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    HUMAN METABOTROPIC GLUTAMATE RECEPTORS, NUCLEIC ACIDS ENCODING SAME AND USES THEREOF
    3.
    发明申请
    HUMAN METABOTROPIC GLUTAMATE RECEPTORS, NUCLEIC ACIDS ENCODING SAME AND USES THEREOF 审中-公开
    人类代谢谷氨酸受体，编码其的核酸及其用途

    公开(公告)号：WO1994029449A1

    公开(公告)日：1994-12-22

    申请号：PCT/US1994006273

    申请日：1994-06-03

    Applicant: THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ASSOCIATES, INC. ,  DAGGETT, Lorrie ,  ELLIS, Steven, B. ,  LIAW, Chen ,  PONTSLER, Aaron ,  JOHNSON, Edwin, C. ,  HESS, Stephen, D.

    Inventor： THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ASSOCIATES, INC.

    IPC: C12N15/12

    CPC classification number: G01N33/5091 ,  A01K2217/05 ,  C07K14/70571 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5058 ,  G01N2333/70571

    Abstract: In accordance with the present invention, there are provided nucleic acids encoding human metabotropic glutamate receptor subtypes and the proteins encoded thereby. In a particular embodiment, the invention nucleic acids encode mGluR1, mGluR2, mGluR3 and mGluR5 subtypes of human metabotropic glutamate receptors. In addition to being useful for the production of metabotropic glutamate receptor subtypes, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits. In addition to disclosing novel metabotropic glutamate receptor subtypes, the present invention also comprises methods for using such receptor subtypes to identify and characterize compounds which affect the function of such receptors, e.g., agonists, antagonists, and modulators of glutamate receptor function.

    Abstract translation: 根据本发明，提供了编码人代谢型谷氨酸受体亚型的核酸和由此编码的蛋白质。 在一个具体实施方案中，本发明的核酸编码人代谢型谷氨酸受体的mGluR1，mGluR2，mGluR3和mGluR5亚型。 除了可用于代谢型谷氨酸受体亚型的生产之外，这些核酸也可用作探针，因此使得本领域技术人员无需过多的实验来鉴定和分离相关的人受体亚单位。 除了揭示新型代谢型谷氨酸受体亚型之外，本发明还包括使用这种受体亚型来鉴定和表征影响这些受体功能的化合物的方法，例如激动剂，拮抗剂和谷氨酸受体功能的调节剂。

    HUMAN N-METHYL-D-ASPARTATE RECEPTOR SUBUNITS, NUCLEIC ACIDS ENCODING SAME AND USES THEREFOR
    4.
    发明申请
    HUMAN N-METHYL-D-ASPARTATE RECEPTOR SUBUNITS, NUCLEIC ACIDS ENCODING SAME AND USES THEREFOR 审中-公开
    人类N-甲基-D-孕激素受体亚型，编码其的核酸及其用途

    公开(公告)号：WO1994024284A1

    公开(公告)日：1994-10-27

    申请号：PCT/US1994004387

    申请日：1994-04-20

    Applicant: THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ASSOCIATES, INC. ,  DAGGETT, Lorrie, P. ,  ELLIS, Steven, B. ,  LIAW, Chen, Wang ,  LU, Chin-Chun

    Inventor： THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ASSOCIATES, INC.

    IPC: C12N15/12

    CPC classification number: G01N33/5008 ,  A01K2217/05 ,  A61K38/00 ,  C07K14/70571 ,  G01N33/502 ,  G01N33/5041 ,  G01N33/5058 ,  G01N33/5091 ,  G01N33/6872 ,  G01N2333/70571

    Abstract: In accordance with the present invention, there are provided nucleic acids encoding human NMDA receptor protein subunits and the proteins encoded thereby. The NMDA receptor subunits of the invention comprise components of NMDA receptors that have cation-selective channels and bind glutamate and NMDA. In one aspect of the invention, the nucleic acids encode NMDAR1 and NMDAR2 subunits of human NMDA receptors. In a preferred embodiment, the invention nucleic acids encode NMDAR1, NMDAR2A, NMDAR2B, NMDAR2C and NMDAR2D subunits of human NMDA receptors. In addition to being useful for the production of NMDA receptor proteins subunit, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits. Functional glutamate receptors can be assembled, in accordance with the present invention, from a plurality of one type of NMDA receptor subunit protein (homomeric) or from a mixture of two or more types of subunit proteins (heteromeric). In addition to disclosing novel NMDA receptor protein subunits, the present invention also comprises methods for using such receptor subunits to identify and characterize compounds which affect the function of such receptors, e.g., agonists, antagonists, and modulators of glutamate receptor function. The invention also comprises methods for determining whether unknown protein(s) are functional as NMDA receptor subunits.

