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    Assay systems for trkB neurotrophin activity
    1.
    发明授权
    Assay systems for trkB neurotrophin activity 失效
    trkB神经营养因子活性检测系统

    公开(公告)号：US5622862A

    公开(公告)日：1997-04-22

    申请号：US339578

    申请日：1994-11-14

    申请人： Stephen P. Squinto ,  David Glass ,  Thomas H. Aldrich ,  Peter DiStefano ,  Trevor Stitt ,  Mark E. Furth ,  George D. Yancopoulos

    发明人： Stephen P. Squinto ,  David Glass ,  Thomas H. Aldrich ,  Peter DiStefano ,  Trevor Stitt ,  Mark E. Furth ,  George D. Yancopoulos

    IPC分类号： A61K38/00 ,  C07K14/71 ,  C12N15/00 ,  C12N5/10

    CPC分类号： C07K14/71 ,  A61K38/00 ,  G01N2333/475

    摘要： The present invention provides for assay systems that may be used to detect and/or measure neurotrophin activity or to identify agents that exhibit neurotrophin-like activity, and for methods of using such assay systems. It is based, at least in part, on the discovery that the trkB protooncogene encodes a tyrosine kinase receptor that may serve as a functional binding protein for BDNF and NT-3. Such assay systems may be of particular value in identifying new neurotrophins or agents with neurotrophin-like activity. In various embodiments, the assay systems and methods of the invention may be used to detect and/or measure the binding of neurotrophin to trkB, either using direct binding studies or the detection of the secondary affects of trkB/neurotrophin binding. The present invention also has diagnostic and therapeutic utilities. In particular embodiments of the invention, methods of detecting aberrancies in trkB function or expression may be used in the diagnosis of neurological disorders. In other embodiments, manipulation of the trkB/neurotrophin interaction may be used in the treatment of neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease).

    摘要翻译： 本发明提供了可用于检测和/或测量神经营养因子活性或鉴定表现出神经营养因子样活性的试剂的测定系统，以及使用该测定系统的方法。 至少部分基于trkB原癌基因编码可能作为BDNF和NT-3的功能性结合蛋白的酪氨酸激酶受体的发现。 鉴定新的神经营养蛋白或具有神经营养蛋白样活性的药剂时，这种测定系统可能是特别有价值的。 在各种实施方案中，本发明的测定系统和方法可以用于使用直接结合研究或trkB /神经营养因子结合的次级影响的检测来检测和/或测量神经营养因子与trkB的结合。 本发明还具有诊断和治疗用途。 在本发明的具体实施方案中，检测trkB功能或表达异常的方法可用于诊断神经障碍。 在其它实施方案中，trkB /神经营养因子相互作用的操作可用于治疗神经障碍，包括阿尔茨海默病，帕金森氏病和肌萎缩性侧索硬化（Lou Gehrig's disease）。

    Method for screening comprising cells expressing the CNTF receptor
    2.
    发明授权
    Method for screening comprising cells expressing the CNTF receptor 失效
    筛选方法包括表达CNTF受体的细胞

    公开(公告)号：US06316206B1

    公开(公告)日：2001-11-13

    申请号：US09211590

    申请日：1998-12-14

    申请人： Samuel Davis ,  Stephen P. Squinto ,  Mark E. Furth ,  George D. Yancopoulos

    发明人： Samuel Davis ,  Stephen P. Squinto ,  Mark E. Furth ,  George D. Yancopoulos

    IPC分类号： G01N3353

    CPC分类号： C07K14/705 ,  A61K38/00 ,  C07K14/70571 ,  C07K2319/00 ,  C12Q1/6883 ,  C12Q2600/158

    摘要： The present invention relates to the ciliary neurotrophic factor (CNTF) receptor, and provides for CNTF receptor nucleic acid and amino acid sequences. It also relates to (i) assay systems for detecting CNTF activity; (ii) experimental model systems for studying the physiologic role of CNTF; (ii) diagnostic techniques for identifying CNTF-related neurologic conditions; (iv) therapeutic techniques for the treatment of CNTF-related neurologic and muscular conditions, and (v) methods for identifying molecules homologous to CNTF and CNTFR.

    摘要翻译： 本发明涉及睫状神经营养因子（CNTF）受体，并提供CNTF受体核酸和氨基酸序列。 它还涉及（i）用于检测CNTF活性的测定系统; （ii）研究CNTF生理作用的实验模型系统; （ii）用于鉴定CNTF相关神经病症的诊断技术; （iv）用于治疗CNTF相关神经和肌肉病症的治疗技术，以及（v）用于鉴定与CNTF和CNTFR同源的分子的方法。

    Ciliary neurotrophic factor receptor
    4.
    发明授权
    Ciliary neurotrophic factor receptor 失效
    睫状神经营养因子受体

    公开(公告)号：US5426177A

    公开(公告)日：1995-06-20

    申请号：US676647

    申请日：1991-03-28

    申请人： Samuel Davis ,  Stephen P. Squinto ,  Mark E. Furth ,  George D. Yancopoulos

