use for the prevention and/or treatment of cancer, in particular for the treatment of glioblastoma. In particular, said combination additionally comprises a miR-222 antagomiR.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to bispecific binding molecules, especially antibodies, targeting HER3 and another antigen selected from HER-2 and EGFR antigens, methods for the production of these molecules, compositions, and uses thereof.

IPC Classes  ?

• C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Abstract

The present invention relates to a compound of formula (I) and its use in the production of interleukin-10 by immune cells. The invention also relates to induced immune cells capable of producing interleukin 10. The invention also relates to the use of the induced immune cells in the prevention and/or treatment of immune-mediated diseases.

IPC Classes  ?

• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61K 40/11 - T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cellsLymphokine-activated killer [LAK] cells
• A61K 40/13 - B-cells
• A61P 37/02 - Immunomodulators
• C07D 471/04 - Ortho-condensed systems
• C12N 5/0781 - B cellsProgenitors thereof

Abstract

Engraftment of hematopoietic stems cells (HSCs) is a potentially life-saving treatment therapy for various conditions including genetic blood cell diseases. In particular, the use of allogeneic HSCs to treat genetic blood cell diseases has become a clinical standard: HSCs can be modified ex vivo and transferred back to the recipient to produce functional, terminally-differentiated cells. There is a medical need for methods for assessing the exhaustion of HSCs for optimizing their therapeutic use, in particular in the context of gene therapy. The inventors performed a clinical trial of lentivirus-based gene therapy for the treatment of X-linked chronic granulomatous disease. Two patients showed stable engraftment and clinical benefits, whereas the other two progressively lost gene-corrected cells. Single-cell transcriptomic analysis revealed a significantly lower frequency of the most immature hematopoietic stem cell (HSC) in CGD patients, more pronounced in patients with defective engraftment. The two patients with defective engraftment presented a profound change in HSC status, a high interferon score, and elevated myeloid progenitor counts. The inventors used elastic-net logistic regression to identify a set of interferon genes and transcription factors that predicted the failure of HSC engraftment. They identified a set of 51 interferon genes and transcription factors that were upregulated specifically in P2 and P5 (including IFI44L, STAT2, IRF9, MX1, SAMD9L, and CEBPB) and that appeared to be predictive of defective HSC engraftment. Accordingly, the identified biomarkers can be very suitable for assessing the exhaustion of hematopoietic stems cells.

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

Here, the inventors report the biochemical and functional characterization of a new PTM on a key ESCRT-III member and its impact during viral budding. They discovered that CHMP2B K6 plays a pivotal role in both abscission and HIV viral budding, highlighting the importance of the novel methylation event. Strikingly, expression of unmethylatable CHMP2B mutants (CHMP2B K6A, CHMP2B K6R) perturbed the localization of ESCRT-III at the ICB with delayed recruitment and distribution of CHMP2B to the cleavage site, ultimately leading to impeded abscission. They reported that expression of CHMP2B mutant bearing a specific lysine point mutation at position 6 drastically reduces the number of viral particles released into the supernatant. Additionally, this mutation impairs the infectivity of the produced virions. This is the first description of the antiviral effect of a point mutant of ESCRT-III proteins. Thus, the present invention relates to an isolated polypeptide derived from unmethylatable mutant CHMP2B and its uses for treating infection.

IPC Classes  ?

• A61P 31/18 - Antivirals for RNA viruses for HIV
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• A61K 38/03 - Peptides having up to 20 amino acids in an undefined or only partially defined sequenceDerivatives thereof
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids

Abstract

The present invention relates to novel synthetic lipidic alkynylcarbinols, in particular as antibacterial agents, preferably against mycobacteria, and more preferably against species from the Mycobacterium tuberculosis complex, and also to therapeutic uses thereof. The present invention also relates to said compounds for use for the treatment of bacterial infections. The present invention further relates to the discovery of the pharmaceutical mechanism and bioactivity of these novel synthetic lipidic alkynylcarbinols.

IPC Classes  ?

• C07C 33/044 - Alkynediols
• C07C 33/048 - Acyclic alcohols with carbon-to-carbon triple bonds with double and triple bonds
• C07C 33/05 - Alcohols containing rings other than six-membered aromatic rings
• C07C 33/12 - Alcohols containing rings other than six-membered aromatic rings containing five-membered rings
• C07C 33/14 - Alcohols containing rings other than six-membered aromatic rings containing six-membered rings
• C07C 33/30 - Alcohols containing only six-membered aromatic rings as cyclic part with unsaturation outside the aromatic rings monocyclic

Abstract

3184-3194219-22529-393184-3194219- 22529-3929-39 were significantly associated with an increased risk of developing MACE, CAD, CV death, and/or CV death. Thus the present invention refers to a method of predicting the risk of having or developing a cardiovascular event in a patient.

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 invention relates to a module intended to be associated with a microscope for full-field optical coherence tomography microscopic imaging of at least one sample, the module comprising an interference device (4) comprising a non-polarising beam splitter element (10) for forming two arms when it is illuminated by a source, namely a “reference arm” associated with the reflection surface and an “object arm” associated with the sample, the device furthermore comprising: a first adjustment unit (11) arranged upstream of the non-polarising beam splitter element for allowing an illumination arm of the non-polarising beam splitter element to be modified during operation, and/or at least one second adjustment unit (18) arranged between the beam splitter element and the reflection surface for allowing the reference arm to be modified during operation.

IPC Classes  ?

• G02B 21/18 - Arrangements with more than one light-path, e.g. for comparing two specimens
• G02B 21/02 - Objectives
• G02B 21/24 - Base structure
• G02B 21/26 - StagesAdjusting means therefor