公开(公告)号：WO1991002002A1

公开(公告)日：1991-02-21

申请号：PCT/US1990004107

申请日：1990-07-20

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  ATKINSON, John, P.

IPC: C07K15/06

CPC classification number: G01N33/68 ,  A61K38/00 ,  C07K14/705 ,  C07K16/18 ,  C07K16/2896 ,  Y10S530/829

Abstract: Human membrane cofactor protein (MCP), a protein involved in regulation of complement activity, has been purified to homogeneity. The cDNAs encoding six isoforms of this protein have been retreived and permit deduction of the complete amino acid sequences and the recombinant production of proteins with this activity. Pharmaceutical compositions in which MCP is the active ingredient for use in treating autoimmune diseases, antibody preparations for diagnosis, and DNA probes are also disclosed.

Abstract translation: 参与调节补体活性的蛋白质的人膜辅助因子蛋白（MCP）已被纯化至均一性。 已经回收了编码该蛋白质的六种同种型的cDNA，并且可以扣除完整的氨基酸序列和用该活性重组产生蛋白质。 还公开了其中MCP是用于治疗自身免疫疾病的活性成分，用于诊断的抗体制剂和DNA探针的药物组合物。

公开(公告)号：WO1998010294A1

公开(公告)日：1998-03-12

申请号：PCT/US1997015114

申请日：1997-09-03

Applicant: WASHINGTON UNIVERSITY ,  HEINECKE, Jay, W.

Inventor： WASHINGTON UNIVERSITY

IPC: G01N33/68

CPC classification number: G01N33/6893 ,  G01N2800/323 ,  G01N2800/52 ,  Y10S436/811

Abstract: A diagnostic method and screening test for atherosclerosis and analogous diseases involving activated phagocytes and/or inflammation is provided which comprises determining the presence of 3-chlorotyrosine in a test sample of a body fluid or tissue at a level which is elevated relative to the level in a normal patient.

Abstract translation: 提供了关于动脉粥样硬化和涉及活化的吞噬细胞和/或炎症的类似疾病的诊断方法和筛选试验，其包括在体液或组织的测试样品中测定3-氯酪氨酸的含量，其水平相对于 一个正常的病人。

公开(公告)号：WO1998009980A1

公开(公告)日：1998-03-12

申请号：PCT/US1997015872

申请日：1997-09-09

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  KORSMEYER, Stanley, J.

IPC: C07H21/02

CPC classification number: C07K14/4747 ,  C07K2319/00

Abstract: A novel death agonist, BID, which contains only a BH3 domain but not the BH1, BH2, BH4 or membrane anchoring domains found in related BCL-2 family members is provided along with derivatives of BID, bid polynucleotides and derivatives thereof and compositions and uses therefor.

Abstract translation: 提供了一种新颖的死亡激动剂BID，其仅含有相关BCL-2家族成员中发现的BH3结构域而不是BH1，BH2，BH4或膜锚定结构域，以及BID，bid多核苷酸及其衍生物的衍生物，组合物和用途 为此。

公开(公告)号：WO1998001756A1

公开(公告)日：1998-01-15

申请号：PCT/US1997011721

申请日：1997-07-03

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  PIWNICA-WORMS, Helen

IPC: G01N33/53

CPC classification number: C12N9/1205

Abstract: Entry into mitosis requires the activity of the Cdc25C phosphatase which functions to activate Cdc2/Cyclin B. In asynchronously growing cells, Cdc25C is stoichiometrically phosphorylated on serine 216. Levels of serine 216 phosphorylation remain constant throughout the G1-, S- and G2-phases of the cell cycle. A human kinase, denoted TcAK1 (for Twenty-five C Associated protein Kinase) that phosphorylates Cdc25C on serine 216 has been cloned and sequenced (see the figure). A method is also provided for measuring levels of TcAK1 in RNA or of TcAK1 protein in cells. Phosphorylation of Cdc25C on serine 216 with TcAK1 creates a 14-3-3 recognition motif. The interaction between Cdc25C and 14-3-3 proceeds in a phosphorylation-specific manner. TcAK1 functions to mediate interaction between 14-3-3 proteins and other cellular proteins associated with oncogenesis of key signalling events.

