Isotopic mass tags for labelling peptides and other biomolecules are provided as well as methods of detecting an analyte by identifying by mass spectrometry one or more of the mass labels or combinations thereof.
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
C07C 237/00 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
2.
Isobaric mass labels having n',n'-dimeihyl piperazine-2-carboxylic acid reporter moieties
wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
C07B 59/00 - Introduction of isotopes of elements into organic compounds
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
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
C12Q 1/6872 - Methods for sequencing involving mass spectrometry
C40B 40/04 - Libraries containing only organic compounds
wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
G01N 33/60 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances involving radioactive labelled substances
G01N 33/532 - Production of labelled immunochemicals
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
4.
Isotopic methods for measurement of tryptophan and metabolites thereof
Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.
The invention relates to panels of biomarkers including proteins phosphatase 1 regulatory subunit 14A and/or 2′,3′-cyclic-nucleotide 3′-phosphodiesterase and/or phosphorylated tau or fragments thereof and methods using thereof for diagnosing, staging, treating and assessing the response of a treatment for a neurocognitive disorder characterised by tau toxicity, in particular for Alzheimer's disease. The present invention shows that the biomarkers disclosed herein are elevated in the brain of subjects with an advanced stage of a neurocognitive disorder (Braak stage V/VI) and/or are regulated in the CSF of AD subjects in comparison to cognitively affected non-AD controls; and/or regulated in response to two casein kinase 1 delta inhibitors.
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 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
A61P 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
6.
Materials and methods for diagnosis and treatment of Alzheimer's disease
Alzheimer's disease (AD) is the most common type of dementia in aging adults with the number of people living with AD projected to increase, making the search for treatments and tools to diagnose and measure disease progression increasingly urgent. In particular, ideal biomarkers for diagnosis of AD should not only have high specificity for disease versus non-disease and high sensitivity for distinguishing between disease types but also should be able to detect changes at a very early stage of the disease. Using microglia activation as an early event of AD's onset, the present inventors have identified a panel of biomarkers in CSF which has the potential to diagnose, stage and determine the likelihood of developing AD.
Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. In the past, AD could only be definitively diagnosed by brain biopsy or upon autopsy after a patient died. These methods, which demonstrate the presence of the characteristic plaque and tangle lesions in the brain, are still considered the gold standard for the pathological diagnoses of AD. However, in the clinical setting brain biopsy is rarely performed and diagnosis depends on a battery of neurological, psychometric and biochemical tests, including the measurement of biochemical markers such as the ApoE and tau proteins or the beta-amyloid peptide in cerebrospinal fluid and blood. The present invention discloses and describes panels of makers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of makers associated with neurocognitive disorders. Such biomarker panel might have considerable value in triaging patients with early memory disorders to yet more specific but more invasive and costly approaches such as molecular markers in CSF and on PET imaging in clinical trials and possibly in clinical practice.
The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
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
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C40B 70/00 - Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or barcodes
G01N 27/00 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C40B 70/00 - Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or barcodes
G01N 27/00 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
The present invention relates to a set of two or more mass labels. Each mass label comprises: X-L-M-Re; X is a reporter moiety having exact mass; L is a bond cleavable by collision in a mass spectrometer; M is a mass modifier; Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte. Each mass label in the set has the same integer mass; wherein the set comprises two or more subsets of mass labels, each subset comprising one or more mass labels; wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets; each mass label is distinguishable by mass spectrometry.
Provided is a method of assaying for an analyte, including combining a test sample having the analyte, with a calibration sample having at least two different aliquots of the analyte, each aliquot having a different known quantity of the analyte. The test sample and each aliquot are differentially labeled with one or more isobaric mass labels each with a mass spectrometrically distinct mass marker group, such that the test sample and each aliquot of the calibration sample can be distinguished by mass spectrometry. The method further includes determining by mass spectrometry the quantity of analyte in the test sample and in each aliquot, and calibrating the quantity of analyte in the test sample against known and determined quantities of analytes in the aliquots.
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
H01J 49/00 - Particle spectrometers or separator tubes
G01N 33/96 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
14.
ISOTOPIC METHODS FOR MEASUREMENT OF TRYPTOPHAN AND METABOLITES THEREOF
Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.
Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.
2 of the bifunctional linker attached to the analyte reacts with a mass label to form a labelled analyte, wherein each mass label is relatable to an analyte by mass spectrometry.
