The invention relates to a method for the diagnosis of TB in a subject, the method comprising (a) providing a sample from said subject, said sample being selected from the group consisting of: blood, serum and plasma; (b) determining the concentration in said sample of the following biomarkers: IL-1ra, IL6, IL-7, IL-8, IL-12p70, FGF-basic, IP- 10, and VEGF; (c) converting each biomarker concentration determined in (b) into a decile value; and (d) converting each decile value into a binary presence or absence by comparing the decile values of (c) to the following specific quantile cut off values wherein a decile value matching or exceeding the specific quantile cut-off value is converted into the binary presence of the biomarker, and a decile value lower than the specific quantile cut-off value is converted into the binary absence of the biomarker; wherein detecting the presence of each of said biomarkers indicates that the subject has TB. The invention also relates to uses, kits and devices.
G01N 33/569 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour micro-organismes, p. ex. protozoaires, bactéries, virus
A61K 38/00 - Préparations médicinales contenant des peptides
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
2.
CONFORMATIONALLY STRAINED TRANS-CYCLOALKENES FOR RADIOLABELING
Processes for recovering colloids of carboxylate ligand modified ferric iron hydroxide materials such as IHAT (Iron Hydroxide Adipate Tartrate) are described based on the use of water miscible non-aqueous solvents, such as ethanol, methanol and acetone. The processes produce materials with advantageous properties such as improved bioavailability, reduced aggregation and/or agglomeration and/or increased iron content.
The invention relates to 2-sulfonylpyrimidine compounds and salts and solvates thereof for use in the treatment of a proliferative disease such as cancers. The 2- sulfonyl-primidine compounds may be administered, either simultaneously or sequentially, with one or more pharmacologically active compounds and salts and solvates thereof such as an inhibitor of glutamate cysteine ligase. The 2- sulfonylpyrimidine compound may be represented by formula (I): (I) wherein: R1 is selected from C1-6 alkyl, C6-12 aryl, C7-18 aralkyl, 6- to 15-membered heteroaralkyl and 6- to 12-membered heterocyclylalkyl wherein each of these groups are optionally substituted with from one to three optional substituents; R2 is selected from CF3, O-C(O)-R6, C(O)R7, C(O)NHR7 and NHC(O)R7; R3 is selected from H, F, CI, Br, I, OH, C1-6 alkyl, OC1-6 alkyl, CH2F, CHF2, CF3, CN, NO2, CO2R8, C(O)NHR10, NHC(O)R10, (CH2)z-NR8R9 and (CH2)z-NH-C(=NH)-NH2; R4 is selected from H, C1-6 alkyl and CH2R11; R5 is selected from C1-6 alkyl; R6 is selected from H and C1-6 alkyl; R7 is selected from 5 to 9-membered heteroaryl groups, and phenyl wherein these groups are optionally substituted with from one to three optional substituents; and wherein the heteroaryl group is attached to the rest of compound of formula (I) by a carbon ring atom; R8 and R9 are independently selected from H, C1-6 alkyl and benzyl; R10 is selected from 5- to 9-membered heteroaryl groups, 5- and 6-membered heterocyclyl, and phenyl wherein these groups are optionally substituted with from one to three optional substituents; R11 is phenyl optionally substituted; and z is selected from an integer selected from o to 6.
C07D 417/12 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes de soufre et d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
A61K 31/506 - PyrimidinesPyrimidines hydrogénées, p. ex. triméthoprime non condensées et contenant d'autres hétérocycles
The invention relates to a method of aiding the diagnosis of dysplasia in a subject, said method comprising: (a) providing a sample from the oesophagus of said subject; (b) assaying said sample for expression of each of the genes shown in the '40 genes' column of Table 1; (c) normalising the expression levels of the genes in part (b) to expression levels of reference gene(s) from a non-dysplastic sample; (d) determining from the normalised expression levels of (c) a gene signature score for the sample, wherein a gene signature score greater than a reference threshold indicates presence of dysplasia in said subject. The invention also relates to devices, compositions, primer sets, arrays, methods of treatment and computer programs.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
6.
ANTIBACTERIAL COMPOSITIONS COMPRISING COPPER OXO-HYDROXIDE NANOPARTICLES AND THEIR USES AS BIOCIDAL AGENTS
Antibacterial compositions comprising nanoparticles formed from copper oxo-hydroxide are described that are capable of delivering biocidal concentrations of copper, typically in the form of free copper ions (Cu2+). The nanoparticle compositions generally comprise small particles, typically having mean diameters in the range of 1-100nm, having comparatively high surface area-to-volume ratio and enhanced reactivity compared to the corresponding bulk counterpart materials and which are sufficiently labile to release the free copper efficiently.
The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.
C07C 281/18 - Composés contenant l'un des groupes p. ex. aminoguanidine l'autre atome d'azote étant lié de plus par une liaison double à un atome de carbone, p. ex. guanylhydrazones
C07D 253/00 - Composés hétérocycliques contenant des cycles à six chaînons comportant trois atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe
8.
METHODS FOR SELECTING PHOSPHATASE SELECTIVE AND NON-SELECTIVE PHOSPHATASE INHIBITORS
The present invention discloses a method to discover selective inhibitors of phosphatases. Thus the invention provides a method for screening a test compound to determine whether the compound binds a holophosphatase selectively or non-selectively comprising: i) providing a first holophosphatase wherein said holophosphatase is captured/immobilised; ii) testing a test compound for its ability to bind to the first holophosphatase; iii) providing a second holophosphatase wherein said second holophosphatase is captured/immobilised; iv) testing the same test compound for its ability to bind to the second holophosphatase; v) comparing the binding of the test compound to said first holophosphatase with the binding to said second phosphatase wherein a compound that binds a holophosphatase selectively will bind to said first holophosphatase but not said second holophosphatase; or will bind to said second holophosphatase but not said first; or wherein a compound that binds a holophosphatase non-selectively will bind to both said first holophosphatase and said second holophosphatase.
C07C 281/18 - Composés contenant l'un des groupes p. ex. aminoguanidine l'autre atome d'azote étant lié de plus par une liaison double à un atome de carbone, p. ex. guanylhydrazones
C07D 253/00 - Composés hétérocycliques contenant des cycles à six chaînons comportant trois atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe
C12Q 1/42 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une hydrolase une phosphatase
An inorganic phosphate-binding molecule is described comprising a mutant phosphate-binding protein (PBP) which undergoes a conformational change from a first conformation to a second conformation upon binding of inorganic phosphate (Pi), said mutant PBP comprising: (i) at least one label; and (ii) at least one mutation that increases flexibility in the hinge region of the PBP as compared to a PBP that does not comprise the at least one mutation in the hinge region; wherein said mutant PBP has a lower affinity for Pi as compared to a reference PBP; and wherein the label emits a detectable signal upon changing from said first conformation to said second conformation.
The invention relates to an ATP binding molecule comprising a polypeptide which undergoes a conformational change from a first conformation to a second conformation upon binding of ATP, said polypeptide comprising amino acid sequence corresponding to at least amino acids 5 to 497 of SEQ ID NO:1, said polypeptide having at least 21% sequence identity to SEQ ID NO:1, said polypeptide having a value of RMSD <4 Å relative to RpMat B in the ATP-bound conformation, wherein said polypeptide comprises a cysteine residue for attachment of at least one reporter moiety, and comprises at least one reporter moiety attached thereto, wherein said cysteine residue for attachment of at least one reporter moiety is positioned such that said reporter moiety undergoes a change in fluorescence upon changing from said first conformation to said second conformation. The invention also relates to use of such a sensor, and to methods for assay of ATP.
C12N 9/00 - Enzymes, p. ex. ligases (6.)ProenzymesCompositions les contenantProcédés pour préparer, activer, inhiber, séparer ou purifier des enzymes
C12Q 1/00 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions
THE UNIVERSITY COURT OF THE UNIVERSITY OF EDINBURGH (Royaume‑Uni)
Inventeur(s)
Sims, Andrew
Dixon, John Michael
Turnbull, Arran
Abrégé
The present invention relates to methods and kits for predicting an individual's response to cancer therapy, predicting the progression and predicting the prognosis of cancer in an individual, and for selecting a treatment for cancer in an individual.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
The invention relates to a method for incorporating an unnatural amino acid into a protein of interest in a eukaryotic cell, said method comprising the steps of: i) providing a eukaryotic cell expressing an orthogonal tRNA synthetase - t RNA pair, a nucleic acid sequence of interest encoding said protein of interest, and a mutant eRF1, said mutant eRF1 having amino acid sequence having at least 60% sequence identity to the human wild type eRF1 sequence of SEQ ID NO: 4, said nucleic acid sequence of interest comprising a codon recognised by the tRNA at the position for incorporation of an unnatural amino acid; ii) incubating the eukaryotic cell in the presence of an unnatural amino acid to be incorporated into a protein encoded by the nucleic acid sequence of interest, wherein said unnatural amino acid is a substrate for the orthogonal tRNA synthetase; and iii) incubating the eukaryotic cell to allow incorporation of said unnatural amino acid into the protein of interest via the orthogonal tRNA synthetase - t RNA pair. The invention also relates to uses, host cells, combinations and kits.
