Abstract

The present invention provides novel SMNDC1 inhibitors, specifically the compounds of formula (I), (I) as well as pharmaceutical compositions containing these compounds. The SMNDC1 inhibitors provided herein exhibit particularly beneficial properties in terms of potency and selectivity, which renders these compounds highly advantageous for use in therapy, including, e.g., in the treatment or prevention of cancer or diabetes.

IPC Classes  ?

• A61K 31/4436 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
• C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
• C07D 277/46 - Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
• C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• C07D 487/04 - Ortho-condensed systems
• C07D 491/10 - Spiro-condensed systems
• C07K 5/097 - Tripeptides the first amino acid being heterocyclic, e.g. Pro, His, Trp, e.g. thyroliberin, melanostatin
• A61P 5/50 - Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to compounds of the formula (I) as bifunctional protein targeting chimeras (PROTACs), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. These compounds, pharmaceutically acceptable salts, and pharmaceutical compositions thereof are useful in the treatment or prophylaxis of a cancer, an autoimmune disease, or an inflammatory disease, in paticular, associated with and/or caused by PDEdelta (PDEδ) / K-Ras or B lymphoid kinase (BLK) /Bruton´s tyrosine kinase (BTK) or cyclin-dependent kinase 9 (CDK9).

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• 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 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
• A61P 35/00 - Antineoplastic agents
• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems

Abstract

The invention relates to a method for sequencing oligonucleotides comprising RNA, wherein two indexing sequences are introduced in RNA oligonucleotides. The invention furthermore relates to uses of such methods and devices used for such methods. Further provided are kits comprising one or more components used in the methods of the invention.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing

Abstract

The present invention provides 1,2,4-triazolo[1,5-a]pyrimidine-based compounds of formula (I), Formula (I) and pharmaceutically acceptable salts thereof, which have been found to be advantageously potent and selective inhibitors of SLC16A3, as well as their use in the treatment or prevention of SLC16A3-associated diseases/disorders such as cancer.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61P 35/00 - Antineoplastic agents

Abstract

in vitro in vivo inviroviro, e.g., for adoptive cell transfer. Combinations of a RHOG modulator according to the invention and synthetic antigen receptors such as CARs are also encompassed by the present invention. Furthermore, the present invention provides specific CRISPR gRNAs and specific combinations of CRISPR gRNAs and CRISPR modifiers.

IPC Classes  ?

• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes

Abstract

The present invention relates to a method for monitoring the effect of an environmental factor on the proteome of a cell. Furthermore, cell populations are provided that comprise multiple cells each comprising an inserted tag sequence in an intron of said cell, wherein the tag is inserted in-frame with the preceding exonic sequence and wherein the intron into which the tag is inserted is different between cells.

IPC Classes  ?

• C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Abstract

The present invention relates to a compound of formula (I) or its pharmaceutically acceptable salt. The present invention further relates to a pharmaceutical composition comprising the compound of formula (I) or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable carrier. The compounds of formula (I) are useful as medicaments, for use in treatment or prevention of an autoimmune disorder or inflammatory condition, in particular an autoimmune disorder being systemic lupus erythematosus, or an inflammatory condition selected from inflammatory bowel disease, psoriasiform dermatitis, and endosomal TLR-dependent inflammation. Preferably, the autoimmune disorder to be treated with the compound of formula (I) is a disorder associated with SLC15 peptide transporter. The compound of formula (I) has been demonstrated to inhibit SLC15 peptide transporter.

IPC Classes  ?

• A61P 37/02 - Immunomodulators
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• C07D 215/16 - Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon 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 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

Abstract

The present invention relates to an antibody, or an antigen-binding fragment thereof, specifically binding to APRIL for use in the prevention and/or treatment of hypertriglyceridemia, metabolic syndrome, non-alcoholic steatohepatitis, diabetes mellitus type 2, abdominal aortic aneurysm, atherogenic dyslipidemia, cardiovascular events (e.g., myocardial infarction and stroke) and/or atherosclerosis. The invention further relates to a polynucleotide that encodes and/or a pharmaceutical composition that comprises the antibody or an antigen-binding fragment of the invention. The invention also relates to a kit and/or method for quantifying the concentration of nc-APRIL, canonical APRIL or total APRIL in a sample. Further, the invention relates to a nephelometric assay for quantifying nc-APRIL. Further, the invention relates to a method for predicting mortality risk in subjects suffering from, and/or for determining whether a subject is susceptible to the treatment of hypertriglyceridemia, metabolic syndrome, abdominal aortic aneurysm, non-alcoholic steatohepatitis, diabetes mellitus type 2, atherogenic dyslipidemia, cardiovascular events and/or atherosclerosis.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61P 3/06 - Antihyperlipidemics
• G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

The present invention relates to compounds of formula compounds of formulae (I) by which transmembrane proteins such as SLC transporters can be unlocked to chemically-induced degradation, whereby a multitude of diseases can be addressed for the first time. Particularly, the present invention relates to compounds with the ability to induce degradation of SLC transporters via the ubiquitin-proteasome pathway. The invention also relates to the compounds and composition for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as degraders of SLC transporters which are, e.g., associated with cancer and for use in the treatment of various diseases such as cancer. Furthermore, the present invention relates to a method for treating a disease or condition, such as cancer, comprising administering the compound of the present invention.

IPC Classes  ?

• A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

The present invention relates to a method for obtaining an intron-tagged pool of cells representing and/or comprising tagged introns. Furthermore, the present invention relates to a pool of cells that may be obtainable by said method, in particular an intron-tagged pool of cells. The present invention furthermore provides for a method for automated recognition of the identity of the tagged intron(s) comprised in the genome of an intron- tagged cell within an intron-tagged pool of cells and a method for assessing the effect of a perturbation on the proteome and/or gene expression levels of an intron-tagged cell within an intron-tagged pool of cells.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters

Abstract

The present invention provides 1,2,4-triazolo[1,5-a]pyrimidine-based compounds of formula (I), Formula (I) and pharmaceutically acceptable salts thereof, which have been found to be advantageously potent and selective inhibitors of SLC16A3, as well as their use in the treatment or prevention of SLC16A3-associated diseases/disorders such as cancer.

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 35/00 - Antineoplastic agents
• C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
• C07D 487/04 - Ortho-condensed systems

Abstract

The present invention provides 3-(phthalazin-1-yl)benzenesulfonamide-based compounds of formula (I), Formula (I) and pharmaceutically acceptable salts thereof, which have been found to be advantageously potent and selective inhibitors of SLC16A3, as well as their use in the treatment or prevention of SLC16A3-associated diseases/disorders such as cancer.

IPC Classes  ?

• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• 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 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 35/00 - Antineoplastic agents
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The present invention relates to an antibody, or an antigen-binding fragment thereof, specifically binding to APRIL for use in the prevention and/or treatment of hypertriglyceridemia, metabolic syndrome, non-alcoholic steatohepatitis, diabetes mellitus type 2, abdominal aortic aneurysm, atherogenic dyslipidemia, cardiovascular events (e.g., myocardial infarction and stroke) and/or atherosclerosis. The invention further relates to a polynucleotide that encodes and/or a pharmaceutical composition that comprises the antibody or an antigen-binding fragment of the invention. The invention also relates to a kit and/or method for quantifying the concentration of nc-APRIL, canonical APRIL or total APRIL in a sample. Further, the invention relates to a nephelometric assay for quantifying nc-APRIL. Further, the invention relates to a method for predicting mortality risk in subjects suffering from, and/or for determining whether a subject is susceptible to the treatment of hypertriglyceridemia, metabolic syndrome, abdominal aortic aneurysm, non- alcoholic steatohepatitis, diabetes mellitus type 2, atherogenic dyslipidemia, cardiovascular events and/or atherosclerosis.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61P 3/06 - Antihyperlipidemics

Abstract

The present invention relates to an antibody, or an antigen-binding fragment thereof, specifically binding to APRIL for use in the prevention and/or treatment of hypertriglyceridemia, metabolic syndrome, non-alcoholic steatohepatitis, diabetes mellitus type 2, abdominal aortic aneurysm, atherogenic dyslipidemia, cardiovascular events (e.g., myocardial infarction and stroke) and/or atherosclerosis. The invention further relates to a polynucleotide that encodes and/or a pharmaceutical composition that comprises the antibody or an antigen-binding fragment of the invention. The invention also relates to a kit and/or method for quantifying the concentration of nc-APRIL, canonical APRIL or total APRIL in a sample. Further, the invention relates to a nephelometric assay for quantifying nc-APRIL. Further, the invention relates to a method for predicting mortality risk in subjects suffering from, and/or for determining whether a subject is susceptible to the treatment of hypertriglyceridemia, metabolic syndrome, abdominal aortic aneurysm, non- alcoholic steatohepatitis, diabetes mellitus type 2, atherogenic dyslipidemia, cardiovascular events and/or atherosclerosis.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61P 3/06 - Antihyperlipidemics
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

The present invention relates to compounds with the ability to stimulate/induce ubiquitination of a target protein/target proteins. The compounds of the present invention may stimulate/induce ubiquitination of a target protein/target proteins; i.e. via degradation of a target protein/target proteins by the cullin-RING ubiquitin ligase (CRL). Such target protein/ target proteins may be proteins involved in diseases, like cancer, metabolic disorder, infectious disease and/or neurological disorder. The invention also relates to the compounds and composition for use as medicaments as well as pharmaceutical compositions comprising these compounds. Particularly, the compounds of the present invention may degrade proteins associated with cancer, metabolic disorder, infectious disease and/or neurological disorder. Furthermore, the present invention relates the compounds for use as a medicament, such as for use in treating cancer, metabolic disorder, infectious disease and/or neurological disorder and to a method for treating a disease, such as cancer, metabolic disorder, infectious disease and/or neurological disorder, comprising administering the compound of the present invention.

IPC Classes  ?

• C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• C07D 213/75 - Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• C07D 277/46 - Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
• C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• 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 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 417/12 - 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 chain containing hetero atoms as chain links
• C07D 471/04 - Ortho-condensed systems
• C07D 513/04 - Ortho-condensed systems
• A61P 3/00 - Drugs for disorders of the metabolism
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• A61P 35/00 - Antineoplastic agents
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings

Abstract

A computer-implemented method for semi-automatic segmentation of medical imaging data, the method comprising steps of a) obtaining from the medical imaging data a sequence of slices in which at least one anatomical structure appears; b) for each of the slices, performing a thresholding to identify a plurality of anatomical structure pixels and delineating an initial contour of the anatomical structures, thereby defining a plurality of anatomical structure regions; c) interactively selecting a reference slice in which the anatomical structure regions sufficiently correspond to the anatomical structures appearing therein and/or interactively refining the reference slice by modifying at least one of the anatomical structure regions so that the at least one modified organ region corresponds more closely to the respective anatomical structure; and d) correcting the definition of the anatomical structure regions of at least one of the remaining slices based on information acquired for the reference slice.

IPC Classes  ?

• G06T 7/11 - Region-based segmentation
• G06T 7/136 - SegmentationEdge detection involving thresholding
• G06T 7/155 - SegmentationEdge detection involving morphological operators

Abstract

The present invention relates to a method for monitoring the effect of an environmental factor on the proteome of a cell. Furthermore, cell populations are provided that comprise multiple cells each comprising an inserted tag sequence in an intron of said cell, wherein the tag is inserted in-frame with the preceding exonic sequence and wherein the intron into which the tag is inserted is different between cells.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters

Abstract

The present invention relates to compounds with the ability to stimulate/induce ubiquitination of a target protein/target proteins. The compounds of the present invention may stimulate/induce ubiquitination of a target protein/target proteins; i.e. via degradation of a target protein/target proteins by the cullin-RING ubiquitin ligase (CRL). Such target protein/ target proteins may be proteins involved in diseases, like cancer, metabolic disorder, infectious disease and/or neurological disorder. The invention further relates to a method for identifying/obtaining and/or testing a compound able to induce ubiquitination of a target protein/target proteins. The invention also relates to the compounds and composition for use as medicaments as well as pharmaceutical compositions comprising these compounds. Particularly, the compounds of the present invention may degrade proteins associated with cancer, metabolic disorder, infectious disease and/or neurological disorder. Furthermore, the present invention relates the compounds for use as a medicament, such as for use in treating cancer, metabolic disorder, infectious disease and/or neurological disorder and to a method for treating a disease, such as cancer, metabolic disorder, infectious disease and/or neurological disorder, comprising administering the compound of the present invention.

IPC Classes  ?

• A61P 35/00 - Antineoplastic agents
• C07D 487/04 - Ortho-condensed systems
• A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine

Abstract

The present invention relates to compounds of formula compounds of formulae (I) by which transmembrane proteins such as SLC transporters can be unlocked to chemically-induced degradation, whereby a multitude of diseases can be addressed for the first time. Particularly, the present invention relates to compounds with the ability to induce degradation of SLC transporters via the ubiquitin-proteasome pathway. The invention also relates to the compounds and composition for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as degraders of SLC transporters which are, e.g., associated with cancer and for use in the treatment of various diseases such as cancer. Furthermore, the present invention relates to a method for treating a disease or condition, such as cancer, comprising administering the compound of the present invention.

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 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to compounds of formula compounds of formulae (I) by which transmembrane proteins such as SLC transporters can be unlocked to chemically-induced degradation, whereby a multitude of diseases can be addressed for the first time. Particularly, the present invention relates to compounds with the ability to induce degradation of SLC transporters via the ubiquitin-proteasome pathway. The invention also relates to the compounds and composition for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as degraders of SLC transporters which are, e.g., associated with cancer and for use in the treatment of various diseases such as cancer. Furthermore, the present invention relates to a method for treating a disease or condition, such as cancer, comprising administering the compound of the present invention.

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 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61P 35/00 - Antineoplastic agents
• A61P 35/02 - Antineoplastic agents specific for leukemia

Abstract

The present invention relates to compounds with the ability to stimulate/induce ubiquitination of a target protein/target proteins. The compounds of the present invention may stimulate/induce ubiquitination of a target protein/target proteins; i.e. via degradation of a target protein/target proteins by the cullin-RING ubiquitin ligase (CRL). Such target protein/target proteins may be proteins involved in diseases, like cancer, metabolic disorder, infectious disease and/or neurological disorder. The invention further relates to a method for identifying/obtaining and/or testing a compound able to induce ubiquitination of a target protein/target proteins. The invention also relates to the compounds and composition for use as medicaments as well as pharmaceutical compositions comprising these compounds. Particularly, the compounds of the present invention may degrade proteins associated with cancer, metabolic disorder, infectious disease and/or neurological disorder. Furthermore, the present invention relates the compounds for use as a medicament, such as for use in treating cancer, metabolic disorder, infectious disease and/or neurological disorder and to a method for treating a disease, such as cancer, metabolic disorder, infectious disease and/or neurological disorder, comprising administering the compound of the present invention.