The invention relates to panels of biomarkers including proteins phosphatase 1 regulatory subunit 14A and/or 2',3'-cyclic-nucleotide 3'-phosphodiesterase and/or phosphorylated tau or fragments thereof and methods using thereof for diagnosing, staging, treating and assessing the response of a treatment for a neurocognitive disorder characterised by tau toxicity, in particular for Alzheimer's disease. The present invention shows that the biomarkers disclosed herein are elevated in the brain of subjects with an advanced stage of a neurocognitive disorder (Braak stage V/VI) and/or are regulated in the CSF of AD subjects in comparison to cognitively affected non-AD controls; and/or regulated in response to two casein kinase 1 delta inhibitors.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
The invention relates to panels of biomarkers including proteins phosphatase 1 regulatory subunit 14A and/or 2',3'-cyclic-nucleotide 3'-phosphodiesterase and/or phosphorylated tau or fragments thereof and methods using thereof for diagnosing, staging, treating and assessing the response of a treatment for a neurocognitive disorder characterised by tau toxicity, in particular for Alzheimer's disease. The present invention shows that the biomarkers disclosed herein are elevated in the brain of subjects with an advanced stage of a neurocognitive disorder (Braak stage V/VI) and/or are regulated in the CSF of AD subjects in comparison to cognitively affected non-AD controls; and/or regulated in response to two casein kinase 1 delta inhibitors.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl) carbonyl] indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.
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
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
The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl) carbonyl] indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.
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
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
21.
MATERIALS AND METHODS FOR DIAGNOSIS AND TREATMENT OF ALZHEIMER'S DISEASE
Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. The present invention discloses and describes panels of markers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of markers associated with neurocognitive disorders. In some aspects, the marker panel comprises phosphoglucomutase 1 and/or thymosin beta-4, or an isoform, a variant or a fragment of either protein, alone or in combination with additional markers.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
C12Q 1/44 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving esterase
C12Q 1/533 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving isomerase
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
Alzheimer's disease (AD) is the most common type of dementia in aging adults with the number of people living with AD projected to increase, making the search for treatments and tools to diagnose and measure disease progression increasingly urgent. In particular, ideal biomarkers for diagnosis of AD should not only have high specificity for disease versus non-disease and high sensitivity for distinguishing between disease types but also should be able to detect changes at a very early stage of the disease. Using microglia activation as an early event of AD's onset, the present inventors have identified a panel of biomarkers in CSF which has the potential to diagnose, stage and determine the likelihood of developing AD.
The present invention provides a method for diagnosing or assessing a neurodegenerative disease in a test subject, comprising: (i) providing a protein-containing sample that has been obtained from the test subject; (ii) determining the concentration, amount or degree of expression of at least one specific protein isoform and/or glycoform derived from a protein biomarker selected from the group consisting of: clusterin precursor; apolipoprotein A-IV precursor; apolipoprotein C-III precursor; transthyretin; galectin 7; complement C4 precursor; alpha-2-macroglobulin precursor; Ig alpha-1 chain C; histone 2B; Ig lambda chain C region; fibrinogen gamma chain precursor; complement factor H; inter-alpha-trypsin heavy chain H4 precursor; complement C3 precursor; gamma or beta actin; haptoglobin precursor; and the serum albumin precursor, or a fragment thereof; (iii) comparing said concentration, amount or degree determined in (ii) with a reference from a control subject with a specific neurodegenerative disease, dementia or stage of disease, or from a control subject that does not have a neurogenerative disease or dementia; and (iv) based on the level of the at least one specific protein isoform and/or glycoform of the protein biomarker in the test subject relative to the reference, making a diagnosis or assessment as to the presence of and/or stage of neurodegenerative disease or dementia of the test subject. Also provided are related products and systems for use in such a method.
The invention relates to pharmaceutical compositions having casein kinase 1 delta (CK1δ) inhibitors and to the use of the inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
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 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07D 209/42 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 277/68 - Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
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 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 413/06 - 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 carbon chain containing only aliphatic carbon atoms
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/4045 - Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C07D 207/06 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
C07D 207/404 - 2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
C07D 207/06 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
The invention relates to pharmaceutical compositions having casein kinase 1 delta (CK1δ) inhibitors and to the use of the inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07D 209/42 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 277/68 - Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
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 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 413/06 - 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 carbon chain containing only aliphatic carbon atoms
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/4045 - Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
28.
MASS LABELS AND METHODS OF USE THEREOF FOR LABELLING ANALYTES
The present invention provides a method for labelling one or more analytes in a sample, the method comprising: a) contacting the sample with one or more bifunctional linker reagents having the general formula Re1-L1-Re2, wherein Re1 is a first reactive group, L1 is a linker moiety and Re2 is a second reactive group, wherein Re1 reacts with an analyte to form a modified analyte; and b) contacting the sample with one or more mass labels, wherein Re2 of the bifunctional linker attached to the analyte reacts with a mass label to form a labelled analyte, wherein each mass label is relatable to an analyte by mass spectrometry.
The present invention provides a method for labelling one or more analytes in a sample, the method comprising: a) contacting the sample with one or more bifunctional linker reagents having the general formula Re1-L1-Re2, wherein Re1 is a first reactive group, L1 is a linker moiety and Re2 is a second reactive group, wherein Re1 reacts with an analyte to form a modified analyte; and b) contacting the sample with one or more mass labels, wherein Re2 of the bifunctional linker attached to the analyte reacts with a mass label to form a labelled analyte, wherein each mass label is relatable to an analyte by mass spectrometry.
Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. In the past, AD could only be definitively diagnosed by brain biopsy or upon autopsy after a patient died. These methods, which demonstrate the presence of the characteristic plaque and tangle lesions in the brain, are still considered the gold standard for the pathological diagnoses of AD. However, in the clinical setting brain biopsy is rarely performed and diagnosis depends on a battery of neurological, psychometric and biochemical tests, including the measurement of biochemical markers such as the ApoE and tau proteins or the beta-amyloid peptide in cerebrospinal fluid and blood. The present invention discloses and describes panels of makers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of makers associated with neurocognitive disorders. Such biomarker panel might have considerable value in triaging patients with early memory disorders to yet more specific but more invasive and costly approaches such as molecular markers in CSF and on PET imaging in clinical trials and possibly in clinical practice.
Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. In the past, AD could only be definitively diagnosed by brain biopsy or upon autopsy after a patient died. These methods, which demonstrate the presence of the characteristic plaque and tangle lesions in the brain, are still considered the gold standard for the pathological diagnoses of AD. However, in the clinical setting brain biopsy is rarely performed and diagnosis depends on a battery of neurological, psychometric and biochemical tests, including the measurement of biochemical markers such as the ApoE and tau proteins or the beta-amyloid peptide in cerebrospinal fluid and blood. The present invention discloses and describes panels of makers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of makers associated with neurocognitive disorders. Such biomarker panel might have considerable value in triaging patients with early memory disorders to yet more specific but more invasive and costly approaches such as molecular markers in CSF and on PET imaging in clinical trials and possibly in clinical practice.
KING'S COLLEGE HOSPITAL NHS FOUNDATION TRUST (United Kingdom)
Inventor
Ward, Malcolm Andrew
Pike, Ian Hugo
Britton, David James
Mitra, Vikram
Heaton, Nigel David
Zen, Yoh
Quaglia, Alberto
Abstract
The invention relates to materials and methods for diagnosing liver tumor types, and assessing patient prognosis. Specifically, but not exclusively, the invention concerns the determination of marker protein which enable primary liver tumors to be identified and classified according to the latest WHO classification. Particularly, the invention provides potential markers proteins which allow non- neoplastic and neoplastic hepatocytes and biliary epithelial cells to be distinguished. This allows grading of tumor differentiation to be refined and differential diagnosis of primary liver tumors and pathogenesis of sub-types of cholangiocarcinoma.
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
G06F 19/10 - Bioinformatics, i.e. methods or systems for genetic or protein-related data processing in computational molecular biology (in silico methods of screening virtual chemical libraries C40B 30/02;in silico or mathematical methods of creating virtual chemical libraries C40B 50/02)
33.
MATERIALS AND METHODS RELATING TO PANCREATIC CANCER
KING'S COLLEGE HOSPITAL NHS FOUNDATION TRUST (United Kingdom)
Inventor
Yoh, Zen
Heaton, Nigel
Quaglia, Alberto
Britton, David
Ward, Malcolm
Pike, Ian
Mitra, Vikram
Abstract
The present invention concerns materials and methods relating to pancreatic cancer and personalised medicine as applied to pancreatic cancer. Particularly, the invention relates to materials and methods for the determination of significantly modulated protein phosphorylation and/or expression as well as the activity of signaling pathways collectively providing a tumour profile that can guide selection of the most appropriate treatment regime based on the likelihood of tumour recurrence; or the identity of activated drug targets in pancreatic cancer tissue.
The invention relates to methods and compositions relating Alzheimer's disease. There is provided a panel of optimal biomarkers which allow diagnosis of Alzheimer's disease and discrimination between Alzheimer's disease and its earlier precursor, mild cognitive impairment (MCI).
The present invention provides a method for diagnosing or assessing a neurodegenerative disease in a test subject, comprising: (i) providing a protein-containing sample that has been obtained from the test subject; (ii) determining the concentration, amount or degree of expression of at least one specific protein isoform and/or glycoform derived from a protein biomarker selected from the group consisting of: clusterin precursor; apolipoprotein A-IV precursor; apolipoprotein C-III precursor; transthyretin; galectin 7; complement C4 precursor; alpha-2-macroglobulin precursor; Ig alpha-1 chain C; histone 2B; Ig lambda chain C region; fibrinogen gamma chain precursor; complement factor H; inter-alpha-trypsin heavy chain H4 precursor; complement C3 precursor; gamma or beta actin; haptoglobin precursor; and the serum albumin precursor, or a fragment thereof; (iii) comparing said concentration, amount or degree determined in (ii) with a reference from a control subject with a specific neurodegenerative disease, dementia or stage of disease, or from a control subject that does not have a neurogenerative disease or dementia; and (iv) based on the level of the at least one specific protein isoform and/or glycoform of the protein biomarker in the test subject relative to the reference, making a diagnosis or assessment as to the presence of and/or stage of neurodegenerative disease or dementia of the test subject. Also provided are related products and systems for use in such a method.
