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    A METHOD AND DEVICE FOR OPTICAL QUANTIFICATION OF OXYGEN PARTIAL PRESSURE IN BIOLOGICAL TISSUES
    11.
    发明申请
    A METHOD AND DEVICE FOR OPTICAL QUANTIFICATION OF OXYGEN PARTIAL PRESSURE IN BIOLOGICAL TISSUES 审中-公开

    公开(公告)号：WO2021234140A1

    公开(公告)日：2021-11-25

    申请号：PCT/EP2021/063642

    申请日：2021-05-21

    Applicant: ERASMUS UNIVERSITY MEDICAL CENTER ROTTERDAM ,  LABORATORY FOR FUNCTIONAL AND METABOLIC IMAGING SWISS FEDERAL INSTITUTE OF TECHNOLOGY (EPFL)

    Inventor： CROIZAT, Gauthier ,  MIK, Egbert G. ,  WAGNIÈRES, Georges ,  GERELLI, Emmanuel

    IPC: G01N21/64 ,  A61B5/1455 ,  A61B5/00

    Abstract: The disclosure relates to methods and devices for monitoring the concentration of a substance, preferably oxygen, in a cell or tissue, e.g., in cells of the human skin. In particular, it provides a method for determining the concentration of a quencher, such as oxygen and/or the concentration of a probe, e.g., a heme precursor such as protoporphyrin IX (PplX), wherein the probe is capable of exhibiting luminescence (delayed fluorescence (DF) or phosphorescence) and or transient triplet absorption, preferably, deDF, in a living cell. The method comprises steps of exciting the probe, measuring the lifetime of the luminescence exhibited by said probe, wherein, in the presence of the quencher, the lifetime is shortened as compared to the lifetime in the absence of the quencher, and correlating said lifetime with said concentration. The disclosed method leads to more precise results than conventional methods, because of adaptations based on the understanding of the influence of the concentration of the probe and its excitation fluence rate (intensity) on the analysis. For example, the simultaneous time-resolved detection of the probe excimer and monomer DF allows estimation of the probe concentration and compensation of the probe self-quenching effect in the quencher concentration calculation, increasing the measurement precision. Taking into account second order triplet interactions also permits the interpretation of non-exponential decays and further improvement of the quencher and probe concentration estimation. Disclosed methods rely, e.g., on measurement at different emission wavelengths and application of an adaptive Stern-Volmer relationship, the decay central fitting method and/or a mixed orders approach. Said method can be applied, e.g., for bedside monitoring of patients. Also disclosed is the use of the PplX precursor 5-aminolevulinic acid (5-ALA), or derivatives thereof, in this method, and a device suitable therefor.

    BIOINSPIRED FLUORESCENT PROBES FOR REVERSIBLE STAINING OF THE ENDOPLASMIC RETICULUM AND FOR FURTHER ANALYTICAL APPLICATIONS
    12.
    发明申请
    BIOINSPIRED FLUORESCENT PROBES FOR REVERSIBLE STAINING OF THE ENDOPLASMIC RETICULUM AND FOR FURTHER ANALYTICAL APPLICATIONS 审中-公开

