Abstract

A method of treating an inflammatory disease selected from the group of atherosclerosis, ankylosing spondylitis, and Sjogren syndrome. The method includes administering a quinoline derivative to a patient in need thereof. The quinoline derivative is a compound of formula (I) A method of treating an inflammatory disease selected from the group of atherosclerosis, ankylosing spondylitis, and Sjogren syndrome. The method includes administering a quinoline derivative to a patient in need thereof. The quinoline derivative is a compound of formula (I) A method of treating an inflammatory disease selected from the group of atherosclerosis, ankylosing spondylitis, and Sjogren syndrome. The method includes administering a quinoline derivative to a patient in need thereof. The quinoline derivative is a compound of formula (I) or a pharmaceutically acceptable salt thereof.

IPC Classes  ?

• C07D 215/38 - Nitrogen atoms
• A61K 31/47 - QuinolinesIsoquinolines
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• 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
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

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

IPC Classes  ?

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

Abstract

Ackr4Ackr4 as a biomarker for prognosing clinical outcome in a male subject suffering from a B-Cell Non-Hodgkin Lymphoma. It also relates to methods for predicting clinical outcome and methods for monitoring the effect of a therapy or the progression of a B-Cell Non-Hodgkin lymphoma. Another aspect of the invention relates to the ACKR4 protein for use in the treatment or the prevention of a B-Cell Non-Hodgkin Lymphoma.

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

Abstract

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

IPC Classes  ?

• A61K 31/546 - Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula , e.g. cephalosporins, cefaclor, cephalexine containing further heterocyclic rings, e.g. cephalothin
• A61K 38/00 - Medicinal preparations containing peptides
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

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

IPC Classes  ?

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

Abstract

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

IPC Classes  ?

• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• A61K 38/20 - Interleukins
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

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

IPC Classes  ?

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

Abstract

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

IPC Classes  ?

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

Abstract

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

IPC Classes  ?

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

Abstract

A computer-implemented method for determining and quantifying modes of activation of biological pathways in individual cells, including: receiving sequencing data obtained by a single-cell RNA sequencing method, and a plurality of gene lists, determining a gene-cell expression matrix based on the sequencing data and the plurality of gene lists, carrying out a principal component analysis (PCA) on said gene-cell expression matrix, so as to determine a plurality of modes of activation of at least one among the biological pathways, selecting a subset of so-called effective modes of activation among the plurality of modes of activation, determining a matrix referred to as activity matrix, the activity matrix including scores quantifying a level of activity of each effective mode of activation among the subset of effective modes of activation within each individual cell among the set of individual cells.

IPC Classes  ?

• G16B 30/10 - Sequence alignmentHomology search

Abstract

A computer-implemented method for determining and quantifying modes of activation of biological pathways in individual cells, including: receiving sequencing data obtained by a single-cell RNA sequencing method, and a plurality of gene lists, determining a gene-cell expression matrix based on the sequencing data and the plurality of gene lists, carrying out a principal component analysis (PCA) on said gene-cell expression matrix, so as to determine a plurality of modes of activation of at least one among the biological pathways, selecting a subset of so-called effective modes of activation among the plurality of modes of activation, determining a matrix referred to as activity matrix, the activity matrix including scores quantifying a level of activity of each effective mode of activation among the subset of effective modes of activation within each individual cell among the set of individual cells.

IPC Classes  ?

• G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation

Abstract

The invention relates to methods and pharmaceutical compositions for the treatment of cancer, particularly BRCA-associated cancer and chemo-resistance BRCA-associated cancer. The inventors investigated the role of NMNAT1 in cancer, particularly in BRCA-associated cancer. The inventors demonstrated that NMNAT1 inhibition kills BRCA1 and BRCA2-mutated tumor cells but does not affect the survival of non-BRCA-mutated cells. The inventors also demonstrated that NMNAT1, a nuclear enzyme other than PARP1, is crucial for the survival of HRD cells and indicate that NMNAT1 is a key factor which activities are necessary for the survival of HRD cells. The inventors also demonstrated that inhibition of NMNAT1 kills PARP-inhibitor and cisplatin-resistant BRCA1 and BRCA2-mutated tumors and show that targeting NMNAT1 kills chemo-resistance HRD cells, particularly PARPi-resistant HRD cells. Altogether, the present invention highlights the role of NMNAT1 inhibitors in cancer and the use of NMNAT1 inhibitors in the treatment of cancer, particularly BRCA-associated cancer including BRCA-associated cancer with acquired drug resistance in mono- or combination therapy with PARPi. In the present invention, the inventors provide in vitro evidences towards a direct role of NMNAT1 in BRCA-associated cancer. Thus, the present invention relates to NMNAT1 inhibitor for use in the treatment of cancer, particularly HRD cancer. BRCA-associated cancer and chemo-resistance BRCA-associated cancer.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61K 33/243 - PlatinumCompounds thereof
• A61P 35/00 - Antineoplastic agents

Abstract

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

IPC Classes  ?

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

Abstract

The present application provides means for associating Transposal Elements (TEs) expression in T cells with a stage of T cell differentiation. The present application also relates to methods for differentiating progenitor exhausted T cells (Tpex) from Terminally exhausted T cells (Tex). The present invention is also related to methods and means for identifying Tpex from Tex by analysing Transcription Factor Fli1 expression. The present invention is also related to the use of TEs expression and/or Fli1 expression in T cells, in particular in Tpex and Tex, as biomarker(s) of the likeliness to positively respond to immunotherapy, in particular in a patient having a cancer or a chronic viral infection, in particular in response to an anti-PD-1 or anti-PD-L1 immunotherapy.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

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

IPC Classes  ?

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

Abstract

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

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/7084 - Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12N 15/86 - Viral vectors