The invention provides an antibody or antigen binding fragment thereof capable of binding to the antigen binding pocket of the AP33 antibody, wherein said antibody or antigen binding fragment thereof comprises VL CDR1 (L1), VL CDR2 (L2), and VL CDR3 (L3) consisting of the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:23 respectively, and comprises VH CDR1 (H1), VH CDR2 (H2), and VH CDR3 (H3) consisting of the amino acid sequences of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26 respectively. The invention also provides compositions, methods, nucleic acids and uses.
Methods for treating a human subject who has X-linked Retinitis Pigmentosa (XLRP) or another clinically-defined ophthalmological condition due to a loss-of-function mutation in the gene encoding the retinitis pigmentosa GTPase regulator (RPGR) protein, the method comprising administering to the subject a nucleic acid comprising an adeno-associated viral vector comprising an abbreviated human RPGR cDNA.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
The invention relates to a succinate dehydrogenase inhibitor or a prodrug and/or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of reperfusion injury, such as ischemia-reperfusion injury, by inhibiting the accumulation of succinate, wherein the inhibitor or prodrug and/or pharmaceutically acceptable salt thereof is a cell-permeable reversible inhibitor of succinate dehydrogenase.
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
The invention relates to a polypeptide comprising an amino acid having a cyclopropene group wherein said cyclopropene group is joined to the amino acid via a carbamate group. Suitably the cyclopropene group is a 1,3-disubstituted cyclopropene such as a 1,3-di methylcyclopropene. Suitably the cyclopropene group is present as a residue of a lysine amino acid. The invention also relates to methods of making the polypeptides. The invention also relates to an amino acid comprising cyclopropene wherein said cyclopropene group is joined to the amino acid moiety via a carbamate group.
C12N 9/36 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2) agissant sur les liaisons bêta-1, 4 de l'acide N-acétylmuramique avec l'acétylamino-2 déoxy-2-D-glucose, p. ex. lysozyme
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
Stabilised and aquated polymeric silicate compositions are described in which the compositions are poorly condensed compositions in which the silicates are resorbable and are capable of undergoing efficient dissolution to provide bioavailable soluble silicic acid. In particular, stabilised and aquated polymeric silicates are described that are capable of intravenous delivery, useful in the treatment of cancer or systemic infection, or for topical administration, e.g. in the form of a solid or semi-solid ointment useful in the treatment of wounds or the prevention of bacterial infection.
Stabilised silicate compositions and methods of making them are disclosed, and more particularly to compositions comprising polysilicic acids, optionally stabilised by a growth retardant, and their uses as antiperspirant compositions.
A61K 8/49 - Cosmétiques ou préparations similaires pour la toilette caractérisés par la composition contenant des composés organiques contenant des composés hétérocycliques
The invention relates to compounds having Formula (1): A-L-B or pharmaceutically acceptable salts thereof, wherein: A is a dicarbonyl sequestering moiety comprising a substituted aryl group or a substituted heteroaryl group; L is an optional linker moiety; and B is a mitochondrial targeting moiety. The invention also relates to pharmaceutical compositions containing such compounds and salts, and to the use of such compounds and salts for treating diabetes, preferably hyperglycaemic diabetes. A mass spectrometry probe and to a method of labelling a biological molecule 1 for mass spectrometry detection are also described.
Amorphous magnesium-substituted calcium, phosphate compositions and their medical uses are described, in particular for use in delivering cargo materials, such as cargo molecules or cargo nanoparticles contained in pores of the amorphous magnesium- substituted calcium phosphate to cells of the immune system, fo example as therapeutic approaches for the treatment of inflammatory bowel diseases, and in particular Crohn's disease, autoimmune diseases, allergy and for therapeutic vaccination.
In one aspect, provided herein is a method for detecting tuberculosis in a subject, comprising (a) determining a level of one or more host immune system biomarkers in a sputum sample obtained from the subject; and (b) comparing the levels of the biomarkers in the sputum sample to one or more reference values; wherein the levels of the biomarkers in the sputum sample compared to the reference values are indicative of the presence or absence of tuberculosis in the subject.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
23.
ELECTRON MICROSCOPY SAMPLE SUPPORT COMPRISING POROUS METAL FOIL
An electron microscopy sample support comprises: a support member; and a metal foil comprising a porous region. The support member is configured to give structural stability to the metal foil, and the porous region of the metal foil is configured to receive an electron microscopy sample. Also provided is a method of manufacturing such an electron microscopy sample support, a method of imaging using such an electron microscopy sample support and an apparatus operable to perform such imaging. An electron microscopy specimen support in accordance with aspects and embodiments may reduce particle motion and/or sample charging in electron microscopy, and thus improve information content available from electron micrographs. Appropriately designed and constructed supports may lead to an increased resolution per particle and increased accuracy of angular assignments in 3D reconstructions of, for example, biological specimens. This may enable the determination of structures of smaller and more difficult proteins than was previously possible using EM techniques.
The invention relates to a support for receiving a biological sample, the support comprising at least one support member, and comprising graphene attached to said at least one support member, wherein said graphene is partially hydrogenated graphene. The invention also relates to use of a partially hydrogenated graphene surface to support a biological molecule for electron microscopy. The invention also relates to a method for making a partially hydrogenated graphene, the method comprising applying a hydrogen ion or hydrogen atom to the surface of graphene, hwerein said hydrogen ion or hydrogen atom is applied at an energy in the range 1 to 21 eV. The invention also relates to a sensor comprising a surface capable of adsorbing a biological molecule thereto, wherein said surface comprises partially hydrogenated graphene. The invention also relates to a method for cleaning a graphene surface, comprising contacting said graphene surface with a hydrogen plasma or a helium plasma or a neon plasma for a time sufficient to remove surface impurities.
A method is disclosed for the rapid synthesis and isolation of peptide-cargo conjugates in which a peptide is chemically conjugated to a cargo molecule.
An object handling device, a method of handling an object and a computer program product operable to perform the method of handling an object. The object handling device comprises: a source of variable suction; a suction cup operable to receive an object to be handled and coupled, via a conduit, to the source of variable suction; a sensor operable to determine an operational parameter of fluid in the conduit; and a controller operable to receive an indication of the determined operational parameter and adjust the variable suction source in dependence upon the received indication. Aspects and embodiments described herein provide a means by which a pick and place device may be operable to handle delicate objects, for example, delicate sectioned biological tissue. The delicate objects may be moveable by a device in accordance with aspects and embodiments by direct engagement with a delicate object itself or by gripping a surrounding support material.
The invention relates to a method for collecting information useful in aiding the diagnosis and treatment of familial hypercholesterolaemia (FH), the method comprising providing a sample of DNA from the subject, assaying said DNA for (i) mutation in one or more genes which is indicative of FH diagnosis (ii) presence of one or more SNPs indicative of incremental risk of high cholesterol; and (iii) mutation in a gene which is indicative of likelihood of statin toxicity; wherein assaying said DNA comprises the step of contacting said DNA sample with one or more primers for amplification and/or sequencing of the relevant segment(s) of said DNA characterised in that each of said assays of steps (i), (ii) and (iii) is carried out in a single assay cycle. The invention also relates to a method of treatment, and to primers.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
A method for determining the sequence of nucleotide bases in a polynucleotide analyte is provided. It is characterised by the steps of (1) generating a stream of single nucleotide bases from the analyte by pyrophosphorolysis; (2) producing captured molecules by reacting each single nucleotide base with a capture system labelled with detectable elements in an undetectable state; (3) releasing the detectable elements from each captured molecule in a detectable state and (4) detecting the detectable elements so released and determining the sequence of nucleotide bases therefrom. The method can be used advantageously in sequencers involving the use of microdroplets.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
A method for determining the sequence of nucleotide bases in a polynucleotide analyte is provided. It is characterised by the steps of (1) generating a stream of single nucleotide bases from the analyte; (2) producing captured molecules by reacting each single nucleotide base with a capture system; (3) amplifying at least part of the captured molecule to produce a plurality of amplicons characteristic of the single nucleotide base; (4) labelling the amplicons with a corresponding probe having a characteristic detectable element and (5) detecting a property characteristic of the detectable element.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
30.