    公开(公告)号：WO2021228776A1

    公开(公告)日：2021-11-18

    申请号：PCT/EP2021/062350

    申请日：2021-05-10

    Applicant: TECHNISCHE UNIVERSITÄT MÜNCHEN ,  DEUTSCHES KREBSFORSCHUNGSZENTRUM

    Inventor： DELIUS, Judith ,  HOFMANN, Thomas ,  KALLENBERGER, Stefan

    IPC: C09B1/00 ,  C09B67/42 ,  G01N33/58 ,  C07F5/02

    Abstract: The present invention relates to the field of fluorescent compounds and dyes. In particular, it provides the use of a polyphenol, such as quercetin or luteolin, and a diaryl borinic compound, e.g., 2-aminoethoxydiphenyl borate (also referred to as 2-APB, diphenylborinic acid 2-aminoethyl ester, DPBA or Neu's reagent), in combination with an agent capable of providing an aprotic environment selected from the group consisting of the endoplasmic reticulum (ER) of an animal cell, a protein, a polypeptide, and a solid preferably, crystalline phase of a complex formed by the polyphenol and the diaryl borinic compound, for generating an increased fluorescence. The invention teaches the use of a polyphenol and a diaryl borinic compound for selective fluorescent staining of the endoplasmic reticulum (ER) of an animal cell and a corresponding method as well as kits useful to this end. Advantageously, the ER can be reversibly stained, and, depending on the selection of the polyphenol, different wavelengths of fluorescence can be obtained. Also provided is the use of a polyphenol, a diaryl borinic compound, and an agent capable of providing an aprotic environment, e.g., a protein, for determining the proton-donating ability of a solvent, or determining the presence and/or concentration of the agent, the polyphenol or the diaryl borinic compound. Complexes of the invention, e.g., in solid or crystalline form, may also be used as fluorescent dyes or paints, or for providing light, e.g., in a display.

    METHOD AND KIT FOR TESTING POTENCY OF IMMUNOGLOBULIN COMPOSITIONS
    13.
    发明申请
    METHOD AND KIT FOR TESTING POTENCY OF IMMUNOGLOBULIN COMPOSITIONS 审中-公开

    公开(公告)号：WO2020245327A1

    公开(公告)日：2020-12-10

    申请号：PCT/EP2020/065568

    申请日：2020-06-05

    Applicant: BIOTEST AG

    Inventor： HEIM, Katharina ,  GUTSCHER, Marcus

    IPC: C07K16/12 ,  G01N33/569 ,  C07K14/315 ,  G01N33/577 ,  C07K16/00

    Abstract: The present invention relates to the field of immunotherapeutics. It provides a method for characterisation and quality control, in particular for determining the potency of an immunoglobulin composition comprising immunoglobulins derived from a plurality of human donors, the method comprising contacting the immunoglobulin composition with pneumolysin, adding erythrocytes to the immunoglobulin composition and determining lysis of the erythrocytes. The invention also provides a corresponding use of pneumolysin, as well as a kit and composition useful in said method. The method can be used for quality control of immunoglobulin concentrate, e.g., of an IgM-containing immunoglobulin composition comprising IgM, IgA and IgG antibodies, and in a method of preparing an immunoglobulin composition. The immunoglobulin compositions obtainable from said method may be used, e.g., in the treatment of pneumonia, e.g., severe community-acquired pneumonia, which may be caused, e.g., by Streptococcus pneumoniae.

    SPECIFIC T CELL RECEPTORS AGAINST EPITOPES OF MUTANT MYD88L265P PROTEIN FOR ADOPTIVE T CELL THERAPY
    14.
    发明申请
    SPECIFIC T CELL RECEPTORS AGAINST EPITOPES OF MUTANT MYD88L265P PROTEIN FOR ADOPTIVE T CELL THERAPY 审中-公开

    公开(公告)号：WO2020152161A1

    公开(公告)日：2020-07-30

    申请号：PCT/EP2020/051405

    申请日：2020-01-21

    Applicant: CHARITÉ - UNIVERSITÄTSMEDIZIN BERLIN

    Inventor： PEZZUTTO, Antonio ,  CINAR, Özcan

    IPC: C07K14/705 ,  A61K38/17 ,  A61K35/17 ,  C07K14/725 ,  A61K31/711 ,  A61K35/00 ,  A61K38/00

    Abstract: The present invention is directed to the field of immunotherapy, in particular, adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer. The invention provides a nucleic acid encoding at least one TCR alpha or beta chain construct of a TCR construct capable of specifically binding to a MYD88 L265P peptide of SEQ ID NO: 2 in the context of HLA-B*07:02 having a high avidity to said peptide/HLA complex. The invention also provides corresponding proteins and host cells, preferably, CD8+ T cells, as well as the medical use of such nucleic acids, proteins or host cells, in particular, in the diagnosis, prevention and/or treatment of a MyD88 L265P expressing cancer such as a non-Hodgkin B-cell lymphoma selected from the group comprising diffuse large B-cell lymphoma (DLBCL), e.g., activated B-cell-like DLBCL (ABC-DLBCL) or pCNS DLBCL, cutaneous DLBCL, leg-type DLBCL or testicular DLBCL; lymphoplasmacytic lymphoma (LPL), e.g., Waldenstrom macroglobulinemia (WM); and IgM monoclonal gammopathy (IgM MGUS).

