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1. 发明申请

US20110231943A1 TRANSGENIC ANIMALS AND USES THEREOF 审中-公开
标题翻译：转基因动物及其用途
公开(公告)号：US20110231943A1
公开(公告)日：2011-09-22
申请号：US13080923
申请日：2011-04-06
申请人： JAMES M. ROBL , YOSHIMI KUROIWA , POOTHAPPILLAI KASINATHAN , ISAO ISHIDA , KAZUMA TOMIZUKA
发明人： JAMES M. ROBL , YOSHIMI KUROIWA , POOTHAPPILLAI KASINATHAN , ISAO ISHIDA , KAZUMA TOMIZUKA
IPC分类号： A01K67/027
CPC分类号： A01K67/0271 , A01K67/0273 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/072 , A01K2217/075 , A01K2227/101 , A01K2267/01 , A01K2267/02 , A01K2267/0343 , C07K2317/00 , C07K2317/21 , C12N15/8509 , C12N15/8771
摘要： In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.
摘要翻译：通常，本发明的特征在于遗传修饰的非人哺乳动物（例如牛和其他有蹄类动物）以及制造这些哺乳动物的方法。特别地，本发明具有具有降低的内源性IgM重链和/或朊病毒蛋白水平的转基因有蹄类动物。

2. 发明授权

US07928285B2 Method of producing xenogenous antibodies using a bovine 有权
标题翻译：使用牛制备异种抗体的方法
公开(公告)号：US07928285B2
公开(公告)日：2011-04-19
申请号：US12215085
申请日：2008-06-25
申请人： James M. Robl , Yoshimi Kuroiwa , Poothappillai Kasinathan , Isao Ishida , Kazuma Tomizuka
发明人： James M. Robl , Yoshimi Kuroiwa , Poothappillai Kasinathan , Isao Ishida , Kazuma Tomizuka
IPC分类号： A01K67/00 , A01K67/027 , A01K67/033 , C12P21/00 , C12N15/00
CPC分类号： A01K67/0271 , A01K67/0273 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/072 , A01K2217/075 , A01K2227/101 , A01K2267/01 , A01K2267/02 , A01K2267/0343 , C07K2317/00 , C07K2317/21 , C12N15/8509 , C12N15/8771
摘要： In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.
摘要翻译：通常，本发明的特征在于遗传修饰的非人哺乳动物（例如牛和其他有蹄类动物）以及制造这些哺乳动物的方法。特别地，本发明具有具有降低的内源性IgM重链和/或朊病毒蛋白水平的转基因有蹄类动物。

3. 发明授权

US07420099B2 Transgenic animals and uses thereof 失效
标题翻译：转基因动物及其用途
公开(公告)号：US07420099B2
公开(公告)日：2008-09-02
申请号：US11111310
申请日：2005-04-21
申请人： James M. Robl , Yoshimi Kuroiwa , Poothappillai Kasinathan , Isao Ishida , Kazuma Tomizuka
发明人： James M. Robl , Yoshimi Kuroiwa , Poothappillai Kasinathan , Isao Ishida , Kazuma Tomizuka
IPC分类号： A01K67/027 , C12P21/00 , C12N15/00
CPC分类号： A01K67/0271 , A01K67/0273 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/072 , A01K2217/075 , A01K2227/101 , A01K2267/01 , A01K2267/02 , A01K2267/0343 , C07K2317/00 , C07K2317/21 , C12N15/8509 , C12N15/8771
摘要： In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.
摘要翻译：通常，本发明的特征在于遗传修饰的非人哺乳动物（例如牛和其他有蹄类动物）以及制造这些哺乳动物的方法。特别地，本发明具有具有降低的内源性IgM重链和/或朊病毒蛋白水平的转基因有蹄类动物。

