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1. 发明专利

IL255154D0 Novel inhibitors of the enzyme activated factor xii fxiia 未知
公开(公告)号：IL255154D0
公开(公告)日：2017-12-31
申请号：IL25515417
申请日：2017-10-19
申请人： ECOLE POLYTECHNIQUE FED LAUSANNE EPFL , HEINIS CHRISTIAN , BAERISWYL VANESSA , MIDDENDORP SIMON , WILBS JONAS ALFRED KARL
发明人： HEINIS CHRISTIAN , BAERISWYL VANESSA , MIDDENDORP SIMON , WILBS JONAS ALFRED KARL
IPC分类号： C07K20060101
摘要： The present invention relates to a bicyclic inhibitor of the coagulation enzyme activated factor XII (FXIIa) comprising or consisting of the peptide) (X1)(X2)(X3)n(X4)RL(X5)(X6)m(X7)(X9)l(X10)(X11)(X12)(X13)(X14)k(X15)(X16), wherein (X1) is present or absent and, if present, is an amino acid; (X2) is an amino acid with a side chain; (X3) is an amino acid and n is between 0 and 3, preferably 0 or 1 and most preferably 0; (X4) is an aliphatic L-amino acid or a cyclic L-amino acid, preferably L, P or an aromatic L-amino acid, and most preferably an aromatic L-amino acid; (X5) is an amino acid; (X6) is an amino acid and m is between 0 and 3, preferably 0 or 1 and most preferably 0; (X7) is an amino acid with a side chain; (X9) is an amino acid and l is between 0 and 3, preferably 0 or 1 and most preferably 0; (X10) is an amino acid; (X11) is an amino acid, preferably Q; (X12) is a hydrophobic L-amino acid, preferably an aliphatic L-amino acid, and is most preferably L; (X13) is an amino acid; (X14) is an amino acid and k is between 0 and 3, preferably 0 or 1 and most preferably 0, (X15) is an amino acid with a side chain; and (X16) is present or absent and, if present, is an amino acid; and wherein the side chains of (X2), (X7) and (X15) are connected via a connecting molecule, said connecting molecule having at least three functional groups, each functional group forming a covalent bond with one of the side chains of (X2), (X7) and (X15).

2. 发明申请

WO2009098450A3 METHODS AND COMPOSITIONS 审中-公开
标题翻译：方法和组合物
公开(公告)号：WO2009098450A3
公开(公告)日：2009-10-29
申请号：PCT/GB2009000301
申请日：2009-02-04
申请人： MEDICAL RES COUNCIL , WINTER GREGORY , HEINIS CHRISTIAN
发明人： WINTER GREGORY , HEINIS CHRISTIAN
IPC分类号： C12N15/10 , A61K47/48 , C40B30/04 , C40B40/02 , G01N33/68
CPC分类号： C12N15/1062 , A61K47/54 , A61K47/55 , A61K47/64 , C07K1/1075 , C07K1/1077 , C07K14/005 , C12N15/1037 , C12N15/1041 , C12N15/1068 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/56983
摘要： The invention relates to a complex comprising a phage particle, said phage particle comprising (i) a polypeptide; (ii) a nucleic acid encoding the polypeptide of (i); (iii) a connector compound attached to said polypeptide wherein said connector compound is attached to the polypeptide by at least three discrete covalent bonds. The invention also relates to libraries, and to methods for making complexes and to methods of screening using same.
摘要翻译：本发明涉及包含噬菌体颗粒的复合物，所述噬菌体颗粒包含（i）多肽; （ii）编码（i）的多肽的核酸; （iii）连接到所述多肽上的连接化合物，其中所述连接化合物通过至少三个离散的共价键与多肽连接。本发明还涉及文库，以及制备复合物的方法和使用它们的筛选方法。