    发明人： Samuel Davis ,  Stephen P. Squinto ,  Mark E. Furth ,  George D. Yancopoulos

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C12Q1/68

    CPC分类号： C12Q1/6883 ,  C07K14/705 ,  A61K38/00 ,  C07K2319/00 ,  C12Q2600/158 ,  Y10S530/839

    摘要： The present invention relates to the ciliary neurotrophic factor (CNTF) receptor, and provides for CNTF receptor nucleic acid and amino acid sequences. It also relates to (i) assay systems for detecting CNTF activity; (ii) experimental model systems for studying the physiologic role of CNTF; (ii) diagnostic techniques for identifying CNTF-related neurologic conditions; (iv) therapeutic techniques for the treatment of CNTF-related neurologic and muscular conditions, and (v) methods for identifying molecules homologous to CNTF and CNTFR.

    摘要翻译： 本发明涉及睫状神经营养因子（CNTF）受体，并提供CNTF受体核酸和氨基酸序列。 它还涉及（i）用于检测CNTF活性的测定系统; （ii）研究CNTF生理作用的实验模型系统; （ii）用于鉴定CNTF相关神经病症的诊断技术; （iv）用于治疗CNTF相关神经和肌肉病症的治疗技术，以及（v）用于鉴定与CNTF和CNTFR同源的分子的方法。

    Multitrophic and multifunctional chimeric neurotrophic factors, and nucleic acids and plasmids encoding the chimeras
    7.
    发明授权
    Multitrophic and multifunctional chimeric neurotrophic factors, and nucleic acids and plasmids encoding the chimeras 失效
    多功能和多功能基本神经营养因子，以及编码CHIMERAS的核酸和等离子体

    公开(公告)号：US5169764A

    公开(公告)日：1992-12-08

    申请号：US564929

    申请日：1990-08-08

    申请人： Eric M. Shooter ,  Ulrich Suter ,  Nancy Ip ,  Stephen P. Squinto ,  Mark E. Furth ,  Ronald M. Lindsay ,  George D. Yancopoulos

    发明人： Eric M. Shooter ,  Ulrich Suter ,  Nancy Ip ,  Stephen P. Squinto ,  Mark E. Furth ,  Ronald M. Lindsay ,  George D. Yancopoulos

    IPC分类号： A61K38/00 ,  A61K38/22 ,  A61P25/00 ,  C07K14/00 ,  C07K14/475 ,  C07K14/48 ,  C07K14/52 ,  C07K14/82 ,  C07K19/00 ,  C12N15/00 ,  C12N15/16 ,  C12N15/18 ,  C12P21/02 ,  C12Q1/68

    CPC分类号： C07K14/475 ,  C07K14/48 ,  C07K14/82 ,  C12Q1/6876 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/41 ,  C07K2319/75 ,  Y10S530/839 ,  Y10S930/12

    摘要： The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors. Chimeric neurotrophic factors may be used to provide, for example, the activity of two neurotrophic factors in a single molecule, or may serve as superagonists of an endogenous neurotrophic factor, thereby enabling an increased biological response at lower doses. Nucleic acids and plasmids encoding the chimeras are disclosed.

    摘要翻译： 本发明涉及嵌合神经营养因子，其包含至少一部分天然存在的细胞因子和至少一种其它分子的一部分，使得所得的嵌合分子具有神经营养活性。 其部分基于以下发现：包含NGF和BDNF两部分的嵌合分子可能具有神经营养活性，并且在一些情况下表现出比任一亲本分子更大的活性谱。 进一步基于以下发现：包含神经营养因子序列以及另外的肽序列的嵌合分子可以保留神经营养活性，并且在一些情况下可能表现出比母体因子更有效的活性。 本发明的嵌合神经营养因子分子相对于天然存在的神经营养因子提供了许多优点。 嵌合神经营养因子可用于提供例如单个分子中的两种神经营养因子的活性，或者可以作为内源性神经营养因子的增生因子，从而能够以较低剂量增加生物反应。 公开了编码嵌合体的核酸和质粒。

    Multitrophic and multifunctional chimeric neurotrophic factors
    8.
    发明授权
    Multitrophic and multifunctional chimeric neurotrophic factors 失效
    多功能和多功能嵌合神经营养因子

    公开(公告)号：US5512661A

    公开(公告)日：1996-04-30

    申请号：US308625

    申请日：1994-09-19

    申请人： Eric M. Shooter ,  Ulrich Suter ,  Nancy P. Ip ,  Stephen P. Squinto ,  Mark E. Furth ,  Ronald M. Lindsay

    发明人： Eric M. Shooter ,  Ulrich Suter ,  Nancy P. Ip ,  Stephen P. Squinto ,  Mark E. Furth ,  Ronald M. Lindsay

    IPC分类号： A61K38/00 ,  A61K38/22 ,  A61P25/00 ,  C07K14/00 ,  C07K14/475 ,  C07K14/48 ,  C07K14/52 ,  C07K14/82 ,  C07K19/00 ,  C12N15/00 ,  C12N15/16 ,  C12N15/18 ,  C12P21/02 ,  C12Q1/68

    CPC分类号： C07K14/475 ,  C07K14/48 ,  C07K14/82 ,  C12Q1/6876 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/41 ,  C07K2319/75 ,  Y10S530/839 ,  Y10S930/12

    摘要： The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors. Chimeric neurotrophic factors may be used to provide, for example, the activity of two neurotrophic factors in a single molecule, or may serve as superagonists of an endogenous neurotrophic factor, thereby enabling an increased biological response at lower doses.