The present invention provides a method for diagnosing or assessing a neurodegenerative disease in a test subject, comprising: (i) providing a protein-containing sample that has been obtained from the test subject; (ii) determining the concentration, amount or degree of expression of at least one specific protein isoform and/or glycoform derived from a protein biomarker selected from the group consisting of: clusterin precursor; apolipoprotein A-IV precursor; apolipoprotein C-III precursor; transthyretin; galectin 7; complement C4 precursor; alpha-2-macroglobulin precursor; Ig alpha-1 chain C; histone 2B; Ig lambda chain C region; fibrinogen gamma chain precursor; complement factor H; inter-alpha-trypsin heavy chain H4 precursor; complement C3 precursor; gamma or beta actin; haptoglobin precursor; and the serum albumin precursor, or a fragment thereof; (iii) comparing said concentration, amount or degree determined in (ii) with a reference from a control subject with a specific neurodegenerative disease, dementia or stage of disease, or from a control subject that does not have a neurogenerative disease or dementia; and (iv) based on the level of the at least one specific protein isoform and/or glycoform of the protein biomarker in the test subject relative to the reference, making a diagnosis or assessment as to the presence of and/or stage of neurodegenerative disease or dementia of the test subject. Also provided are related products and systems for use in such a method.
The present invention provides set of two or more mass labels, wherein each mass label in the set has the same integer mass as every other label in the set, and each mass label in the set has an exact mass which is different to the mass of all other mass labels in the set such that all the mass labels in the set are distinguishable from each other by mass spectrometry.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
C07D 403/00 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group
38.
MATERIALS AND METHODS FOR DETERMINING SENSITIVITY POTENTIAL OF COMPOUNDS
The invention concerns in vitro proteomic analysis of cells to determine the sensitizing potential (including allergic potential) of compounds on said cells. Several protein markers are provided that allow assays to be performed to determine whether a chemical has a sensitizing potential of contact sensitizers.
The invention concerns in vitro proteomic analysis of cells to determine the sensitizing potential (including allergic potential) of compounds on said cells. Several protein markers are provided that allow assays to be performed to determine whether a chemical has a sensitizing potential of contact and/or respiratory sensitizers.
The invention identifies and describes proteins that are differentially expressed in platelets resistant to anti- platelet agents such as aspirin (acetylsalicyclic acid) compared to those platelets that are sensitive to such agents. Methods for determining further such differentially expressed proteins and methods for determining an individual's sensitivity to anti-platelet agents, such as aspirin, prior to administration.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemicals for use in industry; chemicals, namely, buffer and
standard solutions used in analytical chemistry; reagents
for chemical analyses; reagents for use in scientific
apparatus for chemical or biological analysis; research
reagents for industrial use, namely, for food and chemical
safety testing; chemical test preparations for chemical
safety testing of raw material for laboratory or research
use. Scientific instruments, namely, mass spectrometers and
fluorescent and luminescent detectors for testing consumer
products for the presence of skin irritating potential;
scientific instruments, namely, electronic analyzers for
measuring, testing and detecting contaminants and
environmental pollutants. Testing, analysis and evaluation of the goods and services
of others for the purpose of certification; consumer product
safety testing; research in the field of consumer product
safety testing; scientific and technological services,
namely, testing consumer products for the presence of skin
irritating potential; scientific research and development.
wherein X is a mass marker moiety, L is a cleavable linker, M is a mass normalization moiety, S is a mass series modifying group comprising the following group:
2 and n is 1, and wherein m is at least 1; and Re is a reactive functionality for attaching the mass label to a biological molecule.
C40B 30/10 - Methods of screening libraries by measuring physical properties, e.g. mass
C40B 40/04 - Libraries containing only organic compounds
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
G01N 33/74 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones
C07B 59/00 - Introduction of isotopes of elements into organic compounds
C07D 211/14 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
42 - Scientific, technological and industrial services, research and design
Goods & Services
(1) Scientific and technological services, namely, research and design in the field of proteomics; scientific research, analysis, testing and development in the fields of pharmaceuticals, medical and veterinary diagnostics, and clinical medicine.
42 - Scientific, technological and industrial services, research and design
Goods & Services
scientific and technological services, namely, research and analysis in the field of proteomics; scientific research, analysis, testing and development in the fields of pharmaceuticals, medical[ and veterinary ]diagnostics and clinical medicine
47.
CASEIN KINASE 1DELTA (CK1DELTA) INHIBITORS AND THEIR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES SUCH AS TAUOPATHIES
The invention relates to pharmaceutical compositions comprising casein kinase 1 delta (CK1δ) and to the use of said inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
A61K 31/00 - Medicinal preparations containing organic active ingredients
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 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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
48.