IPC Classes  ?

• A61P 3/00 - Drugs for disorders of the metabolism
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
• A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• A61P 35/00 - Antineoplastic agents
• 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 411/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• C07D 411/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• C07D 487/06 - Peri-condensed systems

Abstract

The invention relates to a method for sequencing oligonucleotides comprising RNA, wherein two indexing sequences are introduced in RNA oligonucleotides. The invention furthermore relates to uses of such methods and devices used for such methods. Further provided are kits comprising one or more components used in the methods of the invention.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay

Abstract

The invention relates to a method for sequencing oligonucleotides comprising RNA, wherein two indexing sequences are introduced in RNA oligonucleotides. The invention furthermore relates to uses of such methods and devices used for such methods. Further provided are kits comprising one or more components used in the methods of the invention.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6869 - Methods for sequencing

Goods & Services

Data networks; Virtual reality software for education; Virtual reality software; Artificial intelligence apparatus; Virtual reality software for medical teaching; Virtual reality software for playing virtual reality games; Audiovisual teaching apparatus; Artificial intelligence software for healthcare; Virtual reality glasses; Virtual reality models; Databases; Artificial intelligence software; Virtual reality games software; Data engines.; Virtual reality headsets; Virtual reality goggles; Virtual reality hardware. Development services relating to virtual reality software; Development of virtual reality software; Medical and pharmacological research services; Advisory services relating to technological research.; Science and technology services; Data mining; Research and development services in the field of gene expression systems; Design and development of computer game software and virtual reality software; Laboratory research in the field of gene expression; Design of virtual reality software; Genetic research; Genetic fingerprinting; Design and development of virtual reality software. RNA or DNA analysis for cancer diagnosis and prognosis; Pharmaceutical services; Medical services; Medical analysis for the diagnosis and treatment of persons.; Consultancy and information services relating to biopharmaceutical products; Human healthcare services; Provision of pharmaceutical information; Consultancy and information services provided via the Internet relating to pharmaceutical products; Providing health information; Genetic counseling; Professional consultancy relating to health; Health care consultancy services [medical]; Health advice and information services; Consultancy and information services relating to pharmaceutical products; Performing diagnosis of diseases; Health screening; Pharmaceutical advice; Medical testing services relating to the diagnosis and treatment of disease.

Abstract

The present invention relates to a method for identifying compounds or agents able to induce ubiquitination of a protein of interest. Further, the present invention relates to compounds/agents obtainable by the method of the present invention. Furthermore, the present invention relates to a method for treating cancer or other diseases comprising administering the chemical compound or agent obtainable by the method of the present invention. Moreover, the present invention relates to a eukaryotic cell comprising enhanced cullin-RING ubiquitin ligase (CRL) activity and/or constantly neddylated cullin-RING ubiquitin ligases/CRLs.

IPC Classes  ?

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

Abstract

The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Goods & Services

Chemical preparations for use in RNA analysis and/or DNA analysis [other than medical]; Reagents for use in scientific apparatus for chemical or biological analysis; Biomolecule labelling kits comprising reagents for use in scientific research; Chemicals for use in immuno-assay testing [other than medical or veterinary]; ln-vivo diagnostic reagents for scientific use; Diagnostic testing materials, other than for medical use; Diagnostic preparations, other than for medical or veterinary purposes; Diagnostic reagents, other than for medical laboratory use; Diagnostic reagents, except for medical or veterinary use; Diagnostic reagents for in-vitro use [other than medical]; Diagnostic chemicals [other than for medical or veterinary use]; Clinical diagnostics, other than for medical or veterinary use; Diagnostic reagents and preparations, except for medical or veterinary use; Diagnostic reagents, other than for medical use for sale in kit form; Diagnostic reagents for in vitro use in biochemistry, clinical chemistry and microbiology; Diagnostic preparations for scientific or research use other than for medical use; Reagents for use in diagnostic tests [other than for medical or veterinary purposes]; Chemical reagents for use in diagnostic tests, other than for medical or veterinary use; Diagnostic substances, other than for medical use; Diagnostic reagents for scientific or research use; Diagnostic preparations for scientific or research use; Biochemicals, namely biochemicals for industrial and scientific purposes, in particular biochemicals for industrial and scientific purposes for the investigation of cells, chromatin, proteins, nucleic acids, in particular of RNA and/or DNA, protein nucleic acid reactions; Biochemical reagents or Chemical reagents, in particular biochemical reagents or chemical reagents for in-vitro use in laboratories for scientific use. Apparatus, namely column or magnet-based apparatus for chromatin immunoprecipitation, chromatin analysis, chromatin purification, nucleic acid purification and analysis, in particular of RNA and/or DNA; Scientific, electric, photographic, optical, measuring apparatus, namely sequencers for next generation sequencing; scientific, electric apparatus preparing nucleic acids for sequencing; computer hardware and computer software for processing and displaying and interpreting data, in particular for scientific purposes; Diagnostic apparatus, not for medical purposes. Treatment of nucleic acids, proteins and chromatin; treatment of nucleic acids with enzymatic reactions; treatment of chromatin with enzymatic reactions; Treatment of nucleic acids for sequencing, in particular for sequencing of RNA and/or DNA. Research and development services; industrial research in the field of biology; industrial development in the field of human biology and diseases like cancer and inflammation/ immune disorders; Laboratory services for detecting protein-DNA interactions and/or for detecting protein-RNA interactions; Scientific services for the analysis of laboratory results; Computer programming; DNA and RNA testing for purposes of scientific research; Biochemical analysis; Biological analysis; Preparation of biological samples for analysis in research laboratories; Preparation of biological samples for testing and analysis in research laboratories; Research and development in the field of diagnostic preparations. Blood bank services; Medical assistance; Hospitals; Animal healthcare services; Advisory services relating to health; Medical analysis services for diagnostic and treatment purposes provided by medical laboratories; Medical screening, in particular for diagnostic and therapeutic purposes; Nucleic acids screening for medical use; Genetic and molecular biological analysis, in particular with tissues, cells, nucleic acids for medical purposes.