MUTANT MEMBRANE PROTEINS AND METHODS FOR THEIR PRODUCTION
The present invention relates to mutant transmembrane proteins which have increased conformational stability when compared to their parent protein, methods of selection and production. In particular the invention relates to mutant transmembrane proteins which are mutated in or in the proximity of the transmembrane alpha helices or in a kinked region or in an alpha-helix adjacent to a kink. The mutant transmembrane proteins have use in crystallisation studies and also in screening to identify compounds for use in drug discovery and therapy.
The invention relates to a method of aiding detection of a surface abnormality in the oesophagus of a subject, wherein said surface abnormality is selected from the group consisting of low-grade dysplasia (LGD), high-grade dysplasia (HGD), asymptomatic oesophageal adenocarcinoma (OAC) and intra-mucosal cancer (IMC), the method comprising: a) providing a sample of cells from said subject, wherein said sample comprises cells collected from the surface of the subject's oesophagus; 10 b) assaying said cells for at least two markers selected from (i) p53; (ii) c-Myc; (iii) AURKA or PLK1, preferably AURKA; and (iv) methylation of MyoD and Runx3; wherein detection of abnormal levels of at least two of said markers infers that the subject has an increased likelihood of a surface abnormality in the oesophagus. The invention also relates to certain kits, apparatus and uses.
Methods for estimating the size of disease-associated polynucleotide repeat expansions in genes are disclosed which use restriction enzymes that do not cut within a repeat expansion and which are frequent cutting restriction enzymes that cut genomic DNA outside of the expansion into fragments of a size below the threshold capable of detection. A hybridisation probe that can bind to multiple sites within the expansion is then used to estimate its length and to correlate that to the diagnosis or prognosis of disease.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
33.
BENZYLIDENEGUANIDINE DERIVATIVES AND THERAPEUTIC USE FOR THE TREATMENT OF PROTEIN MISFOLDING DISEASES
The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein:R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7,OR7and NR8R9; R7, R8and R9 are each independently selected from alkyl, cycloalkyl, aralkyl,cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2,COO-alkyl,aralkyl,SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy;X and Z are each independently CR11, and Y is selected from CR11and N; and R11is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.
C07C 281/18 - Composés contenant l'un des groupes p. ex. aminoguanidine l'autre atome d'azote étant lié de plus par une liaison double à un atome de carbone, p. ex. guanylhydrazones
C07D 253/075 - Deux hétéro-atomes, en positions 3 et 5
C07D 213/61 - Atomes d'halogènes ou radicaux nitro
A61K 31/44 - Pyridines non condenséesLeurs dérivés hydrogénés
A61K 31/53 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec trois azote comme seuls hétéro-atomes d'un cycle, p. ex. chlorazanil, mélamine
A61P 3/10 - Médicaments pour le traitement des troubles du métabolisme de l'homéostase du glucose de l'hyperglycémie, p. ex. antidiabétiques
A61P 25/00 - Médicaments pour le traitement des troubles du système nerveux
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
In one aspect, provided herein is a polypeptide comprising a modified angiopoietin receptor or fragment thereof, wherein the polypeptide binds preferentially to angiopoietin-2 compared to angiopoeitin-1. Nucleic acid sequences encoding the polypeptide, as well as pharmaceutical uses of the polypeptide in treating diseases such as cancer and inflammation are also provided.
C07K 14/71 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire pour des facteurs de croissanceRécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire pour des régulateurs de croissance
C12N 9/12 - Transférases (2.) transférant des groupes contenant du phosphore, p. ex. kinases (2.7)
35.
BLOOD TRANSCRIPTIONAL SIGNATURES OF ACTIVE PULMONARY TUBERCULOSIS AND SARCOIDOSIS
IMPERIAL COLLEGE HEALTHCARE NHS TRUST (Royaume‑Uni)
Inventeur(s)
O'Garra, Anne
Bloom, Chloe
Berry, Matthew, Paul Reddoch
Banchereau, Jacques, F.
Chaussabel, Damien
Pascual, Maria, Virginia
Abrégé
The present invention includes a method of determining a lung disease from a patient suspected of sarcoidosis, tuberculosis, lung cancer or pneumonia comprising: obtaining a sample from whole blood of the patient suspected of sarcoidosis, tuberculosis, lung cancer or pneumonia; detecting expression of (although not exclusive) six or more disease genes, markers, or probes selected from SEQ ID NOS.: 1 to 1446, wherein increased expression of mRNA of upregulated sarcoidosis, tuberculosis, lung cancer and pneumonia markers of SEQ ID NOS.: 1 to 1446 and/or decreased expression of mRNA of downregulated sarcoidosis, tuberculosis, lung cancer or pneumonia markers of SEQ ID NOS.: 1 to 1446 relative to the expression of the mRNAs from a normal sample; and determining the lung disease based on the expression level of the six or more disease markers of SEQ ID NOS.: 1 to 1446 based on a comparison of the expression level of sarcoidosis, tuberculosis, lung cancer, and pneumonia.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
36.
VCP INHIBITOR FOR USE IN THE PREVENTION OF VIRUS INFECTION
A61K 31/517 - PyrimidinesPyrimidines hydrogénées, p. ex. triméthoprime condensées en ortho ou en péri avec des systèmes carbocycliques, p. ex. quinazoline, périmidine
The present invention concerns nanoparticle formulations suitable for the delivery of one or more therapeutic agents, the formulations comprising: a cationic cholesterol derivative; a neutral phospholipid; cholesterol or a neutral cholesterol derivative; and a saturated fatty acid, PEGylated neutral derivative of phosphatidylethanolamine or phosphatidylcholine.
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
38.
INHIBITION OF HIV-1 INFECTION BY INHIBITION OF BINDING OF CPSF TO VIRAL CAPSID
The invention describes a method for identifying a compound capable of inhibiting infection by HIV, comprising contacting a HIV CA polypeptide with a CPSF6 polypeptide in the presence of the compound, and determining the influence of the compound on the binding of HIV CA to CPSF6, by measuring the interaction of CPSF6 with HIV CA at one or more of residues 53, 56-57, 66-67, 70, 73-74, 105, 7, 109 and 130 thereof.
G01N 33/569 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour micro-organismes, p. ex. protozoaires, bactéries, virus
METHODS OF INCORPORATING AN AMINO ACID COMPRISING A BCN GROUP INTO A POLYPEPTIDE USING AN ORTHOGONAL CODON ENCODING IT AND AN ORTHORGONAL PYLRS SYNTHASE.
The invention relates to a polypeptide comprising an amino acid having a bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) group, particularly when said BCN group is present as: a residue of a lysine amino acid. The invention also relates to a method of producing a polypeptide comprising a BCN group, said method comprising genetically incorporating an amino acid comprising a BCN group into a polypeptide. The invention also relates to an amino acid comprising bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN), particularly and amino acid which is bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) lysine. In addition the invention relates to a PylRS tRNA synthetase comprising the mutations Y271M, L274G and C313A.
The invention relates to a method for aiding prediction of the likelihood of progression from Barrett's esophagus to high grade dysplasia or esophageal adenocarcinoma in a subject, the method comprising (a) providing an oesophagal sample from said subject (b) determining if said sample stains abnormally with Aspergillus oryzae lectin; (c) determining if there is a DNA content abnormality in said sample; and (d) determining if there is low grade dysplasia in said sample; wherein if (b) is abnormal and (c) is abnormal and low grade dysplasia is present, then an increased likelihood of progression is determined. The invention also relates to an apparatus, and to different uses of certain materials.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer
41.
METHODS TO ASSESS THE LIKELIHOOD OF DYSPLASIA OR ESOPHAGEAL ADENOCARCINOMA
The invention relates to a method for aiding assessment of the likelihood of dysplasia or esophageal adenocarcinoma being present in a subject, the method comprising (a) providing an oesophagal sample from said subject (b) determining the methylation status of (i)SLC22A18, (ii)PIGR, (iii)GJA12 and (iv)RIN2 in said sample wherein if 2 or more of said genes are methylated then an increased likelihood of presence of dysplasia or esophageal is determined. The invention also relates to apparatus for same.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
42.