Abstract

Cell fusion techniques have been used to produce hybrids between myeloma cells and antibody-producing cells. The hybrid lines derived are permanently adapted to grow in tissue culture and are capable of inducing antibody-producing tumors in mice. Cell fusion techniques have been used to produce hybrids between myeloma cells and antibody-producing cells. The hybrid lines derived are permanently adapted to grow in tissue culture and are capable of inducing antibody-producing tumors in mice. Spleens from mice immunized against sheep red blood cells (SRBC) were fused to an 8-azaguanine-resistant clone (X63-Ag8) of MOPC 21 myeloma. Over 50% of the derived hybrid lines produce and secrete immunoglobulins different from the MOPC 21 myeloma. About 10% of the hybrid lines exhibit anti-SRBC activity. The high proportion of antibody-producing hybrids suggests that the fusion involves a restricted fraction of the spleen cell population, probably cells committed to antibody production. Cell fusion techniques have been used to produce hybrids between myeloma cells and antibody-producing cells. The hybrid lines derived are permanently adapted to grow in tissue culture and are capable of inducing antibody-producing tumors in mice. Spleens from mice immunized against sheep red blood cells (SRBC) were fused to an 8-azaguanine-resistant clone (X63-Ag8) of MOPC 21 myeloma. Over 50% of the derived hybrid lines produce and secrete immunoglobulins different from the MOPC 21 myeloma. About 10% of the hybrid lines exhibit anti-SRBC activity. The high proportion of antibody-producing hybrids suggests that the fusion involves a restricted fraction of the spleen cell population, probably cells committed to antibody production. In order to avoid the presence of the MOPC 21 heavy chain in the specific hybrids, another myeloma cell line (NSI/Ag4-1) has been used. This is a nonsecreting variant of the MOPC 21 myeloma which does not express heavy chains. Cell fusion techniques have been used to produce hybrids between myeloma cells and antibody-producing cells. The hybrid lines derived are permanently adapted to grow in tissue culture and are capable of inducing antibody-producing tumors in mice. Spleens from mice immunized against sheep red blood cells (SRBC) were fused to an 8-azaguanine-resistant clone (X63-Ag8) of MOPC 21 myeloma. Over 50% of the derived hybrid lines produce and secrete immunoglobulins different from the MOPC 21 myeloma. About 10% of the hybrid lines exhibit anti-SRBC activity. The high proportion of antibody-producing hybrids suggests that the fusion involves a restricted fraction of the spleen cell population, probably cells committed to antibody production. In order to avoid the presence of the MOPC 21 heavy chain in the specific hybrids, another myeloma cell line (NSI/Ag4-1) has been used. This is a nonsecreting variant of the MOPC 21 myeloma which does not express heavy chains. Three anti-SRBC (probably of the μ, γ2b and γ1 classes, respectively) and two anti-2,4,6-trinitrophenyl (of the μ class antibody-producing hybrids have been repeatedly cloned. By random selection and by selection of specific clones according to their lytic activity (clone plaque selection), a number of different lines have been constructed. Such lines express different combinations of the four possible chains of each hybrid line: the myeloma γ and k chains and the specific antibody heavy and light chains. In three cases (Sp1, Sp2 and Sp7) it is shown that only the specific H and L combination has activity and that the myeloma chains are unable to substitute for them. In most cases lines have been derived which no longer express the MOPC 21 chains but only the specific antibody chains.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

The present invention relates to nitrogen-containing derivatives of salinomycin having the formula (I), as well as pharmaceutically acceptable salt thereof, and synthesis and uses thereof, in particular for the treatment and/or prevention of cancer including for preventing cancer metastasis and/or for preventing cancer recurrence and/or for decreasing resistance to a chemotherapy in a subject.

IPC Classes  ?

• C07D 493/20 - Spiro-condensed systems
• A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
• A61P 35/00 - Antineoplastic agents

Abstract

The invention relates to a method implemented by computer means for determining the influence of a plurality of regions in a medical image (I) of a patient on a prediction of a pretrained prediction model (PM) based on said image (I), comprising: (a) determining image features (F1, F2, F3) of a plurality of regions (A1, A2, A3) on said image (I), (b) transforming said features (F1, F2, F3) of each region (A1, A2, A3) in an aggregated tensor (F) inputted into said pretrained prediction model, (c) calculating, based on said features, the Shapley value of each region, said Shapley value representing the influence of said region on said prediction.

IPC Classes  ?

• G06T 7/00 - Image analysis
• G06N 3/00 - Computing arrangements based on biological models
• G06N 20/10 - Machine learning using kernel methods, e.g. support vector machines [SVM]
• G06N 20/20 - Ensemble learning
• G06N 3/0464 - Convolutional networks [CNN, ConvNet]
• G06N 5/01 - Dynamic search techniquesHeuristicsDynamic treesBranch-and-bound

Abstract

wherein said tumor neoantigenic peptide binds to at least one Major Histocompatibility Complex (MHC) molecule of said subject. The present disclosure also relates to tumor neoantigenic peptide obtained according to the present method, vaccine or immunogenic composition, antibodies and immune cells derived thereof and their use in therapy of cancer.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 14/74 - Major histocompatibility complex [MHC]
• C12N 5/078 - Cells from blood or from the immune system

Abstract

The present invention relates to novel tumor specific peptides derived from the translated ORF sequence from long noncoding RNA (lncRNA), and the uses thereof. The invention more particularly relates to the use of tumor specific peptides in cancer vaccines and cell therapy.

IPC Classes  ?

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

Abstract

The present invention relates to novel serotonin derivatives of formula (I): The present invention relates to novel serotonin derivatives of formula (I): The present invention relates to novel serotonin derivatives of formula (I): or a pharmaceutically acceptable salt and/or solvate thereof. The present invention relates to novel serotonin derivatives of formula (I): or a pharmaceutically acceptable salt and/or solvate thereof. Another object of the present invention relates to the use of compound of formula (I) as a drug, in particular in the prevention and/or the treatment of iron overload-associated disorders.

IPC Classes  ?

• A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
• A61P 7/06 - Antianaemics
• 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
• C07D 209/16 - Tryptamines
• 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

Abstract

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

IPC Classes  ?

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

Abstract

Type 1 conventional dendritic cells (cDC1s) and plasmacytoid dendritic cells (pDCs) are thought to be critical for anti-tumor or antiviral immunity. In vitro differentiation systems have unlocked the ability to produce large numbers of these cells. However, a method is lacking to systematically identify the cell-intrinsic factors controlling their differentiation and functions that remain therefore poorly understood, in contrast to the situation in mice. Here, the inventors developed a workflow for efficient gene silencing and its tracing in human cDC1s/pDCs generated in vitro. They demonstrate the key role of IRF8 in their development, and of IRF7/MyD88 in human pDC production of interferons-α/λ. They found that SAMHD1 and RAB7B promote human cDC1 differentiation, while SEPT3 promotes human pDC differentiation. Finally, they identified that the transcription factors ID2 and DC-SCRIPT versus BCL11A promote cDC1 versus pDC development respectively. This approach will enable broader genetic screens to advance our understanding of human cDC1s/pDCs and harness them against viral infections or cancer. Thus, the present invention relates to a method for inducing the differentiation of human hematopoietic stem cells into type 1 conventional dendritic cells or plasmacytoid dendritic cells, while genetically manipulating the hematopoietic stem cells to modulate the differentiation and/or functions of their dendritic cell progeny.

IPC Classes  ?

