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    Human inhibin
    1.
    发明授权
    Human inhibin 失效
    人抑制素

    公开(公告)号：US4737578A

    公开(公告)日：1988-04-12

    申请号：US848924

    申请日：1986-04-07

    申请人： Ronald M. Evans ,  Michael G. Rosenfeld ,  Gail Cerelli ,  Kelly E. Mayo ,  Joachim Spiess ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    发明人： Ronald M. Evans ,  Michael G. Rosenfeld ,  Gail Cerelli ,  Kelly E. Mayo ,  Joachim Spiess ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    IPC分类号： A61K38/00 ,  C07K14/575 ,  C07K7/10 ,  C07K13/00

    CPC分类号： C07K14/575 ,  A61K38/00 ,  Y10S930/26

    摘要： Proteins with inhibin activity having a weight of about 32,000 daltons. The molecule is composed of two chains having molecular weights of about 18,000 and about 14,000 daltons, respectively, which are bound together by disulfide bonding. The 18K chain is obtained from the human inhibin gene and has the formula: H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu-Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Leu-Asn-Ile-Ser-Phe-Gln-Glu-Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R.sub.65 -Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His-Ile-Pro-Pro-Asn-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly-Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pro-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly-Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH, wherein R.sub.65 is Ile or Arg. The 18K chain is connected by disulfide bonding to the 14K chain.

    摘要翻译： 具有约32,000道尔顿重量的具有抑制素活性的蛋白质。 该分子由分子量分别为约18,000和约14,000道尔顿的两条链组成，它们通过二硫键结合在一起。 18K链由人抑制素基因得到，具有下式：H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Le-Asn-Ile-Ser-Phe-Gln-Glu- Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R65-Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His- Ile-Pro-Pro-As n-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly -Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pr-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly- Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH，其中R65是Ile或Arg。 18K链通过二硫键与14K链连接。

    DNA encoding human CGRP
    2.
    发明授权
    DNA encoding human CGRP 失效
    编码人CGRP的DNA

    公开(公告)号：US4736023A

    公开(公告)日：1988-04-05

    申请号：US707946

    申请日：1985-03-04

    申请人： Ronald M. Evans ,  Michael G. Rosenfeld

    发明人： Ronald M. Evans ,  Michael G. Rosenfeld

    IPC分类号： A61K38/00 ,  C07K14/575 ,  C07H15/12

    CPC分类号： C07K14/57527 ,  A61K38/00

    摘要： Human CGRP (calcitonin-gene-related peptide) has the formula: H-Ala-Cys-Asn-Thr-Ala-Thr-Cys-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser-Arg-Ser-Gly-Gly-Val-Val-Lys-Asn-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH.sub.2. Human CGRP or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals, including humans, to influence memory, mood and pain appreciation and to achieve a substantial lowering of blood pressure or gastric acid secretion over an extended period of time. They also may be administered to affect ingestion behavior, taste and sensory perception. By using human CGRP to generate production of antibodies, it should be possible to diagnose human medullary thyroid carcinoma via immunoassay techniques.

    摘要翻译： 人CGRP（降钙素基因相关肽）具有下式：H-Ala-Cys-Asn-Thr-Ala-Thr-Cys-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser- Arg-Ser-Gly-Gly-Val-Val-Lys-Asn-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Ly-Ala-Phe-NH2。 分散在药学上可接受的液体或固体载体中的人CGRP或其药学上可接受的盐可以被给予包括人在内的哺乳动物，以影响记忆，情绪和疼痛的升高，并且能够实现血压或胃酸分泌的显着降低 延长一段时间 它们也可以被施用以影响摄取行为，味觉和感觉知觉。 通过使用人CGRP产生抗体，应该可以通过免疫测定技术诊断人甲状腺髓样癌。

    Human CGRP
    4.
    发明授权
    Human CGRP 失效
    人类CGRP

    公开(公告)号：US4549986A

    公开(公告)日：1985-10-29

    申请号：US565035

    申请日：1983-12-23

    申请人： Ronald M. Evans ,  Michael G. Rosenfeld

    发明人： Ronald M. Evans ,  Michael G. Rosenfeld

    IPC分类号： A61K38/00 ,  C07K14/575 ,  C07C103/52

    CPC分类号： C07K14/57527 ,  A61K38/00 ,  Y10S530/80 ,  Y10S530/806

    摘要： Human CGRP (calcitonin-gene-related peptide) has the formula: H-Ala-Cys-Asn-Thr-Ala-Thr-Cys-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser-Arg-Ser-Gly-Gly-Val-Val-Lys-Asn-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe-NH.sub.2. Human CGRP or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals, including humans, to influence memory, mood and pain appreciation and to achieve a substantial lowering of blood pressure or gastric acid secretion over an extended period of time. They also may be administered to affect ingestion behavior, taste and sensory perception. By using human CGRP to generate production of antibodies, it should be possible to diagnose human medullary thyroid carcinoma via immunoassay techniques.

    摘要翻译： 人CGRP（降钙素基因相关肽）具有下式：H-Ala-Cys-Asn-Thr-Ala-Thr-Cys-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser- Arg-Ser-Gly-Gly-Val-Val-Lys-Asn-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Ly s-Ala-Phe-NH2。 分散在药学上可接受的液体或固体载体中的人CGRP或其药学上可接受的盐可以被给予包括人在内的哺乳动物，以影响记忆，情绪和疼痛的升高，并且能够实现血压或胃酸分泌的显着降低 延长一段时间 它们也可以被施用以影响摄取行为，味觉和感觉知觉。 通过使用人CGRP产生抗体，应该可以通过免疫测定技术诊断人甲状腺髓样癌。

    Methods of Identifying Functional Characteristics of Promoters, Transcription Modifying Proteins and Transcription Modulating Agents
    7.
    发明申请
    Methods of Identifying Functional Characteristics of Promoters, Transcription Modifying Proteins and Transcription Modulating Agents 审中-公开
    鉴定启动子，转录修饰蛋白和转录调节剂功能特征的方法

    公开(公告)号：US20110263454A1

    公开(公告)日：2011-10-27

    申请号：US13061500

    申请日：2009-08-28

    申请人： Johan W. Jonker ,  Michael Downes ,  Ronald M. Evans

    发明人： Johan W. Jonker ,  Michael Downes ,  Ronald M. Evans

    IPC分类号： C40B30/06 ,  C40B60/12

    CPC分类号： C12Q1/6897 ,  C12N15/1086

    摘要： Provided herein is, inter alia, methods and compositions useful in therapeutic interrogation of complex physiologic pathways by massively parallel and permissive transcriptional screening. Thus, methods and compositions are provided herein that are useful for high-throughput functional analysis of complex, transcriptionally regulated physiological pathways. While examples are provided relating to nuclear receptors, the methods and composition can be generalized and applied to any class of transcription factor or any class of gene product that can regulate the activity of transcription. For example, in addition to nuclear receptors, the methods and compositions provided herein are generally applicable to all known transcription factors and any gene encoded product that modulates said transcription factor activity. Moreover, data obtained through the methods provided herein are directly comparable thereby facilitating high-throughput functional analysis.

    摘要翻译： 本文提供了通过大规模平行和允许的转录筛选在治疗性询问复杂生理学途径中有用的方法和组合物。 因此，本文提供了可用于复杂的转录调节生理学途径的高通量功能分析的方法和组合物。 虽然提供了与核受体相关的实例，但是该方法和组成可以被推广并应用于可以调节转录活性的任何类型的转录因子或任何类型的基因产物。 例如，除了核受体之外，本文提供的方法和组合物通常可应用于调节所述转录因子活性的所有已知转录因子和任何基因编码产物。 此外，通过本文提供的方法获得的数据是直接可比的，因此有助于高通量功能分析。

    Structure of the farnesoid X receptor ligand binding domain and methods of use therefor
    9.
    发明授权
    Structure of the farnesoid X receptor ligand binding domain and methods of use therefor 失效
    法呢酯X受体配体结合域的结构及其用途