METHOD FOR DETERMINING IF A SUBJECT HAS AN INCREASED LIKELIHOOD OF HIGH GRADE DYSPLASIA OR ESOPHAGEAL ADENOCARCINOMA
The invention related to a method for determining if a subject has an increased likelihood of high grade dysplasia (HGD) or esophagal adenocarcinoma (EC), the method comprising; a) providing a sample from an AFI patch of said subject's oesophagus b) assaying said sample for (i) aneuploidy, and (ii) abnormal p53, and (iii) abnormal Cyclin A c) wherein if said sample shows the presence of at least two of (i), (ii) and (iii), then said subject is determined as having an increased likelihood of high grade dysplasia (HGD) or esophagal adenocarcinoma (EC). The invention also relates to certain methods of medical treatment.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
43.
POLYMERASE CAPABLE OF PRODUCING NON-DNA NUCLEOTIDE POLYMERS.
The invention relates to a nucleic acid polymerase capable of producing a non-DNA nucleotide polymer from a DNA nucleotide polymer template, said polymerase comprising amino acid sequence having at least 36% identity to the amino acid sequence of SEQ ID NO: 1, wherein said amino acid sequence is mutated relative to the amino acid sequence of SEQ ID NO: 1, wherein said amino acid sequence comprises the mutations P657T, E658Q, K659H, Y663H, D669Α, K671N, and T676I; wherein said amino acid sequence is further mutated relative to the amino acid sequence of SEQ ID NO: 1 at residue: E664 and wherein said amino acid sequence comprises the mutation E664K. The invention also relates to methods of making nucleotide polymers comprising use of this polymerase. Suitably the nucleotides are arabino nucleotides such as ARA: or FANA nucleotides.
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
44.
EARLY DETECTION OF TUBERCULOSIS TREATMENT RESPONSE
IMPERIAL COLLEGE HEALTHCARE NHS TRUST (Royaume‑Uni)
Inventeur(s)
O'Garra, Anne
Bloom, Chloe
Berry, Matthew, Paul Reddoch
Wilkinson, Robert
Banchereau, Jacques, F.
Chaussabel, Damien
Pascual, Maria, Virginia
Abrégé
The present invention includes methods for early detection of a treatment response in a patient suspected of being infected with Mycobacterium tuberculosis. Changes in the blood transcriptome are detectable within two weeks of the initiation of antituberculosis therapy.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
G01N 33/48 - Matériau biologique, p. ex. sang, urineHémocytomètres
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
45.
CONJUGATE COMPRISING AN AGENT AND AN ANTIVIRAL LIGAND AND ITS USE IN A METHOD FOR DELIVERING THE AGENT INTRACELLULARLY
There is provided a method for killing virally infected cells comprising exposing cells to an a cytotoxic agent conjugated to a virus-specific ligand, in the presence of the virus which infects the cells. Conjugates and intracellular complexes comprising virus and cytotoxic agents are also provided.
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
C07K 16/08 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant de virus
A61K 31/337 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à quatre chaînons, p. ex. taxol
46.
NORBORNENE MODIFIED PEPTIDES AND THEIR LABELLING WITH TETRAZINE COMPOUNDS
The invention relates to a polypeptide comprising an amino acid having a norbornene group. Suitably said norbornene group is present as an amino acid residue of a norbornene lysine. The invention also relates to a method of producing a polypeptide comprising a norbornene group, said method comprising genetically incorporating an amino acid comprising a norbornene group into a polypeptide. The polypeptide comprising the norbornene group can be specifically labelled by inverse electron demand Diels-Alder reaction with a tetrazine compound.
In the past decade a great deal of structural information for class A-GPCRs (G protein-coupled receptors) has emerged. However, the structural and electronic basis of ligand selectivity for closely related receptor subtypes such as the angiotensin receptors AT1aR and AT2R, which present completely diverse biological functions in response to the same ligand, is poorly understood. In order to monitor complex responses in bio systems it is useful to have ligands that present a gradient in terms of selectivity. In this study we present an efficient method to tune ligand selectivity for the two angiotensin II receptor subtypes, AT1aR and AT2R, by controlling aromatic - prolyl interactions in angiotensin II, through alternation of aromatic electronics. On the basis of this strategy, an AT2R selective and high affinity agonist analogue (Ki=3 nM) was obtained.
G01N 33/566 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet utilisant un support spécifique ou des protéines réceptrices comme réactifs pour la formation de liaisons par ligand
C07K 7/06 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 5 à 11 amino-acides
A61K 38/08 - Peptides ayant de 5 à 11 amino-acides
G01N 33/74 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des hormones
The invention relates to a method for detecting a foreign cell in a tissue of the upper intestinal tract, sold method comprising: (a) providing a sample of cells from the epithelium layer of the tissue of interest; (b) preparing the cells into a cohesive cluster; (c) staining cells from the cohesive cluster using haematoxylin and eosin (H&E) stain; (d) observing the stained cells; and (e) inferring the presence or absence of foreign cell(s) from the observations of Id), The invention also relates to a method for aiding the diagnosis of an inflammatory condition of the upper intestinal tract in a subject, said method comprising detecting a foreign cell as described above, wherein detection of foreign cell(s) in step (e) infers that the subject has an inflammatory condition of the upper intestinal tract.
C12Q 1/04 - Détermination de la présence ou du type de micro-organismeEmploi de milieux sélectifs pour tester des antibiotiques ou des bactéricidesCompositions à cet effet contenant un indicateur chimique
G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
A61B 10/02 - Instruments pour prélever des échantillons cellulaires ou pour la biopsie
There is described a method for analyzing ubiquitin polymers using linkage-specific deubiquitinase enzymes. Novel specificities of deubiquitinase enzymes are also provided.
C12Q 1/34 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une hydrolase
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
C12Q 1/25 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des enzymes qui ne peuvent pas être classées dans les groupes
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
There is provided a method for producing free polyubiquitin chains linked through a single desired lysine residue, comprising the steps of: (a) selecting an E3 ubiquitin ligase enzyme which is homologous to mammalian HECT E3 ligases and possesses the desired lysine residue specificity; (b) incubating the E3 enzyme with an E1 ubiquitin activating enzyme, an E2 ubiquitin conjugating enzyme and monomeric ubiquitin; and (c) if undesired linkages are present, removing the undesired linkages by exposure to a DUB enzyme having the appropriate specificity.
C07K 1/08 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation utilisant des agents d'activation
C07K 1/02 - Procédés généraux de préparation de peptides en solution
51.
SYSTEMS AND METHODS FOR DIMINISHING CELL GROWTH AND INDUCING SELECTIVE KILLING OF TARGET CELLS
The invention relates to a biological system for diminishing cell growth or inducing selective killing of target cells, in particular pathogenic bacterial or fungal cells, or cancer cells. The biological system according to the invention is based on toxin-antitoxin systems, as found in prokaryotic plasmids and their host chromosomes. The biological system comprises a vehicle with a first nucleic acid sequence or amino acid sequence encoding for a prokaryotic toxin of a prokaryotic toxin-antitoxin pair, and a second nucleic acid sequence or amino acid sequence encoding for the corresponding prokaryotic antitoxin of the prokaryotic toxin-antitoxin pair. The system is characterized in that the toxin and/or the antitoxin is operably linked to a protein output modifier (POM) that comprises a nucleic acid sequence or amino acid sequence that modifies the relative rate of transcription, mRNA stability, mRNA translatability or protein stability of the toxin and/or antitoxin thereby changing the relative ratio in the concentration of the toxin and/or the antitoxin within the target cells and/or, where applicable, within non-target cells by either decreasing the antitoxin outputs in the target cells (killing) and/or increasing the antitoxin outputs in the non-target cells (protection) relative to the toxin outputs, and/or by increasing the toxin outputs in the target cells (killing) and/or decreasing the toxin outputs in the non-target cells (protection) relative to the antitoxin outputs. The invention also relates to a pharmacological composition to be used in the treatment of pathogenic diseases. The invention further relates to the use of the biological system for therapy of a pathological condition, diagnostics, theranosis, drug discovery, Screening, creating animal models, target molecule identification and validation. In a further aspect, the invention also relates to a drug delivery system for delivering a vehicle to target cells by means of biologically-derived nanocells (minicells). The invention also relates to a method for delivery of a substance to target cells.
The present invention relates to a modified HGF-1K1 polypeptide (such as that shown in Seq ID No:4), and certain mutations for the disruption of an identified glycosylation site, DNA sequences encoding those proteins (such as those sequences in Seq ID NO: 5 and 6) and various methods for their production. The invention also relates to pharmaceutical compositions containing the modified HGF-1K1 polypeptides and to their use in the treatment of various diseases such as COPD, broncheolitis obliterans, acute lung injury (ALI), idiopathic pulmonary fibrosis (IPF), myocardial infarction, liver fibrosis and kidney fibrosis.
