公开(公告)号：WO2014128460A3

公开(公告)日：2014-11-06

申请号：PCT/GB2014050484

申请日：2014-02-19

Applicant: CAMBRIDGE ENTPR LTD ,  MEDICAL RES COUNCIL

Inventor： FITZGERALD REBECCA ,  ROSS-INNES CARYN

IPC: G01N33/574

CPC classification number: G01N33/57407 ,  C12Q1/6886 ,  C12Q2600/154 ,  G01N2333/4703 ,  G01N2333/4748 ,  G01N2333/912

Abstract: 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.

Abstract translation: 本发明涉及一种辅助检测受试者食管表面异常的方法，其中所述表面异常选自低度发育不良（LGD），高级别异型增生（HGD），无症状食管腺癌 （OAC）和粘膜内癌（IMC），所述方法包括：a）提供来自所述受试者的细胞样品，其中所述样品包含从受试者食管表面收集的细胞; 10）测定所述细胞中至少两种选自（i）p53; （ii）c-Myc; （iii）AURKA或PLK1，优选AURKA; 和（iv）MyoD和Runx3的甲基化; 其中至少两个所述标记物的异常水平的检测推测受试者在食道中具有增加的表面异常的可能性。 本发明还涉及某些试剂盒，装置和用途。

公开(公告)号：WO2013171489A8

公开(公告)日：2014-01-23

申请号：PCT/GB2013051254

申请日：2013-05-16

Applicant: MEDICAL RES COUNCIL

Inventor： FITZGERALD REBECCA ,  BIRD-LIEBERMAN ELIZABETH

IPC: C12Q1/68 ,  G01N33/574

CPC classification number: G01N33/57407 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N2333/38 ,  G01N2333/4739 ,  G01N2333/4748 ,  G01N2333/70596 ,  G01N2400/00 ,  G01N2800/06

Abstract: 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.

Abstract translation: 本发明涉及一种用于帮助预测从Barrett食管进入高分级异型增生或食管腺癌的可能性的方法，所述方法包括（a）从所述对象提供食管样品（b）确定所述样品是否异常染色 用米曲霉凝集素; （c）确定所述样品中是否存在DNA含量异常; 和（d）确定所述样品中是否存在低度不典型增生; 其中如果（b）是异常的，（c）是异常的并且存在低等级的不典型增生，则确定进展的可能性增加。 本发明还涉及一种装置，以及某些材料的不同用途。

公开(公告)号：WO2013108044A3

公开(公告)日：2013-11-28

申请号：PCT/GB2013050121

申请日：2013-01-21

Applicant: MEDICAL RES COUNCIL ,  UNIV NORTH CAROLINA STATE

Inventor： CHIN JASON ,  DEITERS ALEXANDER

IPC: C07K1/13 ,  A61K49/00 ,  C12P21/02

CPC classification number: A61K49/0017 ,  C07C271/34 ,  C07C2601/16 ,  C07C2602/42 ,  C07K1/13 ,  C12N9/93 ,  C12P21/02 ,  C12Y601/01026 ,  G01N33/582

Abstract: 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.

Abstract translation: 本发明涉及包含具有降冰片烯基团的氨基酸的多肽。 降冰片烯基团合适地表示为降冰片烯赖氨酸的氨基酸残基。 本发明还涉及生产包含降冰片烯基团的多肽的方法，所述方法包括将包含降冰片烯基团的氨基酸遗传并入多肽中。 包含降冰片烯基团的多肽可以通过与四嗪化合物的反电子需求狄尔斯 - 阿尔德反应来具体标记。

公开(公告)号：WO2013091883A3

公开(公告)日：2013-10-24

申请号：PCT/EP2012005323

申请日：2012-12-21

Applicant: MEDICAL RES COUNCIL

Inventor： TZAKOS ANDREAS ,  MAGNANI FRANCESCA

IPC: G01N33/566 ,  A61K38/08 ,  A61P25/00 ,  A61P35/00 ,  C07K7/06 ,  G01N33/74

CPC classification number: C07K7/14 ,  A61K38/085 ,  C07K5/08 ,  C07K7/06 ,  G01N2333/575 ,  G01N2500/10 ,  G06F19/16

Abstract: 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.