5-(1,3-BENZOXAZOL-2-YL)-4-(PYRIDIN-4-YL)PYRIMIDIN-2-AMINE AND ITS USE AS A CASEIN KINASE 1DELTA INHIBITOR
The invention relates to pharmaceutical compositions comprising casein kinase 1 delta (CK1õ) and to the use of said inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
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
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
The invention relates to pharmaceutical compositions comprising casein kinase 1 delta (CK1õ) and to the use of said inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
A61K 31/00 - Medicinal preparations containing organic active ingredients
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 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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
RECERCA INSTITUT DE RECERCA HOSPITAL UNIVERSITARI VALL D'HEBRON (Spain)
ELECTROPHORETICS LIMITED (United Kingdom)
Inventor
Dayon, Loïc, Gérard
Sanchez, Jean-Charles
Montaner Villalonga, Joan
Abstract
The invention relates to a method of aiding the diagnosis of acute brain damage in a subject, said method comprising (i) assaying the concentration of at least one oxidative stress polypeptide selected from the group consisting of: PRDX1, PRDX6 and GSTP1 in a sample from said subject; and (ii) assaying the concentration of at least one further polypeptide selected from Panel A; (Hi) comparing the concentrations of (i) and (ii) to the concentrations of the polypeptides in a reference standard and determining quantitative ratios for said polypeptides; (iv) wherein a finding of a quantitative ratio of each of the assayed polypeptides in the sample to the polypeptides in the reference standard of greater than 1.3 indicates an increased likelihood of acute brain damage having occurred in said subject.
The disclosure provides a method for assaying for a target analyte, comprising providing a plurality of samples which may comprise the target analyte, wherein each sample is differentially labelled with a mass label or a combination of mass labels, wherein the mass labels are from a set of mass labels, wherein each mass label is an isobaric mass label comprising a mass spectrometrically distinct mass marker group, such that the samples can be distinguished by mass spectrometry and determining from the mass spectrum the quantity of the target analyte in each sample.
A reactive mass label for labelling a biological molecule for detection by mass spectrometry, which label comprises a reactive functionality for labelling thiol groups or carbonyl groups. Also provided is a reactive mass label for labelling a biological molecule for detection by mass spectrometry, wherein the mass label comprises the following structure: X-L-M-S-Re wherein X is a mass marker moiety, L is a cleavable linker comprising an amide bond, M is a mass normalization moiety comprising a straight or branched C1-C20 substituted or unsubstituted aliphatic group and/or one or more substituted or unsubstituted amino acids, S is a mass series modifying group comprising the following group: Formula (I), wherein J is C=O, K is NH, and n is 2 or J and K are both CH2 and n is 1, and wherein m is at least 1; and Re is a reactive functionality for attaching the mass label to a biological molecule.
C07B 59/00 - Introduction of isotopes of elements into organic compounds
C07D 211/14 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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
A reactive mass label for labelling a biological molecule for detection by mass spectrometry, which label comprises a reactive functionality for labelling thiol groups or carbonyl groups. Also provided is a reactive mass label for labelling a biological molecule for detection by mass spectrometry, wherein the mass label comprises the following structure: X-L-M-S-Re wherein X is a mass marker moiety, L is a cleavable linker, M is a mass normalization moiety, S is a mass series modifying group comprising the following group: Formula (I), wherein J is C=O, K is NH, and n is 2 or J and K are both CH2 and n is 1, and wherein m is at least 1; and Re is a reactive functionality for attaching the mass label to a biological molecule.
C07B 59/00 - Introduction of isotopes of elements into organic compounds
C07D 211/14 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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
The present invention relates to a method for the in vitro diagnosis of stroke and transient ischemic attack (TIA) in an individual, comprising the following steps: (a) measuring the level of proBNP(1 -108), or of fragments of proBNP(1 -108) comprising a RAPRSP sequence (SEQ ID NO: 1 ), in a biological sample of the individual; (b) measuring the level of nucleoside diphosphate kinase A (NDKA) in a biological sample of the individual; (c) comparing the level of proBNP(1 -108), or of fragments of proBNP(1 -108), and the level of NDKA, with one or several cut-off values; (d) determining therefrom whether a stroke or a TIA has occurred in the individual.
The invention provides a method for aiding the diagnosis or prognostic monitoring of Alzheimer's disease in a subject, said method comprising; providing a sample of blood obtained from said patient; assaying the amount of gelsolin present in said sample; comparing the amount of gelsolin present in said sample to a reference amount of gelsolin present in a sample from a healthy subject,, wherein detection of a gelsolin level in the sample from said patient which is lower than the gelsolin level in the reference sample indicates an increased likelihood of Alzheimer's disease in said patient. Other markers are Cl protease inhibitor and ceruloplasmin. Both blood samples and tissue samples have been investigated.
