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    Method for the identification of protein-protein interactions in disease related protein networks
    31.
    发明公开
    Method for the identification of protein-protein interactions in disease related protein networks 审中-公开
    蛋白质 - 蛋白质 - 蛋白质-Wechselwirkungen在krankheitsbezogenen Proteinnetzwerken的Verfahren zur Identifizierung von

    公开(公告)号：EP1677113A1

    公开(公告)日：2006-07-05

    申请号：EP04030994.0

    申请日：2004-12-29

    申请人： Max-Delbrück-Centrum für Molekulare Medizin (MDC)

    发明人： Wanker, Erich ,  Lalowski, Maciej ,  Stelzl, Ulrich ,  Strödicke, Martin ,  Hänig, Christian ,  Worm, Uwe ,  Göhler, Heike

    IPC分类号： G01N33/68 ,  C12N15/10 ,  C12N15/00 ,  C12N5/00 ,  C07K16/00 ,  C07K14/00 ,  A61K38/00 ,  A61K39/395 ,  A61K48/00

    CPC分类号： C12N15/1055

    摘要： The present invention relates to a method for identification of a protein-protein interaction of protein interaction partners in a disease-related network of proteins comprising the steps of (a) identifying nucleic acid molecules by at least partial 5'sequencing and, optionally, additionally adding recombinantly cloned and sequenced nucleic acid molecules, wherein said nucleic acid molecules encode a selection of proteins suspected to contain one or several of said interaction partners and wherein said nucleic acid molecules are annotated with a positional information; (b) in frame cloning of the nucleic acid molecules of step (a) into prey and bait vectors, wherein one copy of each nucleic acid molecule is cloned into said prey vector and a second copy of each nucleic acid molecule is cloned into said bait vector; (c) transforming a first suitable host cell with the prey vector obtained in step (b) and a second suitable host cell with the bait vector obtained in step (b), wherein said first and said second host cell have a different genetic constitution and can be mated; (d) mating the first suitable host cell of step (c) with the second suitable host cell of step (c), and expressing the proteins encoded by the nucleic acid molecules obtained in step (b); (e) selecting the mated host cell obtained in step (d) on the basis of a selection advantage which is caused by the protein-protein interaction between the protein interaction partner encoded by the nucleic acid molecule of the prey vector contained in said cell and the protein interaction partner encoded by the nucleic acid molecule of the bait vector contained in said cell; and (f) identifying with the positional information obtained in step (a) the protein interaction partners of step (e) and thereby identifying the protein-protein interaction.

    摘要翻译： 本发明涉及用于鉴定蛋白质相互作用伴侣蛋白质相互作用的蛋白质相互作用的方法，所述方法包括以下步骤：（a）通过至少部分的5'-测序鉴定核酸分子，以及任选地另外 加入重组克隆和测序的核酸分子，其中所述核酸分子编码怀疑含有一个或几个所述相互作用配偶体的蛋白质的选择，并且其中所述核酸分子用位置信息注释; （b）将步骤（a）的核酸分子的框架克隆入猎物和诱饵载体，其中每个核酸分子的一个拷贝被克隆到所述猎物载体中，并且将每个核酸分子的第二个拷贝克隆到所述诱饵中 向量; （c）用步骤（b）中获得的猎物载体转化第一合适的宿主细胞，和用步骤（b）中获得的诱饵载体的第二合适的宿主细胞转化，其中所述第一和所述第二宿主细胞具有不同的遗传构成， 可以交配; （d）将步骤（c）的第一合适宿主细胞与步骤（c）的第二适合宿主细胞交配，并表达由步骤（b）中获得的核酸分子编码的蛋白质; （e）基于由所述细胞中包含的被捕获载体的核酸分子编码的蛋白质相互作用伴侣之间的蛋白质 - 蛋白质相互作用引起的选择优势，选择步骤（d）中获得的配对宿主细胞;以及 由所述细胞中所含的诱饵载体的核酸分子编码的蛋白质相互作用伴侣; 和（f）用步骤（a）中获得的位置信息鉴定步骤（e）的蛋白质相互作用伴侣，从而鉴定蛋白质 - 蛋白质相互作用。