• C12N 5/0784 - Dendritic cellsProgenitors thereof

Abstract

The present invention pertains to an improved method for the diagnosis of homologous recombination deficiency (HRD) in a tumor The method according to the invention particularly comprises evaluating the number of large-scale genomic alterations (LGA) by obtaining the copy number alterations (CNA) profile by shallow coverage whole genome sequencing (sWGS) in a tumor sample, and determining a LGA-score which corresponds to the LGA number adjusted by the genome complexity of the tumor and the presence of one or two markers selected from the group of markers consisting of (1) cyclin dependent kinase 12 (CDK12) mutation-associated phenotype with multiple interstitial gains in the CNA profile, (2) Cyclin E1 (CCNE1) amplification, (3) human epidermal growth factor receptor-2 (HER2) amplification and (4) multifocal amplification phenotype.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The invention relates to a pharmaceutical composition for use in a method for the treatment of cancer and/or immune deficiency diseases and/or infectious diseases, comprising a metal ion and optionally hyaluronate (HA) or a hyaluronate conjugate, wherein said method comprises the intralymphatic administration of the pharmaceutical composition to a subject. The invention also relates to a pharmaceutical combination for use in a method for the treatment of cancer, the pharmaceutical combination comprising: (i) at least one metal ion, preferably selected in the group consisting of iron (Fe), copper (Cu), manganese (Mn), calcium (Ca), magnesium (Mg),zinc (Zn), and mixtures thereof; and (ii) hyaluronate (HA) or a hyaluronate conjugate, wherein said method comprises the simultaneous, separate or sequential administration of (i) and (ii) directly into the lymphatic system, preferably into a lymph node or a lymph vessel.

IPC Classes  ?

• A61K 33/06 - Aluminium, calcium or magnesiumCompounds thereof
• A61K 33/26 - IronCompounds thereof
• A61K 33/30 - ZincCompounds thereof
• A61K 33/32 - ManganeseCompounds thereof
• A61K 33/34 - CopperCompounds thereof
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• A61P 35/00 - Antineoplastic agents
• A61P 37/04 - Immunostimulants

Abstract

The manufacture and use of compounds of formula (Ia) or a pharmaceutically acceptable salt thereof for preventing, inhibiting or treating cancer, AIDS and/or premature aging. The compounds of formula (Ia) being: The manufacture and use of compounds of formula (Ia) or a pharmaceutically acceptable salt thereof for preventing, inhibiting or treating cancer, AIDS and/or premature aging. The compounds of formula (Ia) being: The manufacture and use of compounds of formula (Ia) or a pharmaceutically acceptable salt thereof for preventing, inhibiting or treating cancer, AIDS and/or premature aging. The compounds of formula (Ia) being: where: R independently represents a hydrogen atom, a halogen atom, a (C1-C3)alkyl group, a —CN group, a hydroxyl group, a —COOR1 group, a (C1-C3)fluoroalkyl group, a —NO2 group, a —NR1R2 group, or a (C1-C3)alkoxy group; R′ is a hydrogen atom, a halogen atom, a (C1-C3)alkyl group, a —NO2 group, a (C1-C3)alkoxy group, or a —NR1R2 group; and R1 and R2 are a hydrogen atom or a (C1-C3)alkyl group.

IPC Classes  ?

• C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• C07D 215/38 - Nitrogen atoms
• C07D 215/42 - Nitrogen atoms attached in position 4
• C07D 215/46 - Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
• C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
• C07D 241/44 - Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• C07D 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 403/12 - 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 chain containing hetero atoms as chain links

Abstract

The present invention relates to the combination of anti-CD3 agent, in particular monoclonal antibody, with immunotherapeutic agents, and its use in oncology, for treating T Cell Acute Lymphoblastic Leukemia (T-ALL). The invention also relates to a pharmaceutical composition comprising said combination and the use of said combination to induce cell death of T-ALL cells.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

The invention relates to a method of producing extracellular vesicles from producer cells, comprising the steps of: a) placing producer cells in a liquid medium in a vessel comprising a baffle structure inside the vessel; b) rotating the vessel so as to generate extracellular vesicles from the producer cells; and c) collecting the generated extracellular vesicles; wherein the step b) of rotating the vessel comprises repeatedly changing the rotational motion of the vessel.

IPC Classes  ?

• C12M 1/24 - Apparatus for enzymology or microbiology tube or bottle type
• C12M 1/00 - Apparatus for enzymology or microbiology
• C12M 3/04 - Tissue, human, animal or plant cell, or virus culture apparatus with means providing thin layers

Abstract

The present invention relates to humanized HER2 single domain antibodies and variants thereof and their use in therapy and for cancer diagnosis. The invention most particularly proposes chimeric antigen receptors including said humanized HER2 sdAb in their antigen binding domain and their use in cancer cell therapy.

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
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 14/725 - T-cell receptors
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

in vitroin vitro. The treatment of mice engrafted with DDLPS patient-derived xenografts (PDX) with inhibitor of TGFP reduce tumor growth and restore adipocytic differentiation of DD cells. Thus, the present invention more particularly relates to TGFP inhibitor for use in the treatment of DDLPS, particularly of advanced DDLPS.

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 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The invention relates to methods and pharmaceutical compositions for the treatment of HRD cancer, particularly BRCA-associated cancer and chemo-resistance BRCA-associated cancer The inventors investigated the role of VPS4B in HRD cancer, particularly in BRCA- associated cancer. The inventors demonstrated that HR-deficient cells have NE vulnerability, increased NE rupture and are sensitive to inhibitor of NE repair factors. The inventors also demonstrated that VPS4B is synthetic lethal in BRCA1/2-mutated cells and indicate that BRCA2-/- cells were extremely sensitive to VPS4B inhibition. Altogether, the present invention highlights the role of nuclear envelope (NE) repair factors, particularly VPS4B inhibitors in HRD cancer and the use of VPS4B inhibitors in the treatment of HRD cancer, particularly BRCA-associated cancer and BRCA-associated cancer with acquired drug resistance. Thus, the present invention relates to VPS4B inhibitor for use in the treatment of HRD cancer, particularly BRCA-associated cancer and chemo-resistance BRCA-associated cancer.

IPC Classes  ?

• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61K 33/243 - PlatinumCompounds thereof
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents
• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol

Abstract

The invention relates to methods and pharmaceutical compositions for the treatment of HRD cancer, particularly BRCA-associated cancer and chemo-resistance BRCA-associated cancer The inventors investigated the role of farnesyl transferase in HRD cancer, particularly in BRCA-associated cancer. The inventors demonstrated that HR-deficient cells have NE vulnerability, increased NE rupture and are sensitive to inhibitor of NE repair factors. The inventors also demonstrated that farnesyl transferase is synthetic lethal in BRCA1/2-mutated cells and indicate that BRCA2-/- cells were extremely sensitive to farnesyl transferase inhibition. Altogether, the present invention highlights the role of nuclear envelope (NE) repair factors, particularly farnesyl transferase inhibitors in HRD cancer and the use of farnesyl transferase inhibitors in the treatment of HRD cancer, particularly BRCA-associated cancer and BRCA-associated cancer with acquired drug resistance. Thus, the present invention relates to farnesyl transferase inhibitor for use in the treatment of HRD cancer, particularly BRCA- associated cancer and chemo-resistance BRCA-associated cancer.

IPC Classes  ?

• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• 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 31/4545 - 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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61K 33/243 - PlatinumCompounds thereof
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

Methods and pharmaceutical compositions for the treatment of BAP1 deficient cancer are based on investigation of the role of BET (Bromodomain and Extra-Terminal motif proteins) in BAP1 deficient cancer and screened isogenic cells (BAP1 WT vs KO). BET inhibitors show more anti-proliferative activity against cells KO for BAP1. Using isogenic cell lines and uveal melanoma PDX derived cell lines with different status of expression for BAP1 showed a highest dose response to a BET inhibitors (OTX015 and BI894999) in BAP1 KO isogenic cells compared to WT cells and an enhanced dose response to OTX015 in a BAP1 mutated uveal melanoma (UM) derived cells compared to UM cells expressing BAP1. BET inhibitors have a role in BAP1 deficient cancer, and BET inhibitors are useful in the treatment of BAP1 deficient cancer, particularly BAP1 deficient Uveal Melanoma, clear cell Renal Carcinoma, cholangiocarcinoma and mesothelioma.

IPC Classes  ?

• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

Macrophages (MØ) are critical for the detection and clearance of pathogens and yet also serve as replication niches for multiple infectious agents. This delicate balance between viral replication and antiviral response remains poorly understood at the molecular level. Addressing this question is of physiological importance given the ever-present threat posed by emerging viral pathogens. Now, the inventors show that the expression of GAS7 in macrophages limits the replication of viral pathogens belonging to all the major viral groups. They show that the antiviral activity of GAS7 is present even in conditions where the classical antiviral response mediated by type I Interferon is neutralized. In particular, the inventor shows that in human monocyte-derived macrophages, silencing GAS7 boosts the replication of multiple viral pathogens representative of the most relevant viral groups. These include the retroviruses HIV- 1 and HIV-2, the RNA viruses ZIKA (RNAss +), SINDBIS (RNAss +), Sendai (RNAss-), VSV (RNAss-) and Measles (RNAss-), and the DNA virus HSV-1 (DNA ds). Importantly, the antiviral activity of GAS7 is present even in conditions where type I Interferon is neutralized, by the addition of the B18R protein (which blocks efficiently type I receptor). Moreover, the inventors show that enforcing the over-expression of GAS7 by macrophages further protects them against HIV-1 infection, compared with cells expressing normal levels of this factor. Accordingly, the present invention relates to the modulation of the expression and/or activity of GAS7 for modulating viral replication in a population of macrophages.

IPC Classes  ?

• A61P 31/12 - Antivirals
• C12N 15/67 - General methods for enhancing the expression

Abstract

The inventors investigated new mechanism of adipocytic differentiation in dedifferentiated liposarcomas (DDLPS). The inventors demonstrate that DDLPS tumor cells are vulnerable to TGFβ inhibition and provide rationale for the development of therapeutic strategies based on TGFβ inhibition. Treatment of DD tumor cells with TGFβ impairs adipocytic differentiation of DD cells, whereas TGFβ inhibitors restores their adipocytic phenotype in vitro. The treatment of mice engrafted with DDLPS patient-derived xenografts (PDX) with inhibitor of TGFβ galunisertib reduce tumor growth and restore adipocytic differentiation of DD cells. Altogether, the present invention highlights the role of TGFβ in adipocytic differentiation in DDLPS, particularly advanced DDLPS and the use of TGFβ inhibitors in the treatment of DDLPS, particularly advanced DDLPS. Thus, the present invention relates to TGFβ inhibitor for use in the treatment of DDLPS, particularly advanced DDLPS.

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 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

A compound of formula (I) or any of its pharmaceutically acceptable salt for use in the treatment and/or prevention of a RNA virus infection, and a RNA virus infection from group IV or V of the Baltimore classification A compound of formula (I) or any of its pharmaceutically acceptable salt for use in the treatment and/or prevention of a RNA virus infection, and a RNA virus infection from group IV or V of the Baltimore classification A compound of formula (I) or any of its pharmaceutically acceptable salt for use in the treatment and/or prevention of a RNA virus infection, and a RNA virus infection from group IV or V of the Baltimore classification wherein R3 represents a chlorine atom or a hydrogen atom, R represents a (C1-C4)alkyl group, a (C3-C6)cycloalkyl group, a halogen atom, a (C1-C5)alkoxy group, a —SO2—NRaRb group, a —SO3H group, a —OH group, a —O—SO2—ORc group or a —O—P(═O)—(ORc)(ORd) group, R1 represents (i) a CF3 group, (ii) a (C1-C10)alkyl group, (iii) a (C3-C6)cycloalkyl or a (C3-C6)heterocycloalkyl group or (iv) a phenyl group or a naphthyl group, and R2 represents a hydrogen atom, a (C1-C10)alkyl group, a (C3-C6)cycloalkyl or a (C3-C6)heterocycloalkyl group and further relates to new compounds, to pharmaceutical compositions containing them and to synthesis process for manufacturing them.

IPC Classes  ?

• C07D 215/38 - Nitrogen atoms
• A61P 31/14 - Antivirals for RNA viruses
• 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 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

Abstract

The invention relates to methods and pharmaceutical compositions for the treatment of resistant HRD cancer, particularly resistant BRCA-associated cancer, chemo-resistant HRD cancer and chemo-resistant BRCA-associated cancer.

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 the identification of a sub-group of patients having a cancer having an activating alteration of FGFR3 as sensitive to a treatment with a TRAIL-based therapeutic, optionally in combination with a Smac mimetic for a synergistic effect.

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 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents

Abstract

Provided herein is a method for detecting a tumour that can be applied to cell-free samples, to cell-free detect circulating tumour DNA. The method utilizes detection of adjacent methylation signals within a single sequencing read as the basic positive tumour signal, thereby decreasing false positives. The method comprises extracting DNA from a cell-free sample obtained from a subject, bisulphite converting the DNA, amplifying regions methylated in cancer (CpG islands, CpG shores, and/or CpG shelves), generating sequencing reads, and detecting tumour signals. To increase sensitivity, biased primers designed based on bisulphite converted methylated sequences can be used. Target methylated regions can be selected from a pre-validated set according to the specific aim of the test. Absolute number, proportion, and/or distribution of tumour signals may be used for tumour detection or classification. The method is also useful in, predicting, prognosticating, and/or monitoring response to treatment, tumour load, relapse, cancer development, or risk.

IPC Classes  ?

• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• 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
• G16B 25/00 - ICT specially adapted for hybridisationICT specially adapted for gene or protein expression
• G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
• G16B 35/00 - ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
• G16B 99/00 - Subject matter not provided for in other groups of this subclass

Abstract

Provided herein is a method for detecting a tumour that can be applied to cell-free samples, to cell-free detect circulating tumour DNA. The method utilizes detection of adjacent methylation signals within a single sequencing read as the basic positive tumour signal, thereby decreasing false positives. The method comprises extracting DNA from a cell-free sample obtained from a subject, bisulphite converting the DNA, amplifying regions methylated in cancer (CpG islands, CpG shores, and/or CpG shelves), generating sequencing reads, and detecting tumour signals. To increase sensitivity, biased primers designed based on bisulphite converted methylated sequences can be used. Target methylated regions can be selected from a pre-validated set according to the specific aim of the test. Absolute number, proportion, and/or distribution of tumour signals may be used for tumour detection or classification. The method is also useful in, predicting, prognosticating, and/or monitoring response to treatment, tumour load, relapse, cancer development, or risk.

IPC Classes  ?

• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• 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
• G16B 25/00 - ICT specially adapted for hybridisationICT specially adapted for gene or protein expression
• G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
• G16B 35/00 - ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
• G16B 99/00 - Subject matter not provided for in other groups of this subclass

Abstract

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

IPC Classes  ?

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

Abstract

The present invention relates to a fusion protein comprising a nuclease domain from the class 2 CRISPR system, in particular Cpf1, and a Spo11 domain, as well as the use of this protein in order to induce targeted meiotic recombinations in an eukaryotic cell.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 9/90 - Isomerases (5.)
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/81 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts

Abstract

The present disclosure relates to a splice-switching antisense oligonucleotide (SSO) that modulates the expression of a tumor protein derived from TE-exon junction (JET) transcript in a tumor cell and its use in the treatment of a cancer in a subject in need thereof.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• 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 31/7088 - Compounds having three or more nucleosides or nucleotides

Abstract

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

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• A61K 31/131 - Amines, e.g. amantadine acyclic
• A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• A61K 31/282 - Platinum compounds
• A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61K 33/243 - PlatinumCompounds thereof
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism

Abstract

The present disclosure relates to a method for detecting a mutation in a microsatellite sequence locus of a target fragment from a DNA sample, comprising a step of subjecting said DNA sample to a digital polymerase chain reaction (PCR) in the presence of a PCR solution comprising: a pair of primers suitable for amplifying said target fragment of the DNA sample including said microsatellite sequence; a first MS oligonucleotide (MS) hydrolysis probe, labeled with a first fluorophore, wherein said first MS oligonucleotide probe is complementary to a wild-type sequence including the microsatellite sequence; a second oligonucleotide reference (REF) hydrolysis probe, labeled with a second fluorophore, wherein said second oligonucleotide REF probe is complementary to a wild-type sequence of said target DNA fragment which does not include said microsatellite sequence.

IPC Classes  ?

• C12Q 1/6858 - Allele-specific amplification
• 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 21/64 - FluorescencePhosphorescence

Abstract

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

IPC Classes  ?

• A61K 31/546 - Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula , e.g. cephalosporins, cefaclor, cephalexine containing further heterocyclic rings, e.g. cephalothin
• A61K 38/00 - Medicinal preparations containing peptides
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/02 - Antineoplastic agents specific for leukemia
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12N 9/10 - Transferases (2.)
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The invention relates to tumor-associated FOLR2+ macrophages and gene signature thereof as a biomarker of favorable outcome and anti-tumor immunity useful for the prognosis and monitoring of cancer patients. The invention relates also to FOLR2+ macrophages as a therapeutic target for enhancing T cell immunity in the prevention and treatment of cancer and infectious diseases.

IPC Classes  ?

• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12Q 1/6886 - 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 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses

Abstract

The present invention relates to ureal derivatives of formula (I) and pharmaceutical compositions comprising such derivatives for use in the treatment of uveal melanoma.

IPC Classes  ?

• C07D 277/82 - Nitrogen atoms
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/423 - Oxazoles condensed with carbocyclic rings
• A61K 31/428 - Thiazoles condensed with carbocyclic rings
• A61P 35/00 - Antineoplastic agents
• C07D 235/30 - Nitrogen atoms not forming part of a nitro radical
• C07D 263/58 - BenzoxazolesHydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2

Abstract

The present invention relates to a compound having the formula (I) or one of its pharmaceutically acceptable salts, for use in treating a pathology due to a deregulation of MKlp2 or a pathology wherein the MKlp2 pathway is deregulated, preferably in treating cancer, bacterial infections or viral infections.

IPC Classes  ?

• A61K 31/404 - Indoles, e.g. pindolol
• 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
• A61P 31/04 - Antibacterial agents
• A61P 31/12 - Antivirals
• A61P 35/00 - Antineoplastic agents
• C07D 209/18 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• C07D 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

Abstract

Viral infection is a common threat to prokaryotic and eukaryotic life, which has resulted in the evolution of a myriad of antiviral systems. Some of these eukaryotic systems are thought to have evolved from prokaryotic antiphage proteins, with which they may display sequence and structural homology. Here, the inventors show that homologs of recently discovered antiphage systems are widespread in eukaryotes. They demonstrate that such homologs can retain a function in immunity by unveiling that eukaryotic proteins of the anti-transposon piRNA pathway display domain homology with the antiphage system Mokosh. The inventors further utilize this conservation to discover novel human antiviral genes related to the Eleos and Lamassu prokaryotic systems.

IPC Classes  ?

• A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• A61P 31/12 - Antivirals

Abstract

A method for preparing a compound of formula (I), a powder, and a pharmaceutical composition are disclosed. The method includes: (i) reacting a compound of formula (II) with a compound of formula (III), to form the hydrochloride salt of the compound of formula (I), and (ii) recovering the compound of formula (I) in the form of a free base through addition of a base. In step (i), the molar ratio of the compound of formula (II) to the compound of formula (III) is in a range of from 1.00:0.80 to 1.00:1.20, and no metal catalyst is present. A powder including the composition of formula (I) may be obtained by the method. The powder may have a particle size distribution with specific D50, D90 and/or D10 values. A pharmaceutical composition may include the powder and at least one pharmaceutically acceptable excipient.

IPC Classes  ?

• C07D 215/38 - Nitrogen atoms

Abstract

Invention belongs to the field of molecular biology. Invention relates to a fully functional tagged Rad51 protein which constitutes a valuable tool for studying the homologous recombination pathway and alternative lengthening of telomeres. More particularly the invention relates to a fully functional tagged Rad51 protein comprising a tag between residues 54 and 55 of Rad 51 protein of SEQ ID NO:1 or between corresponding residues of any budding yeast ortholog thereof. Accordingly, the invention relates also to methods of screening candidate compounds capable of interfering with such mechanisms and to method of screening drugs useful in cancer treatment.

IPC Classes  ?