Goods & Services

Chemical preparations for use in RNA analysis and/or DNA analysis [other than medical]; Reagents for use in scientific apparatus for chemical or biological analysis; Biomolecule labelling kits comprising reagents for use in scientific research; Chemicals for use in immuno-assay testing [other than medical or veterinary]; ln-vivo diagnostic reagents for scientific use; Diagnostic testing materials, other than for medical use; Diagnostic preparations, other than for medical or veterinary purposes; Diagnostic reagents, other than for medical laboratory use; Diagnostic reagents, except for medical or veterinary use; Diagnostic reagents for in-vitro use [other than medical]; Diagnostic chemicals [other than for medical or veterinary use]; Clinical diagnostics, other than for medical or veterinary use; Diagnostic reagents and preparations, except for medical or veterinary use; Diagnostic reagents, other than for medical use for sale in kit form; Diagnostic reagents for in vitro use in biochemistry, clinical chemistry and microbiology; Diagnostic preparations for scientific or research use other than for medical use; Reagents for use in diagnostic tests [other than for medical or veterinary purposes]; Chemical reagents for use in diagnostic tests, other than for medical or veterinary use; Diagnostic substances, other than for medical use; Diagnostic reagents for scientific or research use; Diagnostic preparations for scientific or research use; Biochemicals, namely biochemicals for industrial and scientific purposes, in particular biochemicals for industrial and scientific purposes for the investigation of cells, chromatin, proteins, nucleic acids, in particular of RNA and/or DNA, protein nucleic acid reactions; Biochemical reagents or Chemical reagents, in particular biochemical reagents or chemical reagents for in-vitro use in laboratories for scientific use; none of the aforesaid goods for the treatment of human infertility, reproductive medicine and the treatment of sterility via assisted reproduction techniques. Apparatus, namely column or magnet-based apparatus for chromatin immunoprecipitation, chromatin analysis, chromatin purification, nucleic acid purification and analysis, in particular of RNA and/or DNA; Scientific, electric, photographic, optical, measuring apparatus, namely sequencers for next generation sequencing; scientific, electric apparatus preparing nucleic acids for sequencing; computer hardware and computer software for processing and displaying and interpreting data, in particular for scientific purposes; Diagnostic apparatus, not for medical purposes. Treatment of nucleic acids, proteins and chromatin; treatment of nucleic acids with enzymatic reactions; treatment of chromatin with enzymatic reactions; Treatment of nucleic acids for sequencing, in particular for sequencing of RNA and/or DNA. Research and development services; industrial research in the field of biology; industrial development in the field of human biology and diseases like cancer and inflammation/ immune disorders; Laboratory services for detecting protein-DNA interactions and/or for detecting protein-RNA interactions; Scientific services for the analysis of laboratory results; Computer programming; DNA and RNA testing for purposes of scientific research; Biochemical analysis; Biological analysis; Preparation of biological samples for analysis in research laboratories; Preparation of biological samples for testing and analysis in research laboratories; Research and development in the field of diagnostic preparations; none of the aforesaid services for the treatment of human infertility, reproductive medicine and the treatment of sterility via assisted reproduction techniques. Blood bank services; Medical assistance; Hospitals; Animal healthcare services; Advisory services relating to health; Medical analysis services for diagnostic and treatment purposes provided by medical laboratories; Medical screening, in particular for diagnostic and therapeutic purposes; Nucleic acids screening for medical use; Genetic and molecular biological analysis, in particular with tissues, cells, nucleic acids for medical purposes; none of the aforesaid services for the treatment of human infertility, reproductive medicine and the treatment of sterility via assisted reproduction techniques.

Goods & Services

Chemical preparations for use in RNA analysis and/or DNA analysis [other than medical]; Reagents for use in scientific apparatus for chemical or biological analysis; Biomolecule labelling kits comprising reagents for use in scientific research; Chemicals for use in immuno-assay testing [other than medical or veterinary]; ln-vivo diagnostic reagents for scientific use; Diagnostic testing materials, other than for medical use; Diagnostic preparations, other than for medical or veterinary purposes; Diagnostic reagents, other than for medical laboratory use; Diagnostic reagents, except for medical or veterinary use; Diagnostic reagents for in-vitro use [other than medical]; Diagnostic chemicals [other than for medical or veterinary use]; Clinical diagnostics, other than for medical or veterinary use; Diagnostic reagents and preparations, except for medical or veterinary use; Diagnostic reagents, other than for medical use for sale in kit form; Diagnostic reagents for in vitro use in biochemistry, clinical chemistry and microbiology; Diagnostic preparations for scientific or research use other than for medical use; Reagents for use in diagnostic tests [other than for medical or veterinary purposes]; Chemical reagents for use in diagnostic tests, other than for medical or veterinary use; Diagnostic substances, other than for medical use; Diagnostic reagents for scientific or research use; Diagnostic preparations for scientific or research use; Biochemicals, namely biochemicals for use in industry and science, in particular biochemicals for use in industry and science for the investigation of cells, chromatin, proteins, nucleic acids, in particular of RNA and/or DNA, protein nucleic acid reactions; Biochemical reagents or Chemical reagents, in particular biochemical reagents or chemical reagents for in-vitro use in laboratories for scientific use. Apparatus, namely column or magnet-based apparatus for chromatin immunoprecipitation, chromatin analysis, chromatin purification, nucleic acid purification and analysis, in particular of RNA and/or DNA; Scientific, electric, photographic, optical, measuring apparatus, namely sequencers for next generation sequencing; scientific, electric apparatus preparing nucleic acids for sequencing; computer hardware and computer software for processing and displaying and interpreting data, in particular for scientific purposes; Diagnostic apparatus, not for medical purposes. Treatment of nucleic acids, proteins and chromatin; treatment of nucleic acids with enzymatic reactions; treatment of chromatin with enzymatic reactions; Treatment of nucleic acids for sequencing, in particular for sequencing of RNA and/or DNA. Research and development services; industrial research in the field of biology; industrial development in the field of human biology and diseases like cancer and inflammation/ immune disorders; Laboratory services for detecting protein-DNA interactions and/or for detecting protein-RNA interactions; Scientific services for the analysis of laboratory results; Computer programming; DNA and RNA testing for purposes of scientific research; Biochemical analysis; Biological analysis; Preparation of biological samples for analysis in research laboratories; Preparation of biological samples for testing and analysis in research laboratories; Research and development in the field of diagnostic preparations.

Abstract

The invention relates to methods for determining the selectivity of a test compound and related methods such as methods for determining whether a subject suffering from cancer will respond or is responsive to treatment with a test compound or compositions comprising more than one test compound.

IPC Classes  ?

• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
• C12N 5/078 - Cells from blood or from the immune system
• C12N 5/077 - Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells

Abstract

The present invention relates to a sulfonylurea compound for use in the treatment and/or amelioration of a disease that is associated with UV-induced DNA damage, wherein the subject to be treated expresses enzymatically active mutY homolog (MUTYH), wherein the sufonylurea compound preferably is acetohexamide or a derivative thereof, or glimepiride or a derivative thereof. The invention furthermore relates to pharmaceutical compositions comprising a sulfonylurea compound for use in the treatment and/or amelioration of a disease that is associated with UV-induced DNA damage. Also, a screening method for identifying a compound that treats and/or ameliorates a disease that is associated with UV-induced DNA damage in a subject that expresses enzymatically active MUTYH is provided. The invention also relates to a method for monitoring the therapeutic success during the treatment of a disease that is associated with UV-induced DNA damage in a subject and a method for identifying a subject which responds to a treatment with a sulfonylurea compound.

IPC Classes  ?