    Abstract translation: 根据本发明，提供了编码人NMDA受体蛋白质亚基的核酸和由此编码的蛋白质。 本发明的NMDA受体亚基包含具有阳离子选择性通道并结合谷氨酸和NMDA的NMDA受体的组分。 在本发明的一个方面，核酸编码人NMDA受体的NMDAR1和NMDAR2亚基。 在优选的实施方案中，本发明核酸编码人NMDA受体的NMDAR1，NMDAR2A，NMDAR2B，NMDAR2C和NMDAR2D亚基。 除了可用于制备NMDA受体蛋白亚基之外，这些核酸也可用作探针，因此使得本领域技术人员无需过多的实验来鉴定和分离相关的人受体亚单位。 功能性谷氨酸受体可以根据本发明从多种一种NMDA受体亚基蛋白（同型）或两种或更多种亚基蛋白（异聚体）的混合物组装。 除了公开新的NMDA受体蛋白质亚基之外，本发明还包括使用这些受体亚基来鉴定和表征影响这些受体功能的化合物的方法，例如激动剂，拮抗剂和谷氨酸受体功能的调节剂。 本发明还包括用于确定未知蛋白质是否作为NMDA受体亚基起作用的方法。

    MIXED FEED RECOMBINANT YEAST FERMENTATION
    6.
    发明申请
    MIXED FEED RECOMBINANT YEAST FERMENTATION 审中-公开
    混合饲料重组酵母发酵

    公开(公告)号：WO1990003431A1

    公开(公告)日：1990-04-05

    申请号：PCT/US1989004164

    申请日：1989-09-25

    Applicant: THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ...

    Inventor： THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ... ,  BRIERLEY, Russell, Arthur ,  SIEGEL, Robert, Steven ,  BUSSINEAU, Christopher, Michael ,  CRAIG, William, Scot ,  HOLTZ, Gregory, Clyde ,  DAVIS, Geneva, Ruth ,  BUCKHOLZ, Richard, Gordon ,  THILL, Gregory, Patrick ,  WONDRACK, Lillian, Margaret ,  DIGAN, Mary, Ellen ,  HARPOLD, Michael, Miller ,  LAIR, Stephen, Vernon ,  ELLIS, Steven, Bradley ,  WILLIAMS, Mark, Edward

    IPC: C12N05/00

    CPC classification number: C12N9/0089 ,  C07K14/485 ,  C12N9/2462 ,  C12N15/815

    Abstract: The invention provides a method of increasing the production of a recombinant gene product from a culture of a recombinant methylotrophic yeast host, wherein said product is made by expression from a recombinant gene sequence operably associated with a methanol-responsive expression control element. In the method of the invention, the methylotrophic yeast host is first cultured on a medium with a high concentration of multi-carbon, carbon-source nutriment, such as glycerol, but with little or no methanol, in order to increase the density of the host cells with little or no expression of the recombinant gene product. When the host cells have achieved a suitable density in the culture medium, the culture is subjected to a phase during which the concentration of multi-carbon, carbon-source nutriments is maintained sufficiently low that the methanol-responsive control element controlling expression of the recombinant gene encoding the desired product is derepressed. Finally, the culture is subjected to a phase of high production of the recombinant gene product by increasing the concentration of methanol while maintaining the concentration of multi-carbon, carbon-source nutriments at a low level. The invention is illustrated with production, using Pichia pastoris, of bovine lysozyme c2, human lysozyme, human epidermal growth factors (1-52) and (1-48), and human superoxide dismutase.