• C12N 9/14 - Hydrolases (3.)
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

The present invention relates to lnc-ZNF30-3 as biomarker of cancer and its targeting for new therapeutic treatment of cancer.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The present invention relates to a beam shaping element (13) configured to shape the intensity profile of an excitation light beam in an optical imaging system in order to have a confined excitation with a uniform excitation intensity over the thickness of the excitation light beam, the beam shaping element (13) comprising: - a beam shaper (131) comprising a predetermined pattern, the beam shaper (131) being a digital micromirror device or a mask; and - a plurality of dichroic mirrors (132-135); wherein the beam shaper (131) is configured to shape the intensity profile of the excitation light beam according to the predetermined pattern in order to obtain a uniform excitation intensity over the thickness of the excitation light beam. The present invention also relates to an optical imaging system and methods for selective and homogeneous volumetric imaging of a sample.

IPC Classes  ?

• G02B 21/00 - Microscopes
• G02B 27/09 - Beam shaping, e.g. changing the cross-sectioned area, not otherwise provided for
• G02B 27/00 - Optical systems or apparatus not provided for by any of the groups ,

Abstract

The present invention concerns a modified cell comprising a transgene coding for interleukin-2 (IL-2). Said modified cell comprises a first vector comprising a sequence coding for IL-2 under the control of an inducible or constitutive promoter, which notably enables a locally contained expression of IL-2. It also relates to therapeutic uses thereof.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/55 - IL-2
• C12N 5/0786 - MonocytesMacrophages

Abstract

The invention provides immune cells defective for SUV39H1 with enhanced properties

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

A chimeric antigen receptor including: a binding domain, the full DAP 10 protein, the full DAP 12 protein, or a functional variant thereof, and a hook binding domain. Also, a vector system comprising one or more vector including: a nucleic acid comprising a nucleic acid sequence encoding a chimeric antigen receptor and optionally a nucleic acid encoding a hook fusion protein, preferably having a streptavidin core; wherein the nucleic acids are located on the same or on different vectors. Further, a lentiviral vector particles system, host cell and kit including the nucleic acids or vector system, and their use as a medicament, notably for immunotherapy.

IPC Classes  ?

• C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to a polynucleotide comprising a gene encoding a hook protein and a gene encoding a protein of interest, said protein of interest being either a secretory protein or a cell membrane-anchored protein, wherein: said gene encoding the hook protein is under the control of a first transcription-activating signal, said gene encoding the protein of interest is under the control of a second transcription-activating signal, said second transcription-activating signal allowing a lower rate or frequency of transcription initiation than the first transcription-activating signal, said hook protein is fused to a cellular compartment-retention peptide, and said protein of interest is fused to a hook protein-binding domain The present invention relates to a polynucleotide comprising a gene encoding a hook protein and a gene encoding a protein of interest, said protein of interest being either a secretory protein or a cell membrane-anchored protein, wherein: said gene encoding the hook protein is under the control of a first transcription-activating signal, said gene encoding the protein of interest is under the control of a second transcription-activating signal, said second transcription-activating signal allowing a lower rate or frequency of transcription initiation than the first transcription-activating signal, said hook protein is fused to a cellular compartment-retention peptide, and said protein of interest is fused to a hook protein-binding domain It also related to vectors comprising the polynucleotide, cells comprising the polynucleotide or the vector and compositions comprising the same. It further relates to methods and uses for modulating the secretion or cell membrane-anchorage of a protein of interest, or for preventing and/or treating a disease in a subject in need thereof.

IPC Classes  ?

• C12P 21/00 - Preparation of peptides or proteins
• C07K 14/36 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from ActinomycesPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Streptomyces (G)
• C07K 14/54 - Interleukins [IL]
• C07K 14/55 - IL-2
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells

Abstract

The present invention relates to a method for inducing proximity between two biological molecules in a sample, to an assay relying on the induction of proximity between two biological molecules in a sample, and to a proximity inducing system comprising two polypeptides and a molecular inducer of proximity.

IPC Classes  ?

• G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• C07D 277/34 - Oxygen atoms

Abstract

The invention relates to tissue-imprinting molecular program and the associated T cell progenitors in tumors and draining lymph nodes and their therapeutic application.

IPC Classes  ?

• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes

Abstract

The invention relates to a method of extracting a bead from a droplet, comprising the steps of: – providing a droplet of a first fluid within a second fluid, the first fluid being immiscible with the second fluid, the droplet containing a bead; – passing the droplet through a constriction in a main channel, and supplying a third fluid second fluid immiscible with the first fluid in a downstream channel, downstream of the constriction so as to extract the bead from the droplet.

IPC Classes  ?

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

Abstract

The invention relates to methods for determining the methylation profile of DNA sequences of interest and methods for accurately distinguishing between a healthy methylation profile and a cancerous methylation profile, as well as to kits to implement them.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids

Abstract

The invention relates to a probe comprising a bead, a first binding assembly and a second binding assembly, wherein: – the first binding assembly comprises a first bead-binding portion and a first probe portion, – the second binding assembly comprises a second bead-binding portion, a second probe portion, and a cleavable portion between the second bead-binding portion and the second probe portion, – the first and second bead-binding portions are attached to the bead; – the first probe portion is a portion capable of binding to a first analyte; – the second probe portion is a portion capable of binding to a second analyte.

IPC Classes  ?

• C12Q 1/6834 - Enzymatic or biochemical coupling of nucleic acids to a solid phase
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA

Abstract

Modified monomers of a Shiga toxin B-subunit (STxB) protein including at least one of: an addition of a reactive unnatural amino acid residue at the C-terminal extremity, and/or a substitution with a reactive unnatural amino acid residue at an amino acid position among Asp 3, Lys 8, Glu 10, Tyr 11, Lys 23, Lys 27, Thr 49, Lys 53, His 58, Asn 59, and Arg 69, reference made to the numbering of STxB from Shigella dysenteriae. Also relates to STxB conjugates, and oligomers, in particular pentamers, of these modified STxB proteins and STxB conjugates; as well as to compositions including the same and their use in treatment, vaccination and diagnosis methods.

IPC Classes  ?

• 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 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof

Abstract

A hook fusion protein, which includes a hook domain and at least one cytoplasmic carboxyl endoplasmic reticulum (ER) retention signal and/or at least one cytoplasmic amino terminal endoplasmic reticulum (ER) retention signal; wherein the hook fusion protein is a soluble protein that localizes in the cytoplasm. Also, a nucleic acid system for intracellular targeting control including a nucleic acid encoding a target fusion protein including a hook fusion protein, and a nucleic acid encoding a target fusion protein including a hook-binding domain; wherein the target fusion protein is a membrane protein; and wherein the hook fusion protein localizes in the ER when bound to the target fusion protein. Additionally, a vector system, viral particle system, host cell and kit include these nucleic acids. Further, the vector system, viral particle system, host cell or kit for use as a medicament, in particular for immunotherapy.

IPC Classes  ?