Abstract translation: 进入有丝分裂需要用于激活Cdc2 /细胞周期蛋白B的Cdc25C磷酸酶的活性。在异步生长的细胞中，Cdc25C在丝氨酸216上化学计量地磷酸化。丝氨酸216磷酸化水平在整个G1-，S-和G2期保持不变 的细胞周期。 已经克隆并测序了在丝氨酸216上磷酸化Cdc25C的TcAK1（用于二十五个C相关蛋白激酶）的人类激酶（见图）。 还提供了一种用于测量细胞中RNA或TcAK1蛋白中的TcAK1水平的方法。 具有TcAK1的丝氨酸216上的Cdc25C的磷酸化产生了14-3-3识别基序。 Cdc25C和14-3-3之间的相互作用以磷酸化特异性方式进行。 TcAK1介导14-3-3蛋白与其他与关键信号传导事件的肿瘤发生相关的细胞蛋白质之间的相互作用。

公开(公告)号：WO1997047970A1

公开(公告)日：1997-12-18

申请号：PCT/US1997009741

申请日：1997-06-04

Applicant: WASHINGTON UNIVERSITY ,  THE BOARD OF REGENTS OF THE LELAND STANFORD JUNIOR UNIVERSITY ,  BOIME, Irving ,  HSUEH, Aaron, J., W.

Inventor： WASHINGTON UNIVERSITY ,  THE BOARD OF REGENTS OF THE LELAND STANFORD JUNIOR UNIVERSITY

IPC: G01N33/566

CPC classification number: G01N33/74 ,  G01N33/566 ,  G01N33/76 ,  G01N2500/00

Abstract: A method to determine the site of action of a receptor modulating compound is disclosed. The method comprises: a) determining the effect of said compound on a first host cell that has been modified to display a mutant form of said receptor, wherein said mutant produces the activated state of its cognate signaling pathway, wherein said determining comprises measuring the intracellular level of cyclic AMP or other post-binding event; b) determining the effect of said compound on a second host cell that has been modified to display a derivative of said receptor which is formed by coupling an agonist for said receptor covalently to said receptor; wherein said determining comprises measuring the intracellular level of cyclic AMP or other post-binding event; and c) comparing the effect of said compound as determined in steps a) and b); whereby a compound that alters the level of cyclic AMP or downstream event in both a) and b) has a site of action at the binding site for agonists, and a compound that alters the level of cyclic AMP or post-binding event in step a) but not in step b) has a site of action other than at the agonist binding site.

Abstract translation: 公开了确定受体调节化合物的作用位点的方法。 该方法包括：a）确定所述化合物对经修饰以显示所述受体的突变形式的第一宿主细胞的作用，其中所述突变体产生其同源信号通路的活化状态，其中所述测定包括测量细胞内 环AMP或其他后结合事件的水平; b）确定所述化合物对已被修饰以显示所述受体的衍生物的第二宿主细胞的作用，所述受体的衍生物通过将所述受体的激动剂共价偶联到所述受体而形成; 其中所述确定包括测量环AMP或其他后结合事件的细胞内水平; 和c）比较步骤a）和b）中确定的所述化合物的作用; 其中在a）和b）中改变环AMP或下游事件水平的化合物在激动剂的结合位点具有作用位点，以及在步骤a中改变环AMP或结合后事件水平的化合物 ）但不在步骤b）中具有除激动剂结合位点以外的作用位点。

公开(公告)号：WO1997019101A1

公开(公告)日：1997-05-29

申请号：PCT/US1996016671

申请日：1996-10-18

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  WASHINGTON UNIVERSITY

Inventor： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  WASHINGTON UNIVERSITY ,  POT, David, A. ,  WILLIAMS, Lewis, T. ,  JEFFERSON, Anne, Bennett ,  MAJERUS, Philip, W.