    GENOME ARCHITECTURE MAPPING ON CHROMATIN
    15.
    发明申请
    GENOME ARCHITECTURE MAPPING ON CHROMATIN 审中-公开
    染色体上的基因组建图谱

    公开(公告)号：WO2016156469A1

    公开(公告)日：2016-10-06

    申请号：PCT/EP2016/057025

    申请日：2016-03-31

    Applicant: MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN

    Inventor： POMBO, Ana ,  DEAR, Paul ,  BRANCO, Miguel

    IPC: C12Q1/68

    CPC classification number: C12Q1/6816 ,  C12Q1/6827 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2523/101 ,  C12Q2565/133

    Abstract: The present invention relates to the field of analysis of the three-dimensional structure of the genome, i.e., for genome architecture mapping on chromatin (GAM-ch). The invention provides a method of determining interaction of a plurality of nucleic acid loci in a compartment comprising nucleic acids, such as the cell nucleus, comprising separating nucleic acids from each other depending on their interaction in the compartment by crosslinking nucleic acids with each other directly or indirectly, fragmenting the nucleic acids of the compartment to obtain fragments and/or cross-linked complexes of fragments, and dividing the fragmented nucleic acids to obtain a collection of fractions such that every fraction contains, on average, less than one copy of every locus; determining the presence or absence of the plurality of loci in said fractions; and determining the co-segregation of said plurality of loci in the fractions. Co-segregation may then be analysed with statistical methods to determine interactions. The method can be used e.g., for identifying the frequency of interactions across a cell population between a plurality of loci; and mapping loci and/or genome architecture, e.g., in the nucleus, an organelle, a microorganism or a virus; identification of regulatory regions directing expression of a specific gene through spatial contacts; identifying the spatial contacts between loci that depend on their co-association with specific protein(s) or RNA and/or diagnosing a disease associated with a disturbed co- segregation of loci. Chromatin immunoprecipitation (ChIP) can be combined with the method of the invention.

    Abstract translation: 本发明涉及基因组三维结构的分析领域，即对染色质（GAM-ch）的基因组结构图谱的分析。 本发明提供了确定包含核酸（例如细胞核）的隔室中的多个核酸基因座的相互作用的方法，其包括通过将核酸彼此交联直接地将核酸彼此之间的相互作用相互分离来分离核酸 或间接地分裂隔室的核酸以获得片段和/或交联的片段复合物，并分割片段化的核酸以获得级分的集合，使得每个级分平均含有少于一份每份 轨迹; 确定所述级分中存在或不存在多个基因座; 以及确定所述分数中所述多个基因座的共分离。 然后可以用统计学方法分析共分离以确定相互作用。 该方法可以用于例如识别多个基因座之间的细胞群体的相互作用的频率; 和映射基因座和/或基因组结构，例如在细胞核中，细胞器，微生物或病毒; 通过空间接触指导特定基因表达的调控区域的鉴定; 鉴定依赖于与特定蛋白质或RNA的共同缔合的基因座和/或诊断与受干扰的基因座共分离相关疾病的基因座之间的空间接触。 染色质免疫沉淀（ChIP）可以与本发明的方法组合。

    NON-THIOPURINE METHYLTRANSFERASE RELATED EFFECTS IN 6-MERCAPTOPURINE THERAPY
    17.
    发明申请
    NON-THIOPURINE METHYLTRANSFERASE RELATED EFFECTS IN 6-MERCAPTOPURINE THERAPY 审中-公开
    6-MERCAPTOPURINE治疗中的非 - 三硝基甲基转移酶相关作用

    公开(公告)号：WO2009047001A1

    公开(公告)日：2009-04-16

    申请号：PCT/EP2008/008593

    申请日：2008-10-10

    Applicant: GUY'S AND ST. THOMAS' NHS FOUNDATION TRUST ,  SANDERSON, Jeremy, D. ,  MARINAKI, Anthony, M. ,  SMITH, Melissa, A.