• A61K 31/64 - Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
• A61P 43/00 - Drugs for specific purposes, not provided for in groups
• C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions

Abstract

The present invention relates to methods for determining the propensity of cells to interact in a population of cells comprising at least two distinguishable subpopulations of cells. In addition, the present invention provides methods for diagnosing a disease or predisposition to a disease of a cell donor, wherein the method comprises the determination of the propensity of cells to interact in a population of cells obtained from the donor, wherein the population of cells comprises at least two distinguishable subpopulations of cells. The invention also provides methods for determining whether a subject suffering from or predisposed to a disease will respond or is responsive to treatment with a therapeutic agent by determining the alteration of the propensity of cells to interact in a population of ceils obtained from the subject, wherein the population of cells comprises at least two distinguishable subpopulations of cells. The invention also relates to methods for screening for a therapeutic agent comprising the determination whether one or more test substances alter the propensity of cells to interact.

IPC Classes  ?

• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention relates to methods for determining the propensity of cells to interact in a population of cells comprising at least two distinguishable subpopulations of cells. In addition, the present invention provides methods for diagnosing a disease or predisposition to a disease of a cell donor, wherein the method comprises the determination of the propensity of cells to interact in a population of cells obtained from the donor, wherein the population of cells comprises at least two distinguishable subpopulations of cells. The invention also provides methods for determining whether a subject suffering from or predisposed to a disease will respond or is responsive to treatment with a therapeutic agent by determining the alteration of the propensity of cells to interact in a population of ceils obtained from the subject, wherein the population of cells comprises at least two distinguishable subpopulations of cells. The invention also relates to methods for screening for a therapeutic agent comprising the determination whether one or more test substances alter the propensity of cells to interact.

IPC Classes  ?

• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention provides a novel method for preparing a sequencing library and studying molecular interactions involving a nucleic acid. In particular, the invention relates to a method for preparing a sequencing library, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; and obtaining a sequencing library. Moreover, the present invention relates to a method for mapping of molecular interactions involving a nucleic acid, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; amplification of nucleic acid; sequencing of amplified nucleic acid; and identifying molecular interactions.

IPC Classes  ?

• C40B 50/06 - Biochemical methods, e.g. using enzymes or whole viable microorganisms
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C07K 16/44 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere
• C40B 50/04 - Methods of creating libraries, e.g. combinatorial synthesis using dynamic combinatorial chemistry techniques
• C40B 50/08 - Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creationParticular methods of cleavage from the liquid support

Abstract

The present invention relates to the combination of an antiandrogen with a vitamin K antagonist or with a γ-glutamyl carboxylase inhibitor for use in the treatment or prevention of an androgen receptor positive cancer, such as prostate cancer, or a hyperactive androgen receptor signaling disease/disorder. The invention also relates to a vitamin K antagonist or a γ-glutamyl carboxylase inhibitor for use in resensitizing an antiandrogen-resistant prostate cancer to the treatment with an antiandrogen. The invention further provides a pharmaceutical composition comprising an antiandrogen, a vitamin K antagonist or a γ-glutamyl carboxylase inhibitor, and a pharmaceutically acceptable excipient.

IPC Classes  ?

• A61K 31/37 - Coumarins, e.g. psoralen
• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61P 35/00 - Antineoplastic agents
• A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin

Abstract

The present invention relates to the combination of a BRD4 inhibitor with an antifolate (particularly an MTHFD1 inhibitor) for use in the treatment or prevention of cancer. The invention also relates to an antifolate (particularly an MTHFD1 inhibitor) for use in resensitizing a BRD4 inhibitor-resistant cancer to the treatment with a BRD4 inhibitor. The invention further provides a pharmaceutical composition comprising a BRD4 inhibitor, an antifolate (particularly an MTHFD1 inhibitor), and a pharmaceutically acceptable excipient. Moreover, the invention provides a method of assessing the susceptibility or responsiveness of a subject to the treatment with a BRD4 inhibitor, wherein the subject has been diagnosed as suffering from cancer or is suspected of suffering from cancer, the method comprising determining the level of nuclear folate and/or the level of expression of MTHFD1 in a sample obtained from the subject.

IPC Classes  ?

• A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• G01N 33/00 - Investigating or analysing materials by specific methods not covered by groups
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The invention relates to a multiwell imaging plate and a method for incubating non- adherent cells. The multiwell imaging plate includes multiple wells, at least some of the wells having a first chamber, a second chamber arranged on top of the first chamber, and a disturbance blocking structure provided between the first chamber and the second chamber. The first chamber is formed by one or more first sidewalls and a bottom wall while the second chamber is formed by one or more second sidewalls and includes an opening for introducing liquids. The disturbance blocking structure includes at least one through hole that provides a liquid connection between the first and second chambers.

IPC Classes  ?

• B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
• C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus

Abstract

The present invention relates to lactam derivatives of formula (I) for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as inhibitors of the bromodomain-containing protein TAF1 (i.e., transcription initiation factor TFIID subunit 1) and for use in the treatment or prevention of cancer.

IPC Classes  ?

• C07D 217/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• 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 407/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen 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 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
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Goods & Services

Chemical preparations for use in medical diagnostics, in particular preparations for personalised medicine and/or gene analysis and/or genome sequencing; diagnostic and analytical preparations for medical purposes, in particular for personalised medicine and/or gene analysis and/or genome sequencing. Scientific and technological services and research and design relating thereto, in particular for personalised medicine and/or gene analysis and/or genome sequencing; industrial analysis and research services. Medical and veterinary services, in particular treatment methods for personalised medicine and/or gene analysis and/or genome sequencing; medical analysis, in particular test methods for personalised medicine and/or gene analysis and/or genome sequencing; medical services.

Abstract

ROS1 inhibitor for use in the treatment of a subject suffering from ROS1 positive cancer, wherein the inhibitor is tivozanib.

IPC Classes  ?

• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention provides a novel method for preparing a sequencing library and studying molecular interactions involving a nucleic acid. In particular, the invention relates to a method for preparing a sequencing library, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; and obtaining a sequencing library. Moreover, the present invention relates to a method for mapping of molecular interactions involving a nucleic acid, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; amplification of nucleic acid; sequencing of amplified nucleic acid; and identifying molecular interactions.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

The present invention provides a novel method for preparing a sequencing library and studying molecular interactions involving a nucleic acid. In particular, the invention relates to a method for preparing a sequencing library, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; and obtaining a sequencing library. Moreover, the present invention relates to a method for mapping of molecular interactions involving a nucleic acid, the method comprising the addition of an agent binding to chromatin to a sample comprising a nucleic acid; isolating chromatin bound by said agent; addition of transposase to the isolated chromatin; isolating nucleic acid from chromatin; amplification of nucleic acid; sequencing of amplified nucleic acid; and identifying molecular interactions.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids

Abstract

The present invention relates to the combination of an antiandrogen with a vitamin K antagonist or with a γ-glutamyl carboxylase inhibitor for use in the treatment or prevention of an androgen receptor positive cancer, such as prostate cancer, or a hyperactive androgen receptor signaling disease/disorder. The invention also relates to a vitamin K antagonist or a γ-glutamyl carboxylase inhibitor for use in resensitizing an antiandrogen-resistant prostate cancer to the treatment with an antiandrogen. The invention further provides a pharmaceutical composition comprising an antiandrogen, a vitamin K antagonist or a γ-glutamyl carboxylase inhibitor, and a pharmaceutically acceptable excipient.

IPC Classes  ?

• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61K 31/37 - Coumarins, e.g. psoralen
• A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• A61P 5/28 - Antiandrogens
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to substituted 4-(phenylamino)quinoline derivatives of formula (I) for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as inhibitors of MTH1 and for use in the treatment or prevention of cancer.

IPC Classes  ?

• A61K 31/4706 - 4-Aminoquinolines8-Aminoquinolines, e.g. chloroquine, primaquine
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The present invention relates to oxoquinoline derivatives of formula (I) for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as inhibitors of MTH1 and for use in the treatment or prevention of cancer.

IPC Classes  ?

• A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to 2,3-dihydrocyclopenta[bJquinoline derivatives of formula (I) as well as pharmaceutical compositions comprising these compounds for use in the treatment or prevention of cancer, and particularly for use as inhibitors of MTH1.

IPC Classes  ?

• A61K 31/473 - QuinolinesIsoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention relates to 4-aminoquinazoline derivatives of formula (I) for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as inhibitors of MTH1 and for use in the treatment or prevention of cancer.

IPC Classes  ?

• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution

Abstract

The present disclosure relates to an antibody that specifically binds to a mutant calreticulin protein, wherein the variable region of the heavy chain of said antibody comprises a CDR-H3 region having an amino acid sequence as depicted in SEQ ID NO.: 3, or a CDR sequence having 75% or more amino acid identity to said CDR; or wherein the variable region of the heavy chain of said antibody comprises a CDR-H3 region having an amino acid sequence as depicted in SEQ ID NO.: 6, or a CDR sequence having 75% or more amino acid identity to said CDR. Hybridoma 8B2-H6-10.7 deposited under accession number DSM ACC3249 with the depositary institute DSMZ on September 12, 2014 as well as antibodies obtainable therefrom are subject of the present disclosure. The antibodies provided herein can be used in the diagnosis of or therapeutic intervention in myeloid malignancies.

IPC Classes  ?

• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells

Abstract

The present invention relates to an antagonist of the methyltransferase Setdb2 for use in treating an infection. Also provided herein are methods for treating, preventing or ameliorating infections comprising the administration of an antagonist of Setdb2 to a subject in need of such treatment. Herein preferred is the treatment of superinfections, in particular bacterial superinfections. The infection, in particular the bacterial superinfection, can be preceded by a viral infection.

IPC Classes  ?

• A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
• A61K 31/404 - Indoles, e.g. pindolol
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• A61K 31/428 - Thiazoles condensed with carbocyclic rings
• A61K 31/433 - Thiadiazoles
• A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/52 - Purines, e.g. adenine
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 31/538 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
• A61K 31/548 - 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 having two or more sulfur atoms in the same ring
• A61K 31/5513 - 1,4-Benzodiazepines, e.g. diazepam

Goods & Services

Chemical preparations for use in DNA analysis [other than medical]; reagents for use in scientific apparatus for chemical or biological analysis; biomolecule labeling kits comprising reagents for use in scientific research; chemicals for use in immuno-assay testing [other than medical or veterinary]; in-vivo diagnostic reagents for scientific use; diagnostic testing materials, other than for medical use; diagnostic preparations, except for medical or veterinary use; diagnostic reagents, other than for medical laboratory use; diagnostic reagents, except for medical or veterinary use; diagnostic reagents for in-vitro use [other than medical]; diagnostic chemicals [other than for medical or veterinary use]; diagnostic preparations, other than for medical or veterinary purposes; clinical diagnostics, other than for medical or veterinary use; diagnostic reagents and preparations, except for medical or veterinary use; diagnostic reagents, other than for medical use for sale in kit form; diagnostic reagents for in-vitro use in biochemistry, clinical chemistry and microbiology; diagnostic preparations for scientific or research use other than for medical use; reagents for use in diagnostic tests [other than for medical or veterinary purposes]; chemical reagents for use in diagnostic tests, other than for medical or veterinary use; diagnostic substances, other than for medical use; diagnostic reagents for scientific or research use; diagnostic preparations for scientific or research use; biochemical products, in particular biochemical products used in industry and science, in particular biochemical products used in industry and science to study cells, chromatin, proteins, nucleic acids, protein-nucleic acid interactions; biochemical reagents or chemical reagents, in particular biochemical reagents or chemical reagents for in-vitro use in laboratories for scientific use. Apparatus, namely column- or magnet-based apparatus for chromatin immunoprecipitation, chromatin analysis, chromatin purification, nucleic acid purification and analysis; scientific, electric, photographic, optical, measuring apparatus, namely sequencers for next generation sequencing; scientific, electric apparatus preparing nucleic acids for sequencing; computer hardware and computer software for processing and displaying and interpreting data, in particular for scientific purposes; testing apparatus for diagnostic purposes [other than medical]. Treatment of nucleic acids, proteins and chromatin; treatment of nucleic acids with enzymatic reactions; treatment of chromatin with enzymatic reactions; treatment of nucleic acids for sequencing. Research and development services; industrial research in the field of biology; industrial development in the field of human biology and diseases like cancer and inflammation/ immune disorders; laboratory services for detecting protein-DNA interactions; services for analysis relating thereto; computer programming; DNA screening for scientific research purposes; biochemical analysis; biological analysis; preparation of biological samples for analysis in research laboratories; preparation of biological samples for testing and analysis in research laboratories; research and development in the field of diagnostic preparations.

Abstract

The invention relates to peripheral blood mononuclear cell (PBMC) monolayers or bone-marrow cell monolayers and methods for its culture and corresponding uses of said monolayers. The present invention also relates, in some aspects, to screening methods comprising the PBMC monolayer or bone-marrow cell monolayer of the invention for determination of response or lack of response of a disease to a therapeutic agent and/or drug screening methods. In some aspects, the invention further relates to methods for diagnosing a disease or predisposition to a disease in a PBMC donor or bone-marrow cell donor comprising the PBMCs/bone-marrow cells cultured according to the method of the invention and/or to methods for determining whether the disease is likely to respond or is responsive to treatment with a therapeutic agent.

IPC Classes  ?

• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
• C12N 5/078 - Cells from blood or from the immune system
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The invention relates to peripheral blood mononuclear cell (PBMC) monolayers or bone-marrow cell monolayers and methods for its culture and corresponding uses of said monolayers. The present invention also relates, in some aspects, to screening methods comprising the PBMC monolayer or bone-marrow cell monolayer of the invention for determination of response or lack of response of a disease to a therapeutic agent and/or drug screening methods. In some aspects, the invention further relates to methods for diagnosing a disease or predisposition to a disease in a PBMC donor or bone-marrow cell donor comprising the PBMCs/bone-marrow cells cultured according to the method of the invention and/or to methods for determining whether the disease is likely to respond or is responsive to treatment with a therapeutic agent.

IPC Classes  ?

• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
• C12N 5/078 - Cells from blood or from the immune system
• A61K 35/14 - BloodArtificial blood
• C12M 3/04 - Tissue, human, animal or plant cell, or virus culture apparatus with means providing thin layers
• C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving viable microorganisms
• G01N 33/15 - Medicinal preparations
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Goods & Services

[ Treatment of nucleic acids, proteins and chromatin; treatment of nucleic acids with enzymatic reactions; treatment of chromatin with enzymatic reactions; treatment of nucleic acids for sequencing ] Chemical preparations for use in DNA analysis other than for medical use; reagents for use in scientific apparatus for chemical or biological analysis; biomolecule labeling kits comprising reagents for use in scientific research; chemicals for use in immuno-assay testing other than for medical or veterinary use; in-vivo diagnostic reagents for scientific use; diagnostic testing preparations, other than for medical use; diagnostic preparations, except for medical or veterinary use; diagnostic reagents, other than for medical laboratory use; diagnostic reagents, except for medical or veterinary use; diagnostic reagents for in-vitro use, other than for medical use; diagnostic chemicals, other than for medical or veterinary use; diagnostic preparations, other than for medical or veterinary purposes; clinical diagnostic preparations, other than for medical or veterinary use; diagnostic reagents and preparations, except for medical or veterinary use; diagnostic reagents, other than for medical use for sale in kit form; diagnostic reagents for in-vitro use in biochemistry, clinical chemistry and microbiology; diagnostic preparations for scientific or research use other than for medical use; reagents for use in diagnostic tests, other than for medical or veterinary purposes; chemical reagents for use in diagnostic tests, other than for medical or veterinary use; diagnostic substances in the nature of chemicals and preparations, other than for medical use; diagnostic reagents for scientific or research use; diagnostic preparations for scientific or research use; biochemical products, in particular biochemicals used in industry and science to study cells, chromatin, proteins, nucleic acids, protein-nucleic acid interactions, other than for medical use; biochemical reagents and chemical reagents, in particular biochemical reagents and chemical reagents for in-vitro use in laboratories for scientific use [ Apparatus, namely, column- and magnet-based apparatus for chromatin immunoprecipitation, chromatin analysis, chromatin purification, nucleic acid purification and analysis for laboratory use; scientific, electric, photographic, optical, measuring apparatus, namely, sequencers for next generation genetic sequencing for laboratory use; scientific, electric apparatus preparing nucleic acids for sequencing for laboratory use; computer hardware and computer software for processing and displaying and interpreting data, in particular for scientific purposes; testing apparatus for testing samples comprising a nucleic acid for for diagnostic purposes, other than medical purposes ] [ Scientific research and development services; industrial research in the field of biology; industrial research in the field of human biology and diseases like cancer and inflammation and immune disorders; laboratory services for detecting protein-DNA interactions; Laboratory analysis relating to protein-DNA interactions; computer programming; DNA screening for scientific research purposes; biochemical analysis; biological analysis; preparation of biological samples for analysis in research laboratories; preparation of biological samples for testing and analysis in research laboratories; research and development in the field of diagnostic preparations ]

Abstract

The present invention relates to an antagonist or modulator of SLC38A9 for use in treating a disease associated with mTORC1 activation, like a proliferative disease (e.g. a cancerous disease or benign proliferative disease), a metabolic disorder, a disorder of the immune system, a disorder causing premature aging, an ophthalmic disorder or a neurological disorder. Exemplary diseases to be treated are cancerous diseases like lung cancer, breast cancer, bladder cancer, pancreatic cancer, ovarian cancer, colon carcinoma, leukemia, lymphoma, melanoma, esophageal cancer and stomach cancer; or metabolic disorders like overweight (pre-obesity), obesity or diabetes. Also provided herein are methods for treating, preventing or ameliorating such diseases comprising the administration of an antagonist of SLC38A9 to a subject in need of such a treatment, prevention or amelioration. Furthermore, the present invention provides methods for assessing the activity of a candidate molecule suspected of being an antagonist of SLC38A9 and identification of such antagonists.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants

Abstract

The invention refers to BTBD9 binders and gephyrin binders for medical use and in particular an artemisinin compound of general formula I for use in the treatment of a diabetes patient, as well as a method of identifying suitable lead candidates.

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 31/366 - Lactones having six-membered rings, e.g. delta-lactones
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 5/48 - Drugs for disorders of the endocrine system of the pancreatic hormones
• C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues

Goods & Services

Chemical preparations for use in DNA analysis [other than medical]; Reagents for use in scientific apparatus for chemical or biological analysis; Biomolecule labeling kits comprising reagents for use in scientific research; Chemicals for use in immuno-assay testing [other than medical or veterinary]; ln-vivo diagnostic reagents for scientific use; Diagnostic testing materials, other than for medical use; Diagnostic preparations, except for medical or veterinary use; Diagnostic reagents, other than for medical laboratory use; Diagnostic reagents, except for medical or veterinary use; Diagnostic reagents for in-vitro use [other than medical]; Diagnostic chemicals [other than for medical or veterinary use]; Diagnostic preparations, other than for medical or veterinary purposes; Clinical diagnostics, other than for medical or veterinary use; Diagnostic reagents and preparations, except for medical or veterinary use; Diagnostic reagents, other than for medical use for sale in kit form; Diagnostic reagents for in-vitro use in biochemistry, clinical chemistry and microbiology; Diagnostic preparations for scientific or research use other than for medical use; Reagents for use in diagnostic tests [other than for medical or veterinary purposes]; Chemical reagents for use in diagnostic tests, other than for medical or veterinary use; Diagnostic substances, other than for medical use; Diagnostic reagents for scientific or research use; Diagnostic preparations for scientific or research use; Biochemical products, in particular biochemical products used in industry and science, in particular biochemical products used in industry and science to study cells, chromatin, proteins, nucleic acids, protein-nucleic acid interactions; biochemical reagents or chemical reagents, in particular biochemical reagents or chemical reagents for in-vitro use in laboratories for scientific use. Apparatus, namely column- or magnet-based apparatus for chromatin immunoprecipitation, chromatin analysis, chromatin purification, nucleic acid purification and analysis; Scientific, electric, photographic, optical, measuring apparatus, namely sequencers for next generation sequencing; scientific, electric apparatus preparing nucleic acids for sequencing; computer hardware and computer software for processing and displaying and interpreting data, in particular for scientific purposes; Testing apparatus for diagnostic purposes [other than medical]. Treatment of nucleic acids, proteins and chromatin; treatment of nucleic acids with enzymatic reactions; treatment of chromatin with enzymatic reactions; treatment of nucleic acids for sequencing. Research and development services; industrial research in the field of biology; industrial development in the field of human biology and diseases like cancer and inflammation/ immune disorders; laboratory services for detecting protein-DNA interactions; services for analysis relating thereto; computer programming; DNA screening for scientific research purposes; Biochemical analysis; Biological analysis; Preparation of biological samples for analysis in research laboratories; Preparation of biological samples for testing and analysis in research laboratories; Research and development in the field of diagnostic preparations.

Abstract

Mutations in calreticulin are discovered to be linked to myeloid malignancies. Disclosed are genomic sequences, cDNA sequences, mRNA sequences and protein sequences of mutant calreticulin that are linked to myeloid malignancies. Also disclosed are methods for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also disclosed are related compositions, kits and methods, including the medical use of inhibitors of mutant calreticulin.

IPC Classes  ?

• G01N 33/53 - ImmunoassayBiospecific binding assayMaterials therefor
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

IPC Classes  ?