IPC: C07K02/00

CPC classification number: C12N9/16 ,  A61K38/00 ,  C07K14/4702 ,  C07K16/18

Abstract: The present invention generally relates to novel GRB2 associating proteins and nucleic acids which encode these proteins. In particular, these novel proteins possess inositol polyphosphate 5-phosphatase and phosphatidylinositol 5-phosphatase activities, important in growth factor mediated signal transduction. As such, the proteins, nucleic acids encoding the proteins, cells capable of expressing these nucleic acids and antibodies specific for these proteins will find a variety of uses in a variety of screening, therapeutic and other applications.

Abstract translation: 本发明一般涉及编码这些蛋白质的新型GRB2缔合蛋白和核酸。 特别地，这些新型蛋白质具有肌醇多磷酸5-磷酸酶和磷脂酰肌醇5-磷酸酶活性，在生长因子介导的信号转导中是重要的。 因此，编码蛋白质的蛋白质，能够表达这些核酸的细胞和对这些蛋白质特异的抗体将在各种筛选，治疗和其它应用中发现多种用途。

公开(公告)号：WO1997017457A2

公开(公告)日：1997-05-15

申请号：PCT/US1996017807

申请日：1996-11-07

Applicant: WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH ,  WASHINGTON UNIVERSITY ,  ORY, Daniel, S. ,  SADELAIN, Michel ,  MULLIGAN, Richard, C. ,  SCHAFFER, Jean, E.

Inventor： WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH ,  WASHINGTON UNIVERSITY

IPC: C12N15/86

CPC classification number: C12N15/86 ,  C12N2740/13052

Abstract: The present invention relates to a stable, pseudotyped retrovirus packaging cell line comprising packaging cells which generate helper-free recombinant pseudotyped retrovirus. The packaging cell line comprises one or more non-retroviral expression constructs, such as an expression construct with the human cytomegalovirus (CMV) immediate early promoter or derivatives of this promoter (e.g., pMD), which direct expression of: (a) retroviral gagpol genes and (b) a non-retroviral gene which is under the control of an inducible operator system and whose gene product pseudotypes retroviral core virions. The present invention further relates to a method of making a stable, pseudotyped retrovirus packaging cell line which generates helper-free recombinant pseudotyped retrovirus. The present invention further relates to the particular packaging cell lines described herein (i.e., H29 gagpol, H29 new gagpol) and the particular cells and constructs (i.e., packaging elements) used to produce the stable, pseudotyped retrovirus packaging cell line described herein (e.g., H29 cells and pMD, pMDtet, pMDtet.G, PMD.gagpol, pMD.new gagpol constructs). The present invention relates to a retroviral vector for producing a cDNA library for expression in mammalian cells, comprising two retroviral long terminal repeats, a cloning site for insertion of cDNA and a cytomegalovirus promoter. The invention also relates to a cDNA library for expression in mammalian cells, the library comprising retroviral vectors of the present invention. The present invention also relates to a method of expression cloning in mammalian cells. The present invention also relates to a method of cDNA expression cloning in mammalian cells. The present invention also relates to a method of identifying a gene defect responsible for a mutant phenotype using cDNA expression cloning by complementation in mammalian cells.

Abstract translation: 本发明涉及稳定的假型逆转录病毒包装细胞系，其包含产生无辅助重组假型逆转录病毒的细胞。 包装细胞系包含一个或多个非逆转录病毒表达构建体，例如具有人巨细胞病毒（CMV）立即早期启动子或该启动子的衍生物（例如，pMD）的表达构建体，其直接表达：（a）逆转录病毒gagpol 基因和（b）非诱导型操纵子系统控制下的非逆转录病毒基因，其基因产物假型为逆转录病毒核心病毒粒子。 本发明还涉及制备稳定的假型逆转录病毒包装细胞系的方法，该细胞系产生无辅助重组假型逆转录病毒。 本发明还涉及本文所述的特定包装细胞系（即，H29加格尔波尔，H29新加格尔）以及用于产生本文所述的稳定的假型逆转录病毒包装细胞系的特定细胞和构建体（即包装元件）（例如， ，H29细胞和pMD，pMDtet，pMDtet.G，PMD.gagpol，pMD.新的gagpol构建体）。 本发明涉及用于产生用于在哺乳动物细胞中表达的cDNA文库的逆转录病毒载体，其包含两个逆转录病毒长末端重复序列，用于插入cDNA的克隆位点和巨细胞病毒启动子。 本发明还涉及用于在哺乳动物细胞中表达的cDNA文库，该文库包含本发明的逆转录病毒载体。 本发明还涉及在哺乳动物细胞中表达克隆的方法。 本发明还涉及哺乳动物细胞中cDNA表达克隆的方法。 本发明还涉及使用哺乳动物细胞中互补的cDNA表达克隆来鉴定负责突变体表型的基因缺陷的方法。