Abstract translation: 在过去十年中，出现了大量关于A-GPCR（G蛋白偶联受体）的结构信息。 然而，对于紧密相关的受体亚型的配体选择性的结构和电子基础，例如对相同配体响应而呈现完全不同的生物学功能的血管紧张素受体AT1aR和AT2R的结构和电子学基础知之甚少。 为了监测生物系统中的复杂反应，使用具有选择性梯度的配体是有用的。 在这项研究中，我们提出了一种有效的方法来调节两种血管紧张素II受体亚型，AT1aR和AT2R的配体选择性，通过芳香族电子交替控制血管紧张素II中的芳香 - 脯氨酰相互作用。 基于该策略，获得AT2R选择性和高亲和力激动剂类似物（Ki = 3nM）。

公开(公告)号：WO2011117583A3

公开(公告)日：2012-01-12

申请号：PCT/GB2011000420

申请日：2011-03-23

Applicant: MEDICAL RES COUNCIL ,  CHIN JASON ,  NGUYEN DUY P ,  VIRDEE SATPAL

Inventor： CHIN JASON ,  NGUYEN DUY P ,  VIRDEE SATPAL

IPC: C07K14/00 ,  C12N9/00

CPC classification number: C07K14/4702 ,  C07K1/064 ,  C07K1/065 ,  C07K1/068 ,  C07K1/1075 ,  C07K1/1077 ,  C07K14/435 ,  C12N9/50 ,  C12N9/93 ,  C12P21/02 ,  C12P21/06 ,  Y02P20/55

Abstract: 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).

Abstract translation: 本发明涉及一种修饰包含至少两个赖氨酸残基的多肽中的特定赖氨酸残基的方法，所述方法包括（a）提供包含被第一保护基团保护的靶赖氨酸残基的多肽和至少一种赖氨酸残基 ; （b）处理多肽以保护所述另外的赖氨酸残基，其中所述另外的赖氨酸残基的保护基与靶赖氨酸残基的保护基不同; （c）选择性脱保护目标赖氨酸残基; 和（d）修饰（c）的去保护的赖氨酸残基。

公开(公告)号：WO2010089115A8

公开(公告)日：2011-12-22

申请号：PCT/EP2010000689

申请日：2010-02-04

Applicant: MEDICAL RES COUNCIL ,  WINTER GREGORY PAUL ,  HEINIS CHRISTIAN ,  BERNARD ELISE ,  LOAKES DAVID ,  TITE JOHN PAUL ,  VAYSBURD MARINA ,  TEUFEL DANIEL PAUL ,  RIECHMANN LUTZ

Inventor： WINTER GREGORY PAUL ,  HEINIS CHRISTIAN ,  BERNARD ELISE ,  LOAKES DAVID ,  TITE JOHN PAUL ,  VAYSBURD MARINA ,  TEUFEL DANIEL PAUL ,  RIECHMANN LUTZ

IPC: A61K47/48 ,  G01N33/68

CPC classification number: C12N15/1037 ,  A61K47/55 ,  A61K47/64 ,  A61K47/643 ,  C07K14/001 ,  C12N15/1044 ,  C12N15/1058 ,  C40B40/08 ,  C40B40/10 ,  C40B50/06 ,  G01N33/531

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2011039519A3

公开(公告)日：2011-06-23

申请号：PCT/GB2010001848

申请日：2010-10-01

Applicant: MEDICAL RES COUNCIL UNITED KINGDOM ,  NEUMANN HEINZ ,  CHIN JASON

Inventor： NEUMANN HEINZ ,  CHIN JASON

IPC: C12N9/00 ,  C12P21/02

CPC classification number: C12P21/02 ,  C12N9/93

Abstract: The invention relates to a tRNA synthetase capable of binding Ne-acetyl lysine, wherein said synthetase comprises a polypeptide having at least 90 % sequence identity to the amino acid sequence of MbPyIRS, and wherein said synthetase comprises a L266M mutation.

Abstract translation: 本发明涉及能够结合新乙酰赖氨酸的tRNA合成酶，其中所述合成酶包含与MbPyIRS的氨基酸序列具有至少90％序列同一性的多肽，其中所述合成酶包含L266M突变。

公开(公告)号：WO2010139948A2

公开(公告)日：2010-12-09

申请号：PCT/GB2010001083

申请日：2010-06-02

Applicant: MEDICAL RES COUNCIL ,  UNIV NORTH CAROLINA STATE ,  NGUYEN DUY P ,  NEUMANN HEINZ ,  DEITERS ALEXANDER ,  CHIN JASON ,  LUSIC HRVOJE

Inventor： NGUYEN DUY P ,  NEUMANN HEINZ ,  DEITERS ALEXANDER ,  CHIN JASON ,  LUSIC HRVOJE

IPC: C12N15/70

CPC classification number: C12N15/67 ,  C07C233/49 ,  C07C271/22 ,  C12N9/93 ,  C12P21/02

Abstract: 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.

