Abstract

The present invention relates to methods and kits of assessing status, risk or prognosis of type 1 diabetes. There is still a need for improved methods of prognosis of type 1 diabetes. The inventors have observed different alterations of iNKT and MAIT cells quantity, frequency and markers in T1D patients compared to controls and also in children with recent onset T1D compared to control children or children with established T1D. The present invention relates to a method of assessing status, risk or prognosis of type 1 diabetes in a subject comprising i) quantifying at least one population of innate-like T-cells in a blood sample obtained from the subject, ii) comparing the quantification value determined at step i) with a predetermined reference value and iii) detecting differential in the quantification value determined at step i) and the predetermined reference value is indicative of the status, risk of prognosis of type 1 diabetes.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
• A61P 3/02 - Nutrients, e.g. vitamins, minerals
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Abstract

The present invention relates to methods and pharmaceutical compositions for the treatment of choroddal neovascularisation. In particular, the present invention relates to a method of treating choroidial neovascularisation in a subject in need thereof comprising administering to the subject of therapeutically effective amount of a mineralocorticoid receptor antagonist.

IPC Classes  ?

• A61K 31/585 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 27/02 - Ophthalmic agents
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/16 - Agglomerates; Granulates; Microbeadlets

Abstract

The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising i) determining in a tumor sample obtained from the patient the gene expression level of at least 7 genes selected from the group consisting of CCR2, CD3D, CD3E, CD3G, CD8A, CXCL10, CXCL11, GZMA, GZMB, GZMK, GZMM, IL15, IRF1, PRF1, STAT1, CD69, ICOS, CXCR3, STAT4, CCL2, and TBX21, ii) comparing every expression level determined at step i) with their predetermined reference value and iii) providing a good prognosis when all expression levels determined at step i) are higher than their predetermined reference values, or providing a bad prognosis when all expression levels determined at step i) are lower than their predetermined reference values or providing an intermediate prognosis when at least one expression level determined value is higher than its predetermined value. The method is also particularly suitable for predicting the responsiveness of the patient to a treatment.

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 methods and pharmaceutical compositions of inducing immune tolerance by mucosal vaccination with Fc-coupled antigens. In particular, the present invention relates to a method for inducing tolerance to one antigen of interest in a subject in need thereof, comprising the mucosal administration to the subject of a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and an antigen-containing moiety.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection

Abstract

The invention relates to a method of processing data representative of a person's binocular motricity, the method comprising the following steps: - stimulating the binocular motricity of a person by means of a binocular motricity stimulation device (21) configured to specifically stimulate saccades, vergences or a combination of both or of a reading test (22); physical stimuli in 3D real space seen with both eyes naturally (without artifices); - acquiring the movement of the right eye (RE) and the left eye (LE) of a person (P) during said stimulation and, if applicable, a stimulation signal from the binocular motor stimulation device; the method comprising the following steps implemented in a processing unit (3); - determination from the movement of the left eye (LE) and the right eye (RE), of an effective trajectory (Tr1) of the eyes in response to each stimulation, an effective trajectory corresponding to a saccade and/or a vergence movement of the eyes.

IPC Classes  ?

• A61B 3/113 - Objective types, i.e. instruments for examining the eyes independent of the patients perceptions or reactions for determining or recording eye movement
• A61B 3/08 - Subjective types, i.e. testing apparatus requiring the active assistance of the patient for testing binocular or stereoscopic vision, e.g. strabismus

Abstract

The present invention concerns an optical system for spatiotemporally shaping the wavefront of the electric field of a light beam (1) to be projected into a target volume (5), where the propagation axis is axis z, to create 3D patterned illumination in the target volume (5), comprising a pulsed laser source, configured to have an illumination pattern whose transversal surface at the target volume being superior to the diffraction limit of the optical system, at least one intermediate optical element (4) which is a dispersive grating for performing temporal focusing of the light beam (1), located, on the propagation axis (z), where an image of the illumination pattern is formed, for modulating the phase and/or the amplitude of the electric field of the light beam, and a second optical element (3) which is a spatiallight modulator for modulating the phase of the electric field of the input light beam, and for realizing spatiotemporal multiplexing to create 3D patterned illumination in the target volume (5) by replicating the illumination pattern, so as to have several replicated illumination patterns in the target volume (5), and controlling the position with transversal coordinates X, Y and axial coordinate Z of each replicated illumination pattern in the target volume (5).

IPC Classes  ?

• G02B 21/06 - Means for illuminating specimen
• G02B 5/32 - Holograms used as optical elements
• G02B 27/10 - Beam splitting or combining systems
• G03F 7/20 - Exposure; Apparatus therefor

Abstract

The present invention relates to a digital method for detecting and/or quantifying at least one target biomolecules in a sample, said biomolecules being selected from DNA, RNA, and proteins based on isothermal amplification. The present invention further relates to different applications of the digital method and to a kit.5

IPC Classes  ?

• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6853 - Nucleic acid amplification reactions using modified primers or templates

Abstract

The present invention relates to a digital multiplex method for detecting and/or quantifying multiple target biomolecules in a sample, said biomolecules being selected from DNA, RNA, and proteins. The present invention further relates to different applications of the digital multiplex method and to a kit.

IPC Classes  ?

• C12Q 1/682 - Signal amplification
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6853 - Nucleic acid amplification reactions using modified primers or templates

Abstract

The present invention relates to a method for treating a Leber congenital amaurosis in a patient harbouring the mutation c.2991+1655 A>G in the CEP290 gene, comprising the step of administering to said patient at least one antisense oligonucleotide complementary to nucleic acid sequence that is necessary for preventing splicing of the cryptic exon inserted into the mutant c. 2991+1655 A>G CEP290 mRNA.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Abstract

The present invention is directed to 5-membered heteroaryl compounds containing a hydroxamate moiety of Formula I, pharmaceutically acceptable salts or solvates thereof, and their use as sensitizers for chemotherapy of malignant tumors.

IPC Classes  ?

• 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
• C07D 231/38 - Nitrogen atoms
• 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 403/04 - 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 directly linked by a ring-member-to-ring- member bond
• C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 413/12 - 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 linked by a chain containing hetero atoms as chain links
• C07D 249/04 - 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
• C07D 271/06 - 1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
• A61P 35/00 - Antineoplastic agents
• A61K 31/4192 - 1,2,3-Triazoles
• A61K 31/4245 - Oxadiazoles
• A61K 31/415 - 1,2-Diazoles
• A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole

Abstract

Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRPl and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g. anti-PD1 antibody) could efficiently repress tumor growth in human cancer. The present invention also relates to multispecific antibodies comprising at least one binding site that specifically binds to an immune checkpoint molecule (e.g. PD-1), and at least one binding site that specifically binds to NRP-1. The present invention also relates to a population of cells engineered to express a chimeric antigen receptor (CAR) and wherein the expression of NRP-1 in said cells is repressed.

IPC Classes  ?

• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer

Abstract

A method for quantifying the balance of an individual recording, on a memory, at least one statokinesigram of the individual obtained from a platform comprising pressure and/or force sensors; extracting, by a processor and from the at least one statokinesigram of the individual recorded on the memory, values of at least one position trajectory parameter of the pressure center and values of at least one stability trajectory parameter of the pressure center; determining, by the processor, the value of a plurality of quantifiers, from the values of the trajectory parameters extracted; comparing, by the processor, said values of the plurality of quantifiers with the values of the same quantifiers obtained from reference statokinesigrams; and determining, by the processor, said value representative of the balance of the individual at the end of the comparison.

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons

Abstract

The invention relates to the combined use of selective serotonin reuptake inhibitors (SSRIs) and hematopoietic growth factors as a drug and particularly for treating cytopenia related to hematopoietic diseases or chemotherapy, and also to a pharmaceutical kit comprising both SSRIs and hematopoietic growth factors. This combination is more particularly used for treating patients presenting cytopenia, and patients in need of chemotherapy and more particularly to reduce length of chemotherapy-induced aplasia.

IPC Classes  ?