    DISEASE RELATED PROTEIN NETWORK
    32.
    发明公开
    DISEASE RELATED PROTEIN NETWORK 审中-公开
    蛋白质网络，与医疗意识相关联

    公开(公告)号：EP1636362A2

    公开(公告)日：2006-03-22

    申请号：EP04740062.7

    申请日：2004-06-18

    申请人： MAX-PLANCK-GESELLSCHAFT ZUR FÖRDERUNG DER WISSENSCHAFTEN E.V. ,  Max-Delbrück-Centrum für Molekulare Medizin (MDC)

    发明人： WANKER, Erich ,  LEHRACH, Hans ,  GÖHLER, Heike ,  STRÖDICKE, Martin ,  STELZL, Ulrich ,  LALOWSKI, Maciej

    IPC分类号： C12N15/10

    CPC分类号： C40B30/04 ,  C12N15/1055 ,  G01N33/6896

    摘要： The present invention relates to a method for generating a network of direct and indirect interaction partners of a disease-related (poly)peptide comprising the steps of (a) contacting a selection of (poly)peptides suspected to contain one or several of said direct or indirect interaction partners with said disease-related (poly)peptides and optionally with known direct or indirect interaction partners of said diseaserelated (poly)peptide under conditions that allow the interaction between interaction partners to occur; (b) detecting (poly)peptides that interact with said disease-related (poly)peptide or with said known direct or indirect interaction partners of said disease-related (poly) peptide; (c) contacting (poly)peptides detected in step (b) with a selection of (poly) peptides suspected to contain one or several (poly)peptides interacting with said (poly)peptides detected in step (b) under conditions that allow the interaction between interaction partners to occur; (d) detecting proteins that interact with said (poly) peptides detected in step (b); (e) contacting said disease related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide, said (poly)peptides detected in steps (b) and (d) and a selection of proteins suspected to contain one or several (poly)peptides interacting with any of the afore mentioned (poly)peptides under conditions that allow the interaction between interaction partners to occur; (f) detecting (poly)peptides that interact with said disease-related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide or with said (poly)peptides identified in step (b) or (d); and (g) generating a (poly)peptide(poly)peptide interaction network of said disease-related (poly)peptide and optionally said known direct or indirect interaction partners of said disease-related (poly)peptide and said (poly)peptides identified in steps (b), (d) and (f). Moreover, the present invention relates to a protein complex comprising at least two proteins and to methods for identifying compounds interfering with an interaction of said proteins. Finally, the present invention relates to a pharmaceutical composition and to the use of compounds identified by the present invention for the preparation of a pharmaceutical composition for the treatment of Huntington's disease.

    TRANSPOSON-BASED TARGETING SYSTEM
    33.
    发明公开
    TRANSPOSON-BASED TARGETING SYSTEM 有权
    基于TRANSPOSON的瞄准系统

    公开(公告)号：EP1594972A2

    公开(公告)日：2005-11-16

    申请号：EP04709603.7

    申请日：2004-02-10

    申请人： Max-Delbrück-Centrum für Molekulare Medizin (MDC)

    发明人： IVICS, Zoltán ,  IZSVAK, Zsuzsanna

    IPC分类号： C12N15/90 ,  C12N15/09

    CPC分类号： C12N15/90

    摘要： The present invention relates to a targeting system comprising, preferably as distinct components, (a) a transposon which is devoid of a polynucleotide encoding a functional transposase comprising a polynucleotide of interest; and (b) a fusion protein comprising (ba) a transposase or a fragment or derivative thereof having transposase function; and (bb) a DNA targeting domain; or (bc) a (poly)peptide binding domain that binds to a cellular or engineered (poly)peptide comprising a DNA targeting domain; or (bd) a (poly)peptide comprising the DNA targeting domain of (bb) or the (poly)peptide binding domain of (bc), wherein the transposase or a fragment or derivative thereof having transposase function of (a) is joined by a linker to the domain of (bb) or to the domain of (bc) or to the (poly)peptide of (bd); or (c) a polynucleotide encoding the fusion protein of (b).