    Inventor： SANDERSON, Jeremy, D. ,  MARINAKI, Anthony, M. ,  SMITH, Melissa, A.

    IPC: C12Q1/68

    CPC classification number: C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156

    Abstract: The present invention provides methods for predicting tolerance associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. In particular, the present invention provides methods for predicting a patient's risk of an adverse drug reaction (or tolerance) to a 6-mercaptopurine drug by genotyping a patient at a polymorphic site in at least one gene selected from the group consisting of a xanthine dehydrogenase (XDH) gene, molybdenum cofactor sulfurase (MOCOS) gene, and aldehyde oxidase (AOX) gene. The present invention further provides methods for optimizing therapeutic efficacy in a patient receiving a 6-mercaptopurine drug by determining whether the patient should be given an alternative drug based on the presence or absence of a polymorphism in at least one of the XDH, MOCOS, and AOX genes.

    Abstract translation: 本发明提供了预测与6-巯基嘌呤药物治疗免疫介导的胃肠道疾病如炎症性肠病有关的耐受性的方法。 特别地，本发明提供了通过在选自黄嘌呤脱氢酶的至少一种基因中的多态性位点对患者进行基因分型来预测患者对6-巯嘌呤药物的不良药物反应（或耐受性）的风险的方法 （XDH）基因，钼辅因子硫酶（MOCOS）基因和醛氧化酶（AOX）基因。 本发明还提供了通过基于XDH，MOCOS和/或其中至少一种中存在或不存在多态性来确定是否应该给予患者替代药物来优化接受6-巯嘌呤药物的患者治疗功效的方法 AOX基因。

    METHOD AND KIT FOR TESTING IMMUNOMODULATORY POTENCY OF IMMUNOGLOBULIN COMPOSITIONS, E.G., FOR TREATMENT OF COVID-19
    19.
    发明申请
    METHOD AND KIT FOR TESTING IMMUNOMODULATORY POTENCY OF IMMUNOGLOBULIN COMPOSITIONS, E.G., FOR TREATMENT OF COVID-19 审中-公开

    公开(公告)号：WO2022106546A1

    公开(公告)日：2022-05-27

    申请号：PCT/EP2021/082154

    申请日：2021-11-18

    Applicant: BIOTEST AG

    Inventor： BOHLÄNDER, Fabian ,  FAUST, Stefanie

    IPC: G01N33/96 ,  C07K16/06

    Abstract: The present invention relates to the field of immunotherapeutics, in particular to a method for characterization and/or quality control of immunotherapeutics. It provides a method of testing potency of an immunoglobulin composition, e.g., plasma or a plasma-derived immunoglobulin composition such as an intravenous immunoglobulin composition (IVIG), as well as to use of a bead coated with an antigen and an antibody specifically bound to said antigen for testing po- tency of an immunoglobulin composition. Said immunoglobulin composition, or immunoglobulin test composition can be an IVIG, particularly and IgA- and/or IgM enriched (also sometimes re- ferred to as IVIG-AM). The potency is tested by the capability of the composition to inhibit an ef- fector function of an Fc-receptor expressing immune effector cell, such as a neutrophil, e.g., a HL60 cell, preferably, production of an inflammatory cytokine such as IL-8. The invention also relates to a method of preparing a standardized immunoglobulin composition, to a kit for carry- ing out the method, as well as a composition. The immunoglobulin compositions obtainable from said method may be used, e.g., in the treatment of inflammation, e.g., in the context of COVID-19 or pneumonia, e.g., severe community-acquired pneumonia.

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