• A61P 7/06 - Antianaemics
• A61K 31/138 - Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• A61K 38/20 - Interleukins
• A61K 38/18 - Growth factors; Growth regulators
• A61K 38/19 - Cytokines; Lymphokines; Interferons
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/135 - Amines, e.g. amantadine having aromatic rings, e.g. methadone
• A61K 31/15 - Oximes (C=N—O—); Hydrazines (N—N); Hydrazones (N—N=)
• A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom

Abstract

regregex vivoin vivoin vitroin vitro, was associated to temporary or lasting remission of disease in spontaneously diabetic NOD mice.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 9/14 - Particulate form, e.g. powders
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/51 - Nanocapsules
• A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution

Abstract

FOXP3FOXP3), which leads to the loss of function of thymus-derived CD4+CD25+ regulatory T (tTreg) cells. Preclinical and clinical studies suggest that T cell gene therapy approaches designed to selectively restore the repertoire of Treg cells by transfer of wild type FOXP3 gene is a promising potential cure for IPEX. However, there is still a need for a vector that can be used efficiently for the preparation of said Treg cells. The inventors thus compared 6 different lentiviral constructs according to 4 criteria (vector titers, level of transduction of human CD4+ T cells, level of expression of FOXP3 and ΔLNGFR genes, degree of correlation between both expression) and selected one construct comprising a bidirectional PGK-EF1a promoter that showed remarkable efficiency.

IPC Classes  ?

• C12N 15/86 - Viral vectors

Abstract

Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors explained by germline or somatic mutations in about 70% of cases. Patients with SDHB mutations are at high- risk of developing a metastatic disease, yet no biomarkers are available to predict metastatic potential. Here, the inventors performed a comprehensive analysis of long non-coding RNAs (lncRNAs) using a mining approach of transcriptome data from a well-characterized series of 187 PPGL. They aimed at identifying lncRNAs specific for molecular groups and for metastatic progression of SDHB-mutated tumors. Consensus clustering analyses identified four lncRNA-based subtypes strongly correlated with mRNA expression clusters. This classification was validated in an independent series of 51 PPGL. Receiver operating characteristic curve analyses identified one putative lncRNAs (GenBank: BC063866) that accurately discriminates metastatic from benign tumors in patients at high-risk of progression. Expression of this transcript was validated by RT- qPCR in both discovery and validation series of PPGL. Moreover, cox proportional hazards regression analysis for metastasis-free survival (MFS) demonstrated that BC063866 is an independent risk factor associated with poor clinical outcome of SDHx carriers (log-rank test P = 2.29×10-05). The findings extend the spectrum of transcriptional dysregulations in PPGL to lncRNAs and provide a novel biomarker that could be useful to identify potentially metastatic tumors in patients carrying SDHx mutations.

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

Conditioning regimens aiming at preparing a subject to hematopoietic stem cell transplantation are associated with immediate and delayed toxicities. Accordingly, there is a need for new method that will allow full ablation of hematopoiesis. The inventors identify such a novel target. Indeed, the inventors get interested in three patients presenting a severe SCID form at birth associated with septicaemia. Genetic studies of patients' fibroblasts lead them to identify the same mutation in the Ras-related C3 botulinum toxin substrate 2 (RAC2) gene. More particularly, they showed that introduction of the mutation in hematopoietic stem and progenitor cell (HSPC) leads to a drastic decrease of the proliferation and differentiation toward different lineages (T cells, granulocytes, and monocytes). These results thus suggest that inhibition of RAC2 would be suitable for inducing ablation of hematopoiesis.

IPC Classes  ?

• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

The present invention relates to a compound or a pharmaceutically acceptable salt thereof of formulae (I) and (II), and a pharmaceutical composition comprising such compound for use for treating a cancer, particularly a cancer overexpressing CXCR1 and CXCR2 receptors, such as medulloblastoma, head and neck and kidney cancer. The invention further relates to such compounds for use for treating macular degeneration.

IPC Classes  ?

• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/428 - Thiazoles condensed with carbocyclic rings
• A61P 35/00 - Antineoplastic agents
• A61P 27/00 - Drugs for disorders of the senses

Abstract

Activated cardiac fibroblasts are essential for the production of extracellular matrix proteins that accumulate during cardiac fibrosis, and PW1+cardiac adult stem cells were recently proposed as a cellular source of fibroblasts in the ischemic hearts. Here the inventors identify αV-integrin (or CD51) as an essential regulator of PW1+cardiac adult stem cells fibrogenic behavior. Inhibition of αV-integrin reduce the profibrotic gene expression profile and the ability to differentiate into fibroblasts of cardiac PW1+ cells. The pharmacological blockade of αV-containing integrins improved cardiac function and survival after MI by reducing infarct size and attenuating the extension of reactive cardiac fibrosis. Notably, the total cardiac fibrotic area as well as interstitial fibrosis in the remote myocardial area are significantly reduced after pharmacological blockade of αV-containing integrins. These data identify a new mechanism that regulates cardiac fibrosis in response to an ischemic injury and suggest that pharmacological targeting of αV-integrin may provide clinical benefit in the treatment of cardiac fibrosis.

IPC Classes  ?

• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61K 38/12 - Cyclic peptides
• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum

Abstract

The present invention relates to the field of neonatal cholestasis, in particular the treatment of neonatal biliary atresia or diseases associated with biliary system destruction. Also, the invention relates to methods and/or compounds for treating or preventing biliary atresia or disease associated with biliary system destruction. It further relates to methods and/or compounds for slowing the progression of biliary atresia or disease associated with biliary system destruction.

IPC Classes  ?

• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• A61K 31/195 - Carboxylic acids, e.g. valproic acid having an amino group
• A61K 31/4406 - Non-condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
• A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Abstract

Olmsted syndrome (OS) is a rare genodermatosis classically characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques. The inventors obtained remarkable results with a treatment with a EGFR inhibitor (e.g. erlotinib) in 3 patients with Olmsted Syndrome and erythemalgia linked to different TRPV3 mutations. In less than 3 months, the drug induced a complete disappearance of the hyperkeratosis and the pain. Anorexia and insomnia disappeared with an improvement of the growth. Accordingly, the present invention relates to the use of EGFR inhibitors for the keratodermas.

IPC Classes  ?

• A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61P 17/12 - Keratolytics, e.g. wart or anti-corn preparations
• A61P 17/00 - Drugs for dermatological disorders

Abstract

The present invention relates to the field of memory and cognitive functions. Here the inventors show that memory stimulations induce autophagy in the mouse hippocampus, while local pharmacological and genetic modulations of hippocampal autophagy strongly influence memory acquisition. More, the inventors observe that hippocampal autophagy declines during aging and they find that restoring autophagy specifically in the hippocampus of aged mice, following autophagy inducers (such as TAT-Beclin-1), can significantly reverse age-related memory decline. Their results reveal a novel physiological role of autophagy in regulating hippocampal-dependent memory functions, and demonstrate the potential therapeutic benefits of modulating autophagy in order to prevent and/or reverse the deleterious effects of aging on cognitive function. The present invention relates to an activator of the autophagy for use in the restoration and/or improvement of cognitive functions in a subject in need thereof.

IPC Classes  ?

• C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans

Abstract

The invention relates to a device for quantifying the dexterity of the fingers of a hand, comprising: a main body, and a plurality of assemblies for measuring the movement of and/or the force applied by a finger in a pressing direction, each measurement assembly comprising a deformation sensor, the deformation sensor comprising a deformable body. The device is characterised in that each measurement assembly also comprises: a guiding bearing which is fixedly joined to the main body; a shaft having a bearing surface, said bearing surface being in contact with the deformable body; a tube which can slide in translation in the guiding bearing and about the shaft in the pressing direction, said tube having a head suitable for attaching the finger to the tube; a first spring which connects the bearing to the tube; and a second spring which connects the shaft to the tube, the first spring and the second spring being prestressed so as to prestress the deformable body.

IPC Classes  ?

• A61B 5/11 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb
• A61B 5/22 - Ergometry; Measuring muscular strength or the force of a muscular blow
• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons

Abstract

FGFR3FGFR3 gain-of-function mutations are responsible for a family of chondrodysplasias namely, achondroplasia (ACH) the most common form of dwarfism, a lethal form of dwarfism thanatophoric dysplasia (TD) as well as and hypochondroplasia. Recent data demonstrate that Infigratinib (NVP-BGJ398) corrects pathological hallmarks of ACH and support it as a 10 potential therapeutic approach for FGFR3-related skeletal diseases. Now the inventors has investigated the feasibility to treat the defective growth of the skeleton during the pregnancy with the drug. They treated pregnant female Fgfr3Neo/Y367Cmice with the drug (4mg/kg) that was injected subcutaneously at day E14.5 continuing daily through day 1 (after birth). The data indicated that BGJ398 treatment during 5 days in pregnant mice successfully repressed skeletal 15 anomalies that occurred during embryonic stages. Accordingly, the present invention relates to methods for treatment of FGFR3-related skeletal diseases during pregnancy with Infigratinib.