6 alkyl group, a substituted or unsubstituted aliphatic cyclic group, a substituted or unsubstituted aromatic group or a substituted or unsubstituted heterocyclic group; and y is an integer from 0-10, L is a cleavable linker comprising an amide bond and M is a mass normalization moiety.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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 239/04 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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 207/404 - 2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
C07K 5/078 - Dipeptides the first amino acid being heterocyclic, e.g. Pro, His, Trp
Provided is a set of mass labels, each mass label in the set comprising a mass marker moiety attached via a cleavable linker to a mass normalization moiety, each mass label in the set having a common mass; wherein the set comprises a plurality of groups of mass labels, the mass of the mass marker moiety being the same for mass labels within a group, the mass of the mass marker moiety being different between groups; the mass marker moiety is capable of fragmentation into two or three fragments; and the mass of at least one fragment of the mass marker moiety differs between mass labels within a group.
C40B 70/00 - Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or barcodes
C40B 20/04 - Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
G01N 33/532 - Production of labelled immunochemicals
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
C07B 59/00 - Introduction of isotopes of elements into organic compounds
The disclosure provides a method for assaying for a target analyte, comprising providing a plurality of samples which may comprise the target analyte, wherein each sample is differentially labelled with a mass label or a combination of mass labels, wherein the mass labels are from a set of mass labels, wherein each mass label is an isobaric mass label comprising a mass spectrometrically distinct mass marker group, such that the samples can be distinguished by mass spectrometry and determining from the mass spectrum the quantity of the target analyte in each sample.
A method for assaying for a target analyte, which method comprises: (a) providing a plurality of samples which may comprise the target analyle, wherein each sample is differentially labelled with a mass label or a combination of mass labels, wherein the mass labels are from a set of mass labels, wherein each mass label is an isobaric mass label comprising a mass spectrometrically distinct mass marker group, such that the samples can be distinguished by mass spectrometry; (b) mixing the plurality of labelled samples to produce an analysis mixture and introducing the analysis mixture into a mass spectrometer; (c) selecting ions having a first mass to charge ratio equivalent to an ion of the target analyte labelled with a specific number of mass labels; (d) fragmenting ions of the first mass to charge ratio into a plurality of fragment ions, wherein a proportion of the plurality of fragment ions comprise at least one intact mass label; (e) selecting ions of a second mass to charge ratio equivalent to an ion of a fragment of the target analyte comprising at least one intact mass label; (f) fragmenting ions of the second mass to charge ratio into a plurality of further fragment ions, wherein a proportion of the further fragment ions are ions of the mass marker groups; (g) producing a mass spectrum of the further fragment ions produced in step (f); and (h) determining from the mass spectrum the quantity of the target analyte in each sample.
Provided is a method of assaying for an analyte, which method comprises: a) combining a test sample, which may comprise the analyte, with a calibration sample comprising at least two different aliquots of the analyte, each aliquot having a known quantity of the analyte, wherein the sample and each aliquot are differentially labelled with one or more isobaric mass labels each with a mass spectrometrically distinct mass marker group, such that the test sample and each aliquot of the calibration sample can be distinguished by mass spectrometry; b) determining by mass spectrometry the quantity of the analyte in the test sample and the quantity of analyte in each aliquot in the calibration sample, and calibrating the quantity of the analyte in the test sample against the known and determined quantities of the analytes in the aliquots in the calibration sample.
Provided is a method of assaying for an analyte, which method comprises: a) combining a test sample, which may comprise the analyte, with a calibration sample comprising at least two different aliquots of the analyte, each aliquot having a known quantity of the analyte, wherein the sample and each aliquot are differentially labelled with one or more isobaric mass labels each with a mass spectrometrically distinct mass marker group, such that the test sample and each aliquot of the calibration sample can be distinguished by mass spectrometry; b) determining by mass spectrometry the quantity of the analyte in the test sample and the quantity of analyte in each aliquot in the calibration sample, and calibrating the quantity of the analyte in the test sample against the known and determined quantities of the analytes in the aliquots in the calibration sample.
The invention provides a method of diagnosis of a spongiform encephalopathy in a diagnostic sample of a valid body tissue taken from a subject, which comprises detecting an increased proteolytic activity in the diagnostic sample, compared with a sample from a control subject.
Stroke is diagnosed in a subject by determining the concentration of at least one polypeptide selected from Apo C-III, Serum Amyloid A, Apo C-I, Antithrombin III fragment and Apo A-I in a sample of body fluid taken from the subject.