3. 发明申请

WO2005085431A9 MUTANTS OF O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE 审中-公开
标题翻译： O6-ALKYLGUANINE-DNA烷基转移酶的突变体
公开(公告)号：WO2005085431A9
公开(公告)日：2006-10-12
申请号：PCT/EP2005050899
申请日：2005-03-01
申请人： EPFL ECOLE POLYTECHNIQUE FEDERALE LAUSANNE , BARNIKOV JAN , CHIDLEY CHRISTOPHER , GRONEMEYER THOMAS , HEINIS CHRISTIAN , JACCARD HUGHES , JOHNSSON KAI , JUILLERAT ALEXANDRE , KEPPLER ANTJE
发明人： BARNIKOV JAN , CHIDLEY CHRISTOPHER , GRONEMEYER THOMAS , HEINIS CHRISTIAN , JACCARD HUGHES , JOHNSSON KAI , JUILLERAT ALEXANDRE , KEPPLER ANTJE
IPC分类号： C12N9/10
CPC分类号： C12N9/10 , C07K2319/00 , C12N9/1007
摘要： The invention relates to AGT mutants showing, when compared to the wild type human AGT, two or more advantageous properties selected from (a) reduced DNA interaction; (b) localisation of the expressed protein in eukaryotic cells that is no longer restricted to the nucleus; (c) improved expression yield as soluble protein and improved stability in various hosts; (d) improved stability under oxidising conditions; (e) improved stability within cells after reaction with a substrate; (f) improved stability outside cells before and after reaction with a substrate; (g) improved in vitro solubility; (h) improved reactivity against 0 6 -alkylguanine substrates; (1) reduced reactivity against DNA-based substrates; and (j) reduced reactivity against N 9 -substituted 0 6 -alkylguanine substrates. Such AGT mutants with the mentioned improved properties are mutants wherein between 1 and 25 amino acids of the wild type human AGT are substituted by other amino acids, and optionally I to 5 amino acids out of the continuous chain at one, two or three positions are deleted or added and/or 1 to 4 amino acids at the N-terminus or 1 to 40 amino acids at the C-terminus are deleted. The invention further relates to a method for detecting and/or manipulating a protein of interest wherein the protein of interest is incorporated into a fusion protein with the AGT mutants of the invention. Another object of the invention are AGT fusion proteins comprising such AGT mutants and the protein of interest.
摘要翻译：本发明涉及AGT突变体，当与野生型人AGT相比时，显示出选自（a）减少的DNA相互作用的两种或更多种有利性质; （b）表达的蛋白质在不再限于细胞核的真核细胞中的定位; （c）提高作为可溶性蛋白质的表达产率和改善各种宿主的稳定性; （d）改善氧化条件下的稳定性; （e）在与底物反应后改善细胞内的稳定性; （f）在与底物反应之前和之后提高细胞外的稳定性; （g）提高体外溶解度; （h）改善对0-6个 - 烷基鸟嘌呤底物的反应性; （1）降低对DNA基底层的反应性; 和（j）对N 9 - 取代的0-6-烷基鸟嘌呤底物的反应性降低。具有上述改进性质的这种AGT突变体是突变体，其中野生型人AGT的1至25个氨基酸被其它氨基酸取代，并且在一个，两个或三个位置上，连续链中任选地I至5个氨基酸是在N-末端缺失或添加和/或1至4个氨基酸或C末端的1至40个氨基酸被缺失。本发明还涉及用于检测和/或操纵感兴趣的蛋白质的方法，其中将目的蛋白质与本发明的AGT突变体掺入融合蛋白中。本发明的另一个目的是包含这种AGT突变体和目的蛋白质的AGT融合蛋白。

4. 发明申请

WO2011018227A3 PEPTIDE LIBRARIES 审中-公开
标题翻译：肽库
公开(公告)号：WO2011018227A3
公开(公告)日：2011-04-07
申请号：PCT/EP2010004948
申请日：2010-08-12
申请人： MEDICAL RES COUNCIL , WINTER PAUL GREGORY , HEINIS CHRISTIAN , BERNARD ELISE , LOAKES DAVID , TEUFEL DANIEL PAUL
发明人： WINTER PAUL GREGORY , HEINIS CHRISTIAN , BERNARD ELISE , LOAKES DAVID , TEUFEL DANIEL PAUL
IPC分类号： C12N15/10 , A61K47/00 , A61K47/48 , C12N15/00 , C40B40/02 , G01N33/00 , G01N33/68
CPC分类号： C12N15/1037 , C07K1/00 , C07K1/042 , C07K1/113 , C07K2318/00
摘要： 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).
摘要翻译：本发明涉及用于改变多肽配体的第一组库的构象多样性的方法，所述方法包括多个多肽，所述多肽包含至少两个反应基团，所述反应基团通过共价连接至与所述反应基团形成共价键的分子支架的环状序列分开，以产生第二多肽配体库，包括从所述第一库所的多肽和结构支架组装所述第二库，并入以下改变之一：（a）改变至少一个反应基团; 或（b）改变分子支架的性质; 或（c）改变至少一个反应性基团与分子支架之间的键; 或（d）（a），（b）或（c）的任何组合。

5. 发明申请

WO2010089116A1 STRUCTURED PEPTIDE PROCESSING 审中-公开
标题翻译：结构肽加工
公开(公告)号：WO2010089116A1
公开(公告)日：2010-08-12
申请号：PCT/EP2010/000690
申请日：2010-02-04
申请人： MEDICAL RESEARCH COUNCIL , WINTER, Paul, Gregory , HEINIS, Christian , BERNARD, Elise , LOAKES, David , VAYSBURD, Marina
发明人： WINTER, Paul, Gregory , HEINIS, Christian , BERNARD, Elise , LOAKES, David , VAYSBURD, Marina
IPC分类号： A61K47/48 , G01N33/68
CPC分类号： C12N15/1037 , A61K47/55 , A61K47/64 , A61K47/643 , C07K14/001 , C12N15/1044 , C12N15/1058 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/531
摘要： 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.
摘要翻译：本发明涉及一种修饰一种或多种肽配体的方法，其包括在两个或更多个氨基酸残基处与分子支架共价连接的多肽，包括提供一个或多个肽配体的步骤，其中所述多肽包含两个或多个反应性基团其形成与分子支架的共价键，以及至少一个环，其包含在两个所述反应性基团之间对位的两个或更多个氨基酸的序列; 将肽配体暴露于一种或多种蛋白酶; 并根据蛋白水解切割的程度对配体进行分选。

6. 发明申请

WO2005030957A1 VERFAHREN ZUR IN VITRO EVOLUTION VON POLYPEPTIDEN 审中-公开
标题翻译：程序对体外进化的多肽
公开(公告)号：WO2005030957A1
公开(公告)日：2005-04-07
申请号：PCT/CH2004/000610
申请日：2004-10-01
申请人： ETH ZÜRICH , BERTSCHINGER, Julian , HEINIS, Christian
发明人： BERTSCHINGER, Julian , HEINIS, Christian
IPC分类号： C12N15/10
CPC分类号： C12N15/1075
摘要： Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung und Zuordnung von Nukleinsäuren und der dadurch kodierten Polypeptide, das zur evolutionären Auswahl von Polypeptiden in vitro verwendet werden kann. Das erfindungsgemäße Verfahren ermöglicht nicht nur die Zuordnung von Nukleinsäuren zu den dadurch kodierten Polypeptiden, sondern darüber hinaus die Auswahl und Isolierung von Nukleinsäuren, die Polypeptide mit ausgewählten Eigenschaften kodieren. Des Weiteren ist die Erfindung auf die Verwendung von (Cytosin-5)-Methyltransferasen und auf die Verwendung von Fusionspolypeptiden oder damit kovalent gebundenen Nukleinsäure-Fusionspolypeptid-Komplexen in den erfindungsgemäßen Verfahren gerichtet.
摘要翻译：本发明涉及一种用于可用于体外多肽的进化选择的核酸和编码的多肽的生产和分配的处理。本发明的方法不仅允许的核酸与由其编码的多肽的关联，而且，其具有选定的性质编码多肽的核酸的选择和隔离。此外，本发明涉及使用（胞嘧啶-5）-methyltransferases和在本发明的方法中使用的融合多肽或共价键合的核酸融合多肽复合物的被引导。

7. 发明授权

US08680022B2 Methods and compositions 有权
标题翻译：方法和组成
公开(公告)号：US08680022B2
公开(公告)日：2014-03-25
申请号：US12866214
申请日：2009-02-04
申请人： Winter Gregory , Heinis Christian
发明人： Winter Gregory , Heinis Christian
IPC分类号： C40B50/06
CPC分类号： C12N15/1062 , A61K47/54 , A61K47/55 , A61K47/64 , C07K1/1075 , C07K1/1077 , C07K14/005 , C12N15/1037 , C12N15/1041 , C12N15/1068 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/56983
摘要： The invention relates to a complex comprising a phage particle, said phage particle comprising (i) a polypeptide; (ii) a nucleic acid encoding the polypeptide of (i); (iii) a connector compound attached to said polypeptide wherein said connector compound is attached to the polypeptide by at least three discrete covalent bonds. The invention also relates to libraries, and to methods for making complexes and to methods of screening using same.
摘要翻译：本发明涉及包含噬菌体颗粒的复合物，所述噬菌体颗粒包含（i）多肽; （ii）编码（i）的多肽的核酸; （iii）连接到所述多肽的连接剂化合物，其中所述连接体化合物通过至少三个不连续的共价键与多肽连接。本发明还涉及文库，以及制备复合物的方法和使用其的筛选方法。

8. 发明申请

US20100317547A1 METHODS AND COMPOSITIONS 有权
标题翻译：方法和组成
公开(公告)号：US20100317547A1
公开(公告)日：2010-12-16
申请号：US12866214
申请日：2009-02-04
申请人： Winter Gregory , Heinis Christian
发明人： Winter Gregory , Heinis Christian
IPC分类号： C40B40/08 , C12N7/00 , C12N7/02 , C12Q1/70 , C07K2/00
CPC分类号： C12N15/1062 , A61K47/54 , A61K47/55 , A61K47/64 , C07K1/1075 , C07K1/1077 , C07K14/005 , C12N15/1037 , C12N15/1041 , C12N15/1068 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/56983
摘要： The invention relates to a complex comprising a phage particle, said phage particle comprising (i) a polypeptide; (ii) a nucleic acid encoding the polypeptide of (i); (iii) a connector compound attached to said polypeptide wherein said connector compound is attached to the polypeptide by at least three discrete covalent bonds. The invention also relates to libraries, and to methods for making complexes and to methods of screening using same.
摘要翻译：本发明涉及包含噬菌体颗粒的复合物，所述噬菌体颗粒包含（i）多肽; （ii）编码（i）的多肽的核酸; （iii）连接到所述多肽的连接剂化合物，其中所述连接体化合物通过至少三个不连续的共价键与多肽连接。本发明还涉及文库，以及制备复合物的方法和使用其的筛选方法。

9. 发明申请

WO2013050615A1 MODULATION OF STRUCTURED POLYPEPTIDE SPECIFICITY 审中-公开
标题翻译：结构多肽特异性的调节
公开(公告)号：WO2013050615A1
公开(公告)日：2013-04-11
申请号：PCT/EP2012/069897
申请日：2012-10-08
申请人： BICYCLE THERAPEUTICS LIMITED , TITE, John , WALKER, Edward , STACE, Catherine , HEINIS, Christian
发明人： TITE, John , WALKER, Edward , STACE, Catherine , HEINIS, Christian
IPC分类号： C40B40/02 , C07K1/107
CPC分类号： C07K7/56 , A61K38/10 , A61K38/12 , C07K1/00 , C07K1/1075 , C07K2/00 , C07K7/08
摘要： The invention describes a method for selecting a polypeptide ligand having a desired level of specificity for a target, wherein the polypeptide ligand comprises a polypeptide comprising at least three reactive groups, separated by at least two loop sequences, and a molecular scaffold which formscovalent bonds with the reactive groups of the polypeptide such that at least two polypeptide loops are formed on the molecular scaffold, comprising (i) screening at least two different sets of polypeptide ligands against the target, and selecting one or more ligands from each library which interact with the target; (ii) comparing the activity of the selected ligands with one or more paralogues or orthologues of the target; and (iii) further selecting one or more ligands according to their activity towardssaid one or more paralogues or orthologues; wherein said two or more different sets of ligands differ in the length of the polypeptide loops formed on the molecular scaffold.
摘要翻译：本发明描述了一种用于选择对靶标具有期望的特异性水平的多肽配体的方法，其中多肽配体包含多肽，该多肽配体包含至少三个由至少两个环序列分开的反应性基团的多肽，以及分子支架，其与所述多肽的反应性基团使得在分子支架上形成至少两个多肽环，其包含（i）筛选针对靶的至少两种不同组的多肽配体，以及从每个文库中选择一个或多个与目标; （ii）将所选配体的活性与目标的一个或多个旁系同源物或直向同源物进行比较; 和（iii）根据它们的活性进一步选择一种或多种配体，所述配体依赖于一个或多个旁系同源物或直向同源物; 其中所述两种或更多种不同的配体组在分子支架上形成的多肽环的长度不同。

10. 发明申请

WO2011018227A2 PEPTIDE LIBRARIES 审中-公开
标题翻译：肽图书馆
公开(公告)号：WO2011018227A2
公开(公告)日：2011-02-17
申请号：PCT/EP2010/004948
申请日：2010-08-12
申请人： MEDICAL RESEARCH COUNCIL , WINTER, Paul Gregory , HEINIS, Christian , BERNARD, Elise , LOAKES, David , TEUFEL, Daniel, Paul
发明人： WINTER, Paul Gregory , HEINIS, Christian , BERNARD, Elise , LOAKES, David , TEUFEL, Daniel, Paul
IPC分类号： C07K14/435
CPC分类号： C12N15/1037 , C07K1/00 , C07K1/042 , C07K1/113 , C07K2318/00
摘要： 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).
摘要翻译：本发明涉及一种用于改变多肽配体的第一组分的构象多样性的方法，其包含多个多肽，所述多肽包含至少两个反应性基团，所述反应基团通过共价连接到与所述反应性基团形成共价键的分子支架的环序列分开，以产生多肽配体的第二组成成分，其包括从所述第一组合物的多肽和结构性支架组装所述第二组分，并结合以下改变之一：（a）改变至少一个反应性基团; 或（b）改变分子支架的性质; 或（c）改变至少一个反应性基团和分子支架之间的键; 或（d）（a），（b）或（c）的任何组合。

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