IPC Classes  ?

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

Abstract

The invention relates to a PI3K inhibitor for use in the treatment of neurofibromatosis type 1 and type 2 in a subject in need thereof. Currently there are no treatment of neurofibromatosis type 1 and 2. Patients mainly received supportive care to treat severe symptoms including surgery to remove tumors compressing nearby tissue or damaging organs, stereotactic radiosurgery or cochlear implants. Inventors have worked on immortalized NF1-/- cells and shown that PIK3CA pharmacological inhibition (BYL719) was associated with increased apoptosis as assessed by PARP cleavage in a dose dependent manner. They also decided to expose NF1-/- cells to a multitargeted therapy including BYL719 + selumetinib or BYL719 + selumetinib + IPA-3. Importantly, they found that both combinations led to severe apoptosis with double strand DNA break as assessed by the phosphorylation of H2aX. This new approach with either BYL719 alone or in combination with other therapeutics seem to be very promising in patients with neurofibromatosis.

IPC Classes  ?

• A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
• A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 35/00 - Antineoplastic agents

Abstract

Cachexia is a potentially lethal syndrome afflicting mammals, frequently complicates the treatment of infection, inflammation and cancer. It is characterized by involuntary weight loss, including muscle loss and decrease in protein blood level content. The inventors now show in 2 animal models (mice fed with normal diet and mice fed with high fat diet) that neutralisation of the long fragment of neurotensin with an inhibitor of NTSR1 activation or expression prevents weight loss, muscle loss and protein blood level decrease. Accordingly, the present invention relates to use of an inhibitor of NTSR1 activation or expression for preventing weight loss, muscle loss, and protein blood level decrease in subjects in need thereof.

IPC Classes  ?

• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C07K 16/26 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

HBG1HBG2HBG1HBG2HBG2 genes. They validated these findings in Red Blood Cells (RBCs) derived from genome edited Sickle Cell Disease (SCD) patient hematopoietic stem/progenitor cells. Overall, this study identified a binding site for an HbF repressor as a novel and potent target for the treatment of β-hemoglobinopathies. Accordingly, the present invention relates to a method for increasing fetal hemoglobin content in a eukaryotic cell comprising the step of disrupting the binding site for Leukemia/lymphoma-related factor (LRF) in the HBG1 or HBG2 promoter.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof

Abstract

The present invention relates to a method of treating HER2/NEU overexpressing cancers. The inventors discovered that the heme-mediated formation of dimers and in general oligomers of Trastuzumab is associated with an improved complement-mediated cytotoxicity on breast cancer cells. The present data highlight that the sensitivity to heme of Trastuzumab, may have major repercussion on its therapeutic activity. Thus the invention relates to the combination of an HER2/neu antibody with a heme and/or of its oligomers and its therapeutic composition in the HER2/NEU characteristic cancer treatment.

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents
• C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
• A61K 38/42 - Haemoglobins; Myoglobins

Abstract

The invention relates to a calibration standard for determining an intensity decay related to an evanescent field generated close to the interface between a sample to be tested and a substrate on which said sample is to be deposited, preparation and analysis methods and use thereof.

IPC Classes  ?

• G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
• G01N 21/64 - Fluorescence; Phosphorescence
• G02B 21/34 - Microscope slides, e.g. mounting specimens on microscope slides
• G02B 21/16 - Microscopes adapted for ultraviolet illumination
• G02B 21/36 - Microscopes arranged for photographic purposes or projection purposes
• G02B 27/56 - Optics using evanescent waves, i.e. inhomogeneous waves

Abstract

The invention relates to a method for manufacturing a nanostructured powder comprising nanocrystalline agglomerates containing active pharmaceutical ingredient (API) in its crystalline form, said method comprising (i) Preparing a first solution comprising API and an API solvent; (ii) Mixing the first solution with a second solution comprising an API antisolvent and optionally a stabilizing agent P1 to obtain a third mixture; (iii) Evaporating the third mixture until both the API solvent and the API antisolvent are evaporated, advantageously under vacuum; characterized in that when the stabilizing agent P1 is present, the third mixture has a stabilizing agent P to API weight ratio equal or less than 5, preferably less than 2. The invention also concerns a nanostructured powder and a nanosuspension.

IPC Classes  ?

• A61K 9/14 - Particulate form, e.g. powders
• A61K 9/51 - Nanocapsules
• A61K 31/365 - Lactones
• A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
• A61P 35/00 - Antineoplastic agents

Abstract

The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydro-carbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

IPC Classes  ?

• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells

Abstract

The invention relates to a method for treating cancers. Many cancers harbour stemness signature to de-differentiate into immature progenitors confer to tumor clones the re-expression of genes from fetal development. Inventors have obtained mice per group which received two boosts of vaccine 7 and 14 days with 2x106 irradiated hESCs cells that were mixed with 3 different adjuvants: 500μg of TLR3, 50μg of TLR9 agonist or 50μg/ml of Quil A® Saponin vaccine adjuvant. After 14 days 5x104 4T1 cells were injected into the mammary fat pad of the mice and Valproic acid added in the drinking water at the dose of 4 mg/ml. They have shown that in contrast to the non-vaccinated mice, the mice vaccinated with hESC combined with a TLR3 agonist have generated the highest reduction of breast tumor volume (p<0.001) compared to the use of a TLR9 agonist or to Quil-A® Saponin vaccine adjuvant. Accordingly, the invention relates to a method for treating a subject suffering from a cancer with i) an agent that induces MHC-I presentation of antigens, ii) a vaccine composition containing an immunogenic element and iii) an adjuvant.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
• A61P 35/00 - Antineoplastic agents
• A61K 31/00 - Medicinal preparations containing organic active ingredients

Abstract

The present invention relates to nanoparticles, methods and compositions which are suitable for the detection and/or follow-up and/or treatment of type 1 diabetes. In particular, it relates to biocompatible tolerogenic nanoparticles comprising at least: (i) a ligand which can bind to an aryl hydrocarbon receptor (AHR) transcription factor; an (ii) a diabetes autoantigen selected from : insulin, preproinsulin, proinsulin, or an immunologically active fragment thereof The inventors have shown that such biocompatible tolerogenic nanoparticles are efficient for the identification of type-1 diabetes. It has also been shown that they can accumulate into the pancreas, and induce temporary or lasting remission of disease in spontaneously diabetic NOD mice. Kits and compositions are further provided.

IPC Classes  ?

• A61K 31/135 - Amines, e.g. amantadine having aromatic rings, e.g. methadone
• A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• 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
• A61K 47/52 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals

Abstract

The invention relates to a compound inhibiting the interaction between a Grb14 protein and an insulin receptor of Formula (I) or Formula (II), their salts, solvates, and/or diastereoisomers, for use for therapeutic purposes, in particular for the treatment of insulin resistance, and to pharmaceutical compositions containing such compounds.

IPC Classes  ?

• A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• A61K 31/42 - Oxazoles
• A61K 31/513 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine

Abstract

Disclosed herein are methods for treating patients that may develop or already have pre- existing gene therapy neutralizing antibodies by administering a protease that cleaves peptide bonds present in immunoglobulins or by administering a glycosidase that cleaves carbohydrate residues present on immunoglobulins, or other similar enzymatic cleavage of immunoglobulins in vivo. Also disclosed are methods for utilizing IdeS and other immunoglobulin G-degrading enzyme polypeptides for gene therapy treatment of a disease in a patient in need thereof.

IPC Classes  ?

• A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
• A61K 39/12 - Viral antigens
• C12N 9/64 - Proteinases derived from animal tissue, e.g. rennin

Abstract

The present invention relates to a method for promoting wound healing in a subject suffering from Ectodermal dysplasia in need thereof comprising a step of administering subcutaneously, intradermally or topically to said subject a therapeutically effective amount of a compound which restores the activity of p63. Inventors have performed a primary culture of patient keratinocytes suffering from ectodermal dysplasias with two compounds which restore the activity of p63 (e.g.STIMA-1 and/or PRIMA-1Met). They have shown that there is an important differentiation of the keratinocytes of said patient compared to the cells not treated with these compounds. They observed that the activity of p63 mutated is restored, thus the proliferation and differentiation of keratinocytes from the patient are activated. Moreover, inventors have used PRIMA-1Met by topical application on a young patient suffering from ectodermal dysplasias and shown that said patient presents an improvement on her hand. Typically, severe skin erosions (on hands and feet) are healing when PRIMA-1Met is administered topically on the hand.