    摘要翻译： 本发明涉及嵌合神经营养因子，其包含至少一部分天然存在的细胞因子和至少一种其它分子的一部分，使得所得的嵌合分子具有神经营养活性。 其部分基于以下发现：包含NGF和BDNF两部分的嵌合分子可能具有神经营养活性，并且在一些情况下表现出比任一亲本分子更大的活性谱。 进一步基于以下发现：包含神经营养因子序列以及另外的肽序列的嵌合分子可以保留神经营养活性，并且在一些情况下可能表现出比母体因子更有效的活性。 本发明的嵌合神经营养因子分子相对于天然存在的神经营养因子提供了许多优点。 嵌合神经营养因子可用于提供例如单个分子中的两种神经营养因子的活性，或者可以作为内源性神经营养因子的增生因子，从而能够以较低剂量增加生物反应。

    Retroviral vector particles expressing complement inhibitor activity
    9.
    发明授权
    Retroviral vector particles expressing complement inhibitor activity 失效
    表达补体抑制剂活性的逆转录病毒载体颗粒

    公开(公告)号：US5643770A

    公开(公告)日：1997-07-01

    申请号：US278630

    申请日：1994-07-21

    申请人： James M. Mason ,  Stephen P. Squinto

    发明人： James M. Mason ,  Stephen P. Squinto

    IPC分类号： A61K48/00 ,  C12N15/48 ,  C12N15/867 ,  C12N15/86 ,  C07K14/15

    CPC分类号： C12N15/86 ,  C07K14/005 ,  A61K48/00 ,  C12N2740/13022 ,  C12N2740/13043

    摘要： Modified retroviral vector particles and modified retroviral producer cells producing such particles are provided for facilitating gene therapy procedures involving the transduction of target cells with retroviral vector particles in the presence of complement containing body fluids. The modifications involve genetic alterations to effect the expression by these cells and particles of complement inhibitor activity. The genetic alterations involve the introduction of nucleic acid expression constructs directing the expression of retroviral SU(gp70)/complement inhibitor chimeric proteins into cells from which the producer cells are derived.

    摘要翻译： 提供了产生这种颗粒的修饰的逆转录病毒载体颗粒和修饰的逆转录病毒产生细胞，用于促进涉及在含补体的体液存在下用逆转录病毒载体颗粒转导靶细胞的基因治疗方法。 修饰涉及遗传改变以影响这些细胞和补体抑制剂活性颗粒的表达。 遗传改变涉及将逆转录病毒SU（gp70）/补体抑制剂嵌合蛋白的表达引入导入生产细胞的细胞中的核酸表达构建体。

    Retroviral transduction of cells using soluble complement inhibitors
    10.
    发明授权
    Retroviral transduction of cells using soluble complement inhibitors 失效
    使用可溶性补体抑制剂逆转录病毒转导细胞

    公开(公告)号：US5562904A

    公开(公告)日：1996-10-08

    申请号：US278550

    申请日：1994-07-21

    申请人： Russell P. Rother ,  Scott A. Rollins ,  James M. Mason ,  Stephen P. Squinto

    发明人： Russell P. Rother ,  Scott A. Rollins ,  James M. Mason ,  Stephen P. Squinto

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K39/395 ,  A61K45/00 ,  A61K48/00 ,  A61P43/00 ,  C07K16/18 ,  C12P21/08 ,  B61K39/395

    CPC分类号： C07K16/18 ,  A61K38/00

    摘要： Methods and compositions are provided for facilitating gene therapy procedures involving the transduction of target cells with retroviral vector particles in the presence of complement containing body fluids. The administration of soluble complement inhibitor molecules to body fluids prevents the complement mediated inactivation of the retroviral vector particles, and provides a safety mechanism for such gene therapy procedures, as the action of soluble complement inhibitors is transient, and any retroviral vector particles present after the return of uninhibited complement activity will be inactivated. Preferred soluble complement inhibitors for use in the practice of the present invention include complement inhibitory anti-complement component mAbs (including complement inhibitory anti C5 antibodies).

    摘要翻译： 提供了方法和组合物，用于促进涉及在含补体的体液存在下用逆转录病毒载体颗粒转导靶细胞的基因治疗方法。 向体液施用可溶性补体抑制剂分子可防止补体介导的逆转录病毒载体颗粒的失活，并为此类基因治疗程序提供安全机制，因为可溶性补体抑制剂的作用是暂时的，并且任何逆转录病毒载体颗粒存在于 不受限制的补体活动的返回将被灭活。 用于实施本发明的优选的可溶性补体抑制剂包括补体抑制性抗补体成分mAb（包括补体抑制性抗C5抗体）。