4. 发明授权

US06602672B1 Recombinant construct encoding epitope tagged PrP protein 失效
标题翻译：编码表位标记的PrP蛋白的重组构建体
公开(公告)号：US06602672B1
公开(公告)日：2003-08-05
申请号：US09669516
申请日：2000-09-25
申请人： Stanley B. Prusiner , Glenn C. Telling , Fred E. Cohen , Michael R. Scott
发明人： Stanley B. Prusiner , Glenn C. Telling , Fred E. Cohen , Michael R. Scott
IPC分类号： G01N3353
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/0318 , A01K2267/0337 , A01K2267/0343 , A61K47/645 , A61K49/0008 , C07K14/42 , C07K14/47 , G01N2800/2828
摘要： DNA constructs are provided of epitope-tagged proteins or protein fragments which are conveniently purified with immunoaffinity chromatography such as epitope-tagged prion proteins (PrP). Transgenic animals expressing an epitope-tagged protein are provided, including transgenic animals expressing epitope-tagged PrP. Methods for distinguishing between the conformational shapes of a protein and a convenient method for isolating a tagged protein by immunoaffinity chromatographic methods are provided.
摘要翻译：提供了表位标记的蛋白质或蛋白质片段的DNA构建体，其通过免疫亲和层析如表位标记的朊蛋白（PrP）方便地纯化。提供了表达表位标签蛋白的转基因动物，包括表达表位标记的PrP的转基因动物。提供了通过免疫亲和层析方法区分蛋白质的构象形状和分离标记蛋白质的方便方法。

5. 发明授权

US06509515B2 Transgenic mice expressing mutant human APP and forming congo red staining plaques 失效
标题翻译：表达突变型人APP的转基因小鼠并形成刚果红染色斑块
公开(公告)号：US06509515B2
公开(公告)日：2003-01-21
申请号：US09260897
申请日：1999-03-02
申请人： Karen Hsiao , David R. Borchelt , Sangram S. Sisodia
发明人： Karen Hsiao , David R. Borchelt , Sangram S. Sisodia
IPC分类号： A01K6700
CPC分类号： C12N15/8509 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/0312 , A01K2267/0318 , A01K2267/0343 , A01K2267/0356 , A61K38/00 , A61K49/0008 , C07K14/4711 , C12N2830/008
摘要： Provided is a transgenic non-human eukaryotic animal whose germ cells and somatic cells contain the amyloid precursor protein sequence introduced into the animal, or an ancestor of the animal, at an embryonic stage. In mice, an age-related CNS disorder characterized by agitation, neophobia, seizures, inactivity, diminished cerebral glucose utilization, cortico-limbic gliosis, and death, develops. An acceleration of this disorder occurs in transgenic mice expressing human and mouse Alzheimer amyloid precursor proteins (APP) produced using a hamster prion protein gene-derived cosmid vector that confers position-independent, copy number-dependent expression. In transgenic mice the disorder develops in direct relationship to brain levels of transgenic APP, but mutant APP confers the phenotype at lower levels of expression than wild-type APP. The disorder occurs in the absence of extracellular amyloid deposition, indicating that some pathogenic activities of APP are dissociated from amyloid formation.
摘要翻译：提供了一种转基因非人类真核动物，其生殖细胞和体细胞在胚胎期含有引入动物或动物祖先的淀粉样蛋白前体蛋白质序列。在小鼠中，发展为以激动，恐惧症，癫痫发作，不活动，脑葡萄糖利用减少，皮层边缘胶质增生和死亡为特征的年龄相关的中枢神经系统疾病。这种疾病的加速发生在使用赋予与位置无关的拷贝数依赖性表达的仓鼠朊蛋白基因衍生的粘粒载体产生的表达人和小鼠阿尔茨海默氏淀粉样蛋白前体蛋白（APP）的转基因小鼠中。在转基因小鼠中，病症与转基因APP的脑水平直接相关，但是突变体APP赋予表型低于野生型APP的表型。该疾病发生在没有细胞外淀粉样蛋白沉积的情况下，表明APP的一些致病活性与淀粉样蛋白形成分离。