    摘要翻译： 本发明涉及一种靶向系统，其优选包含（a）不含编码包含目的多核苷酸的功能性转座酶的多核苷酸的转座子; 和（b）融合蛋白，其包含（ba）具有转座酶功能的转座酶或其片段或衍生物; 和（bb）DNA靶向结构域; 或（bc）结合包含DNA靶向性结构域的细胞或工程化（多）肽的（多）肽结合结构域; 或（bd）包含（bb）的DNA靶向性结构域或（bc）的（多）肽结合性结构域的（多）肽，其中具有（a）的转座酶功能的转座酶或其片段或衍生物通过 （bb）的结构域或（bc）的结构域或（bd）的（多）肽的结构域的接头; 或（c）编码（b）的融合蛋白的多核苷酸。

    NEURONALLY EXPRESSED TRYPTOPHANE HYDROXYLASE AND ITS USE
    34.
    发明公开
    NEURONALLY EXPRESSED TRYPTOPHANE HYDROXYLASE AND ITS USE 有权
    神经元明示色氨酸羟化酶及其用途

    公开(公告)号：EP1521823A2

    公开(公告)日：2005-04-13

    申请号：EP03763879.8

    申请日：2003-07-16

    申请人： Max Delbrück Centrum für Molekulare Medizin (MDC) Berlin-Buch;

    发明人： WALTHER, Diego ,  BADER, Michael

    IPC分类号： C12N9/02

    CPC分类号： C12N9/0071

    摘要： The present invention relates to novel, specifically neuronal expressed proteins with tryptophane hydroxylase activity, nucleic acid sequences, recombinant nucleic acid molecules containing these nucleic acid sequences or vectors containing these nucleic acid sequences or the recombinant nucleic acid molecules encoding for a neuronal tryptophane hydroxylase. The invention also relates to transgenic organisms containing these nucleic acid sequences, the recombinant nucleic acid molecules or the above cited vectors. The invention moreover refers to mono- or polyclonal antibodies directed against the isolated proteins. Furthermore, the invention relates to the use of these nucleic acid sequences and proteins for diagnosis, predisposition, therapy and monitoring of neuronal diseases. Possible fields of application among others are medicine and the pharmaceutical industry.

    METHOD FOR THE GENERATION OF T CELL HYBRIDOMA FOR CLONING AND ANALYSIS OF RECEPTORS USING ENGINEERED MEASLES VIRUS FUSOGENIC GLYCOPROTEINS
    36.
    发明公开
    METHOD FOR THE GENERATION OF T CELL HYBRIDOMA FOR CLONING AND ANALYSIS OF RECEPTORS USING ENGINEERED MEASLES VIRUS FUSOGENIC GLYCOPROTEINS 审中-公开
    产生T细胞杂交瘤克隆的方法和使用工程化的病毒的融合蛋白

    公开(公告)号：EP3284819A1

    公开(公告)日：2018-02-21

    申请号：EP16184334.7

    申请日：2016-08-16

    申请人： Max-Delbrück-Centrum für Molekulare Medizin (MDC) ,  Humboldt Universität zu Berlin

