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1. 发明授权

US06794160B1 Hormone receptor compositions and methods 失效
标题翻译：激素受体组合物和方法
公开(公告)号：US06794160B1
公开(公告)日：2004-09-21
申请号：US08462817
申请日：1995-06-05
申请人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
发明人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
IPC分类号： C12N1512
CPC分类号： C12Q1/6897 , C07K14/721 , C07K14/723 , C12N15/67
摘要： The present invention provides substantially pure DNA's comprised of sequences which encode proteins having the hormone-binding and/or transcription-activating characteristics of a glucocorticoid receptor, a mineralocorticoid receptor, or a thyroid hormone receptor; various plasmids containing receptor sequences which exemplify these DNA's; receptor proteins, including modified functional forms thereof, expressed from these DNA's (or mRNA's); and a bioassay for determining the functionality of a receptor protein. Use of this bioassay has led to the discovery that a necessary and sufficient condition for activation of transcription of a gene (G), whose transcription is activated by hormones complexed with receptors, is the presence of the hormone and its receptor cell (C) where (G) is located. As a result, two new methods for producing desired proteins in genetically engineered cells were discovered.
摘要翻译：本发明提供基本上纯的DNA，其由编码具有糖皮质激素受体，盐皮质激素受体或甲状腺激素受体的激素结合和/或转录激活特征的蛋白质的序列组成; 含有例证这些DNA的受体序列的各种质粒; 受体蛋白，包括其修饰的功能形式，由这些DNA（或mRNA）表达; 以及用于测定受体蛋白质功能的生物测定。这种生物测定的使用已经导致发现，用于激活基因（G）的转录的必需和充分条件（G），其转录由与受体复合的激素激活，是激素及其受体细胞（C）的存在，其中（G）位于。因此，发现了两种在遗传工程细胞中产生所需蛋白质的新方法。

2. 发明授权

US06806359B1 Hormone receptor compositions and methods 失效
标题翻译：激素受体组合物和方法
公开(公告)号：US06806359B1
公开(公告)日：2004-10-19
申请号：US08464574
申请日：1995-06-05
申请人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
发明人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
IPC分类号： C12N1512
CPC分类号： C12Q1/6897 , C07K14/721 , C07K14/723 , C12N15/67
摘要： The present invention provides substantially pure DNA's comprised of sequences which encode proteins having the hormone-binding and/or transcription-activating characteristics of a glucocorticoid receptor, a mineralocorticoid receptor, or a thyroid hormone receptor. The invention also provides various plasmids containing receptor sequences which exemplify the DNA's of the invention. The invention further provides receptor proteins, including modified functional forms thereof, expressed from the DNA's (or mRNA's) of the invention. In addition to novel receptor DNA, RNA and protein compositions, the present invention involves a bioassay for determining the functionality of a receptor protein. By using our bioassay system we have discovered that a necessary and sufficient condition for activation of transcription of a gene (G), whose transcription is activated by hormones complexed with receptors, is the presence of the hormone and its receptor in the cell (C) where (G) is located. As a result of that discovery we have also invented new methods for producing desired proteins in genetically engineered cells. Two of these methods are methods of the present invention. The first is a method for inducing transcription of a gene whose transcription is activated by hormones complexed with the receptors. The second is a method for engineering a cell and increasing and controlling production of a protein encoded by a gene whose transcription is activated by hormones complexed with receptor proteins.
摘要翻译：本发明提供基本上纯的DNA，其由编码具有糖皮质激素受体，盐皮质激素受体或甲状腺激素受体的激素结合和/或转录激活特征的蛋白质的序列组成; 含有例证这些DNA的受体序列的各种质粒; 受体蛋白，包括其修饰的功能形式，由DNA（或mRNA）表达; 以及用于测定受体蛋白质功能的生物测定。这种生物测定的使用已经导致发现，用于激活基因（G）的转录的必需和充分条件（G），其转录由与受体复合的激素激活，是激素及其受体细胞（C）的存在，其中（G）位于。因此，发现了两种在遗传工程细胞中产生所需蛋白质的新方法。

3. 发明授权

US5597705A DNA encoding thyroid hormone receptor compositions and methods 失效
标题翻译：编码甲状腺激素受体组成和方法的DNA
公开(公告)号：US5597705A
公开(公告)日：1997-01-28
申请号：US165708
申请日：1993-12-10
申请人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
发明人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
IPC分类号： C12N15/09 , C07K14/00 , C07K14/435 , C07K14/575 , C07K14/635 , C07K14/705 , C07K14/71 , C07K14/72 , C12N5/00 , C12N5/10 , C12N15/00 , C12N15/12 , C12N15/67 , C12P21/02 , C12Q1/68 , C12R1/91 , G01N33/50 , C22N15/62
CPC分类号： C12N15/67 , C07K14/721 , C07K14/723 , C12Q1/6897
摘要： The present invention provides a recombinant expression system for production of functional thyroid hormone receptor protein(s). The invention also provides a method to produce thyroid hormone receptor protein(s) by culturing the cells of the invention recombinant expression system. Also provided are thyroid hormone receptor protein(s) produced by the invention method. In addition, the present invention provides recombinant DNAs comprised of sequences which encode proteins having the hormone-binding and/or transcription-activating characteristics of a thyroid hormone receptor. The invention also provides various plasmids containing receptor sequences which exemplify the DNAs of the invention. The invention further provides complementary mRNAs, cells transformed with invention DNAs, and nucleic acid probes derived from invention DNAs.
摘要翻译：本发明提供了用于产生功能性甲状腺激素受体蛋白质的重组表达系统。本发明还提供了通过培养本发明的重组表达系统的细胞产生甲状腺激素受体蛋白的方法。还提供了通过本发明方法产生的甲状腺激素受体蛋白。此外，本发明提供由编码具有甲状腺激素受体的激素结合和/或转录激活特征的蛋白质的序列组成的重组DNA。本发明还提供了含有受体序列的各种质粒，其例证了本发明的DNA。本发明还提供了补体mRNA，用本发明DNA转化的细胞，以及衍生自本发明DNA的核酸探针。

4. 发明授权

US5312732A Hormone receptor compositions and methods 失效
标题翻译：激素受体组合物和方法
公开(公告)号：US5312732A
公开(公告)日：1994-05-17
申请号：US667602
申请日：1991-03-07
申请人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
发明人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
IPC分类号： C12N15/09 , C07K14/00 , C07K14/435 , C07K14/575 , C07K14/635 , C07K14/705 , C07K14/71 , C07K14/72 , C12N5/00 , C12N5/10 , C12N15/00 , C12N15/12 , C12N15/67 , C12P21/02 , C12Q1/68 , C12R1/91 , G01N33/50 , C12N15/63
CPC分类号： C12N15/67 , C07K14/721 , C07K14/723 , C12Q1/6897
摘要： The present invention provides substantially pure DNA's comprised of sequences which encode proteins having the hormone-binding and/or transcription-activating characteristics of a glucocorticoid receptor, a mineralocorticoid receptor, or a thyroid hormone receptor. The invention also provides various plasmids containing receptor sequences which exemplify the DNA's of the invention. The invention further provides receptor proteins, including modified functional forms thereof, expressed from the DNA's (or mRNA's) of the invention. In addition to the novel receptor DNA, RNA and protein compositions, the present invention involves a bioassay for determining the functionality of a receptor protein. By using our bioassay system we have discovered that a necessary and sufficient condition for activation of transcription of a gene (G), whose transcription is activated by hormones complexed with receptors, is the presence of the hormone and its receptor in the cell (C) where (G) is located. As a result of that discovery we have also invented new methods for producing desired proteins in genetically engineered cells. Two of these methods are methods of the present invention. The first is a method for inducing transcription of a gene whose transcription is activated by hormones complexed with the receptors. The second is a method for engineering a cell and increasing and controlling production of a protein encoded by a gene whose transcription is activated by hormones complexed with receptor proteins.
摘要翻译：本发明提供了基本上纯的DNA，其由编码具有糖皮质激素受体，盐皮质激素受体或甲状腺激素受体的激素结合和/或转录激活特征的蛋白质的序列组成。本发明还提供了含有受体序列的各种质粒，其例证了本发明的DNA。本发明还提供了从本发明的DNA（或mRNA）表达的受体蛋白，包括其修饰的功能形式。除了新的受体DNA，RNA和蛋白质组合物之外，本发明涉及用于测定受体蛋白质的功能的生物测定。通过使用我们的生物测定系统，我们已经发现，激活基因（G）的转录的必要和充分条件（G），其转录由与受体复合的激素激活，是细胞中激素及其受体的存在（C）其中（G）位于。作为这一发现的结果，我们还发明了用于在遗传工程细胞中产生所需蛋白质的新方法。这些方法中的两个是本发明的方法。第一种是诱导转录由与受体复合的激素激活的基因的转录的方法。第二种是用于工程化细胞并增加和控制由受体与受体蛋白质复合的激素激活转录的基因编码的蛋白质的产生的方法。

5. 发明授权

US5071773A Hormone receptor-related bioassays 失效
标题翻译：激素受体相关生物多样性
公开(公告)号：US5071773A
公开(公告)日：1991-12-10
申请号：US108471
申请日：1987-10-20
申请人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
发明人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
IPC分类号： C12N15/09 , C07K14/00 , C07K14/435 , C07K14/575 , C07K14/635 , C07K14/705 , C07K14/71 , C07K14/72 , C12N5/00 , C12N5/10 , C12N15/00 , C12N15/12 , C12N15/67 , C12P21/02 , C12Q1/68 , C12R1/91 , G01N33/50
CPC分类号： C12N15/67 , C07K14/721 , C07K14/723 , C12Q1/6897
摘要： The present invention discloses two hormone receptor-related bioassays. The first bioassay is useful for determining whether a protein suspected of being a hormone receptor has transcription-activating properties of a hormone receptor. The second bioassay is useful for evaluating whether compounds are functional ligands for receptor proteins. According to the first bioassay, cells that contain non-endogenous DNA which expresses a protein suspected of being a hormone receptor and which contain a DNA sequence encoding an operative hormone responsive promoter/enhancer element linked to an operative reporter gene, are cultured, the culturing being conducted in a culture medium containing a known hormone, or an analog thereof. The cultured cells are then monitored for induction of the product of the reporter gene as an indication of functional transcription-activating binding between the hormone or hormone analog and the protein suspected of being a hormone receptor. According to the second bioassay, cells that contain non-endogenous DNA which expresses hormone receptor or a functional engineered or modified form thereof, and which also contain a DNA sequence encoding an operative hormone responsive promoter/enhancer element linked to an operative reporter gene, are cultured, the culturing being conducted in culture medium containing at least one compound whose ability to functionally bind the receptor protein is sought to be determined. The cultured cells are then monitored for induction of the product of the report gene as an indicator of functional binding between the compound and the receptor.
摘要翻译：本发明公开了两种与激素受体相关的生物测定。第一种生物测定可用于确定怀疑是激素受体的蛋白质是否具有激素受体的转录激活特性。第二个生物测定可用于评估化合物是否是受体蛋白质的功能性配体。根据第一生物测定法，培养含有表达怀疑是激素受体的蛋白质并含有编码与操作性报告基因连接的操作性激素反应性启动子/增强子元件的DNA序列的非内源性DNA的细胞，培养在含有已知激素或其类似物的培养基中进行。然后监测培养的细胞以诱导报告基因的产物，作为激素或激素类似物与怀疑是激素受体的蛋白质之间的功能性转录激活结合的指示。根据第二生物测定，含有表达激素受体的非内源性DNA或其功能性工程化或修饰形式的细胞，并且还包含编码与有效的报告基因连接的操作性激素反应性启动子/增强子元件的DNA序列的细胞是培养时，寻求在含有至少一种能够与受体蛋白质功能结合的化合物的培养基中进行培养。然后监测培养的细胞以诱导报告基因的产物，作为化合物和受体之间功能性结合的指标。