The present invention discloses cell penetrating peptides (CPP or membrane translocating peptide) and their conjugates with cargo molecules. The peptides are useful as drug delivery systems, particularly as delivery vehicles for nucleotide-based theraputics, such as polynucleotides, oligonucleotides and peptide nucleic acids. A CPPs of the invention provides a balance between good cell entry efficency and low toxicity and comprises three contiguous domains: the central one being hydrophobic and the flanking ones consisting of arginine and aminohexanoic acid or beta-alanine residues. The hydrophobic domain contains a sequence selected from YQFLI, YRFLI, IQFLI and IRFLI.
C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
C07K 7/02 - Peptides linéaires contenant au moins une liaison peptidique anormale
C12N 15/00 - Techniques de mutation ou génie génétiqueADN ou ARN concernant le génie génétique, vecteurs, p. ex. plasmides, ou leur isolement, leur préparation ou leur purificationUtilisation d'hôtes pour ceux-ci
The invention relates to methods of inhibiting inflammation in a system comprising reducing or inhibiting CD63 in said system, wherein said inflammation is IgE-negative. The invention also relates to methods for inhibiting leukocyte recruitment in a system, inhibiting leukocyte rolling in a system, or inhibiting leukocyte extravasation in a system comprising reducing or inhibiting CD63 in said system. The invention also provides a method of reducing P-selectin levels comprising reducing or inhibiting CD63, and a method of reducing P-selectin clustering comprising reducing or inhibiting CD63.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
55.
INCORPORATION OF SUBSTITUTED LYSINES INTO POLYPEPTIDES
The invention related to a tRNA synthetase capable of binding delta-substituted lysine, wherein said tRNA synthetase comprises amino acid sequence corresponding to the amino acid sequence of at least L271 to Y349 of MbPyIRS, wherein said sequence comprises 5 or fewer substitutions within the amino acid sequence corresponding to the amino acid sequence of at least L271 to Y349 of MbPyIRS; and wherein said synthetase comprises W at amino acid position 349 relative to MbPyIRS.
Provided are compounds for use in a method of treatment of a subject who has a lesion or a tumour in which p53 carries a Y220C mutation, in which the compound is selected from compounds of the following formula (I), and pharmaceutically acceptable salts, hydrates, and solvates thereof: (I) R: where A is CR4 or N; -R-1 is selected from -OH, -OMe, -NH2, -SH, -F and -CF3; -R2 is selected from -CI, -Br, -I, and ethynyl (-C≡CH); -R3 is selected from -I, -Br, -CI, ethynyl (-C≡CH), -R35, -H, -OMe, and -N02; wherein -R3S is selected from: and -R5 is selected from -COOH and: 8A formula Ilia formula 1Mb formula 111 o 3 where -R6, -R7A, - R7B, -Rs, and -R8A are as defined in the specification. Compounds of formula (I) are also provided, as is their use in methods of treatment, and methods for their preparation.
C07D 205/04 - Composés hétérocycliques comportant des cycles à quatre chaînons ne contenant qu'un atome d'azote comme unique hétéro-atome du cycle non condensés avec d'autres cycles ne comportant pas de liaison double entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques
C07D 207/09 - Radicaux substitués par des atomes d'azote ne faisant pas partie d'un radical nitro
C07D 207/14 - Atomes d'azote ne faisant pas partie d'un radical nitro
C07D 211/22 - Composés hétérocycliques contenant des cycles pyridiques hydrogénés, non condensés avec d'autres cycles avec uniquement des atomes d'hydrogène et de carbone liés directement à l'atome d'azote du cycle ne comportant pas de liaison double entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques avec des radicaux hydrocarbonés ou des radicaux hydrocarbonés substitués, liés directement aux atomes de carbone du cycle avec des radicaux hydrocarbonés substitués liés aux atomes de carbone du cycle avec des radicaux hydrocarbonés, substitués par des atomes d'oxygène ou de soufre liés par des liaisons simples par des atomes d'oxygène
C07D 211/26 - Composés hétérocycliques contenant des cycles pyridiques hydrogénés, non condensés avec d'autres cycles avec uniquement des atomes d'hydrogène et de carbone liés directement à l'atome d'azote du cycle ne comportant pas de liaison double entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques avec des radicaux hydrocarbonés ou des radicaux hydrocarbonés substitués, liés directement aux atomes de carbone du cycle avec des radicaux hydrocarbonés substitués liés aux atomes de carbone du cycle avec des radicaux hydrocarbonés, substitués par des atomes d'azote
C07D 211/60 - Atomes de carbone comportant trois liaisons à des hétéro-atomes, avec au plus une liaison à un halogène, p. ex. radicaux ester ou nitrile
C07D 211/62 - Atomes de carbone comportant trois liaisons à des hétéro-atomes, avec au plus une liaison à un halogène, p. ex. radicaux ester ou nitrile liés en position 4
C07D 213/28 - Radicaux substitués par des atomes d'oxygène ou de soufre liés par des liaisons simples
C07D 223/04 - Composés hétérocycliques contenant des cycles à sept chaînons ne comportant qu'un atome d'azote comme unique hétéro-atome du cycle non condensés avec d'autres cycles avec uniquement des atomes d'hydrogène, des atomes d'halogènes, des radicaux hydrocarbonés ou hydrocarbonés substitués, liés directement aux atomes de carbone du cycle
Oxygen sensors and their uses are disclosed, and more particularly to oxygen sensors for use in product packaging for storing an article in a packaging envelope under modified atmosphere conditions wherein the oxygen sensors comprise solid oxo-hydroxy metal ion materials, optionally modified with one or more ligands and/or optionally having polymeric structures. The sensors may be present in a hydrated, oxygen permeable matrix, for example formed from a material, such as gelatine. The sensors are useful in many technical fields, and find particular application in the field of food packaging as they are safely disposable (e.g. are environmentally friendly), cheap to manufacture, and provide detectable changes in the presence of oxygen that are easy to read.
The present invention relates to the use of Stefin A as a scaffold protein for the display of inserted peptides, particularly wherein the Stefin A is a human Stefin A. Several mutations are advantageously made in the wild type stefin A sequence to improve it as a scaffold; preferably the Stefin A comprises a heterologous peptide insertion at the Leu 73 site. Furthermore, preferably the scaffold protein comprises a V48D mutation; preferably the scaffold protein comprises a G4W mutation. Preferably the scaffold comprises Leu73, V48D and G4W mutations. The invention also relates to the scaffold proteins themselves, in particular a stefin A polypeptide having the Leu73, V48D and G4W mutations, such as shown as SEQ ID NO: 1. The invention also relates to a method for identifying binding proteins and to peptide A (RLNKPLPSLPV, SEQ ID NO: 30) and its use in treating yeast infections.
The invention relates to a nucleic acid comprising a nucleotide sequence encoding a tRNA orthogonal to a eukaryotic cell, said nucleotide sequence operably linked to a promoter capable of directing transcription by eukaryotic RNA polymerase III. The invention also relates to methods for incorporating unnatural amino acids in eukaryotic cells using same.
The present invention provides methods of identifying genes primarily and causally regulated by epigenetic events such as, for example, DNA methylation. Additionally, the invention provides nucleic acid constructs encoding genes and/or promoter sequences identified as primarily and causally regulated by epigenetic events, operably linked to reporter elements. Such constructs find particular application in the studies designed test the effects of agents on epigenetic events.
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
A compound comprising a ligand which binds, directly or indirectly, specifically to an antigen of a pathogen, provided that said ligand is not the PRYSPRY domain of TRIM21; and a RING domain and/or an inducer of TRIM21 expression.
C07K 16/08 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant de virus
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
62.
METHODS FOR SCREENING FOR COMPOUNDS EXPECTED TO BE USEFUL IN THE MODULATING, FOR EXAMPLE INHIBITING, THE ACTIVITY OF KIAA1018/MTMR15/FAN1.
A method for identifying a compound expected to be useful in modulating, for example inhibiting, the repair of a DNA inter-strand crosslink (ICL), resolution of an iCL-induced double strand break, or homologous recombination in a cell, the method comprising the steps of (1) determining whether a test compound modulates, for example inhibits, the endonuclease or 5'-exonuclease activity of a FAN1 polypeptide on a substrate polynucleotide and (2) selecting a compound which modulates, for example inhibits, the said FAN1 polypeptide endonuclease or 5'-exonuclease activity. Such a compound may be useful in enhancing the effect of platinum based chemotherapy or other ICL-inducing therapy on cancer cells.
