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1. 发明申请

WO2005085431A3 MUTANTS OF O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE 审中-公开
公开(公告)号：WO2005085431A3
公开(公告)日：2005-09-15
申请号：PCT/EP2005/050899
申请日：2005-03-01
申请人： EPFL ECOLE POLYTECHNIQUE FEDERALE DE 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
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.

2. 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。

3. 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。

4. 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。

5. 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。

6. 发明申请

WO2010089117A1 STRUCTURED POLYCYCLIC PEPTIDE 审中-公开
标题翻译：结构化多环肽
公开(公告)号：WO2010089117A1
公开(公告)日：2010-08-12
申请号：PCT/EP2010/000691
申请日：2010-02-04
申请人： MEDICAL RESEARCH COUNCIL , HEINIS, Christian , TOUATI, Jeremy , WINTER, Gregory, Paul
发明人： HEINIS, Christian , TOUATI, Jeremy , WINTER, Gregory, Paul
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 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.
摘要翻译：本发明涉及一种肽配体，其包含在n个连接点处与分子支架连接的多肽，其中所述多肽被环化并形成对分子支架上的所述n个附着点之间的n个分开的环，其中n大于或等于2 。

7. 发明申请

WO2010089115A1 MULTISPECIFIC PEPTIDES 审中-公开
标题翻译：多功能肽
公开(公告)号：WO2010089115A1
公开(公告)日：2010-08-12
申请号：PCT/EP2010/000689
申请日：2010-02-04
申请人： MEDICAL RESEARCH COUNCIL , WINTER, Gregory Paul , HEINIS, Christian , BERNARD, Elise , LOAKES, David , TITE, John Paul , VAYSBURD, Marina , TEUFEL, Daniel Paul
发明人： WINTER, Gregory Paul , HEINIS, Christian , BERNARD, Elise , LOAKES, David , TITE, John Paul , VAYSBURD, Marina , TEUFEL, Daniel Paul
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 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.
摘要翻译：本发明涉及一种提供多特异性肽配体的方法，所述多特异性肽配体包含在三个或更多个氨基酸残基处共价连接到分子支架并能够结合两个或更多个单独靶标的多肽，包括以下步骤：（a）提供第一多肽的所有组成部分，每个多肽包含两个或更多个能够与分子支架共价连接的反应性基团，以及至少一个环，其包含两个或更多个氨基酸的序列，对应于两个所述反应性基团; （b）提供如（a）所述的第二组多肽; （c）将第一组合物中的一个或多个成员的至少一个环连接到第二组合物的一个或多个成员的至少一个环，以形成至少一个包含两个环的多肽，和（d）将复合多肽（ s）至少在三个氨基酸位置分子支架。

8. 发明申请

WO2009098450A2 METHODS AND COMPOSITIONS 审中-公开
标题翻译：方法和组成
公开(公告)号：WO2009098450A2
公开(公告)日：2009-08-13
申请号：PCT/GB2009/000301
申请日：2009-02-04
申请人： MEDICAL RESEARCH COUNCIL , WINTER, Gregory , HEINIS, Christian
发明人： WINTER, Gregory , HEINIS, Christian
IPC分类号： C12N15/10 , C40B40/02 , C40B30/04 , 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。

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