6. 发明授权

US5534418A Controlled expression of recombinant proteins 失效
标题翻译：重组蛋白的控制表达
公开(公告)号：US5534418A
公开(公告)日：1996-07-09
申请号：US166177
申请日：1993-12-10
申请人： Roland M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
发明人： Roland M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
IPC分类号： C12N15/09 , C07K14/00 , C07K14/435 , C07K14/575 , C07K14/635 , C07K14/705 , C07K14/71 , C07K14/72 , C12N5/00 , C12N5/10 , C12N15/00 , C12N15/12 , C12N15/67 , C12P21/02 , C12Q1/68 , C12R1/91 , G01N33/50
CPC分类号： C12N15/67 , C07K14/721 , C07K14/723 , C12Q1/6897
摘要： The present invention provides methods for the controlled production of recombinant proteins in cells. Cells employed in the invention method contain a gene encoding the desired recombinant protein, with transcription of the gene maintained under the control of a transcriptional control element which is activated by a ligand/receptor complex. The ligand/receptor complex is formed when a ligand (which is a hormone or/and analog thereof) is complexed with a receptor (which is a hormone receptor or functional analog thereof which has the transcription activating properties of the receptor). Receptor is produced by the expression of non-endogenous DNA which is also present in the cells used for production of recombinant protein.
摘要翻译：本发明提供了在细胞中控制重组蛋白质生产的方法。本发明方法中使用的细胞含有编码所需重组蛋白的基因，该基因的转录保持在由配体/受体复合物激活的转录控制元件的控制之下。当配体（其是激素或/或其类似物）与受体（其是具有受体的转录激活特性的激素受体或其功能类似物）复合时，形成配体/受体复合物。受体是由用于生产重组蛋白的细胞中也存在的非内源DNA的表达产生的。

7. 发明授权

US5606021A Mineralocorticoid receptor compositions and methods 失效
标题翻译：盐皮质激素受体组合物和方法
公开(公告)号：US5606021A
公开(公告)日：1997-02-25
申请号：US170085
申请日：1993-12-17
申请人： Ronald M. Evans , Cary A. Weinberger , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
发明人： Ronald M. Evans , Cary A. Weinberger , Vincent Giguere , Jeffrey Arriza , Catherine C. Thompson , Estelita S. Ong
IPC分类号： C12N15/09 , C07K14/00 , C07K14/435 , C07K14/575 , C07K14/635 , C07K14/705 , C07K14/71 , C07K14/72 , C12N5/00 , C12N5/10 , C12N15/00 , C12N15/12 , C12N15/67 , C12P21/02 , C12Q1/68 , C12R1/91 , G01N33/50
CPC分类号： C12N15/67 , C07K14/721 , C07K14/723 , C12Q1/6897
摘要： The present invention provides recombinant proteins having the hormone-binding and/or transcription-activating characteristics of a mineralocorticoid receptor. The invention also provides proteins expressed from recombinant DNA encoding a naturally occurring receptor having the hormone-binding and/or transcription-activating characteristics of a mineralocorticoid receptor.
摘要翻译：本发明提供具有盐皮质激素受体的激素结合和/或转录激活特征的重组蛋白。本发明还提供由编码天然存在的受体的重组DNA表达的蛋白质，所述受体具有盐皮质激素受体的激素结合和/或转录激活特征。