Abstract translation: 本发明涉及一种制备包含正交官能团的多肽的方法，所述正交官能团由脂肪族氨基酸或氨基酸衍生物构成，所述方法包括提供宿主细胞; 提供编码目的多肽的核酸; 提供与所述宿主细胞正交的tRNA-tRNA合成酶对; 添加包含所述正交官能团的氨基酸或氨基酸衍生物，其中所述氨基酸或氨基酸衍生物是所述正交tRNA合成酶的底物，其中所述氨基酸或氨基酸衍生物具有脂族碳骨架; 并孵育以允许所述氨基酸或氨基酸衍生物通过正交的tRNA-tRNA合成酶对引入目的多肽。 本发明还涉及某些氨基酸，以及包含其的多肽。

公开(公告)号：WO2009010725A3

公开(公告)日：2010-05-27

申请号：PCT/GB2008002387

申请日：2008-07-11

Applicant: MEDICAL RES COUNCIL ,  JONES PHILIP HOWLETT ,  SIMONS BENJAMIN DAVID ,  KLEIN ALLON ,  CAMBRIDGE ENTPR LTD

Inventor： JONES PHILIP HOWLETT ,  SIMONS BENJAMIN DAVID ,  KLEIN ALLON

IPC: G01N33/50 ,  A61K49/00 ,  C12N15/10

CPC classification number: G01N33/5073

Abstract: The invention relates to a method of detecting an altered behaviour in a population of cells, said method comprising determining at least one of the following characteristics of the population of cells; (i) the proportion of stem cells, proliferating cells and differentiated cells in said cell population; or (ii) the size of stem cell clusters in said cell population; or (iii) the separation of stem cell clusters in said cell population; and comparing said at least one characteristic to a reference value, wherein a difference between the determined value and the reference value indicates an altered behaviour in said population of cells. Preferably the cells are mammalian, more preferably human epithelial cells, more preferably human epidermal cells.

Abstract translation: 本发明涉及一种检测细胞群体中改变的行为的方法，所述方法包括确定细胞群体的以下特征中的至少一个; （i）所述细胞群体中干细胞，增殖细胞和分化细胞的比例; 或（ii）所述细胞群体中的干细胞簇的大小; 或（iii）在所述细胞群中分离干细胞簇; 以及将所述至少一个特性与参考值进行比较，其中所述确定值与所述参考值之间的差表示所述细胞群体中的改变的行为。 优选地，细胞是哺乳动物，更优选人上皮细胞，更优选人表皮细胞。

公开(公告)号：WO2009047513A3

公开(公告)日：2009-08-13

申请号：PCT/GB2008003426

申请日：2008-10-08

Applicant: MEDICAL RES COUNCIL ,  MILLAR ROBERT PETER ,  ROSEWEIR ANTONIA KATHRYN

Inventor： MILLAR ROBERT PETER ,  ROSEWEIR ANTONIA KATHRYN

IPC: A61K38/17 ,  C07K7/06 ,  C07K14/72 ,  G01N33/68

CPC classification number: C07K7/08 ,  A61K38/1709 ,  C07K7/06 ,  G01N2500/04

Abstract: The present invention relates to the use of an antagonist of kisspeptin in the manufacture of a medicament for the treatment of a condition induced and/or worsened by kisspeptin activity in an individual. The invention also provides certain defined peptide molecules, which may act as an antagonist of kisspeptin, which are of use in treating a condition induced and/or worsened by kisspeptin activity in an individual. In addition, the invention provides methods of identifying and/or using antagonists of kisspeptin and/or the defined peptides, and pharmaceutical compositions thereof.

Abstract translation: 本发明涉及kisspeptin拮抗剂在制备用于治疗个体中由kisspeptin活性诱导和/或恶化的病症的药物中的用途。 本发明还提供某些定义的肽分子，其可以充当kisspeptin的拮抗剂，其可用于治疗个体中由kisspeptin活性诱导和/或恶化的病症。 此外，本发明提供了鉴定和/或使用kisspeptin和/或定义的肽的拮抗剂的方法及其药物组合物。