The invention relates to a method of diagnosis of colorectal cancer in a diagnostic sample of a valid body tissue taken from a human subject, which comprises detecting an increased concentration of a protein in the diagnostic sample, compared with a control, normal human sample, the protein being: transforming growth factor-beta induced protein IG-H3 (SwissProt Acc. No. Q15582); suppressor of G2 allele of SKP1 homolog (isoform 2) (SwissProt Acc. No. Q9Y2Z0-2); hypothetical protein (part of URG4) (SwissProt Acc. No. Q9NWR7); calponin-2 (SwissProt Acc. No. Q99439); heat shock protein HSP90-beta (SwissProt Acc. No. P08238); phosphoglycerate mutase 1 (SwissProt Acc. No. P18669); serpin C1 protein (SwissProt Acc. No. P01008); or haptoglobin precursor (SwissProt Acc. No. P00738); or a decreased concentration of a protein in the diagnostic sample, compared with a control, normal human sample, the protein being serotransferrin (SwissProt Acc. No. P02787); 26S proteasome subunit p40.5 (Swiss Prot Acc. No. Q9UNM7); aldo-keto reductase family 1 member B10 (SwissProt Acc. No. O60218); fructosamine-3-kinase (SwissProt Acc. No. Q9H479); peripherin (SwissProt Acc. No. P41219); alpha-2-macroglobulin (SwissProt Acc. No. P01023); serpin C1 protein (SwissProt Acc. No. P01008); or apolipoprotein A IV (SwissProt Acc. No. P06727). The same proteins can be used for prognosis by detecting changes in their concentration in the course of treatment for colorectal cancer.
Provided is a set of mass labels, each mass label in the set comprising a mass marker moiety attached via a cleavable linker to a mass normalisation moiety, each mass label in the set having a common mass; wherein the set comprises a plurality of groups of mass labels, the mass of the mass marker moiety being the same for mass labels within a group, the mass of the mass marker moiety being different between groups; the mass marker moiety is capable of fragmentation into two or more fragments; and the mass of at least one fragment of the mass marker moiety differs between mass labels within a group.
Provided is a set of mass labels, each mass label in the set comprising a mass marker moiety attached via a cleavable linker to a mass normalisation moiety, each mass label in the set having a common mass; wherein the set comprises a plurality of groups of mass labels, the mass of the mass marker moiety being the same for mass labels within a group, the mass of the mass marker moiety being different between groups; the mass marker moiety is capable of fragmentation into two or more fragments; and the mass of at least one fragment of the mass marker moiety differs between mass labels within a group.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
69.
MASS LABELS FOR BIOMOLECULES CONTAINING A 2,6-DIMETHYL-PIPERIDIN-1-YL METHYLENE OR A PYRIMIDIN-2YL THIOMETHYLENE MASS MARKER MOIETY AND A SUCCINIMID-OXY-CARBONYL REACTIVE FUNCTIONAL GROUP
A mass label for labelling and detecting a biological molecule by mass spectroscopy, which label comprises the following structure: X-L-M wherein X is a mass marker moiety comprising the following group: formula (I), wherein the cyclic unit is aromatic or aliphatic and comprises from 0-3 double bonds independently between any two adjacent atoms; each Z is independently N, N(R1), C(R1), CO, CO(R1), C(R1)2, O or S; X is N, C or C(R1); each R1 is independently H, a substituted or unsubstituted straight or branched C1-C6 alkyl group, a substituted or unsubstituted aliphatic cyclic group, a substituted or unsubstituted aromatic group or a substituted or unsubstituted heterocyclic group; and y is an integer from 0-10, L is a cleavable linker comprising an amide bond and M is a mass normalization moiety.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
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
MASS LABELS FOR BIOMOLECULES CONTAINING A 2,6-DIMETHYL-PIPERIDIN-l-YL METHYLENE OR A PYRIMIDIN-2-YL THIOMETHYLENE MASS MARKER MOIETY AND A SUCCINIMID-OXY-CARBONYL REACTIVE FUNCTIONAL GROUP
A mass label for labelling and detecting a biological molecule by mass spectroscopy, which label comprises the following structure: X-L-M wherein X is a mass marker moiety comprising the following group: formula (I), wherein the cyclic unit is aromatic or aliphatic and comprises from 0-3 double bonds independently between any two adjacent atoms; each Z is independently N, N(R1), C(R1), CO, CO(R1), C(R1)2, O or S; X is N, C or C(R1); each R1 is independently H, a substituted or unsubstituted straight or branched C1-C6 alkyl group, a substituted or unsubstituted aliphatic cyclic group, a substituted or unsubstituted aromatic group or a substituted or unsubstituted heterocyclic group; and y is an integer from 0-10, L is a cleavable linker comprising an amide bond and M is a mass normalization moiety.
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
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
71.
DIAGNOSTIC METHOD FOR BRAIN DAMAGE-RELATED DISORDERS
A brain damage-related disorder is diagnosed in a subject by detecting at least one polypeptide, or a variant or mutant there« selected from A-FABP, E- FABP, PGP 9.5, GFAP, Prostaglandin D synthase, Neuromodulin, Neurofflament L, Calcyphosine, RNA binding regulatory subunit, Ubiquitin fusion degradation protein 1 homolog, Nucleoside diphosphate Idnase A, Glutathione S tranférase P, Cathepsin D, DJ-1 protein, Peroxiredoxin 5 and Peptidyl-prolyl cis-trans isomerase A (Cyclophilin A) in a sample of body fluid taken from the subject.
A brain damage-related disorder is diagnosed in a subject by detecting at least one polypeptide, or a variant or mutant there selected from A-FABP, E-FABP, PGP 9.5, GFAP, Prostaglandin D synthase, Neuromodulin, Neurofflament L, Calcyphosine, RNA binding regulatory subunit, Ubiquitin fusion degradation protein 1 homolog, Nucleoside diphosphate Idnase A, Glutathione S tranférase P, Cathepsin D, DJ-1 protein, Peroxiredoxin 5 and Peptidyl-prolyl cis-trans isomerase A (Cyclophilin A) in a sample of body fluid taken from the subject.
Stroke is diagnosed in a subject by determining the concentration of at least one polypeptide selected from Apo C-III, Serum Amyloid A, Apo C-I, Antithrombin III fragment and Apo A-I in a sample of body fluid taken from the subject.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical reagents (not for medicinal or veterinary use);
in-vitro-diagnostics (not for medicinal use). Reagents for medicinal or veterinary use; in-vitro and
in-vivo diagnostics for medicinal use. Chemical and biological analysis for third parties;
chemical, biological and microbiological research; all
aforementioned services exclusively in the field of
"proteomics", in particular in the area of the labeling of
biomolecules, proteins, peptides, DNA, RNA, lipids and
carbohydrates.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical reagents (not for medicinal or veterinary use);
in-vitro-diagnostics (not for medicinal use). Reagents for medicinal or veterinary use; in-vitro and
in-vivo diagnostics for medicinal use. Chemical and biological analysis for third parties;
chemical, biological and microbiological research.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical reagents (not for medicinal or veterinary use);
in-vitro-diagnostics (not for medicinal use). Reagents for medicinal or veterinary use; in-vitro and
in-vivo diagnostics for medicinal use. Chemical and biological analysis for third parties.
01 - Chemical and biological materials for industrial, scientific and agricultural use
42 - Scientific, technological and industrial services, research and design
Goods & Services
(1) Chemical reagents for scientific research use, namely for the labelling of biomolecules, proteins, peptides, DNA, RNA, lipids and carbohydrates. (1) Chemical and biological analysis for third parties; chemical, biological and microbiological research for the labelling and detection of biomolecules, proteins, peptides, DNA, RNA, lipids and carbohydrates.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Reagents for scientific or research use; reagents for medical or veterinary research use; clinical medical reagents; medical diagnostic reagents, diagnostic reagents for clinical or medical laboratory use; in-vitro and in-vivo diagnostic preparations for clinical or medical use; in-vitro diagnostic preparations for scientific or research use;
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical reagents (other than for medical or veterinary purposes); in-vitro diagnostics (not for medical purposes). Reagents for medical or veterinary purposes, except reagents for identifying transmembrane tryptase; in vitro and in vivo diagnostics for medical purposes, except diagnostics for identifying transmembrane tryptase. Chemical and biological analysis, for others; chemical, biological and microbiological research; all the aforesaid services exclusively in the field of proteomics, in particular in the field of labelling biomolecules, proteins, peptides, DNA, RNA, lipids and carbohydrates; all the aforesaid services except analysis and research in the field of transmembrane tryptase.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical reagents (other than for medical or veterinary purposes); in-vitro diagnostics (not for medical purposes). Reagents for medical or veterinary purposes; in-vitro and in-vivo diagnostics for medical purposes. Chemical and biological analysis, for others; chemical, biological and microbiological research.
42 - Scientific, technological and industrial services, research and design
Goods & Services
Development of processes, programs, products, apparatus and
instruments relating to assays for the diagnosis of
diseases, chemical markers for disease states, performing
diagnosis of diseases, determining targets for drugs,
determining protein, peptide and nucleotide sequences and
the disruption of biological material.
01 - Chemical and biological materials for industrial, scientific and agricultural use
42 - Scientific, technological and industrial services, research and design
Goods & Services
Kits containing chemicals, reagents, for the disruption of cells, tissues or other biological material and the extraction of biological molecules like proteins, lipid and fatty acids, carbohydrates and fractions thereof generated by pre-fractionation for cell organelles, vesicles or other cell compartments. Provision of methods, processes, programs, products, apparatus and instruments relating to assays for the diagnosis of diseases, chemical markers for disease states, performing diagnosis of diseases, determining targets for drugs, determining protein, peptide, the disruption of cells, tissues and other biological material and the extraction of biological molecules.
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical, biological and medical analysis of proteins, peptides and glucoproteins for third parties, excluding genetic testing for susceptibility to periodontitis.