• C07K 14/725 - T-cell receptors
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/36 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from ActinomycesPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Streptomyces (G)
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 14/74 - Major histocompatibility complex [MHC]
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression

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
• A61P 7/06 - Antianaemics
• C07D 209/00 - Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom

Abstract

The invention relates to biomarkers and uses thereof for the treatment and diagnosis of neuroblastoma.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61P 35/00 - Antineoplastic agents
• G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers

Abstract

The present invention relates to a device (2) for providing a liquid medium with a controlled flow rate and with a controlled concentration of a dissolved gas, the device (2) comprising: —a liquid reservoir (4) provided with: —at least one gas inlet (7); —at least one gas outlet (8); and—at least one liquid outlet (9); —an admission line (5) configured to provide a gaseous medium into the liquid reservoir (4), the admission line (5) being connected to the at least one gas inlet (7) and comprising at least one control valve (12); and an emission line (6) configured to withdraw the gaseous medium from the liquid reservoir (4), the emission line (6) being connected to the at least one gas outlet (8) and comprising at least one control valve (15). The present invention further relates to an assembly comprising said device, and to a method for providing a liquid medium with a controlled flow rate and with a controlled concentration in a dissolved gas.

IPC Classes  ?

• C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
• C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means

Abstract

The present invention relates to compounds comprising two biguanidyl radicals that can be useful as anti-inflammatory agent, and also to new compounds comprising two biguanidyl radicals and their use as a drug, in particular for treating a cancer, a metabolic disease, a secondary mitochondrial disorder due to copper overload including Indian childhood cirrhosis, Wilson's disease and Idiopathic infantile copper toxicosis or due to iron overload, an infection by a virus such as a coronavirus or an influenza virus, a neurodegenerative disease or disorder and aging.

IPC Classes  ?

• C07C 279/26 - X and Y being nitrogen atoms, i.e. biguanides
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to methods for inducing targeted meiotic recombination in a eukaryotic cell, wherein the method is designed to maintain efficient induction of meiotic recombination using a CRISPR system even after a large number of mitotic cell cycles by reducing of the activity of CRISPR nuclease outside of meiosis and/or using several guide gRNAs specific of different sites in a targeted chromosomal region thereby increasing the probability to retain at least one intact target site for gRNA available in each meiotic cell.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
• C12N 15/81 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
• C12N 15/90 - Stable introduction of foreign DNA into chromosome
• C12N 9/90 - Isomerases (5.)

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 9/90 - Isomerases (5.)
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/81 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
• C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

An in vitro method belonging to the field of medicine, more specifically the field of cancer prognostic and therapeutic management, is disclosed. The method is for classifying a subject afflicted with a solid cancer as having a good prognosis or a poor prognosis. The method comprises detecting in a cancer cell sample from the subject phosphorylated RelB protein at the serine residue 472 and/or detecting a RelB homolog phosphorylated at a corresponding serine. A kit for implementing the method also is disclosed.

IPC Classes  ?

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

Goods & Services

Administration of funds and investments; Administration of financial affairs; Banking; collection of monetary donations for charitable purposes; Fundraising and financial sponsorship; Collection of charitable donations and charitable fund raising, for others; Banking advice; Management of financial assets; Administration of financial affairs; Fund management; Wealth management; Financial management; Financial sponsorship and patronage; Providing funding for non-profit entities; Providing monetary grants to charities; Providing project subsidies in the context of projects for promoting awareness of health-related issues; Providing of grants for environmental and health awareness projects; Provision of funding grants for research; Organisation of charitable collections; Financial sponsorship; Investment of funds for charitable purposes; Banking; Charitable fund raising; Charitable fundraising to support medical research; Fundraising; Providing educational scholarships.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/725 - T-cell receptors
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

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  ?

• G06N 3/02 - Neural networks
• G06N 20/00 - Machine learning
• G06T 7/10 - SegmentationEdge detection
• G06T 7/00 - Image analysis
• G06T 7/11 - Region-based segmentation
• G06T 15/08 - Volume rendering

Abstract

The invention provides compositions and methods for treating a refractory, relapsed or resistant cancer or a chronic infectious disease. In particular the present invention relates to a modified immune cell with reduced SUV39H1 activity, for use in the treatment of a patient suffering from a refractory, relapsed or resistant cancer or suffering from a chronic infectious disease, wherein the cell expresses one or more engineered antigen-specific receptors that bind an antigen associated with the cancer or the chronic infectious disease.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/725 - T-cell receptors
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The present invention relates to a compound of formula (I) and its use for inducing the production of interleukin-10 (IL-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 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• C07D 235/18 - BenzimidazolesHydrogenated benzimidazoles with aryl radicals directly attached in position 2
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 37/00 - Drugs for immunological or allergic disorders
• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues

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 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• C07D 235/18 - BenzimidazolesHydrogenated benzimidazoles with aryl radicals directly attached in position 2
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 37/00 - Drugs for immunological or allergic disorders
• 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
• C12N 5/07 - Animal cells or tissues

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  ?

• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 37/08 - Antiallergic agents
• C07D 471/04 - Ortho-condensed systems
• C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor

Abstract

The invention provides a multispecific molecule capable of simultaneous binding to a Mucosal Associated Invariant T (MAIT) cell and a tumor cell, which multispecific molecule comprises at least one domain that specifically binds a Vα7.2 T cell receptor (TCR) and at least one domain that specifically binds a tumor associated antigen (TAA).

IPC Classes  ?

• C07K 16/46 - Hybrid immunoglobulins
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention concerns a modified myeloid cell comprising a chimeric antigen receptor (CAR), or a modified induced pluripotent stem cell (iPS) or hematopoietic stem cell (HSC) comprising a CAR, wherein said CAR comprises an extracellular antigen-binding domain which binds to a tumor antigen or a tumor microenvironment (TME) antigen; a transmembrane domain; and a first intracellular signaling domain comprising the CD40 cytotail, which is fused to a second intracellular signaling domain comprising the CD3zeta intracellular domain. It also relates to therapeutic uses thereof. Figure : none

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 14/525 - Tumour necrosis factor [TNF]
• C07K 14/725 - T-cell receptors
• C12N 5/0786 - MonocytesMacrophages
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The present invention concerns a modified myeloid cell comprising a chimeric antigen receptor (CAR), or a modified induced pluripotent stem cell (iPS) or hematopoietic stem cell (HSC) comprising a CAR, wherein said CAR comprises an extracellular antigen-binding domain which binds to a tumor antigen or a tumor microenvironment (TME) antigen; a transmembrane domain; and an intracellular signaling domain comprising the CD40 cytotail. It also relates to therapeutic uses thereof.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 14/525 - Tumour necrosis factor [TNF]
• C07K 14/725 - T-cell receptors
• C12N 5/0786 - MonocytesMacrophages
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The invention is in the field of immunotherapy. The present application provides modified RELA protein which are useful for inducing or promoting interferon expression by immune cells, in particular T cells. The invention enables the production of immune cells with an activated or enhanced interferon metabolism. The present application also relates to immune cells, in particular T cells, comprising and/or expressing a modified RELA protein according to the invention, such cells having an activated interferon metabolism. The present invention also provides in vitro and/or ex vivo method of preparing immune cells, in particular T cells, useful in immunotherapy. The invention also relates to methods for treating a patient, in particular a patient who has a cancer or an infectious disease, in particular an infection by a virus.