C12Q 1/44 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une hydrolase une estérase
G01N 33/566 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet utilisant un support spécifique ou des protéines réceptrices comme réactifs pour la formation de liaisons par ligand
G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer
C12N 9/00 - Enzymes, p. ex. ligases (6.)ProenzymesCompositions les contenantProcédés pour préparer, activer, inhiber, séparer ou purifier des enzymes
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
63.
FLUORESCENT -LABELLED DIUBIQUITIN SUBSTRATE FOR A DEUBIQUITINASE ASSAY
There is described a substrate for measuring the activity of a deubiquitinating enzyme (DUB), comprising a diubiquitin molecule, wherein an ubiquitin monomer is labeled with a fluorescent label, as well as an assay for DUB enzymes using such substrates.
C12Q 1/37 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une hydrolase faisant intervenir une peptidase ou une protéinase
64.
ENGINEERED E2 FOR INCREASING THE CONTENT OF FREE LYS11- LINKED UBIQUITIN
The invention provides a chimeric E2 enzyme comprising a Ubc domain fused to a heterologous ubiquitin binding domain (UBD). The chimeric enzymes of the invention are useful in producing elevated levels of free polyubiquitin.
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
65.
METHOD FOR COUNTING CHROMATID COPY NUMBERS IN A SINGLE CELL
The present invention provides a method for counting the absolute copy number of a nucleic acid sequence in a cell, which comprises the following steps: (i) dividing a lysate of the cell or a lysate of a sample of the cell into a plurality aliquots: (ii) providing conditions suitable for the amplification of the nucleic acid sequence in each aliquot: (iii) counting the number of aliquots in which the nucleic acid was amplified in step (ii) and directly deducing the copy number of the nucleic acid sequence in a cell. The method may be used to count chromatid copy number, for example to investigate the ploidy of a cell such as an oocyte or an embryo-derived cell.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
The invention relates to a nucleic acid polymerase capable of producing a non-DNA nucleotide polymer from a DNA nucleotide polymer template, said polymerase comprising amino acid sequence having at least 36% identity to the amino acid sequence of SEQ ID NO:1, wherein said amino acid sequence is mutated relative to the amino acid sequence of SEQ ID NO:1 at one or more residues of the thumb region, said residues selected from: amino acids 651 to 679 (patch 10A); wherein said amino acid sequence is mutated relative to the amino acid sequence of SEQ ID NO:1 at residue E664. In one embodiment said polymerase comprises the mutations Y409G and E664K. In one embodiment said polymerase comprises amino acid sequence corresponding to SEQ ID NO: 12. The invention also relates to A nucleic acid polymerase capable of reverse transcribing a HNA nucleotide polymer into a DNA nucleotide polymer, said polymerase comprising amino acid sequence having at least 36 % identity to the amino acid sequence of SEQ ID NO:1, wherein said amino acid sequence is mutated relative to the amino acid sequence of SEQ ID NO:1 at residue 1521.
A method for assessing the effect of a test compound on LRRK2 in a cell-based system, the method comprising the steps of a) assessing the effect of exposing the cell-based system comprising LRRK2 to the test compound on the phosphorylation state of Ser910 and/or Ser935 of the LRRK2; and/or b) assessing the effect of exposing the cell-based system comprising LRRK2 to the test compound on the binding of the LRRK2 to a 14-3-3 polypeptide. The method may comprise or further comprise the step of assessing the effect of exposing the cell-based system comprising LRRK2 to the test compound on the subcellular location of LRRK2. The method is considered to be useful in assessing the effect of putative LRRK2 inhibitors in cell based systems, including in vivo systems.
C07K 16/40 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre des enzymes
C12N 9/12 - Transférases (2.) transférant des groupes contenant du phosphore, p. ex. kinases (2.7)
G01N 33/573 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour enzymes ou isoenzymes
C12Q 1/48 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une transférase
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
The present invention provides an imaging probe which comprises a lipophilic cation, a hydrophobic moiety and a PET nucleus. The present invention also provides a precursor molecule for the production of such an imaging probe and methods for using the probe for analysing mitochondrial membrane potential in a subject.
The present invention provides a compound which targets the VEGF and/or HIF pathways for use in the treatment and/or prevention of otitis media in a subject. The invention also provides a pharmaceutical composition comprising such a compound and a method for treating and/or preventing otitis media in a subject which comprises the step of administering such a compound or pharmaceutical composition to the subject.
The present invention relates to a method of aiding in the prognosis of a subject with oesophageal and/or gastro-oesophageal junctional (GOJ) adenocarcinoma, the method comprising the steps of: (a) providing a sample from the subject, (b) determining the expression level of biomarkers TRIM44 and SIRT2 in said sample, and either (i) determining the expression level of biomarker PAPPS2 in said sample; or (ii) determining the expression level of biomarkers WT1 and EGFR in said sample; (c) comparing the expression level of each of said biomarkers to a corresponding reference standard, (d) determining the biomarkers of (b) whose expression is dysregulated compared to the reference standard, (e) inferring from the dysregulated biomarkers identified in (d) the prognosis of 5-year survival, wherein the greater the number of said biomarkers which are dysregulated, the greater the reduction in prognosis of 5-year survival. The invention also relates to kits, uses and devices.
The invention relates to a method of modifying a specific lysine residue in a polypeptide comprising at least two lysine residues, said method comprising (a) providing a polypeptide comprising a target lysine residue protected by a first protecting group, and at least one further lysine residue; (b) treating the polypeptide to protect said further lysine residue(s), wherein the protecting group for said further lysine residues is different to the protecting group for the target lysine residue; (c) selectively deprotecting the target lysine residue; and (d) modifying the deprotected lysine residue of (c).
The invention relates to a caged lysine, wherein the caged lysine is according to Formula (I): or salts thereof. The invention further relates to polypeptides comprising a caged lysine, and to methods of making same. The invention further relates to tRNA synthetases capable of charging tRNA with caged lysine.
The invention relates to 16S rRNA comprising a mutation at A1196, and to 16S rRNA further comprising a mutation at C1195 and/or A1197, and to 16S rRNA which comprises (i) C1195A and A1196G; or (ii) C1195T, A1196G and A1197G; or (iii) A1196G and A1197G. The invention also relates to ribosomes comprising such 16S rRNAs and to use of same.
IMPERIAL COLLEGE HEALTHCARE NHS TRUST (Royaume‑Uni)
Inventeur(s)
Banchereau, Jacques, F.
Chaussabel, Damien
O'Garra, Anne
Berry, Matthew
Kon, Onn Min
Abrégé
The present invention includes methods, systems and kits for distinguishing between active and latent Mycobacterium tuberculosis infection in a patient suspected of being infected with Mycobacterium tuberculosis, the method including the steps of obtaining a patient gene expression dataset from a patient suspected of being infected with Mycobacterium tuberculosis; sorting the patient gene expression dataset into one or more gene modules associated with Mycobacterium tuberculosis infection; and comparing the patient gene expression dataset for each of the one or more gene modules to a gene expression dataset from a non-patient; wherein an increase or decrease in the totality of gene expression in the patient gene expression dataset for the one or more gene modules is indicative of active Mycobacterium tuberculosis infection.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
C12N 15/31 - Gènes codant pour des protéines microbiennes, p. ex. entérotoxines
The present invention provides novel liposomes comprising Gd.DOTA.DSA (gadolinium (III) 2-{4,7-bis-carboxymethyl-10-[(N,N-distearylamidomethyl-N`-amido-methyl]-1,4,7,10- tetra-azacyclododec-1-yl}-acetic acid), characterised in that said liposome further comprises a neutral, fully saturated phospholipid component (e.g. DSPC (1,2-distearoyl- sn-glycero-3-phospocholine]), which are of particular use in the preparation of magnetic resonance contrast agents for enhancing a magnetic resonance image of tumours in a mammal.
A61K 49/18 - Préparations de contraste pour la résonance magnétique nucléaire [RMN]Préparations de contraste pour l'imagerie par résonance magnétique [IRM] caractérisées par un aspect physique particulier, p. ex. émulsions, microcapsules, liposomes
The invention relates to a swallowable cell sampling device comprising an abrasive material capable of collecting cells from the surface of the oesophagus, and a means for retrieval wherein the means for retrieval comprises a cord, characterised in that the cord is attached to the abrasive material by means of a hitch knot. The invention also relates to kits and methods involving same.
The invention relates to A method of making a polypeptide comprising at least one Nε-methyl-lysine at a specific site in said polypeptide, said method comprising (a) genetically directing the incorporation of R-Nε-methyl-lysine into said polypeptide, wherein R comprises an auxiliary group; and (b) catalysing the removal of R from the polypeptide of (a). In particular the invention relates to such a method wherein genetically directing the incorporation of R- Nε-methyl-lysine into said polypeptide comprises arranging for the translation of a RNA encoding said polypeptide, wherein said RNA comprises an amber codon, and wherein said translation is carried out in the presence of an amber tRNA charged with R-Nε-methyl-lysine.
The invention relates to a method of analysing the homeostatic balance of a population of cells, which includes the following steps: a) label one or more cells in the population b) incubate the cells for a time t c) determine the clone size distribution of labelled cells at time t d) determine if the clone size distribution of (c) conforms to the scaling formula (I): where Pn(t) is the probability of finding a surviving clone which has n progenitor cells at time t, formula (II) denotes the average number of dividing cells in surviving clones at time t and formula (III): wherein if the clone size distribution conforms to the scaling form above, the cells are identified as being in a normal steady-state homeostatic balance; if the clone size distribution does not conform to the scaling form above, the cells are identified as not being in a normal steady-state homeostatic balance.
G06F 19/10 - Bio-informatique, c. à d. procédés ou systèmes pour le traitement de données génétiques ou se rapportant aux protéines en biologie moléculaire informatique (procédés in silico de criblage de bibliothèques chimiques virtuelles C40B 30/02;procédés mathématiques ou in silicio de création de bibliothèques chimiques virtuelles C40B 50/02)
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
The invention relates to a method for altering the conformational diversity of a first repertoire of polypeptide ligands, comprising a plurality of polypeptides comprising at least two reactive groups separated by a loop sequence covalently linked to a molecular scaffold which forms covalent bonds with said reactive groups, to produce a second repertoire of polypeptide ligands, comprising assembling said second repertoire from the polypeptides and structural scaffold of said first repertoire, incorporating one of the following alterations: (a) altering at least one reactive group; or (b) altering the nature of the molecular scaffold; or (c) altering the bond between at least one reactive group and the molecular scaffold; or (d) any combination of (a), (b) or (c).
C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
C40B 40/02 - Bibliothèques contenues ou présentées dans des micro-organismes, p. ex. des bactéries ou des cellules animalesBibliothèques contenues ou présentées dans des vecteurs, p. ex. des plasmidesBibliothèques contenant uniquement des micro-organismes ou des vecteurs
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
C12N 15/00 - Techniques de mutation ou génie génétiqueADN ou ARN concernant le génie génétique, vecteurs, p. ex. plasmides, ou leur isolement, leur préparation ou leur purificationUtilisation d'hôtes pour ceux-ci
G01N 33/00 - Recherche ou analyse des matériaux par des méthodes spécifiques non couvertes par les groupes
A61K 47/00 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif
The invention relates to a complexing system comprising two polypeptide helices derived from a SNAP protein;one polypeptide helix derived from syntaxin;one polypeptide helix derived from synaptobrevin or a homolog thereof; andone or more cargo moieties attached to the polypeptide helices,wherein the four polypeptide helices can form a stable SNARE complex. The invention also relates to a method of producing the complexing system and the use of the complexing system.
C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
G01N 33/94 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des narcotiques
81.
ENDONUCLEASE G AS TARGET FOR HYPERTENSION AND HYPERTROPHY ASSOCIATED DISEASES
The present invention relates to a method of identifying a molecule that modulates the activity or expression of endonuclease G for the treatment of a disease selected from a hypertension associated and a hypertrophy associated disease. The present invention also provides a method for determining the level of endonuclease G activity and a method for treating or monitoring a hypertension associated and/or a hypertrophy associated disease.
C12Q 1/34 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une hydrolase
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
The invention relates to cochlear implants and to improved methods of operating such implants. We describe cochlear implant apparatus comprising an audio signal processing unit with a wired or wireless coupling to an implantable cochlear stimulation device, wherein said audio signal processing unit has an audio input to receive an audio signal representing a sound, wherein said implantable cochlear stimulation device includes an electrical pulse generator coupled to an electrode array for intracochlear stimulation, wherein the apparatus is configured to apply stimulation to said electrode array to represent said sound, wherein said stimulation comprises application of an electrical pulse across two intracochlear electrodes of said electrode array, and wherein said electrical pulse has a pulse waveshape which is asymmetric under an operation comprising inverting the waveshape about a zero level and then time reversing the waveshape.
A61N 1/36 - Application de courants électriques par électrodes de contact courants alternatifs ou intermittents pour stimuler, p. ex. stimulateurs cardiaques
A61N 1/05 - Électrodes à implanter ou à introduire dans le corps, p. ex. électrode cardiaque
83.
METHOD FOR INCORPORATING ALIPHATIC AMINO ACIDS COMPRISING ALKYNE, AZIDE OR ALIPHATIC KETONE FUNCTIONAL GROUPS USING APPROPRIATE TRNA / TRNA SYNTHASE PAIRS
The invention relates to a method of making a polypeptide comprising an orthogonal functional group, said orthogonal functional group being comprised by an aliphatic amino acid or amino acid derivative, said method comprising providing a host cell; providing a nucleic acid encoding the polypeptide of interest; providing a tRNA-tRNA synthetase pair orthogonal to said host cell; adding an amino acid or amino acid derivative comprising the orthogonal functional group of interest, wherein said amino acid or amino acid derivative is a substrate for said orthogonal tRNA synthetase, wherein said amino acid or amino acid derivative has an aliphatic carbon backbone; and incubating to allow incorporation of said amino acid or amino acid derivative into the polypeptide of interest via the orthogonal tRNA-tRNA synthetase pair. The invention also relates to certain amino acids, and to polypeptides comprising same.
The invention provides methods and compositions for use in treating or preventing an IL-25 mediated disease such as asthma. The methods and compositions involve using TLRl or TLR2 antagonists, such as antibody molecules which bind TLRl or TLR2, or soluble TLRl or TLR2 receptors. The invention also provides methods of screening for antagonists of TLRl or TLR2.
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
The invention provides the antibody D9.2 and antibody molecules based on D9.2 which bind interleukin-17 receptor B. These may be useful in therapy, e.g. the treatment of asthma, ulcerative colitis or Crohn's disease.
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
The invention provides functional mutants of activation-induced cytidine deaminase (AID) protein that have increased activity as compared to a wild-type AID protein. The invention also provides nucleic acids encoding the functional AID mutants, and vectors and cells comprising the nucleic acids. The invention further provides methods of using the functional mutant AID proteins.
C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
C12N 9/78 - Hydrolases (3.) agissant sur les liaisons carbone-azote autres que les liaisons peptidiques (3.5)
C12N 15/00 - Techniques de mutation ou génie génétiqueADN ou ARN concernant le génie génétique, vecteurs, p. ex. plasmides, ou leur isolement, leur préparation ou leur purificationUtilisation d'hôtes pour ceux-ci
A01K 67/027 - Nouvelles races ou races modifiées de vertébrés
87.
PROTEIN KINASE A AND/OR CASEIN KINASE II FOR ALLEVIATING THE INHIBITION OF NEURITE OUTGROWTH
The invention relates to a method for alleviating the inhibition of neurite outgrowth from a neurone, wherein said neurone comprises a Nogo receptor, said method comprising contacting said neurone with a composition capable of causing phosphorylation of a Nogo receptor, wherein said composition comprises protein kinase A or casein kinase
A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
A61P 25/00 - Médicaments pour le traitement des troubles du système nerveux
The invention relates to a method for providing a multispecific peptide ligand comprising a polypeptide covalently linked to a molecular scaffold at three or more amino acid residues and capable of binding to two or more separate targets, comprising the steps of: (a) providing a first repertoire of polypeptides, each polypeptide comprising two or more reactive groups capable of covalent linkage to a molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; (b) providing a second repertoire of polypeptides as described in (a); (c) joining at least one loop of one or more members of the first repertoire to at least one loop of one or more members of the second repertoire to form at least one polypeptide comprising two loops, and (d) conjugating the composite polypeptide(s) to a molecular scaffold at at least three amino acid positions.
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
The invention relates to a peptide ligand comprising a polypeptide linked to a molecular scaffold at n attachment points, wherein said polypeptide is cyclised and forms n separate loops subtended between said n attachment points on the molecular scaffold, wherein n is greater than or equal to 2.
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
The invention relates to a method for modifying one or more peptide ligands, comprising polypeptides covalently linked to a molecular scaffold at two or more amino acid residues, comprising the steps of providing one or more peptide ligands, wherein the polypeptide comprises two or more reactive groups which form a covalent linkage to the molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; exposing the peptide ligands to one or more proteases; and sorting the ligands according to the extent of proteolytic cleavage.