8. 发明授权

US07214511B1 Hormone receptor compositions and methods 失效
标题翻译：激素受体组合物和方法
公开(公告)号：US07214511B1
公开(公告)日：2007-05-08
申请号：US08464262
申请日：1995-06-05
申请人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Estelita S. Ong
发明人： Ronald M. Evans , Cary A. Weinberger , Stanley M. Hollenberg , Estelita S. Ong
IPC分类号： C12N15/12
CPC分类号： C12Q1/6897 , C07K14/721 , C07K14/723 , C12N15/67
摘要： In accordance with the present invention, there are provided expression systems for the production of function glucocorticoid receptor proteins, methods for the recombinant production of glucocorticoid receptor proteins as well as sequences encoding novel members of the steroid/thyroid hormone superfamily of receptors (e.g., glucocorticoid receptor). Invention expression systems comprise host cells containing DNA encoding functional glucocorticoid receptor proteins, wherein the DNA is operably linked to control sequences compatible with host cells, thereby enabling the expression of functional receptor proteins. The invention method is carried out by culturing such recombinant host cells, and recovering the functional glucocorticoid receptor proteins produced thereby. In accordance with the present invention, there are also provided substantially pure DNA's comprised of sequences which encode members of the steroid/thyroid hormone receptor superfamily having the hormone-binding and/or transcription-activating characteristics of a glucocorticoid receptor. The invention also provides various plasmids containing receptor sequences which exemplify the DNA's of the invention. The invention further provides receptor proteins, including modified functional forms thereof, expressed from the DNA's (or mRNA's) of the invention.
摘要翻译：根据本发明，提供了用于产生功能性糖皮质激素受体蛋白质的表达系统，重组生产糖皮质激素受体蛋白质的方法以及编码受体类固醇/甲状腺激素超家族的新成员的序列（例如，糖皮质激素受体）。本发明表达系统包含含有编码功能性糖皮质激素受体蛋白质的DNA的宿主细胞，其中所述DNA可操作地连接到与宿主细胞相容的控制序列，从而使得能够表达功能性受体蛋白质。本发明方法是通过培养这样的重组宿主细胞进行的，并且回收由此产生的功能性糖皮质激素受体蛋白质。根据本发明，还提供了基本上纯的DNA，其由编码具有糖皮质激素受体的激素结合和/或转录激活特性的类固醇/甲状腺激素受体超家族成员的序列组成。本发明还提供了含有受体序列的各种质粒，其例证了本发明的DNA。本发明还提供了从本发明的DNA（或mRNA）表达的受体蛋白，包括其修饰的功能形式。

9. 发明授权

US6005086A Farnesoid activated receptor polypeptides, and nucleic acid encoding the same 失效
标题翻译：法呢活性受体多肽和编码相同的核酸
公开(公告)号：US6005086A
公开(公告)日：1999-12-21
申请号：US372183
申请日：1995-01-13
申请人： Ronald M. Evans , Barry M. Forman , Cary A. Weinberger
发明人： Ronald M. Evans , Barry M. Forman , Cary A. Weinberger
IPC分类号： C12N15/09 , C07K14/705 , C12Q1/02 , C12Q1/68 , C07H17/00 , C07K14/00
CPC分类号： A61K31/045 , A61K31/202 , A61K31/22 , A61K31/336 , C07K14/70567 , G01N33/74 , G01N2333/70567
摘要： Farnesyl pyrophosphate, the metabolically active form of farnesol, is a key precursor in the synthesis of cholesterol, carotenoids, steroid hormones, bile acids and other molecules involved in cellular growth and metabolism. A nuclear receptor has been identified that is transcriptionally activated by farnesol and related molecules. This novel signaling pathway can be modulated by the use of key metabolic intermediates (or analogs and/or derivatives thereof) as transcriptional regulatory signals.
摘要翻译：法呢基焦磷酸法呢酯是代谢活性形式的法呢醇，是合成胆固醇，类胡萝卜素，类固醇激素，胆汁酸和参与细胞生长和代谢的其他分子的关键前体。已经鉴定出由法呢醇和相关分子转录激活的核受体。可以通过使用关键的代谢中间体（或其类似物和/或其衍生物）作为转录调节信号来调节这种新的信号传导途径。

10. 发明授权

US07041498B2 Method for modulating processes mediated by farnesoid activated receptors 失效
公开(公告)号：US07041498B2
公开(公告)日：2006-05-09
申请号：US10155379
申请日：2002-05-24
申请人： Ronald M. Evans , Barry M. Forman , Cary A. Weinberger
发明人： Ronald M. Evans , Barry M. Forman , Cary A. Weinberger
IPC分类号： C12N5/00 , C12N15/24 , C07H17/00
CPC分类号： A61K31/045 , A61K31/202 , A61K31/22 , A61K31/336 , C07K14/70567 , G01N33/74 , G01N2333/70567
摘要： Farnesyl pyrophosphate, the metabolically active form of farnesol, is a key precursor in the synthesis of cholesterol, carotenoids, steroid hormones, bile acids and other molecules involved in cellular growth and metabolism. A nuclear receptor has been identified that is transcriptionally activated by farnesol and related molecules. This novel signaling pathway can be modulated by the use of key metabolic intermediates (or analogs and/or derivatives thereof) as transcriptional regulatory signals.

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