    Abstract translation: 本发明提供了从重组甲基营养酵母宿主的培养物中增加重组基因产物的产生的方法，其中所述产物通过与甲醇应答表达控制元件可操作地相关的重组基因序列的表达来制备。 在本发明的方法中，甲基营养酵母宿主首先在具有高浓度多碳，碳源营养物质的甘油，但几乎不用甲醇或不含甲醇的培养基上培养，以增加其浓度 具有很少或没有表达重组基因产物的宿主细胞。 当宿主细胞在培养基中达到合适的密度时，培养物经历一个阶段，在此阶段，多碳，碳源营养物质的浓度保持足够低，以致控制重组体的表达的甲醇应答控制元件 编码所需产物的基因是去除的。 最后，通过提高甲醇的浓度，同时保持多碳，碳源营养浓度低的水平，使培养物进入高产量的重组基因产物。 使用巴斯德毕赤酵母，牛溶菌酶c2，人溶菌酶，人表皮生长因子（1-52）和（1-48）和人超氧化物歧化酶的生产说明本发明。

    PRODUCTION OF INTERLEUKIN-2 POLYPEPTIDES IN PICHIA PASTORIS YEAST CELLS
    7.
    发明申请
    PRODUCTION OF INTERLEUKIN-2 POLYPEPTIDES IN PICHIA PASTORIS YEAST CELLS 审中-公开
    在PICHIA PASTORIS YEAST细胞中生产INTERLEUKIN-2多糖

    公开(公告)号：WO1990002810A1

    公开(公告)日：1990-03-22

    申请号：PCT/US1989003864

    申请日：1989-09-07

    Applicant: THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ...

    Inventor： THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ... ,  DAVIS, Geneva, Ruth ,  VELICELEBI, Gonul

    IPC: C12P21/00

    CPC classification number: C07K14/55 ,  C12N15/815

    Abstract: This invention relates to a process of recombinant DNA technology and means for producing polypeptides having Interleukin-2 (IL-2) activity in Pichia pastoris (P. pastoris) yeast cells. In another aspect, the invention relates to a process for extracting a polypeptide having IL-2 activity from P. pastoris cells. IL-2 is a naturally-occurring polypeptide that has a great potential in treatment of immunological disorders, bacterial or viral infections and other severe clinical conditions.

    Abstract translation: 本发明涉及重组DNA技术的方法和用于产生在巴斯德毕赤酵母（巴斯德毕赤酵母）酵母细胞中具有白细胞介素-2（IL-2）活性的多肽的方法。 另一方面，本发明涉及从巴斯德毕赤酵母细胞中提取具有IL-2活性的多肽的方法。 IL-2是一种天然存在的多肽，在治疗免疫疾病，细菌或病毒感染和其他严重临床病症方面具有很大的潜力。

    HUMAN NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR COMPOSITIONS AND METHODS EMPLOYING SAME
    9.
    发明申请
    HUMAN NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR COMPOSITIONS AND METHODS EMPLOYING SAME 审中-公开
    人神经酰胺类乙酰胆碱受体组合物及其使用方法

    公开(公告)号：WO1994020617A2

    公开(公告)日：1994-09-15

    申请号：PCT/US1994002447

    申请日：1994-03-08

    Applicant: THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ASSOCIATES, INCORPORATED ,  ELLIOTT, Kathryn, J. ,  ELLIS, Steven, B. ,  HARPOLD, Michael, M.

    Inventor： THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ASSOCIATES, INCORPORATED

    IPC: C12N15/12

    CPC classification number: C07K14/70571

    Abstract: Nucleic acids encoding human neuronal nicotinic acetylcholine receptor alpha and beta subunits, mammalian and amphibian cells containing said nucleic acids, methods for producing alpha and beta subunits and recombinant (i.e., isolated or substantially pure) alpha subunits (specifically alpha 4 and alpha 7) and beta subunits (specifically beta 4) are provided. In addition, combinations of subunits (i.e., alpha 1, alpha 2, alpha 3, alpha 4, and/or alpha 7 subunits in combination with beta 4 subunits; or beta 2, beta 3 and/or beta 4 subunits in combination with alpha 4 and/or alpha 7 subunits) are provided.