    发明人： Bunse, Mario ,  Edes, Inan ,  Uckert, Wolfgang

    IPC分类号： C12N5/0783 ,  C07K14/12

    CPC分类号： C12N5/163 ,  C07K14/12 ,  C07K2319/33 ,  C12N2510/04

    摘要： The invention relates to the field of immunology and immunotherapy, in particular, to adoptive T cell therapy of cancer utilizing T cell receptor (TCR)-engineered T cells. The invention provides novel methods and tools for identification and cloning of TCR, which are also applicable for identification of other receptors such as B cell receptors or antibodies. The invention provides immortalized cell lines able to induce subset specific (e.g. CD4 + or CD8 + specific) hybridization during co-culture, e.g., with primary lymphocytes of mice or men. The immortalized cells are engineered to express two mutated glycoproteins derived from the paramyxovirus family, namely hemagglutinin (H) and fusion (F) or a derivative thereof. H is a chimeric protein not able to bind to its natural ligands, fused to a targeting ligand capable of specifically binding to a specific cell surface antigen such as a lymphocytic subset-marking ligand (e.g. CD4 or CD8); fusion (F) mediates the fusion of cellular membranes of the immortalized cell line and cells, e.g., primary lymphocytes, H has bound to. The methods of the invention comprise preparing a hybridoma cell expressing a receptor, comprising steps of co-culturing a cell expressing a specific cell surface antigen and said receptor with the specific immortalized cells of the invention. The invention also relates to the hybridoma cells obtainable by said method.

    摘要翻译： 本发明涉及免疫学和免疫治疗领域，特别涉及利用T细胞受体（TCR） - 工程化T细胞的癌症的过继性T细胞治疗。 本发明提供了鉴定和克隆TCR的新方法和工具，其也可用于鉴定其他受体如B细胞受体或抗体。 本发明提供了永生化细胞系，其能够在共培养期间（例如与小鼠或男性的原代淋巴细胞）诱导子集特异性（例如CD4 +或CD8 +特异性）杂交。 工程化永生化细胞以表达衍生自副粘病毒科的两种突变糖蛋白，即血凝素（H）和融合蛋白（F）或其衍生物。 H是不能与其天然配体结合的嵌合蛋白，与能够特异性结合特定细胞表面抗原如淋巴细胞亚群标记配体（例如CD4或CD8）的靶向配体融合; 融合体（F）介导永生化细胞系和细胞（例如H已结合的初级淋巴细胞）的细胞膜融合。 本发明的方法包括制备表达受体的杂交瘤细胞，其包括将表达特定细胞表面抗原的细胞和所述受体共同培养于本发明的特定永生化细胞的步骤。 本发明还涉及通过所述方法可获得的杂交瘤细胞。

    USE OF A DNA EXPRESSION CONSTRUCT
    38.
    发明公开
    USE OF A DNA EXPRESSION CONSTRUCT 有权
    VERWENDUNG EINES DNA-EXPRESSIONSKONSTRUKTES

    公开(公告)号：EP2613811A1

    公开(公告)日：2013-07-17

    申请号：EP11767194.1

    申请日：2011-09-08

    申请人： Mologen AG ,  Max-Delbrück-Centrum für Molekulare Medizin (MDC)

    发明人： WALTHER, Wolfgang ,  SCHLAG, Peter M. ,  KOBELT, Dennis ,  SCHMIDT, Manuel

    IPC分类号： A61K48/00

    CPC分类号： A61K31/547 ,  A61K38/191 ,  A61K48/005 ,  A61K48/0066 ,  A61K2039/53 ,  C12N15/85 ,  C12N2800/24

    摘要： The present invention relates to the use of a DNA expression construct comprising a dumbbell- shaped circular strand of deoxyribonucleic acids and provides such a construct with a double- stranded stem and single-stranded loops located at both ends of the stem, wherein the stem comprises complementary deoxyribonucleic acids of the circular strand with a promotor sequence, a coding sequence and a termination signal to be administered by jet injection for the treatment of cancer.

    摘要翻译： 本发明涉及具有共价闭合末端的线性DNA表达构建体，其包含编码用于治疗癌症的基因治疗抗癌剂的编码序列的表达盒，其中所述DNA表达构建体适于施用于 细胞或组织通过物理转染方法。 优选地，所述DNA表达构建体由DNA的哑铃状环状链构成。