• C12N 15/12 - Genes encoding animal proteins
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• 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 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
• C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers

Abstract

The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids

Goods & Services

Biochemical or chemical products for use in industry and science; biochemicals or chemical reagents for in vitro use in laboratories for scientific use, in particular for cell culture, testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues; in vitro diagnostic agents for scientific use; biochemical or chemical products for use in medical science; pharmaceutical and biochemical substances and preparations, in particular reagents for medical research applications and medical diagnosis; biochemicals or chemical reagents for in vitro use in laboratories for medical purposes; biochemicals or chemical reagents for in vitro use in laboratories for medical purposes, in particular for cell culture, testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues. Diagnostic products for medical purposes. Apparatus for cell culture, testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues; scientific, optical, measuring and monitoring apparatus and instruments; electric apparatus and instruments for use in laboratories for medical purposes, in particular for testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues; computer-aided analysis apparatus and installations constructed therefrom, in particular for analysing the effects of drugs on cell types, in particular cells originating from blood or tissues; computer hardware and computer software, in particular for scientific and medical purposes; accessories, namely test microtiter plates. Medical and pharmaceutical research and development; scientific and industrial research and development services; services for cell culture, testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues; professional consultancy services relating to biotechnology, biochemistry, and biomedical science; contract research services; computer programming.

Abstract

he present invention relates to an (S)-enantiomer of an aminoheteroaryl compound for use in treating and/or preventing cancer in a subject. The invention further relates to a pharmaceutical composition comprising said compound. Another aspect of the invention is directed to an in vitro method for determining the effectiveness of said (S)-enantiomer of an aminoheteroaryl compound, or said pharmaceutical composition, the method comprising the steps of: (a) obtaining a cell or tissue sample from a subject; and (b) determining the subject's NUDT1/MTH1 -status; wherein a NUDT1/MTH1-positive cell or tissue sample is indicative of an effective treatment and/or prevention of cancer. In addition, provided herein is a screening method for identifying a target of an (S)-enantiomer of an aminoheteroaryl compound. Furthermore, in context of this invention, the herein described compounds inhibit the biological activity of MTH1.

IPC Classes  ?

• A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• A61P 35/00 - Antineoplastic agents

Goods & Services

Biochemical or chemical products for use in industry and science; biochemicals or chemical reagents for in vitro use in laboratories for scientific use, in particular for cell culture, testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues; in vitro diagnostic agents for scientific use. Biochemical or chemical products for use in medical science; pharmaceutical and biochemical substances and preparations, in particular reagents for medical research applications and medical diagnosis; biochemicals or chemical reagents for in vitro use in laboratories for medical purposes, in particular for cell culture, testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues; diagnostic products for medical purposes. Apparatus for cell culture, testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues; scientific, optical, measuring and monitoring apparatus and instruments; electric apparatus and instruments for use in laboratories for medical purposes; computer-aided analysis apparatus and installations constructed therefrom; computer hardware and computer software, in particular for scientific and medical purposes; accessories, namely test microtiter plates. Medical and pharmaceutical research and development; scientific and industrial research and development services; services for cell culture, testing and/or detecting effects of drugs on cell types, in particular cells originating from blood or tissues; professional consultancy services; contract research services; computer programming.

Goods & Services

Chemical, biochemical and biological products used in industry and science; in-vitro diagnostic preparations (not for medical or veterinary purposes); in-vitro diagnostic preparations for identifying blood malignances, in particular myeloproliferative neoplasms; control reagents used in scientific apparatus and equipment. Pharmaceutical and veterinary preparations; pharmaceutical preparations and substances for the prevention and treatment of blood malignances, in particular myeloproliferative neoplasms; preparations, chemical substances, reagents and agents for diagnostic and medical purposes; sanitary preparations for medical use. Medical services; veterinary services; services in the field of blood malignancies; services and advice related to medical and pharmaceutical preparations and substances; medical clinical services; medical treatment services; therapeutic treatment services; healthcare services; medical services related to blood malignancies and pharmaceuticals; providing for medical and medicinal information in the field of diagnostic, medicine, pharmaceuticals, disorders, diseases, treatments and prevention.

Goods & Services

Chemical preparations for use in medical diagnostics, in particular preparations for personalised medicine and/or gene analysis and/or genome sequencing; Diagnostic and analytical preparations for medical purposes, in particular for personalised medicine and/or gene analysis and/or genome sequencing. Scientific and technological services and research and design relating thereto, in particular for personalised medicine and/or gene analysis and/or genome sequencing; Industrial analysis and research services. Medical and veterinary services, in particular treatment methods for personalised medicine and/or gene analysis and/or genome sequencing; Medical analysis, in particular test methods for personalised medicine and/or gene analysis and/or genome sequencing; Medical services.

Abstract

The present invention relates to a specific sphingomyelinase for use in inhibiting immune response. Another aspect of the invention relates to a pharmaceutical composition comprising said sphingomyelinase for use in treating an autoimmune disorder or a pro-inflammatory response. In addition, another pharmaceutical composition comprising a specific inhibitor of said sphingomyelinase for use in treating an immunodeficiency disorder is comprised. The invention also relates to a diagnostic composition comprising a binding molecule which specifically binds said sphingomyelinase for use in diagnosing an immunodeficiency disorder, an autoimmune disorder or a pro-inflammatory response. The invention further relates to the use of said diagnostic composition for diagnosing an immunodeficiency disorder, an autoimmune disorder or a pro-inflammatory response. Furthermore, the present invention relates an antigen presenting cell that is inhibited in TLR signalling by said sphingomyelinase. In one aspect of the invention, said antigen presenting cell is a macrophage, a dendritic cell or a B cell. The present invention further relates to a non-human animal, wherein the activity and/or the expression of said sphingomyelinase is reduced to boost the immune system of said non-human animal. In addition, the invention relates to a method for producing antibodies against an antigen comprising the administration of said antigen to said non non-human animal. Finally, the invention relates to said method for producing antibodies, wherein said non-human animal is a knock out mouse for the gene encoding said sphingomyelinase, wherein said antibodies are high affinity antibodies.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)

Abstract

A method for determining the responsiveness of a mammalian tumor cell to treatment with an inhibitor of the phosphoinosite 3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) pathway, said method comprising determining the c-MYC and/or NOTCH1 level in said tumor cell, wherein said level is indicative of whether the cell is likely to respond or is responsive to the treatment. It further refers to an in vitro method for the identification of a resistance to treatment or of predicting or monitoring the efficacy of treatment, of solid tumor cancer with an inhibitor of the PI3K and/or mTOR pathway in a patient suffering from said cancer. It further refers to a combination comprising an amount of an inhibitor of the PI3K and/or mTOR pathway, and an amount of a c-MYC and/or NOTCH 1 inhibitor.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids

Abstract

The invention relates to complement Factor H for use in the prevention and treatment of oxidative stress disease conditions in a patient, the use of Factor H in the preparation of a pharmaceutical preparation, and methods of determining the specific binding of Factor H to MDA and/or MAA in a sample.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans

Abstract

The present invention refers to a synthetic microsphere based on malondialdehyde (MDA) coupled to a backbone, with a size ranging between 500 nm and 500 µm, its use for analytic, diagnostic or pharmaceutic purposes, and specifically its use in a method of selecting antagonists of oxidative stress disease from a repertoire of agents possibly binding to oxidation epitopes.

IPC Classes  ?

• A61K 47/08 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing