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    Multitrophic and multifunctional chimeric neurotrophic factors, and nucleic acids and plasmids encoding the chimeras
    2.
    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。

    Method for screening comprising cells expressing the CNTF receptor
    3.
    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。

    Primitive and proximal hepatic stem cells
    5.
    发明授权
    Primitive and proximal hepatic stem cells 有权
    原始和近端肝干细胞

    公开(公告)号：US08691523B2

    公开(公告)日：2014-04-08

    申请号：US11609729

    申请日：2006-12-12

    申请人： Lola M. Reid ,  Nicholas Moss ,  Mark E. Furth ,  John W. Ludlow ,  Andrew T. Bruce

    发明人： Lola M. Reid ,  Nicholas Moss ,  Mark E. Furth ,  John W. Ludlow ,  Andrew T. Bruce

    IPC分类号： C12N5/00

    CPC分类号： C12N5/0672 ,  C12N2500/25 ,  C12N2500/36 ,  C12N2500/90 ,  C12N2501/11 ,  C12N2502/13 ,  G01N33/5005 ,  G01N33/68 ,  G01N2333/705 ,  G01N2333/70525 ,  G01N2333/70596

    摘要： Hepatic progenitors comprise two populations of human hepatic stem cells, primitive and proximal hepatic stem cells, and two populations of committed progenitors, one for biliary cells and one for hepatocytes. Human primitive hepatic stem cells are a very small fraction of the liver cell population and give rise to proximal hepatic stem cells constituting a much larger fraction of the liver. Human proximal hepatic stem cells give rise to biliary and hepatocyte committed progenitors. Primitive and proximal stem cells are the primary stem cells for the human liver. Human primitive hepatic stem cells may be isolated by immunoselection from human livers or culturing human liver cells under conditions which select for a human primitive hepatic stem cell. Proximal hepatic stem cells may be isolated by immunoselection, or by culturing human liver cells under conditions which include a developmental factor. Proximal hepatic stem cells may also be isolated by culturing colonies comprising a primitive hepatic stem cell under conditions which include a developmental factor. Resulting compositions may be used for treating liver disorders and for producing bioartificial organs.

    摘要翻译： 肝祖细胞包含两个人类肝干细胞，原始和近端肝干细胞，以及两个定型祖细胞群，一个为胆汁细胞，一个为肝细胞。 人原始肝干细胞是肝细胞群体的非常小的一部分，并且引起近端肝干细胞构成肝脏的大部分。 人近端肝干细胞产生胆汁和肝细胞定向的祖细胞。 原始和近端干细胞是人类肝脏的主要干细胞。 人原始肝干细胞可以通过人肝脏的免疫选择或在选择人原始肝干细胞的条件下培养人肝细胞来分离。 可以通过免疫选择或通过在包括发育因子的条件下培养人肝细胞来分离近端肝干细胞。 也可以通过在包括发育因子的条件下培养包含原始肝干细胞的菌落来分离近端肝干细胞。 所得组合物可用于治疗肝脏疾病和用于生产生物人造器官。

    Assay systems for trkB neurotrophin activity
    6.
    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）。

    Multitrophic and multifunctional chimeric neurotrophic factors
    7.
    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。

    Ciliary neurotrophic factor receptor
    8.
    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。

    METHOD OF OBTAINING VIABLE HUMAN CELLS, INCLUDING HEPATIC STEM/PROGENITOR CELLS
    9.
    发明申请
    METHOD OF OBTAINING VIABLE HUMAN CELLS, INCLUDING HEPATIC STEM/PROGENITOR CELLS 审中-公开
    获得可行的人类细胞的方法，包括HEPATIC STEM / PROGENITOR CELLS

    公开(公告)号：US20100112689A1

    公开(公告)日：2010-05-06

    申请号：US12465404

    申请日：2009-05-13

    申请人： John W. Ludlow ,  Mark E. Furth ,  Andrew T. Bruce ,  Lola M. Reid ,  Robert L. Susick, JR.

    发明人： John W. Ludlow ,  Mark E. Furth ,  Andrew T. Bruce ,  Lola M. Reid ,  Robert L. Susick, JR.

    IPC分类号： C12N5/071

    CPC分类号： C12N5/067 ,  C12N2509/00

    摘要： The present invention is directed toward a method for obtaining from whole liver or a resection thereof a population of cells comprising viable, functional liver cells enriched in hepatocytes and hepatocyte stem/progenitor cells, compositions thereof, and uses therefore. Compositions include a composition of liver cells enriched in hepatocytes and hepatocyte stem/progenitor cells and a pharmaceutical composition thereof. Uses include treatment of liver diseases, regeneration of liver, toxicity testing, and liver assist devices.

    摘要翻译： 本发明涉及从整个肝脏或其切除方法获得包含富含肝细胞的活的功能性肝细胞和肝细胞干细胞/祖细胞的细胞群，以及其组合物及其用途。 组合物包括富含肝细胞的肝细胞和肝细胞干/祖细胞的组合物及其药物组合物。 用途包括肝脏疾病的治疗，肝脏再生，毒性试验和肝脏辅助装置。