IPC Classes  ?

• A61K 31/4748 - Quinolines; Isoquinolines forming part of bridged ring systems
• A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 47/10 - Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• A61P 17/00 - Drugs for dermatological disorders

Abstract

12M12DD), inference of a generative model, comprising updating topics k which 1 are a set of elements which co-occur in the file vectors, and updating the estimated row clustering Y and the estimated column clustering X on the basis of a statistical criterion, and repeating inference until a convergence criterion is fulfilled, resulting in a co-clustering of rows and columns which is a function of the co-occurrence of elements belonging to the same topics in the file vectors.

IPC Classes  ?

• G06F 16/28 - Databases characterised by their database models, e.g. relational or object models

Abstract

222S in biological fluids by means of this sensor.

IPC Classes  ?

• C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions

Abstract

Choroidal neovascularization (CNV) is a major cause of vision loss, due to exudation of intraretinal or subretinal fluid, hemorrhage, or fibrosis at the macula. Neovascularization arising from the choroidal circulation is seen in are age-related macular degeneration (AMD), pathological myopia (PM), choroidits and central serous chorioretinopathy (CSCR). The current anti-VEGF treatments do not induce a total regression of the CNV requiring repeated injections to maintain vision. Moreover, evidence regarding anti-VEGF therapy resistance suggests a need for alternative medicines for the treatment of CNV. Despite the anatomical separation of choroid from vitreous, the inventors surprisingly found that intravitreal of decorin (DCN) is suitable for inhibiting choroidal neovascularisation. In particular, the inventors show an anti-angiogenic effect of DCN on CNV and demonstrate that laser-induced CNV decreased DCN expression in the RPE-Choroid. Accordingly, the present invention relates to a method of treating choroidal neovascularization comprising delivering a therapeutically effective amount of a decorin polypeptide in the vitreous of the eye.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 27/10 - Ophthalmic agents for accommodation disorders, e.g. myopia
• A61P 27/02 - Ophthalmic agents

Abstract

TUBB1TUBB1Tubb1in vivoTUBB1TUBB1 mutations caused hyperaggregation of human platelets. The data highlight unexpected roles for β1-tubulin in thyroid development and function and in platelet physiology. Accordingly, the present invention relates to a method of diagnosing thyroid dysgenesis in a subject, comprising detecting a mutation in the TUBB1 gene in a sample obtained from said subject, wherein detecting the presence of a mutation in the TUBB1 gene is considered to be indicative of thyroid dysgenesis.

IPC Classes  ?

• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism

Abstract

The present invention relies on the discovery that, surprisingly, when it is produced locally in the epidermis, hepcidin is able to directly initiate the recruitment of neutrophils by increasing the CXCL1 production in keratinocytes. While hepcidin had no direct antimicrobial activity against Group A streptococcus (GAS), injection of hepcidin, at the site of infection prevented GAS systemic spread. Hepcidin agonists may represent a novel therapeutic to prevent life threatening bacteremia not only in streptococcal NF but also in complicated infections due to compromised host immunity. The present invention relates to a method for treating Gram- positive bacterial infection in a patient in need thereof, comprising administering to the patient hepcidin polypetide. More specifically, it concerns method for treating with mature form of hepcidin, gram-positive bacterial infection such as Group A streptococcus infection which could be associated with Necrotizing fasciitis (NF).

IPC Classes  ?

• A61P 31/04 - Antibacterial agents
• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans

Abstract

TP53, EGFRSTK11 TP53, EGFRSTK11TP53, STK11EGFREGFR and concluding that the patient has a high probability to achieve a response with an immune checkpoint inhibitor in function of its mutations profile.

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

1211C11c11abcc, X2- and L as defined in the claims, or a hydrate or a solvate thereof. Compositions and kits comprising same are also described. Said bis-hydrazone derivatives of formula (I), compositions and kits are useful as drugs, in particular for treating or preventing cancers associated with the Epstein-Barr Virus.

IPC Classes  ?

• C07D 401/14 - 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 three or more hetero rings
• A61K 31/47 - Quinolines; Isoquinolines
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 471/04 - Ortho-condensed systems
• A61P 35/00 - Antineoplastic agents

Abstract

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

IPC Classes  ?

• A61K 38/00 - Medicinal preparations containing peptides
• C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61K 38/22 - Hormones

Abstract

The present invention relates to the treatment of latent virus infections and improvement of transgene expression. Using Virus-like Particles (VLPs) containing Vpx in an in vitro HIV-1 latent model, the Inventors evidenced an unexpected capacity of Vpx to reactivate latent proviruses through TASOR binding and subsequent degradation, in a way that is independent from SAMHD1. Besides, the Vpx protein strikingly enhanced viral expression following transduction of a transgene placed under the control of a cytomegalovirus (CMV) promoter in a HIV-1- derived vector or a SIVmac-derived vector. The present invention thus relates to a Vpx protein and/or nucleic acid encoding thereof for use as a medicament, particularly for reactivating a latent virus and/or improving expression of a transgene, for example in the context of gene therapy. The Vpx protein is preferably provided in the form of VLPs. The present invention also relates to the use of a Vpx protein as a transgene activator.

IPC Classes  ?

• C07K 14/155 - Lentiviridae, e.g. human immunodeficiency virus (HIV), visna-maedi virus, equine infectious anaemia virus
• A61K 38/00 - Medicinal preparations containing peptides
• C12N 15/86 - Viral vectors

Abstract

In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-l. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/132 - Amines, e.g. amantadine having two or more amino groups, e.g. spermidine, putrescine
• A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
• A61K 31/19 - Carboxylic acids, e.g. valproic acid
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 31/616 - Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
• A61P 35/00 - Antineoplastic agents
• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum

Abstract

The present invention relates to an in vitro method for identifying and/or characterizing one or more mutations in a hotspot mutation sequence of at least one ESR1 target fragment from a DNA sample, said method comprising subjecting the DNA sample to a drop-off digital polymerase chain reaction (PCR) in the presence of a PCR solution comprising: -a pair of primers suitable for amplifying an ESR1 target fragment; -an oligonucleotide reference (REF) hydrolysis probe, labeled with a fluorophore, wherein said REF oligonucleotide probe is complementary to a wild-type sequence of the target fragment located outside of the hotspot mutation sequence; -an oligonucleotide hotspot (HOTSPOT) hydrolysis probe, labeled with another fluorophore, wherein said oligonucleotide HOTSPOT probe is complementary to a wild-type sequence of the hotspot mutation sequence of the target DNA fragment.

IPC Classes  ?

• C12Q 1/6818 - Hybridisation assays characterised by the detection means involving interaction of two or more labels, e.g. resonant energy transfer
• 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

Abstract

Despite the notion that human CD8+in vitroin vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Secretogranin V (SCG5/7B2) was identified as a novel β-cell antigen, which was processed into HLA-A2- and HLA- A3-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. HLA-A2-bound neo-epitopes were also represented and originated from an alternative SCG5-009 mRNA splice isoform. Accordingly, the present invention relates to antigenic peptides derived from secretogranin V and uses thereof for the diagnosis and treatment of T1D.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
• C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• C07K 14/725 - T-cell receptors

Abstract

Despite the notion that human CD8+T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. PCSK2 was identified as a novel β-cell antigen, which was processed into HLA-A2-restricted epitopes recognized by circulating naïve CD8+T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from PCSK2 and uses thereof for the diagnosis and treatment of T1D.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
• C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans

Abstract

The present invention relates to methods for prognosing and treating metabolic diseases. The inventors demonstrated the association of obesity with the increase of intestinal IDO activity, which shifts tryptophan (Trp) metabolism from indole derivative but also IL-22 production towards kynurenine (Kyn) production. The inventors showed that the rewiring of Trp metabolism is possible towards a microbiota-dependent production of IL-22. In particular, the present invention relates to a method of treating metabolic diseases in a subject in need thereof comprising administering to the subject a therapeutically effective amount of probiotics

IPC Classes  ?

• A61K 35/741 - Probiotics
• A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
• A23L 33/135 - Bacteria or derivatives thereof, e.g. probiotics
• A61P 3/06 - Antihyperlipidemics
• A61P 9/12 - Antihypertensives
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61K 31/405 - Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

IJIJm, the membrane (10) being mechanically held in between the two layers (19), the recesses (14) respectively defining the fractionation microchannel (2) and the auxiliary microchannel (3) on each side of the membrane (10).

IPC Classes  ?

• G01N 30/00 - Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography

Abstract

nmm, wherein: SUPPORT represents a physiologically acceptable chemical or biological substrate, with a particle size of between 1 and 100 nm, SIGNAL is a fluorophore, L is a linker of formula –C(X)-R1-Y-, with X being O, NH or S R1166)alkyl group, optionally R1166)alkyl group, optionally interrupted by 1 to 3 groups selected from –O-, -NH-, -C(O)-, -NHC(O)-, –(O)CNH-, -C(O)NH-N=C-, -N=C-, and (I), Y being NH or a –(O)CNH- group, and BIOVECTOR is a carbohydrate targeting markers of inflammation, advantageously selected from the group consisting of mannose, sialyl LewisX and derivatives thereof, n is greater than or equal to 0.5 and is less than 2, m is between 0 and 30, preferably between 1 and 30, more preferably between 5 and 20, diagnostic compositions comprising same and use thereof as a diagnostic agent (in vivo or ex vivo), or as contrast agent for image-guided surgery.

IPC Classes  ?

• A61K 49/00 - Preparations for testing in vivo

Abstract

T. cacaoFgfr3Y367C/+Y367C/+Fgfr3+/++/+ femurs and improves the whole growth plate cartilage. The present invention thus relates to the use of (-)-epicatechin for the treatment of FGFR3-related chondrodysplasias.

IPC Classes  ?

• A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• A61P 19/00 - Drugs for skeletal disorders

Abstract

The present invention relates to a non-invasive method for detecting/monitoring renal endoplasmic reticulum stress in a subject. More specifically present invention relates to a non- invasive method for detecting/monitoring endoplasmic reticulum (ER) stress in a subject using urinary spliced XBP1 (X-Box binding protein-1) mRNA level. The inventors developed a genetic marker analyse in urine from individuals undergoing scheduled cardiac surgery 10 under cardiopulmonary bypass to investigate the feasibility and the significance of monitoring ER stress response in the kidney. A pioneering method was developed based on fragment analysis that measures urinary spliced XBP1 mRNA levels as a proxy of the activity of IRE1α, noting the sXBP1 has an absolute sensitivity and specificity for the activity of IRE1α, a transducer of the ER stress response. The present invention also relates to diagnostic and 15 monitoring methods of endoplasmic reticulum (ER) stress associated renal disease using urinary spliced XBP1 mRNA level.

IPC Classes  ?

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

Abstract

The present disclosure relates to the use of celiprolol or a pharmaceutically acceptable salt thereof for treating vascular Ehlers-Danlos syndrome in women during pregnancy and peripartum period.

IPC Classes  ?

• A61K 31/17 - Amides, e.g. hydroxamic acids having the group N—C(O)—N or N—C(S)—N, e.g. urea, thiourea, carmustine
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, notably for use as a drug, notably in the treatment of a disease caused by mycobacteria, as well as pharmaceutical compositions containing such a compound and a process to prepare such a compound.

IPC Classes  ?

• C07D 471/08 - Bridged systems
• A61P 31/04 - Antibacterial agents
• A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine

Abstract

The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, notably for use as β-lactamase inhibitors, notably in the treatment of a disease caused by gram negative bacteria, in particular enterobacteria, as well as pharmaceutical compositions containing such a compound and a process to prepare such a compound.

IPC Classes  ?

• C07D 471/08 - Bridged systems
• A61P 31/04 - Antibacterial agents
• A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine

Abstract

The invention relates to a CXCR4 receptor-binding compound for use for increasing or restoring interferon (IFN) level in an individual, wherein the interferon is a type-I interferon (IFN-I).

IPC Classes  ?

• A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• G16C 20/64 - Screening of libraries
• G16B 35/20 - Screening of libraries
• A61K 31/4164 - 1,3-Diazoles
• A61K 31/417 - Imidazole-alkylamines, e.g. histamine, phentolamine
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• G01N 33/566 - Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagent
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Abstract

in vitroin vitro method for testing the cytotoxicity of a candidate compound for living target cells, said method relying on the detection of the massive release of a cytosolic luminescent enzyme in the supernatant of the cells once they have been voluntarily permeabilized. The detection of this release is rapid and reproducible. More precisely, the method of the invention comprises the steps: a) contacting, with a candidate compound,living target cells that constitutively express in their cytosol a luminescent enzyme, b) isolating the supernatant of the coculture of step a) in a second recipient, c) adding in said second recipient the substrate of said luminescent enzyme, and d) measuring the luminescence emitted in said second recipient. The cytotoxicity of said candidate compound is then proportional to the increase in luminescence measured in step d). This method can be advantageously automated so as to assess the cytotoxicity of candidate compounds with high throughput screening devices.

IPC Classes  ?

• C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing

Abstract

The present invention relates to the prognosis of the outcome of a cancer in a patient, which prognosis is based on the quantification of one or several biological markers that are indicative of the presence of, or alternatively the level of, the adaptive immune response of said patient against said cancer.

IPC Classes  ?

• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

Autophagy is a universal anti-aging mechanism the chronic induction of which can extend the health span and lifespan of mammals. Here the inventors show that triethylenetetramine (TETA), also called trientine, a drug that is approved for the treatment of Wilson disease, can induce autophagy in mouse tissues in vivo. In particular, chronic autophagy stimulation by TETA can improve the metabolic characteristics of mice kept on a high-fat or high-sugar diet without reducing their food uptake, yet attenuating their weight gain. TETA attenuates adioposity, signs of obesity related type-2 diabetes and hepatosteatosis. TETA also mediates hepatoprotective effects against acute ethanol intoxication. Hence, TETA can be considered as a novel autophagy-inducing agent and thus can be used for the treatment of various diseases and in particular for the treatment of obesity, as well as obesity-related comorbidities.

IPC Classes  ?

• A61K 31/132 - Amines, e.g. amantadine having two or more amino groups, e.g. spermidine, putrescine
• A61K 31/375 - Ascorbic acid, i.e. vitamin C; Salts thereof
• A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• A61P 3/06 - Antihyperlipidemics
• A61P 3/04 - Anorexiants; Antiobesity agents
• A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• A61P 35/00 - Antineoplastic agents
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

The invention relates to a method for quantifying the balance of an individual in order to obtain a value that represents the balance of said individual, said method being implemented by a device comprising at least one data processing module, a storage means and a classification module, said method particularly comprising the following steps: time-dependent segmentation of the at least one statokinesigram of an individual in such a way as to generate a plurality of statokinesigram portions; extraction, from the statokinesigram portions, of the values of at least one trajectory parameter; determination of the value of at least two quantifiers, from the trajectory parameters extracted in the extraction step, for each of the statokinesigram portions generated in the segmentation step; and determination of said value representing the balance of the individual on the basis of the values of the quantifiers of each of the statokinesigram portions.

IPC Classes  ?

• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons

Abstract

The invention proposes a new method for monitoring a health event in a mammal, comprising detecting at least one abnormal value within a series of values related to at least one biomarker, based on appropriate Z-scores.

IPC Classes  ?

• G16C 20/00 - Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures

Abstract

This invention relates to a method for diagnosing and/or prognosticating HER2-dependent cancer in a subject, comprising a) measuring the amount of moesin in a sample from the subject; b) comparing the amount of moesin measured in step a) to a reference value; c) finding a deviation or no deviation of the amount of moesin measured in step a) from the reference value; and d) attributing said finding of deviation or no deviation to a particular diagnosis and/or prognosis of HER2-dependent cancer in the subject.