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
The present invention relates to methods and compositions for the treatment or prevention of hepatitis C virus comprising the administration of a combination of anti-hepatitis C virus antibodies and a -interferon.
The invention relates to a crystalline EED polypeptide, said polypeptide being bound to a tri-methyllysine histone peptide or an analogue thereof. The invention also relates to methods.
C07K 14/46 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
G06F 19/00 - Équipement ou méthodes de traitement de données ou de calcul numérique, spécialement adaptés à des applications spécifiques (spécialement adaptés à des fonctions spécifiques G06F 17/00;systèmes ou méthodes de traitement de données spécialement adaptés à des fins administratives, commerciales, financières, de gestion, de surveillance ou de prévision G06Q;informatique médicale G16H)
The present invention relates to IL-25 antibody VH domains and target binding members (e.g., antibodies) that comprise such antibody VH domains and bind IL-25. The invention also relates to compositions comprising target binding members {e.g., antibodies) that bind IL-25, methods of producing such target binding members, and uses of such target binding members for the treatment or prevention of diseases and conditions (e.g., asthma, inflammatory bowel disease).
C07K 16/24 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des cytokines, des lymphokines ou des interférons
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
A method for identifying a compound expected to be useful in modulating, for example inhibiting, LRRK2 protein kinase activity, the method comprising the steps of (1) determining whether a test compound modulates, for example inhibits, the protein kinase activity of a LRRK2 polypeptide on a substrate polypeptide and (2) selecting a compound which modulates, for example inhibits, the said LRRK2 polypeptide protein kinase activity, wherein the substrate polypeptide comprises the sequence (W/F/R/K)(W/F/R/K)(R/K)(F/W/H/R)(Y/W/R)(S/T)(L-/V/I)(R/K)(R/K)(A/Y) or (W/ R)(X)(X)(F/Y/H/T)(Y/W/R)(T)(X)(R/T)(R)(X), where X represents any amino acid. Such a compound may be useful in treating Parkinson's Disease or Parkinsonism. The substrate polypeptide may consist or comprise the sequence RLGWWRFYTLRRARQGNTKQR.
C12Q 1/48 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une transférase
C07K 4/00 - Peptides ayant jusqu'à 20 amino-acides dans une séquence indéterminée ou partiellement déterminéeLeurs dérivés
C12N 15/00 - Techniques de mutation ou génie génétiqueADN ou ARN concernant le génie génétique, vecteurs, p. ex. plasmides, ou leur isolement, leur préparation ou leur purificationUtilisation d'hôtes pour ceux-ci
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
The invention relates to an ADP binding molecule comprising a polypeptide, said polypeptide comprising amino acid sequence corresponding to at least amino acids 11 to 310 of SEQ ID NO:1, wherein said polypeptide comprises a substitution relative to SEQ ID NO:1 at amino acid C287, and wherein said polypeptide comprises a further cysteine residue for attachment of at least one reporter moiety, and wherein said polypeptide has at least 68% sequence identity to SEQ ID NO:1 at the amino acid residues corresponding to those shown in column III of table A.
Phosphate binding materials and compositions comprising them which are solid ligand-modif ied poly oxo-hydroxy metal ion materials are disclosed that are based on ferric iron oxo- hydroxides modified with carboxylic acid ligands, or ionised forms thereof. These materials are made and tested in the examples provided in the application to demonstrate that they can bind phosphate in "in vitro" an in "in vivo" studies. They are useful for treating hyperphosphatenia or for removing phosphate from a medium.
Compounds of formula (I): wherein X is selected from CRX and N; RN1 is selected from H and C1-4 alkyl, which may be substituted by SH or halo; RG1 is selected from H and SH; RC2 is selected from H and optionally substituted C1-7 alkyl; RC3 is selected from H and optionally substituted C1-7 alkyl; Rx is selected from H, OH and NH2; RC4 is selected from: (i) an optionally substituted C3-12 N-containing heterocyclyl; (ii) C(=O)NRN5RN6, where RN5 and RN6 are independently selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl or RN5 and RN6 and the nitrogen atom to which they are attached form an optionally substituted N-containing C5-7 heterocyclyl group; (iii) C(=O)ORO1, where RO1 is selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl; (iv) C(=O)NHNHSO2RS1, where RS1 is selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl; (v) OC(=O)RC8, where RC8 is selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl; (vi) OC(=O)NRN7RN8, where RN7 and RN8 are independently selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl or RN7 and RN8 and the nitrogen atom to which they are attached form an optionally substituted N-containing C5-7 heterocyclyl group; and (vii) C(=O)CH2NH C(=O)NHNH2, CHC(CN)2, CHC(CN)C(=O)NH2, and carboxy; RC5 is selected from H, OH and NH2; or RC4 and RC5 together with the carbon atoms to which they are bound form an optionally substituted aromatic ring containing either 5 or 6 ring atoms, of formula: where Q represents O, N, or CRQ1=CRQ2, where RQ1 and RQ2 are independently selected from H, OH and NH2; RC6 is selected from H, OH and NH2; and RC7 is selected from optionally substituted C3-12 N-containing heterocyclyl, NHC(=O)RC9, CH2NRN2RN3 and NHC(=S)NHRN4, where RC9 is selected from optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl, RN2 and RN3 are independently selected from H, optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl or RN2 and RN3 and the nitrogen atom to which they are attached form an optionally substituted N-containing C5-7 heterocyclyl group, and RN4 is selected from optionally substituted C1-7 alkyl, optionally substituted C3-20 heterocyclyl and optionally substituted C5-20 aryl, and when RC4 and RC5 are not bound together, RC3 may additionally be selected from OR02, where RO2 is a C1-4 alkyl group, and C(=O)ORO3, where RO3 is a C1-4 alkyl group and RC2 may additionally be selected from halo, for use in stabilising a p53 protein carrying a Y220C mutation.
C07D 209/86 - CarbazolesCarbazoles hydrogénés avec uniquement des atomes d'hydrogène, des radicaux hydrocarbonés ou des radicaux hydrocarbonés substitués, liés directement aux atomes de carbone du système cyclique
C07D 209/88 - CarbazolesCarbazoles hydrogénés avec des hétéro-atomes ou des atomes de carbone comportant trois liaisons à des hétéro-atomes avec au plus une liaison à un halogène, p. ex. radicaux ester ou nitrile, liés directement aux atomes de carbone du système cyclique
C07D 401/14 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant au moins trois hétérocycles
C07D 403/04 - Composés hétérocycliques contenant plusieurs hétérocycles, comportant des atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une liaison directe de chaînon cyclique à chaînon cyclique
C07D 403/12 - Composés hétérocycliques contenant plusieurs hétérocycles, comportant des atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
C07D 407/14 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'oxygène comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant au moins trois hétérocycles
C07D 413/14 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes d'azote et d'oxygène comme uniques hétéro-atomes du cycle contenant au moins trois hétérocycles
C07D 417/14 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes de soufre et d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant au moins trois hétérocycles
C07D 473/26 - Composés hétérocycliques contenant des systèmes cycliques purine avec des atomes d'oxygène, de soufre ou d'azote, liés directement en position 2 ou 6, mais pas aux deux positions à la fois
A61K 31/403 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à cinq chaînons avec un azote comme seul hétéro-atome d'un cycle, p. ex. sulpiride, succinimide, tolmétine, buflomédil condensés avec des carbocycles, p. ex. carbazole
A01N 43/00 - Biocides, produits repoussant ou attirant les animaux nuisibles, ou régulateurs de croissance des végétaux, contenant des composés hétérocycliques
The invention provides novel scaffold proteins for the display of peptides such as peptide aptamers. The novel scaffold proteins are modifications of Stefin A or STM (a variant of Stefin A) and are useful as scaffold proteins and as display systems.
The present invention relates to methods of modulating the immune response in the field of autoimmune diseases via targeting of the aryl hydrocarbon receptor (AhR) with inhibitors such as flavones antisense or interfering RNA molecules or 2-methyl-2H-pyrazole-3-carboxylic acid- (2-methyl-4-o-tolylazophenyl) -amide.
A61K 31/00 - Préparations médicinales contenant des ingrédients actifs organiques
A61K 31/35 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A61K 31/7125 - Acides nucléiques ou oligonucléotides ayant des liaisons internucléosides modifiées, c.-à-d. autres que des liaisons 3'-5' phosphodiester
A61K 31/713 - Acides nucléiques ou oligonucléotides à structure en double-hélice
G01N 33/564 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour complexes immunologiques préexistants ou maladies auto-immunes
A61K 31/7088 - Composés ayant au moins trois nucléosides ou nucléotides