6. 发明授权

US5891641A Assay for disease related conformation of a protein 失效
标题翻译：测定蛋白质的疾病相关构象
公开(公告)号：US5891641A
公开(公告)日：1999-04-06
申请号：US804536
申请日：1997-02-21
申请人： Stanley B. Prusiner , Jiri G. Safar
发明人： Stanley B. Prusiner , Jiri G. Safar
IPC分类号： G01N33/566 , A61K45/00 , A61P25/28 , C07K14/47 , C07K16/28 , C12N15/09 , C12Q1/37 , G01N33/53 , G01N33/68 , G01N33/537 , G01N33/543
CPC分类号： G01N33/6896 , C07K14/47 , C07K14/4711 , C07K16/2872 , G01N33/68 , A01K2227/10 , A01K2267/0343 , G01N2500/00 , G01N2800/2828 , Y10S435/96 , Y10S435/961
摘要： An assay method is disclosed which makes it possible to determine the presence of a diseased related conformation of a protein (e.g., PrP.sup.Sc) in a sample. A sample is divided into two portions and the first portion is cross-linked to a first solid support and then contacted with a labelled antibody which binds to a non-disease form of the protein with a higher degree of affinity (e.g, 4 to 30 fold higher) than to the disease form of the protein. The second portion is treated in a manner which causes any disease form of the protein to change conformation to a form with a higher binding affinity for the labelled antibody. The treated second portion is then bound to a second solid support and contacted with labelled antibody. The level of labelled antibody binding to a protein in the first and second portions is determined and the amounts measured in each are compared. The difference between the two measurements is an indication of whether the diseased related conformation of the protein was present in the sample.
摘要翻译：公开了一种测定方法，其使得可以确定样品中蛋白质（例如PrPSc）的患病相关构象的存在。将样品分成两部分，第一部分与第一固体支持物交联，然后与标记抗体接触，所述标记抗体以更高亲和力结合非蛋白形式的蛋白质（例如4至30 高于蛋白质的疾病形式。以使得蛋白质的任何疾病形式将构象改变为对标记抗体具有较高结合亲和力的形式的方式处理第二部分。然后将经处理的第二部分与第二固体支持物结合，并与标记的抗体接触。确定与第一部分和第二部分中的蛋白质结合的标记抗体的水平，并比较每个中测量的量。两个测量值之间的差异表明蛋白质的患病相关构象是否存在于样品中。

7. 发明申请

US20090133133A1 Transgenic Mice for Bioassay of Prions from Deer and Elk with Chronic Wasting Disease 审中-公开
标题翻译：转基因小鼠生物测定从鹿和麋鹿与慢性废物疾病的朊病毒
公开(公告)号：US20090133133A1
公开(公告)日：2009-05-21
申请号：US12251183
申请日：2008-10-14
申请人： Glenn C. Telling
发明人： Glenn C. Telling
IPC分类号： G01N33/53 , A01K67/027 , C12N15/31 , C12N15/11
CPC分类号： G01N33/5088 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0343 , C12N15/8509
摘要： The invention relates to the use of transgenic constructs to produce animal models for the study of chronic wasting disease.
摘要翻译：本发明涉及使用转基因构建体来产生用于慢性消耗性疾病研究的动物模型。

8. 发明申请

US20070238195A1 Conformational and topological protein regulation 审中-公开
标题翻译：构象和拓扑蛋白调节
公开(公告)号：US20070238195A1
公开(公告)日：2007-10-11
申请号：US11725066
申请日：2007-03-15
申请人： Vishwanath Lingappa , D. Rutkowski , Ramanujan Hedge
发明人： Vishwanath Lingappa , D. Rutkowski , Ramanujan Hedge
IPC分类号： G01N33/566
CPC分类号： G01N33/5008 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0343 , A01K2267/0356 , A61K39/00 , C07K14/47 , C07K2319/02 , C07K2319/033 , C07K2319/04 , C07K2319/61 , C07K2319/75 , C12N15/625 , C12N15/635 , C12N15/8509 , G01N33/502 , G01N33/5047 , G01N33/5076 , G01N33/5088 , G01N33/68 , G01N33/6842 , G01N33/6845 , G01N33/6878 , G01N33/6896
摘要： Methods and compositions are provided for identifying novel conformers of proteins not known to exist as different conformers. By using chimeric genes replacing a native signal sequence with a different signal sequence resulting in the production of a conformer, one can compare the native protein with the product of the chimeric gene. Where the conformations are different, the different protein may be used for production of antibodies, elucidation of mechanisms associated with the native and different conformer protein, assays for the presence of the different conformer in physiological samples, identification of compounds specifically binding to the conformer, particularly drugs, etc. Where the formation of the conformer is associated with a diseased state, the conformer may be used in screens to identify compounds as drug candidates.
摘要翻译：提供了用于鉴定不知道以不同构象异构体存在的蛋白质的新型构象异构体的方法和组合物。通过使用以不同信号序列代替天然信号序列的嵌合基因导致构象异构体的产生，可以将天然蛋白与嵌合基因的产物进行比较。当构象不同时，不同的蛋白质可用于生产抗体，阐明与天然和不同构象异构体蛋白相关的机制，生理样品中不同构象异构体的存在的测定，特异性结合构象异构体的化合物的鉴定，特别是药物等。如果构象异构体的形成与患病状态相关，构象异构体可用于筛选以鉴定作为候选药物的化合物。