公开(公告)号：WO1997012609A1

公开(公告)日：1997-04-10

申请号：PCT/IB1996001183

申请日：1996-09-25

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  CHOI, Dennis, Wonkyu ,  HEWETT, Sandra, Jeanne

IPC: A61K31/245

CPC classification number: A61K31/196 ,  A61K31/245

Abstract: The present invention comprises the use of a compound of formulae (I), (II), or (III) for reducing glutamate neurotoxicity, and medicaments, containing said compounds, for the treatment of neurotoxic injury; wherein R1 is halogen or methyl; R2 is halogen, lower alkyl, lower alkoxy, benzyloxy or beta , beta , beta -trifluoroethoxy wherein at least one of R1 and R2 are halogen; R3 is hydrogen, halogen or methyl; M is hydrogen, a pharmaceutically acceptable cation or lower-alkyl; more particularly meclofenamate sodium and tolfenamate sodium; wherein R4 is lower alkyl; more particularly mefenamate sodium; more particularly flufenamate sodium, their pharmaceutically acceptable salts and pharmaceutically acceptable esters, inhibit glutamate-induced neurotoxicity.

Abstract translation: 本发明包括使用式（I），（II）或（III）的化合物来降低谷氨酸神经毒性，以及含有所述化合物的药物用于治疗神经毒性损伤; 其中R1是卤素或甲基; R2是卤素，低级烷基，低级烷氧基，苄氧基或β，β，β-三氟乙氧基，其中R1和R2中的至少一个是卤素; R3是氢，卤素或甲基; M是氢，药学上可接受的阳离子或低级烷基; 更特别是麦芽酚酸钠和苯丙芬酸钠; 其中R4是低级烷基; 更特别是甲磺酸钠; 更特别是氟丙胺酸钠，其药学上可接受的盐和药学上可接受的酯抑制谷氨酸诱导的神经毒性。

公开(公告)号：WO1997007122A3

公开(公告)日：1997-02-27

申请号：PCT/US1996013027

申请日：1996-08-09

Applicant: WASHINGTON UNIVERSITY ,  NEWTON SCIENTIFIC, INC.

Inventor： WASHINGTON UNIVERSITY ,  NEWTON SCIENTIFIC, INC. ,  WELCH, Michael, J. ,  McCARTHY, Deborah, W. ,  SHEFER, Ruth ,  KLINKOWSTEIN, Robert, E.

IPC: G21G01/10

公开(公告)号：WO1996024663A1

公开(公告)日：1996-08-15

申请号：PCT/US1996000319

申请日：1996-01-29

Applicant: WASHINGTON UNIVERSITY ,  LEIB, David, A.

Inventor： WASHINGTON UNIVERSITY

IPC: C12N07/01

CPC classification number: A61K39/245 ,  A61K39/12 ,  C12N7/00 ,  C12N2710/16034 ,  C12N2710/16634 ,  Y10S435/948

Abstract: A herpes simplex virus (HSV) mutant, UL41NHB, is disclosed which is deficient in the virion host shutoff ( vhs ) function. This mutant is shown to be profoundly attenuated in its ability to replicate at the periphery and in the nervous system, and in its ability to reactivate from latency.

Abstract translation: 公开了一种单病毒病毒（HSV）突变体UL41NHB，其缺乏病毒体宿主关闭（vhs）功能。 显示出这种突变体在外周和神经系统中复制的能力以及其从潜伏期重新激活的能力被深刻地减弱。