    公开(公告)号：US07647217B2

    公开(公告)日：2010-01-12

    申请号：US10535042

    申请日：2003-11-14

    申请人： Michael R Downes ,  Mark A. Verdicia ,  Joseph P. Noel ,  Ronald M. Evans ,  Lindsey J. Bowman ,  Marianne Bowman

    发明人： Michael R Downes ,  Mark A. Verdicia ,  Joseph P. Noel ,  Ronald M. Evans ,  Lindsey J. Bowman ,  Marianne Bowman

    IPC分类号： G06G7/58 ,  C07K14/00

    CPC分类号： C07K14/70567 ,  C07K2299/00 ,  G01N33/743 ,  G01N2500/00 ,  G06F19/16 ,  G06F19/706

    摘要： The present invention provides compositions comprising the ligand binding domain (LBD) of a farnesoid X receptor (FXR) in crystalline form. In alternative embodiments, the LBD of FXR is complexed with a ligand therefor. There are provided high resolution structures of FXR complexed with a novel high affinity agonist, fexaramine. The discovered structure of a FXR LBD provides the first three-dimensional view of the structural basis for FXR ligand binding. The present invention further provides a computer for producing a three-dimensional representation of FXR or a complex thereof, and a computer for determining at least a portion of the structure coordinates of FXR or a complex thereof. The present invention further provides methods of using this structural information to predict molecules capable of binding to FXR; to identify compounds with agonist, antagonist or partial agonist activity for FXR; and to determine whether a test compound is capable of binding to the LBD of FXR. The present invention further provides compositions comprising compounds identified by such invention methods.

    摘要翻译： 本发明提供了包含结晶形式的法呢甾X受体（FXR）的配体结合结构域（LBD）的组合物。 在替代实施方案中，FXR的LBD与其配体复合。 提供了与新型高亲和力激动剂fexaramine复合的FXR的高分辨率结构。 所发现的FXR LBD的结构提供了FXR配体结合的结构基础的第一个三维视图。 本发明还提供一种用于产生FXR或其复数的三维表示的计算机，以及用于确定FXR的结构坐标的至少一部分或其复合体的计算机。 本发明还提供使用该结构信息来预测能够结合FXR的分子的方法; 识别FXR激动剂，拮抗剂或部分激动剂活性的化合物; 并确定测试化合物是否能够结合FXR的LBD。 本发明还提供包含通过本发明方法鉴定的化合物的组合物。

    Response element compositions and assays employing same
    10.
    发明授权
    Response element compositions and assays employing same 失效
    响应元素组合物和采用其的测定法

    公开(公告)号：US07189510B2

    公开(公告)日：2007-03-13

    申请号：US10302557

    申请日：2002-11-22

    申请人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

    发明人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

    IPC分类号： C12Q1/68

    CPC分类号： C07K14/70567 ,  C07K14/721 ,  C12N15/85 ,  C12N2800/108 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/38 ,  C12N2830/60 ,  C12N2830/85 ,  C12Q1/6897 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5041 ,  G01N33/743

    摘要： DNA segments have been discovered, and characterized by sequence, which are response elements operative to confer responsiveness to ligands for several members of the steroid/thyroid superfamily of receptors, for the transcriptional activation and/or repression of promoters in cells. By using transcriptional control regions comprising response elements of the present invention in combination with a functional promoter, it is now possible to provide recombinant DNA vectors containing a gene, the transcription (and, thereby, also expression) of which is under the control of a promoter, the transcriptional activity of which is responsive to ligands for members of the steroid/thyroid superfamily of receptors.

    摘要翻译： 已经发现了DNA区段，其特征在于序列，其是作用于赋予类固醇/甲状腺超家族受体的若干成员对配体的反应性的响应元件，用于细胞中启动子的转录激活和/或抑制。 通过使用包含本发明的响应元件与功能启动子组合的转录控制区，现在可以提供含有基因的重组DNA载体，其转录（并且由此也由其表达）处于一个 启动子，其转录活性对受体的类固醇/甲状腺超家族成员的配体有反应。