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1. 发明授权

US06699686B1 Modified nuclear glucocorticoid receptor, fusion protein, and DNA fragments coding for said receptor and said fusion protein 失效
标题翻译：修饰的核糖皮质激素受体，融合蛋白和编码所述受体和所述融合蛋白的DNA片段
公开(公告)号：US06699686B1
公开(公告)日：2004-03-02
申请号：US09125491
申请日：1998-08-20
申请人： Jacques Bertrand Brocard , Pierre Henri Chambon , Hinrich Gronemeyer , Daniel Metzger , Jean-Claude Nicolas , Sylvie Roux
发明人： Jacques Bertrand Brocard , Pierre Henri Chambon , Hinrich Gronemeyer , Daniel Metzger , Jean-Claude Nicolas , Sylvie Roux
IPC分类号： C12N1500
CPC分类号： C12N15/90 , A01K2217/05 , A61K38/00 , C07K14/721 , C07K2319/00 , C12N9/00 , C12N15/63
摘要： A DNA fragment coding for a modified nuclear glucocorticoid receptor, particularly one mutated in the region coding for the ligand binding domain, so that receptor activity is more strongly inducible by a synthetic glucocorticoid ligand than by a natural glucocorticoid ligand, is disclosed. A recombination system inducible in mammals by means of a fusion protein produced between a recombinase and the binding domain of the ligand derived from the modified glucocorticoid receptor of which the activity is more strongly inducible by synthetic glucocorticoids than by natural glucocorticoids, is also disclosed.
摘要翻译：公开了编码修饰的核糖皮质激素受体的DNA片段，特别是在编码配体结合结构域的区域中突变的核糖糖皮质激素受体，使得受体活性比合成的糖皮质激素配体比天然糖皮质激素配体更强地诱导。还公开了通过在重组酶和衍生自修饰的糖皮质激素受体的配体的结合结构域之间产生的融合蛋白的复合体系，其通过合成糖皮质激素比天然糖皮质激素更强地诱导其活性。

2. 发明申请

US20140093884A1 Process for Identifying Novel Anti-Inflammatory Molecules with Reduced Direct Transrepression of Genes Induced by Glucocorticoids 审中-公开
标题翻译：识别具有减少由糖皮质激素诱导的基因直接转录的新型抗炎分子的方法
公开(公告)号：US20140093884A1
公开(公告)日：2014-04-03
申请号：US14111495
申请日：2012-04-13
申请人： Pierre Chambon , Daniel Metzger , Milan Surjit
发明人： Pierre Chambon , Daniel Metzger , Milan Surjit
IPC分类号： G01N33/50
CPC分类号： G01N33/5023 , C12Q1/6897
摘要： The present invention relates to a new process for identifying novel anti-inflammatory molecules with reduced direct transrepression of genes induced by glucocorticoids.The inventors have discovered that GCs-mediated transrepression can be mediated not only via the tethering indirect pathway, but also through direct binding of GR to “simple” negative GREs (nGRE), which belongs to a novel family of evolutionary-conserved cis-acting negative response elements (IR nGREs), and are found in numerous GC-repressed genes.
摘要翻译：本发明涉及用糖皮质激素诱导的基因直接逆转抑制来鉴定新的抗炎分子的新方法。本发明人已经发现，GCs介导的转录抑制不仅可以通过连接间接途径介导，而且可以通过将GR直接结合到“简单的”负的GRE（nGRE），其属于进化保守的顺式作用的新家族负反应元件（IR nGRE），并且在许多GC抑制基因中发现。

3. 外观设计

USD594127S1 Electrode array 有权
标题翻译：电极阵列
公开(公告)号：USD594127S1
公开(公告)日：2009-06-09
申请号：US29298138
申请日：2007-11-29
申请人： Elvir Causevic , Christian Christiansen , Daniel Metzger , Greg Holderfield , Elliot Hsu
设计人： Elvir Causevic , Christian Christiansen , Daniel Metzger , Greg Holderfield , Elliot Hsu

4. 外观设计

USD560809S1 Electrode array 有权
标题翻译：电极阵列
公开(公告)号：USD560809S1
公开(公告)日：2008-01-29
申请号：US29238840
申请日：2005-09-22
申请人： Elvir Causevic , Christian Christiansen , Daniel Metzger , Greg Holderfield , Elliott Hsu
设计人： Elvir Causevic , Christian Christiansen , Daniel Metzger , Greg Holderfield , Elliott Hsu