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

This invention relates to a method for diagnosing and/or prognosticating HER2-dependent cancer in a subject, comprising a) measuring the amount of one or more miRNA selected from the group consisting of miRNA 429-3p, miRNA 29c-3p, miRNA 29a-3p, miRNA 29b- 3p, miRNA 200a-3p, miRNA 200b-3p, miRNA 200c-3p, miRNA 141-3p, miRNA 15a-5p, miRNA 15b-5p, miRNA 16-5p, miRNA 424-5p, miRNA 497-5p, miRNA 615-3p, miRNA 451a-3p and miRNA 542-5p in a sample from the subject; b) comparing the amount of one or more miRNA measured in step a) to a reference value; c) finding a deviation or no deviation of the amount of one or more miRNA measured in step a) from the reference value; and d) attributing said finding of deviation or no deviation to a particular diagnosis and/or prognosis of HER2-dependent cancer in the subject.

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

This invention relates to an agent that modulates the activity of a micro ribonucleic acid (miRNA), said miRNA being selected from the group consisting of miRNA 429-3p, miRNA 29c-3p, miRNA 29b-3p, miRNA 200a-3p, miRNA 200b-3p, miRNA 200c-3p, miRNA 141- 3p, miRNA 15a-5p, miRNA 15b-5p, miRNA 16-5p, miRNA 424-5p, miRNA 497-5p, miRNA 615-3p, miRNA 451a-5p and miRNA 542-5p, for use in the treatment of HER2-dependent cancer.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
• A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides

Abstract

Autoimmune myopathy (AIM) represents a group of severe inflammatory diseases. Around 60% of patients with AIM have myositis-specific auto-antibodies (aAbs). Thus, the search for aAbs has substantially improved their diagnosis and may also inform on their prognosis, notably when there is an associated risk of cancer. Accordingly, the discovery of 10 new aAbs will help to improve the diagnosis of AIM. The present invention fulfils the need. In a cohort of 671 patients suffering from patients suffering from AIM, the inventors show that a minor percentage of them were positive for the present of MDH2 aAbs. No patient was found positive for this Ab in other autoimmune diseases. Accordingly, detection of anti-MDH2 aAbs would be suitable for the diagnosis of AIM.15

IPC Classes  ?

• G01N 33/564 - Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease

Abstract

Autophagy is typically activated by starvation, allowing cells and organisms to mobilize their energy reserves. It is known that pharmacological modulation of autophagy represents a therapeutic potential. Here the inventors report that a protein that is released from cells in an unconventional, autophagy-dependent manner, namely, diazepam binding inhibitor (DBI), regulates autophagy. In particular, the inventors demonstrate that DBI inhibits autophagy and that the supply of recombinant DBI to mice enhanced glycolysis, enhanced lipogenesis, and inhibited fatty acid oxidation. The inventors show that neutralisation of DBI by a monoclonal antibody and an active immunization by means of an immunogenic DBI derivative eliciting autoantibodies induce autophagy and lead to metabolic changes that increase starvation-induced weight loss, reduce food intake upon refeeding, and reduce weight gain in response to hypercaloric diets. Accordingly, the present invention relates to methods and pharmaceutical compositions for modulating autophagy based on the modulation of the activity or expression of DBI.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 37/00 - Drugs for immunological or allergic disorders
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans

Abstract

Circulating cell-free DNA in plasma (cirDNA) has gained interest as an element of innate immunity, thrombosis and coagulation. The inventors hypothesized that cirDNA could favor and participate in vaso-occlusions (VOC) in sickle cell disease (SCD). CirDNA levels were increased by 300% in SCD patients (n=87) at steady state versus controls (n=22), and a further 100% rise was observed during acute VOC. This latter rise disappeared within a week of hospitalization, as VOC terminated. In SCD plasma, increased cirDNA levels were coordinated with decreased endogenous plasma DNase activity, during steady state and acute phase VOC. Therapeutic use of DNase-1 diminished RBC aggregate robustness in SCD patient blood and released renal vaso-occlusions in transgenic mice with SCD. Hence, an imbalance between cirDNase activity and cirDNA levels controls vaso-occlusions in SCD and thus would represent a reliable biomarker for determining whether a patient suffering from sickle cell disease has or is at risk of having vaso-occlusions.

IPC Classes  ?

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

Abstract

The present invention relates to the prognostic of cancer and particularly renal cancer. Here, the inventors have investigated the presence and impact of C1q, produced by the macrophages, in the ccRCC TME and showed that it is associated with poor prognosis, particularly in patients with advanced and metastatic tumors. They propose that this is due to the activation of at least the early steps of the complement. Their data provide a novel mechanism of immune modulation of TME in ccRCC that may explain the particularly poor clinical impact of the TME in these tumors. Thus, the invention relates to a method for predicting the survival time of a patient suffering from a cancer by determining the expression level of C1q.

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 compounds of the following general formula (I) or (II): or a pharmaceutically acceptable salt and/or solvate thereof, for use in the treatment and/or in the prevention of ErbB2 dependent cancers, and pharmaceutical compositions containing such compounds.

IPC Classes  ?

• C07D 335/20 - Thioxanthenes with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
• A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents
• C07D 275/04 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
• C07D 279/24 - [b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
• C07D 293/12 - Selenazoles; Hydrogenated selenazoles
• 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
• C07D 409/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The inventors initially participated to the identification of LPIN1 mutations as a cause for massive rhabdomyolysis episodes in children, triggered by febrile illness. The inventors have suggested that TLR9 antagonists would be suitable for the treatment of rhabdomyolysis (WO2017085115). The inventors thus treated 2 patients with lipin-1 disease by a TRL9 antagonist (hydroxychloroquine). They showed that the accumulation of mtDNA in plasma of the two patients before treatment decreases under treatment. When the treatment was stopped, the accumulation of mtDNA reappeared, then normalized when treatment was resumed. Accordingly, the present invention relates to a method for determining whether a patient suffering from rhabdomyolysis achieves a response with a TLR9 antagonist comprising determining the amount of mitochondrial DNA (mtDNA) in a blood sample obtained from the patient (e.g. by PCR).

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

The invention relates to organic cation transporters (OCTs) inhibitors of Formula (A), as well as their pharmaceutically acceptable tautomers, salts or solvates. The invention is also directed to pharmaceutical compositions comprising such OCTs inhibitor of Formula (A) and their use for treating and/or preventing mood-related disorders such as depressive disorders.

IPC Classes  ?

• 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
• A61K 31/47 - Quinolines; Isoquinolines
• A61P 25/22 - Anxiolytics
• A61P 25/24 - Antidepressants

Abstract

meningitidismeningitidis,and more specifically for use in preventing and/or treating meningitis. The present invention further relates to a composition for the use in preventing and/or treating infection caused by bacteria carrying Type IV pili, such as purpura fulminans and meningitis, comprising a phenothiazine derivative of formula (I) and an antibiotic selected from the group consisting of beta-lactams and aminoglycosides, and/ or dexamethasone.

IPC Classes  ?

• C07D 417/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• C07D 279/26 - [b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom without other substituents attached to the ring system
• C07D 279/28 - [b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom with other substituents attached to the ring system
• A61K 31/5415 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• A61P 31/04 - Antibacterial agents

Abstract

Olmsted syndrome (OS) is a rare genodermatosis. The disease is debilitating and progressive keratoderma and auto-amputation of digits can prevent patients from grasping and walking, and confine them to a wheelchair. New therapeutic options are therefore crucial and are expected from a better understanding of the disease mechanisms. The inventors show an abnormal mTOR pathway activation in OS lesional skin. Topical treatment with 1% Sirolimus shows good tolerance and partial but real efficacy on budding, inflammatory and hyperkeratotic lesions of the sole was observed in the treated patient. Accordingly, the present invention relates to a method of treating Olmsted syndrome in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an mTOR inhibitor.

IPC Classes  ?

• A61K 31/436 - 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 six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61P 17/00 - Drugs for dermatological disorders
• A61P 17/12 - Keratolytics, e.g. wart or anti-corn preparations

Abstract

Persistent inflammation is a driving force of fibrosis progression. Mucosal-Associated Invariant T (MAIT) cells are non-conventional T cells that display altered functions during chronic inflammatory diseases. Here, the inventors report a loss of circulating MAIT cells in cirrhotic patients and their hepatic accumulation in an activated phenotype within the fibrotic septa. Using two models of chronic liver injury, the inventors demonstrate that mice enriched in MAIT cells (Vα19TCRTg) show exacerbated liver fibrosis and higher number of hepatic fibrogenic cells than wild type counterparts, whereas MAIT cell-deficient mice (MR1-/-mice) are resistant. The results highlight the profibrogenic functions of MAIT cells and suggest that 1 targeting MAIT cells may constitute an attractive antifibrogenic strategy during chronic liver injury. Accordingly, the present invention relates to a method of treating fibrosis in a patient in need thereof comprising administering to the subject a therapeutically effective amount of an agent capable of inhibiting the activation of MAIT cells.