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
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• A61P 31/18 - Antivirals for RNA viruses for HIV
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention concerns a compound of formula (I), in particular as radiosensitizer agent. The present invention also concerns these new compounds for use for treating cancer such as glioblastoma, lung cancer, or ovarian cancer, in particular in combination with radiotherapy or with an anticancer drug.

IPC Classes  ?

• C07F 15/00 - Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
• A61P 35/00 - Antineoplastic agents

Abstract

The present application relates to fully humanized anti-FGFR4 single domain antibodies (sdAbs) and variants thereof. The present invention further relates to functionalized drug nanocarriers, nucleic acids, vectors, host cells, immune cells comprising said sdAbs, and compositions comprising thereof, as well as their use for therapy.

IPC Classes  ?

• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• 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
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention relates to a method for identifying a cancer patient presenting microsatellite unstable tumor who is likely to benefit from immunotherapy comprising detecting a mutation within a microsatellite sequence by subjecting said sample to a digital polymerase chain reaction. The present invention also encompasses an immune checkpoint inhibitor for use in the treatment of a cancer in a patient who is previously identified as likely benefit from an immunotherapy and a method for evaluating the therapeutic response of an immune checkpoint inhibitor in a patient having a cancer.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6869 - Methods for sequencing

Abstract

The present invention relates to an engineered immune cell defective for SOCS1. Preferably, said engineered immune cell further comprises a genetically engineered antigen receptor that specifically binds a target antigen. The present invention also relates to a method for obtaining a genetically engineered immune cell comprising a step consisting in inhibiting the expression and/or activity of SOCS1 in the immune cell; and further optionally comprising a step consisting in introducing in the said immune cell a genetically engineered antigen receptor that specifically binds to a target antigen. The invention also encompasses said engineered immune cell for their use in adoptive therapy, notably for the treatment of cancer.

IPC Classes  ?

• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• C07K 14/725 - T-cell receptors
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61P 35/00 - Antineoplastic agents

Abstract

The present disclosure provides shared neoantigenic peptides derived from the expression of tumor-specific transposable element, as well as nucleic acids, vaccines, antibodies and immune cells that can be used in cancer therapy.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6869 - Methods for sequencing

Abstract

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 Acute Myeloid Leukemia (AML). 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 Acute Myeloid Leukemia (AML).

IPC Classes  ?

• A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
• A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

The invention relates to a method for monitoring at least one substance which may be produced or consumed by at least one living entity, and to an assembly for implementing the method. The method comprises flowing liquid medium having a controlled concentration of a dissolved gas and a controlled flow rate to a culture system (201) and taking at least one measurement within the culture system (201) so as to determine the presence, concentration or amount of the at least one substance in the liquid medium (205) in the culture system (201); and/or taking at least a first measurement upstream of the culture system (201) and a second measurement downstream of the culture system (201), and determining a concentration or amount of the substance consumed or produced by the at least one living entity based on the difference between the second measurement and the first measurement.

IPC Classes  ?

• C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
• C12M 1/00 - Apparatus for enzymology or microbiology

Abstract

Inflammatory Bowel Diseases (IBDs) represent 3 million cases a year in a continent like the US. Differentially diagnosing Crohn's Disease (60% of IBDs) from Ulcerative Recto-Colitis (URC, 40% of IBDs) is required for differential treatments, but involves time-consuming and expensive batteries of more than 10 analyses, including repeated biopsies, with a 10-20% probability of miss- diagnosis. Here we find that the phosphorylation of GSK3β on Ser9 (pSer9GSK3β) is a single strong discriminant marker of URC patient biopsies compared to Crohn patient biopsies, with a 2-7% probability of miss-diagnosis. pSer9GSK3β is thus an innovative unique and simple sharp test to diagnose IBD type (URC and Crohn's).

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 concerns novel peptides targeting the interaction between Kindlin-1 and β-integrin, and pharmaceutical compositions comprising these peptides. The invention also relates to these peptides and compositions for use in a method for preventing and/or treating cancer in a subject.

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
• A61P 35/00 - Antineoplastic agents
• A61K 38/00 - Medicinal preparations containing peptides
• C07K 19/00 - Hybrid peptides

Abstract

The present invention provides an in vitro method for detecting immunosuppressive fibroblasts, in particular Cancer Associated Fibroblast (CAFs) in a cancer sample from a subject suffering from cancer, wherein the method comprises detecting ANTXR1+ fibroblasts in the cancer sample from said patient. The invention also concerns an in vitro method for predicting a response of a subject suffering from cancer to an immunotherapy treatment, an immunotherapy treatment for use in the treatment of a cancer in a patient, the use of ANTXR1 as a biomarker for the identification of immunosuppressive fibroblasts, in particular immunosuppressive CAFs, an agent targeting ANTXR1+ fibroblasts for use in the treatment of a cancer in a patient, and a product or kit comprising a) an agent targeting ANTXR1+ fibroblasts and b) an immunotherapy treatment.

IPC Classes  ?

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

IPC Classes  ?

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

Abstract

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

IPC Classes  ?

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

Abstract

The present invention relates to a human AMHRII-binding agent for its use for preventing or treating a lung cancer, and especially a non-small call lung cancer (NSCLC), and even more especially a NSCLC selected in a group comprising epidermoid NSCLC, adenocarcinoma NSCLC, large cells NSCLC and squamous cell carcinoma NSCLC and neuroendocrine NSCLC.

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 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• A61P 35/00 - Antineoplastic agents
• A61P 11/00 - Drugs for disorders of the respiratory system

Abstract

The invention relates to the use of an iron-score based on the expression level of at least 2 genes, in particular at least 5, preferably at least 10, and even preferably 11 genes selected in the group consisting of ALAS1, HIF1A, LRP2, HMOX1, HMOX2, HFE, ISCA1, SLC25A37, PPOX, STEAP1 and TMPRSS6 involved in the iron metabolism, as a prognosis marker in subjects having DLBCL, in particular for identifying subjects with a poor outcome such as a relapse and/or death.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to an amorphous solid dispersion comprising ABX464 and at least one pharmaceutically acceptable carrier. The present invention also concerns a pharmaceutical composition comprising said ASD, processes for their preparation, an ASD obtainable by specific processes, their use as a medicament and more particularly their use in the treatment and/or prevention of inflammatory diseases, diseases caused by viruses and/or cancer or dysplasia.

IPC Classes  ?

• A61K 31/47 - QuinolinesIsoquinolines
• A61K 9/20 - Pills, lozenges or tablets
• A61K 9/28 - DrageesCoated pills or tablets
• A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
• A61K 9/16 - AgglomeratesGranulatesMicrobeadlets