5. 发明授权

US06444438B1 Method for the preparation of a protein by yeasts using an inducible system, vectors and correspondence transformed strains 失效
标题翻译：使用诱导系统，载体和对应转化菌株的酵母制备蛋白质的方法
公开(公告)号：US06444438B1
公开(公告)日：2002-09-03
申请号：US08453998
申请日：1995-05-30
申请人： Pierre H. Chambon , Daniel Metzger , John White
发明人： Pierre H. Chambon , Daniel Metzger , John White
IPC分类号： C12P2156
CPC分类号： C12N15/81 , C07K14/721
摘要： The present invention relates to a method for the preparation of a protein by yeasts. In particular, the method of the invention concerns transforming a yeast cell with a first DNA fragment encoding the protein and a second DNA fragment that encodes the receptor. The method further entails culturing the transformed yeast cell, and isolating the protein. The first DNA fragment is under control of elements providing for expression of the DNA fragment in yeast, which elements include a higher eukaryotic positive transcription control sequence consisting of a natural ligand responsive element activating sequence or a variant. The receptor is a natural nuclear receptor selected from the group consisting of receptors for steroids or for retinoids or for thyroid hormones or for vitamin D3. The receptor includes a first fragment that recognizes said ligand and a second fragment that binds to said transcriptional control sequence.
摘要翻译：本发明涉及通过酵母制备蛋白质的方法。特别地，本发明的方法涉及用编码该蛋白质的第一DNA片段和编码该受体的第二DNA片段转化酵母细胞。该方法还需要培养转化的酵母细胞，并分离蛋白质。第一个DNA片段在提供酵母中表达DNA片段的元件的控制下，该元件包括由天然配体反应元件激活序列或变体组成的高级真核阳性转录调控序列。受体是选自类固醇或类维生素A或受体甲状腺激素或维生素D3的受体的天然核受体。受体包括识别所述配体的第一片段和结合所述转录控制序列的第二片段。

6. 发明授权

US08391948B2 Electrode array 有权
标题翻译：电极阵列
公开(公告)号：US08391948B2
公开(公告)日：2013-03-05
申请号：US12067525
申请日：2006-09-22
申请人： Elvir Causevic , Christian Christiansen , Daniel Metzger
发明人： Elvir Causevic , Christian Christiansen , Daniel Metzger
IPC分类号： A61B5/0478 , A61B5/0484
CPC分类号： A61B5/04845 , A61B5/0478 , A61B5/6803 , A61B5/6814 , A61B2562/164
摘要： A disposable electrode array 100, 200 including a flexible member 106, 206 in which a plurality of electrodes 102, 202 are disposed, having a shape adapted to contact the forehead skin surface on a human patient. A pair of ear loops 104, 204 coupled to the disposable electrode array 100, 200 secure the disposable electrode array 100, 200 about the patient's ears, with the flexible member 106, 206 disposed across the patient's bow, retaining the electrodes 102, 202 against the skin surface. Additional electrodes 102, 202 are disposed in proximity to the ear loops 104, 204 and are configured to contact the skin surface behind the patient's ears. An auditory stimulus delivery element 116, 216 is coupled with each of the ear loops 104, 204, and positioned to seat in proximity to the patient's ear canal for the delivery of auditory stimulus. Electrical conductors associated with the electrodes 102, 202 and the stimulus delivery elements 116, 216 are routed within the flexible member 106, 206 to a common external connection point 118, 218 for connection to an external system. The disposable electrode array 100, 200 may be configured for both evoking and measuring evoked bio-potentials in the human subject, or for measuring bio-potentials evoked using a separate stimulus delivery system.
摘要翻译：包括柔性构件106,206的一次性电极阵列100,200，其中设置有多个电极102,202，其具有适于接触人类患者的前额皮肤表面的形状。耦合到一次性电极阵列100,200的一对耳环104,204将患者耳朵周围的一次性电极阵列100,200固定在一起，使柔性构件106,206跨过病人的弓状物设置，保持电极102,202抵抗皮肤表面。附加电极102,202设置在耳环104,204附近，并被配置为接触患者耳朵后面的皮肤表面。听觉刺激传递元件116,216与耳环104,204中的每一个耦合，并被定位成靠近患者的耳道以便传送听觉刺激。与电极102,202和刺激递送元件116,216相关联的电导体在柔性构件106,206内被路由到共同的外部连接点118,218以连接到外部系统。一次性电极阵列100,200可以被配置用于唤醒和测量人类受试者中的诱发生物电位，或者用于测量使用单独的刺激递送系统诱发的生物电位。