IPC Classes  ?

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

Abstract

The present invention relates to a glyco-engineered Fc fragment-bearing compound for its use as an immunosuppression inhibitor in the treatment of a cancer-associated immunosuppression. The invention further relates to a pharmaceutical composition comprising at least this glyco-engineered Fc fragment-bearing compound.

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

Abstract

This invention relates to recombinant viral vectors, preferably retroviral (RV), lentiviral (LV) or adeno-associated viral (AAV) vectors, compositions thereof, the use of the recombinant viral vectors or the compositions thereof, kits of parts comprising said recombinant viral vectors or compositions thereof and a catalytically active Cas9 or Cpfl protein, methods for modifying the genome of a cell, and the cells obtainable by such methods.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 35/76 - Viruses; Subviral particles; Bacteriophages
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

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

IPC Classes  ?

• C12N 15/86 - Viral vectors
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• C07K 14/805 - Haemoglobins; Myoglobins

Abstract

The present invention relates to bisquinolinium derivatives of formula (I): (I) With Y1, Y2, Z1, Z2, X 2- and L as defined in the claims, useful for treating or preventing cancers associated with the Epstein-Barr Virus (EBV-related cancers).

IPC Classes  ?

• A61K 31/4353 - 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
• C07D 401/14 - 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 three or more hetero rings
• A61K 31/4375 - 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 six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
• A61K 31/44 - Non-condensed pyridines; Hydrogenated derivatives thereof
• A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• C07D 401/00 - 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
• C07D 471/04 - Ortho-condensed systems
• A61P 35/00 - Antineoplastic agents

Abstract

The inventors demonstrate for the first time the activation of the Hedgehog (HH) signaling pathway in normal and abnormal human mast cells (MCs). These results prompt the inventors to explore the consequence of the inhibition of the HH pathway, especially the canonical pathway, on MC proliferation. They demonstrate that Hedgehog inhibitors inhibit proliferation and induces apoptosis of mast cells. Accordingly the present invention relates to a method of treating a mast cell disease in a patient in need there of comprising administering to the patient a therapeutically effective amount of a Hedgehog inhibitor.

IPC Classes  ?

• A61K 31/4402 - Non-condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
• A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• A61P 37/00 - Drugs for immunological or allergic disorders
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The invention relates to a method for producing a tablet comprising a nucleic acid vector.

IPC Classes  ?

• A61K 9/127 - Liposomes
• A61K 9/19 - Particulate form, e.g. powders lyophilised
• A61K 9/20 - Pills, lozenges or tablets
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit

Abstract

The present invention relates to a method for detecting or quantifying human immunodeficiency virus 2 (HIV-2) deoxyribonucleic acid (DNA) in a sample containing DNA, which comprises: a) performing a real-time polymerase chain reaction (PCR) on the sample, or a fraction of same comprising the DNA, with at least two primer and probe assemblies each comprising two primers and one marked probe, respectively, intended for detecting or quantifying HIV-2 DNA, in which at least one of the assemblies is chosen from the group made up of: an assembly comprising a primer comprising or consisting of a sequence of SEQ ID NO.: 1 or a sequence that is at least 90% identical with SEQ ID NO.: 1, a primer comprising or consisting of a sequence of SEQ ID NO.: 2 or a sequence that is 90% identical with SEQ ID NO.: 2 or the complements of these sequences, and a marked probe comprising or consisting of a sequence of SEQ ID NO.: 3, or a sequence that is at least 90% identical with SEQ ID NO.: 3 or the complement of these sequences, and an assembly comprising a primer comprising or consisting of a sequence of SEQ ID NO.: 4 or a sequence that is at least 90% identical with SEQ ID NO.: 4, a primer comprising or consisting of a sequence of SEQ ID NO.: 5 or a sequence that is at least 90% identical with SEQ ID NO.: 5 or the complements of these sequences, and a marked probe comprising or consisting of a sequence of SEQ ID NO.: 6, or a sequence that is at least 90% identical with SEQ ID NO.: 6 or the complement of these sequences; and b) determining from same the presence or absence and/or the amount of HIV-2 DNA in the biological sample.

IPC Classes  ?

• C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage

Abstract

The present invention relates to a method for detecting or quantifying CTP in a cell sample comprising at least two nucleotide triphosphates by cationic ion pairing chromatography coupled to mass spectrometry, to a method for detecting or quantifying CTP synthase activity based on the method for detecting or quantifying CTP, and to their use in methods for screening potential immunosuppressive or anti-cancer compounds and in methods for determining the appropriate dose of an immunosuppressive or anti-cancer compound inhibiting CTP synthase activity for a treated subject.

IPC Classes  ?

• C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving enzymes not classifiable in groups
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
• G01N 30/72 - Mass spectrometers
• G01N 30/86 - Signal analysis
• G01N 30/88 - Integrated analysis systems specially adapted therefor, not covered by a single one of groups

Abstract

The invention relates to the identification of a specific genomic and proteomic signature of castration- resistant prostatic cells. In particular, the invention relates to in vitro methods of prognosing the outcome of prostate cancer comprising identifying prostatic cells exhibiting biomarkers from this specific signature.

IPC Classes  ?

• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer

Abstract

The invention relates to methods for treating cardiovascular toxicity induced by anti-cancer and anti-angiogenic compound. The inventors explored the cardiotoxicity induced by the antiangiogenic therapy, sunitinib, in the mouse heart. The inventors showed that sunitinib induces an anaerobic switch of cellular metabolism within the myocardium which is associated with the development of myocardial fibrosis as demonstrated by echocardiography. The capacity of positron emission tomography to detect the changes in cardiac metabolism caused by sunitinib was dependent on fasting status and duration of treatment. Pan proteomic analysis in the myocardium showed that sunitinib induced (i) an early metabolic switch with enhanced glycolysis and reduced oxidative phosphorylation, and (ii) a metabolic failure to use glucose as energy substrate, similar to the insulin resistance found in type 2 diabetes. Co-administration of macitentan, the endothelin receptor antagonist, to sunitinib-treated animals prevented both metabolic defects, restored glucose uptake and cardiac function, and prevented myocardial fibrosis. Thus, the invention relates to a compound selected from the group consisting of endothelin receptor antagonist and inhibitor of endothelin receptor expression for use in the treatment of cardiovascular toxicity induced by anti-cancer and anti-angiogenic compound.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 31/404 - Indoles, e.g. pindolol
• A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The present invention concerns an optical system for spatiotemporally shaping the wavefront of the electric field of a light beam (1) to be projected into a target volume (5), where the propagation axis is axis z, to create 3D patterned illumination in the target volume (5), comprising a pulsed laser source, configured to have an illumination pattern whose transversal surface at the target volume being superior to the diffraction limit of the optical system, at least one intermediate optical element (4) which is a dispersive grating for performing temporal focusing of the light beam (1), located, on the propagation axis (z), where an image of the illumination pattern is formed, for modulating the phase and/or the amplitude of the electric field of the light beam, and a second optical element (3) which is a spatiallight modulator for modulating the phase of the electric field of the input light beam, and for realizing spatiotemporal multiplexing to create 3D patterned illumination in the target volume (5) by replicating the illumination pattern, so as to have several replicated illumination patterns in the target volume (5), and controlling the position with transversal coordinates X, Y and axial coordinate Z of each replicated illumination pattern in the target volume (5).

IPC Classes  ?

• G02B 21/06 - Means for illuminating specimen
• G02B 26/02 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the intensity of light
• G03F 7/20 - Exposure; Apparatus therefor
• G11B 7/135 - Means for guiding the beam from the source to the record carrier or from the record carrier to the detector
• B23K 26/0622 - Shaping the laser beam, e.g. by masks or multi-focusing by direct control of the laser beam by shaping pulses
• G02B 27/10 - Beam splitting or combining systems

Abstract

The inventors report two siblings presenting recurrent EBV infection and Hodgkin lymphoma caused by a homozygous loss-of-function mutation in RASGRPl, a T-cell specific nucleotide exchange factor (GEF) known to activate the RAS-induced MAPK/ERK kinases pathway. In response to TCR stimulation, RASGRP 1 -deficient T cells exhibited defective ERK kinases activation and impaired proliferation that was restored by expression of wild-type RASGRPl. Thus, these results identify a novel primary immunodeficiency that highlights T- cell proliferation and offers the opportunity to develop RASGRPl inhibitor for inhibiting T cell proliferation in a subject in need thereof.