    Abstract translation: 编码人神经元烟碱乙酰胆碱受体α和β亚基的核酸，含有所述核酸的哺乳动物和两栖动物细胞，用于产生α和β亚基和重组（即，分离或基本上纯的）α亚基（特别是α4和α7）的方法和 提供β亚基（特别是beta 4）。 此外，亚单位（即α1，α2，α3，α4和/或α7亚基与β4亚基组合;或β2，β3和/或β4亚基与α组合） 4和/或α7亚基）。

    AUTOMATED ANALYSIS EQUIPMENT AND ASSAY METHOD FOR DETECTING CELL SURFACE PROTEIN AND/OR CYTOPLASMIC RECEPTOR FUNCTION USING SAME
    10.
    发明申请
    AUTOMATED ANALYSIS EQUIPMENT AND ASSAY METHOD FOR DETECTING CELL SURFACE PROTEIN AND/OR CYTOPLASMIC RECEPTOR FUNCTION USING SAME 审中-公开
    用于检测细胞表面蛋白和/或CYPOPLASMIC受体功能的自动分析设备和测定方法

    公开(公告)号：WO1993013423A1

    公开(公告)日：1993-07-08

    申请号：PCT/US1992011090

    申请日：1992-12-18

    Applicant: THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ... ,  AKONG, Michael, Anthony ,  HARPOLD, Michael, Miller ,  VELICELEBI, Gonul ,  BRUST, Paul

    Inventor： THE SALK INSTITUTE BIOTECHNOLOGY/INDUSTRIAL ...

    IPC: G01N35/02

    CPC classification number: G01N33/6872 ,  G01N21/6428 ,  G01N21/6452 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5058 ,  G01N35/028 ,  G01N35/109 ,  G01N2035/042 ,  G01N2333/705 ,  G01N2500/00 ,  Y10S436/80 ,  Y10S436/807 ,  Y10S436/809 ,  Y10T436/11 ,  Y10T436/115831

    Abstract: Highly efficient automated measurement apparatus and methods for automated drug screening procedures are provided. The apparatus is capable of initiating and measuring rapid or transient events such as cell receptor and/or ion channel activity. The apparatus of the invention is capable of aligning with predetermined positions, one or more samples contained in a multi-well container, initiating the reaction with reagent addition and measuring a resultant attribute for a period of time. The apparatus is capable of substantially continuously measuring and recording data corresponding to the measured attribute before, during and after initiation of the reaction so that a time course of the rapid or transient event may be determined. After the reaction(s) are complete in one or more wells of the multi-well container, the apparatus can align one or more different wells to be assayed with the predetermined position and repeat the cycle until a predetermined number of wells are assayed. Automated drug screening methods employing the apparatus are also provided for screening for compounds which activate, inhibit or potentiate cellular ion channel or receptor activity. The assays are fluorescent indicator-based assays which utilize viable cells containing in their cytoplasm effective levels of a fluorescent indicator which is responsive to changes in ion concentration. Activation of the ion channels or receptors is initiated in the automated measurement apparatus by injection into one or more predetermined cell-containing wells of a reagent which is a known or putative activator of the ion channels or receptors of interest. The resultant activity of the ion channels or receptors (which causes changes in ion concentration in the cytoplasm) is determined by measurement of fluorescence intensity changes of the indicator in response to an excitation wavelength.

    Abstract translation: 提供了高效的自动化测量装置和自动化药物筛选程序的方法。 该装置能够启动和测量诸如细胞受体和/或离子通道活性的快速或瞬时事件。 本发明的装置能够与预定位置对齐，一个或多个样品包含在多孔容器中，开始反应，加入试剂并测量所得到的属性一段时间。 该装置能够在反应开始之前，期间和之后基本上连续地测量和记录对应于测量属性的数据，使得可以确定快速或瞬态事件的时间过程。 在多孔容器的一个或多个孔中的反应完成之后，该装置可以将待测定的一个或多个不同孔与预定位置对准，并重复循环，直到测定预定数量的孔。 还提供了使用该装置的自动药物筛选方法，用于筛选激活，抑制或增强细胞离子通道或受体活性的化合物。 该测定法是基于荧光指示剂的测定法，其利用在其细胞质中含有对离子浓度变化有反应的荧光指示剂的有效水平的活细胞。 离子通道或受体的激活在自动化测量装置中通过注射到一个或多个预定的含有细胞的孔中，该试剂是已知或推定的感兴趣的离子通道或受体的激活剂。 通过测量响应于激发波长的指示剂的荧光强度变化来确定离子通道或受体（其引起细胞质中离子浓度变化）的所得活性。

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