7. 发明申请

US20120052570A1 METHOD FOR TEMPORALLY CONTROLLING THE BIOLOGICAL ACTIVITY OF PROTEINS IN VERTEBRATES, AND APPLICATIONS THEREOF 有权
标题翻译：温度控制蛋白质生物活性的方法及其应用
公开(公告)号：US20120052570A1
公开(公告)日：2012-03-01
申请号：US13145752
申请日：2010-01-22
申请人： Daniel Metzger , Pierre Chambon , Huimin Zhao , John Katzenellenbogen
发明人： Daniel Metzger , Pierre Chambon , Huimin Zhao , John Katzenellenbogen
IPC分类号： C12N5/071
CPC分类号： C07K14/721 , C07K2319/715 , C12N9/90
摘要： The present invention relates to a method for tightly temporally controlling the biological activity of a protein of interest in a vertebrate, upon induction of the activity of a fusion protein comprising said protein of interest and an ERM polypeptide containing a mutated ligand binding domain of the human oestrogen receptor α, with a synthetic ligand that does not interfere with oestrogen signalling. In particular, the present invention concerns a method for generating tightly temporally-controlled targeted somatic mutations in a vertebrate, preferably a mouse, by inducing the activity of a fusion protein comprising a site-specific recombinase protein and an ERM polypeptide, with a synthetic ligand devoid of oestrogenic and anti-oestrogenic activities.
摘要翻译：本发明涉及在诱导包含所述目的蛋白质的融合蛋白的活性和含有人的突变配体结合结构域的ERM多肽时紧密地暂时地控制脊椎动物中感兴趣的蛋白质的生物学活性的方法雌激素受体α与不影响雌激素信号传导的合成配体。特别地，本发明涉及通过用合成配体诱导包含位点特异性重组酶蛋白和ERM多肽的融合蛋白的活性，在脊椎动物，优选小鼠中产生紧密的时间控制的靶向体细胞突变的方法没有雌激素和抗雌激素活性。

8. 发明授权

US09273115B2 Method for controlling the biological activity of a protein in a vertebrate cell 有权
标题翻译：控制脊椎动物细胞中蛋白质生物活性的方法
公开(公告)号：US09273115B2
公开(公告)日：2016-03-01
申请号：US13145752
申请日：2010-01-22
申请人： Daniel Metzger , Pierre Chambon , Huimin Zhao , John Katzenellenbogen
发明人： Daniel Metzger , Pierre Chambon , Huimin Zhao , John Katzenellenbogen
IPC分类号： C12N15/00 , C07K14/72 , C12N9/90
CPC分类号： C07K14/721 , C07K2319/715 , C12N9/90
摘要： The present invention relates to a method for tightly temporally controlling the biological activity of a protein of interest in a vertebrate, upon induction of the activity of a fusion protein comprising said protein of interest and an ERM polypeptide containing a mutated ligand binding domain of the human oestrogen receptor α, with a synthetic ligand that does not interfere with oestrogen signalling. In particular, the present invention concerns a method for generating tightly temporally-controlled targeted somatic mutations in a vertebrate, preferably a mouse, by inducing the activity of a fusion protein comprising a site-specific recombinase protein and an ERM polypeptide, with a synthetic ligand devoid of oestrogenic and anti-oestrogenic activities.
摘要翻译：本发明涉及在诱导包含所述目的蛋白质的融合蛋白的活性和含有人的突变配体结合结构域的ERM多肽时紧密地暂时地控制脊椎动物中感兴趣的蛋白质的生物学活性的方法雌激素受体α与不影响雌激素信号传导的合成配体。特别地，本发明涉及通过用合成配体诱导包含位点特异性重组酶蛋白和ERM多肽的融合蛋白的活性，在脊椎动物，优选小鼠中产生紧密的时间控制的靶向体细胞突变的方法没有雌激素和抗雌激素活性。