IPC Classes  ?

• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61P 37/00 - Drugs for immunological or allergic disorders
• A61K 35/02 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution from inanimate materials

Abstract

The invention relates to a method for treating mitochondrial genetic diseases. The inventors have worked with primary fibroblasts from patients and control individuals and collected protein lysates for western blotting. Importantly, they observed that the genetic mitochondrial disorders, show a significant increase in phosphorylation of ribosomal protein S6 (pS6) compared to control fibroblasts, indicative of hyperactivated mTOR signaling. Patients with mitochondrial disorders and controls cells were treated for 48 hours with DMSO or BYL719. All lines from patients with mitochondrial diseases show reduced membrane potential, determined by TMRE staining intensity, and abnormal morphology, fragmentation and the presence of depolarized (low TMRE staining) mitochondria. Treatment with BYL719 attenuated these phenotypes in all MELAS fibroblasts while having no overt impact on the control cells. Similar experiments using flow cytometry confirmed membrane potential (TMRE) rescue by BYL719 treatment in MELAS fibroblasts.

IPC Classes  ?

• A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

Following a prospective clinical study that includes 242 patients, the inventors show that hepatocyte-derived MV levels predicted transplantation-free survival at 6 months in univariate analysis. In multivariate analysis, this association was shown to be independent of Child-Pugh and of MELD score. Thus the present invention thus relates to a method of predicting the transplantation-free survival time of a patient suffering from cirrhosis comprising determining the level of hepatocyte-derived microvesicles (e.g. by an ELISA assay) in a blood sample obtained from the patient.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Abstract

The invention relates to a compound that inhibits interaction between a Grb14 protein and an insulin receptor, of formula (I) or of formula (II), the salts, solvates and/or diastereoisomers thereof, for use for therapeutic purposes, in particular for the treatment of insulin resistance, and pharmaceutical compositions containing such compounds.

IPC Classes  ?

• A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
• A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
• A61K 31/513 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• C07D 261/16 - Benzene-sulfonamido isoxazoles
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Abstract

Plasma levels of different sub-populations of microvesicles (endothelial, leukocyte, platelet and hepatocyte) were measured by flow cytometry or ELISA / filtration on blood samples from 125 patients with cirrhosis, for which 36 of them were diagnosed with HCC at inclusion. The inventors show that the levels of microvesicles of endothelial origin (CD62E +) could predict the occurrence of HCC in patients with cirrhosis. Therefore the present invention relates to a method for determining whether a patient suffering from cirrhosis is at risk of having or developing hepatocellular carcinoma comprising determining the level of endothelial-derived microvesicles (e.g. by flow cytometry) in a blood sample obtained from the patient.

IPC Classes  ?

• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer

Abstract

Blockade of immune checkpoints is one of the most promising approaches for activating therapeutic antitumor immunity. However, the overall benefits of checkpoint blockade cancer immunotherapy vary among individuals. The present inventors demonstrated that a specific single nucleotide polymorphism in the KIT gene is associated with a decrease in intra-tumor CD8 infiltrates. Patients presenting this polymorphism present a low intra-tumor immune adaptive response and treating these patients with a checkpoint blockade cancer immunotherapy would thus be useless. Accordingly the present invention relates to a checkpoint blockade cancer immunotherapy agent for use in a method for treating cancer in an individual who does not display the KIT polymorphism consisting of M541L (KITL541). The present invention further relates to an method for predicting the response of a patient suffering from cancer to a checkpoint blockade cancer immunotherapy by detecting the presence of the M541L KIT polymorphism in a biological sample (such as a tumor sample).

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 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer

Abstract

The present invention relates to methods for assessing the severity of cancer by measuring the expression level of TIM-3 in a tumour sample. The present inventors have determined that the expression of TIM-3 (T-cell immunoglobulin and mucin-domain containing-3) can be correlated with the prognosis and with the responsiveness to treatment of patients suffering from solid cancer. They have particularly demonstrated that the specific ratio of the expression level of TIM-3 to the expression level of a biomarker of the adaptive immune response within the tumour is extremely predictive of patients' survival. Thus, the present invention relates to methods for determining the prognosis patients suffering from a solid cancer by determining the ratio of the expression level of TIM-3 to the expression level of a biomarker of the adaptive immune response in a tumour tissue sample obtained from said patient. Typically, these expression levels are determined by immunohistochemistry.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

Blockade of immune checkpoints is one of the most promising approaches for activating therapeutic antitumor immunity. However, the overall benefits of checkpoint blockade cancer immunotherapy vary among individuals. The present inventors have indeed demonstrated that MET-mutated patients have a better adaptive immune response than non-MET-mutated patients. Accordingly, MET-mutated patients are more likely to respond to a checkpoint blockade cancer. Accordingly, the present invention relates to a method for predicting the response of a patient suffering from cancer to a checkpoint blockade cancer immunotherapy, by determining if the MET gene is mutated in a tumor sample of said patient, wherein a mutation of the MET gene is predictive of a response to the checkpoint blockade cancer immunotherapy.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydrocarbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

IPC Classes  ?

• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes

Abstract

The present invention relates to a device 1 for analysing the regularity and symmetry of a sequence of N walking or running cycles of an individual, comprising sensors 2 for measuring raw time signals of a physical displacement variable of an anatomical segment, a processing unit connected to the measurement sensors 2 and having calculation and processing means arranged for separating the raw time signals into distinct time signals Ci, wherein the series Ci is associated with a given walking or running cycle i of the individual, calculating at least one coefficient of similarity between the signal Ci associated with the walking or running cycle i and another signal Cj associated with a walking or running cycle j of the same individual, display means 4 connected to the processing unit and displaying the matrix M(i,j) in which each value of the coefficient of similarity is represented by a colour located in a graduated colour scale to allow the naked eye to see the similarity between the walking or running cycles i and j.

IPC Classes  ?

• A61B 5/11 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb

Abstract

The present invention relates to methods and pharmaceutical compositions for the treatment of neurodegeneration with brain iron accumulation (NBIA). Studying two novel genes, namely, CRAT encoding the carnitine acetyltransferase and REPS1 involved in endocytosis and vesicle transport, and a series of known NBIA genes, the inventors reported on iron overload related to increased levels and abnormal recycling of transferrin receptor as a common feature in NBIA. They ascribe this anomaly, at least in part, to impaired palmitoylation of the receptor as a common consequence of the various disease causing mutations. Finally, the inventors show that Artesunate improved TfR1 palmitoylation in NBIA fibroblasts. In particular, the present invention relates to a method of treating neurodegeneration with brain iron accumulation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a drug increasing TfR1 palmitoylation.

IPC Classes  ?

• A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• A61K 31/00 - Medicinal preparations containing organic active ingredients
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The present invention relates to a method for monitoring hemostasis in a subject who may or may not be under anticoagulant therapy, comprising the steps of: a) providing a blood sample from said individual comprising a complex between a Factor Xa (FXa) or a modified catalytically active FXa, and a-2 macroglobulin (a2M); b) determining clot formation in the sample from step a) to obtain a test value; and c) comparing the test value from step b) to a reference value, wherein a variation of said test value over said reference is indicative of hemostasis in said subject. In one embodiment, said complex can be used for discriminating a defect in haemostasis due to a non-vitamin K antagonist (non-VKA) anticoagulant therapy from a coagulopathy or a VKA therapy in said subject. Said complex can also be used for preventing or reducing bleeding in a subject undergoing anticoagulant therapy; and/or for binding and inhibiting an exogenously administered anticoagulant in said subject. Pharmaceutical compositions and kits are also disclosed, as well as a method for preparing a complex. The modified catalytically active FXa can be a Gla-domain deficient FXa (Gla-deficient FXa) or a Gla-domainless FXa (GDFXa). The Inventors have shown by in vitro and in vivo (mice) that the novel antidote as described here provides a differential diagnosis in a rapid and sensitive manner, including in Whole Blood (WB) samples, or a fraction thereof.

IPC Classes  ?

• G01N 33/86 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
• C12N 9/64 - Proteinases derived from animal tissue, e.g. rennin
• C12Q 1/56 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
• A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)