9. 发明申请

US20050003489A1 Conformational and topological protein regulation 有权
公开(公告)号：US20050003489A1
公开(公告)日：2005-01-06
申请号：US10911446
申请日：2004-08-03
申请人： Vishwanath Lingappa , D. Rutkowski , Ramanujan Hegde
发明人： Vishwanath Lingappa , D. Rutkowski , Ramanujan Hegde
IPC分类号： G01N33/53 , A61K39/00 , C07K14/47 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/62 , C12N15/63 , C12Q1/02 , G01N30/88 , G01N33/68 , C07H21/04
CPC分类号： G01N33/5008 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0343 , A01K2267/0356 , A61K39/00 , C07K14/47 , C07K2319/02 , C07K2319/033 , C07K2319/04 , C07K2319/61 , C07K2319/75 , C12N15/625 , C12N15/635 , C12N15/8509 , G01N33/502 , G01N33/5047 , G01N33/5076 , G01N33/5088 , G01N33/68 , G01N33/6842 , G01N33/6845 , G01N33/6878 , G01N33/6896
摘要： Methods and compositions are provided for identifying novel conformers of proteins not known to exist as different conformers. By using chimeric genes replacing a native signal sequence with a different signal sequence resulting in the production of a conformer, one can compare the native protein with the product of the chimeric gene. Where the conformations are different, the different protein may be used for production of antibodies, elucidation of mechanisms associated with the native and different conformer protein, assays for the presence of the different conformer in physiological samples, identification of compounds specifically binding to the conformer, particularly drugs, etc. Where the formation of the conformer is associated with a diseased state, the conformer may be used in screens to identify compounds as drug candidates.

10. 发明申请

US20030229907A1 Transgenic non-human mammals with progressive neurologic disease 审中-公开
标题翻译：具有进行性神经系统疾病的转基因非人哺乳动物
公开(公告)号：US20030229907A1
公开(公告)日：2003-12-11
申请号：US10271314
申请日：2002-10-15
申请人： John Hopkins University, a Maryland corporation , Regents of the University of Minnesota, a Minnesota corporation
发明人： Karen Hsiao , David R. Borchelt , Sangram S. Sisodia
IPC分类号： A01K067/027
CPC分类号： C12N15/8509 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/0312 , A01K2267/0318 , A01K2267/0343 , A01K2267/0356 , A61K38/00 , A61K49/0008 , C07K14/4711 , C12N2830/008
摘要： Provided is a transgenic non-human eukaryotic animal whose germ cells and somatic cells contain the amyloid precursor protein sequence introduced into the animal, or an ancestor of the animal, at an embryonic stage. In mice, an age-related CNS disorder characterized by agitation, neophobia, seizures, inactivity, diminished cerebral glucose utilization, cortico-limbic gliosis, and death, develops. An acceleration of this disorder occurs in transgenic mice expressing human and mouse Alzheimer amyloid precursor proteins (APP) produced using a hamster prion protein gene-derived cosmid vector that confers position-independent, copy number-dependent expression. In transgenic mice the disorder develops in direct relationship to brain levels of transgenic APP, but mutant APP confers the phenotype at lower levels of expression than wild-type APP. The disorder occurs in the absence of extracellular amyloid deposition, indicating that some pathogenic activities of APP are dissociated from amyloid formation.
摘要翻译：提供了一种转基因非人类真核动物，其生殖细胞和体细胞在胚胎期含有引入动物或动物祖先的淀粉样蛋白前体蛋白质序列。在小鼠中，发展为以激动，恐惧症，癫痫发作，不活动，脑葡萄糖利用减少，皮层边缘胶质增生和死亡为特征的年龄相关的中枢神经系统疾病。这种疾病的加速发生在使用赋予与位置无关的拷贝数依赖性表达的仓鼠朊蛋白基因衍生的粘粒载体产生的表达人和小鼠阿尔茨海默氏淀粉样蛋白前体蛋白（APP）的转基因小鼠中。在转基因小鼠中，病症与转基因APP的脑水平直接相关，但是突变体APP赋予表型低于野生型APP的表型。该疾病发生在没有细胞外淀粉样蛋白沉积的情况下，表明APP的一些致病活性与淀粉样蛋白形成分离。

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