9. 发明申请

US20100144683A1 METHODS FOR GENERATING MAMMALIAN MODELS OF ATOPIC DISEASES, AND SCREENING FOR THEIR TREATMENT 审中-公开
标题翻译：产生原发性疾病的妈妈模型的方法及其治疗筛选
公开(公告)号：US20100144683A1
公开(公告)日：2010-06-10
申请号：US12307966
申请日：2007-07-24
申请人： Pierre Chambon , Daniel Metzger , Mei Li
发明人： Pierre Chambon , Daniel Metzger , Mei Li
IPC分类号： A61K31/59 , A61P11/06 , A61K31/593 , A61P17/00 , C07C401/00
CPC分类号： A61K31/00 , A61K31/593 , A61K45/06 , A61K2300/00
摘要： The present invention concerns a method for generating a human atopic disease-like phenotype, preferably an atopic dermatitis (AD)-like phenotype in a mammal comprising administering to said mammal at least one compound selected in the group comprising the physiologically active vitamin D3 (1α,25(OH)2D3) and agonistic analogs thereof. The present invention also concerns a method for treating and/or preventing an atopic disease in a patient in a patent comprising administrating to said patient an effective amount of at least one vitamin D3 antagonist.
摘要翻译：本发明涉及在哺乳动物中产生人类特应性疾病样表型，优选特应性皮炎（AD）样表型的方法，包括向所述哺乳动物施用至少一种选自包含生理活性维生素D3（1α），25（OH）2D3）及其激动类似物。本发明还涉及在专利中治疗和/或预防患者特应性疾病的方法，包括向所述患者施用有效量的至少一种维生素D3拮抗剂。

10. 发明申请

US20090018427A1 ELECTRODE ARRAY 有权
标题翻译：电极阵列
公开(公告)号：US20090018427A1
公开(公告)日：2009-01-15
申请号：US12067525
申请日：2006-09-22
申请人： Elvir Causevic , Christian Christiansen , Daniel Metzger
发明人： Elvir Causevic , Christian Christiansen , Daniel Metzger
IPC分类号： A61B5/04
CPC分类号： A61B5/04845 , A61B5/0478 , A61B5/6803 , A61B5/6814 , A61B2562/164
摘要： A disposable electrode array 100, 200 including a flexible member 106, 206 in which a plurality of electrodes 102, 202 are disposed, having a shape adapted to contact the forehead skin surface on a human patient. A pair of ear loops 104, 204 coupled to the disposable electrode array 100, 200 secure the disposable electrode array 100, 200 about the patient's ears, with the flexible member 106, 206 disposed across the patient's bow, retaining the electrodes 102, 202 against the skin surface. Additional electrodes 102, 202 are disposed in proximity to the ear loops 104, 204 and are configured to contact the skin surface behind the patient's ears. An auditory stimulus delivery element 116, 216 is coupled with each of the ear loops 104, 204, and positioned to seat in proximity to the patient's ear canal for the delivery of auditory stimulus. Electrical conductors associated with the electrodes 102, 202 and the stimulus delivery elements 116, 216 are routed within the flexible member 106, 206 to a common external connection point 118, 218 for connection to an external system. The disposable electrode array 100, 200 may be configured for both evoking and measuring evoked bio-potentials in the human subject, or for measuring bio-potentials evoked using a separate stimulus delivery system.
摘要翻译：包括柔性构件106,206的一次性电极阵列100,200，其中设置有多个电极102,202，其具有适于接触人类患者的前额皮肤表面的形状。耦合到一次性电极阵列100,200的一对耳环104,204将患者耳朵周围的一次性电极阵列100,200固定在一起，使柔性构件106,206跨过病人的弓状物设置，保持电极102,202抵抗皮肤表面。附加电极102,202设置在耳环104,204附近，并被配置为接触患者耳朵后面的皮肤表面。听觉刺激传递元件116,216与耳环104,204中的每一个耦合，并被定位成靠近患者的耳道以便传送听觉刺激。与电极102,202和刺激递送元件116,216相关联的电导体在柔性构件106,206内被路由到共同的外部连接点118,218以连接到外部系统。一次性电极阵列100,200可以被配置用于唤醒和测量人类受试者中的诱发生物电位，或者用于测量使用单独的刺激递送系统诱发的生物电位。

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