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1. 发明申请

US20150376651A1 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATIONS AND METHODS OF USE 有权
标题翻译：用于目标基因改变的方法和组合物及其使用方法
公开(公告)号：US20150376651A1
公开(公告)日：2015-12-31
申请号：US14751807
申请日：2015-06-26
申请人： Regeneron Pharmaceuticals, Inc.
发明人： David Frendewey , Gustavo Droguett , Anthony Gagliardi , Junko Kuno , Wojtek Auerbach , David M. Valenzuela
IPC分类号： C12N15/90 , C12N5/0735 , C12N15/85
CPC分类号： C12N15/8509 , A01K67/0275 , A01K67/0276 , A01K67/0278 , A01K2217/075 , A01K2227/105 , A01K2267/02 , A01K2267/0393 , C12N5/0606 , C12N15/907 , C12N2500/60 , C12N2517/00
摘要： Methods and compositions are provided for generating targeted genetic modifications on the Y chromosome or a challenging target locus. Compositions include an in vitro culture comprising an XY pluripotent and/or totipotent animal cell (i.e., XY ES cells or XY iPS cells) having a modification that decreases the level and/or activity of an Sry protein; and, culturing these cells in a medium that promotes development of XY F0 fertile females. Such compositions find use in various methods for making a fertile female XY non-human mammal in an F0 generation.
摘要翻译：提供了用于在Y染色体上或挑战性目标基因座上产生靶向遗传修饰的方法和组合物。组合物包括具有降低Sry蛋白的水平和/或活性的修饰的XY多能和/或全能动物细胞（即，XYES细胞或XY iPS细胞）的体外培养物; 并且在促进XY F0肥沃雌性发育的培养基中培养这些细胞。这样的组合物用于在F0代中制备可育女性XY非人哺乳动物的各种方法。

2. 发明申请

US20090205058A1 GENETICALLY MODIFIED NON-HUMAN MAMMALS AND CELLS 有权
标题翻译：遗传修饰的非人类哺乳动物和细胞
公开(公告)号：US20090205058A1
公开(公告)日：2009-08-13
申请号：US11570087
申请日：2005-06-08
申请人： Teizo Fujita , Hans-Wilhelm Schwaeble , Cordula Margaret Stover
发明人： Teizo Fujita , Hans-Wilhelm Schwaeble , Cordula Margaret Stover
IPC分类号： A01K67/027 , C12N5/06
CPC分类号： A01K67/0278 , A01K67/0276 , A01K2207/15 , A01K2217/00 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/01 , A01K2267/03 , A61K38/00 , C07K16/2851 , C07K16/40 , C07K2317/14 , C12N9/6424 , C12N15/8509 , C12N2510/00 , C12N2517/00 , C12N2800/30
摘要： Genetically modified mammals are described which lack the mannan binding lectin associated serine protease MASP-2, together with methods and constructs for their production. Such mammals are useful as models for disorders of the complement system, and in the identification of treatments for such disorders. Also described are mammals which lack the associated protein MAp19; such mammals may also lack MASP-2.
摘要翻译：描述了缺乏甘露聚糖结合凝集素相关丝氨酸蛋白酶MASP-2的遗传修饰的哺乳动物，以及用于其生产的方法和构建体。这样的哺乳动物可用作补体系统紊乱的模型，以及鉴定这种病症的治疗。还描述了缺乏相关蛋白MAp19的哺乳动物; 这样的哺乳动物也可能缺乏MASP-2。

3. 发明授权

US07476776B2 Method for improving germline transmission efficiency of avian primordial germ cells 失效
标题翻译：提高禽类原始生殖细胞种系传播效率的方法
公开(公告)号：US07476776B2
公开(公告)日：2009-01-13
申请号：US10554030
申请日：2004-04-21
申请人： Jae Yong Han , Tae Sub Park , Yeong Ho Hong , Se Chang Kwon
发明人： Jae Yong Han , Tae Sub Park , Yeong Ho Hong , Se Chang Kwon
IPC分类号： A01K67/027
CPC分类号： C12N15/873 , C12N5/0611 , C12N2500/44 , C12N2501/105 , C12N2501/115 , C12N2501/125 , C12N2501/23 , C12N2501/235 , C12N2517/00
摘要： The present invention relates to a method for improving the germline transmission efficiency of avian primordial germ cells (PGCs), and methods for producing avian chimeras and transgenic using it. The present method comprises the steps of (a) isolating primordial germ cells (PGCs) from an avian embryonic gonad; and (b) culturing said PGCs in vitro for at least 5 days. According to the present method, the germline transmission efficiency of PGCs can be dramatically improved in a feasible manner.
摘要翻译：本发明涉及一种提高禽类原始生殖细胞（PGCs）的种系传播效率的方法，以及用于生产禽类嵌合体的方法和使用它们的转基因。本方法包括以下步骤：（a）从禽类胚性腺分离原始生殖细胞（PGCs）; 和（b）在体外培养所述PGC至少5天。根据本方法，PGC的种系传播效率可以以可行的方式大大提高。

4. 发明申请

US20060218657A1 Method for improving germline transmission efficiency of avian primordial germ cells 失效
公开(公告)号：US20060218657A1
公开(公告)日：2006-09-28
申请号：US10554030
申请日：2004-04-21
申请人： Jae Han , Tae Park , Yeong Hong , Se Kwon
发明人： Jae Han , Tae Park , Yeong Hong , Se Kwon
IPC分类号： A01K67/027
CPC分类号： C12N15/873 , C12N5/0611 , C12N2500/44 , C12N2501/105 , C12N2501/115 , C12N2501/125 , C12N2501/23 , C12N2501/235 , C12N2517/00
摘要： The present invention relates to a method for improving the germline transmission efficiency of avian primordial germ cells (PGCs), and methods for producing avian chimeras and transgenic using it. The present method comprises the steps of (a) isolating primordial germ cells (PGCs) from an avian embryonic gonad; and (b) culturing said PGCs in vitro for at least 5 days. According to the present method, the germline transmission efficiency of PGCs can be dramatically improved in a feasible manner.

5. 发明授权

US06504080B1 Transgenic animal model for neurodegenerative disorders 失效
标题翻译：用于神经变性疾病的转基因动物模型
公开(公告)号：US06504080B1
公开(公告)日：2003-01-07
申请号：US09687731
申请日：2000-10-13
申请人： Petrus Herman Maria Van Der Putten
发明人： Petrus Herman Maria Van Der Putten
IPC分类号： A01K67027
CPC分类号： C12N15/85 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A01K2267/0318 , C07K14/47 , C12N9/0071 , C12N15/8509 , C12N2510/00 , C12N2517/00 , C12N2830/00 , C12N2830/85
摘要： Animal model useful for testing potential therapeutic agents for the treatment of neurodegenerative disorders, in particular disorders associated with the presence of Lewy pathology.
摘要翻译：用于测试用于治疗神经变性疾病的潜在治疗剂的动物模型，特别是与路易病理学存在相关的病症。

6. 发明申请

US20100273658A1 Methods for Assaying Gene Imprinting and Methylated CpG Islands 失效
标题翻译：测定基因印迹和甲基化CpG群岛的方法
公开(公告)号：US20100273658A1
公开(公告)日：2010-10-28
申请号：US12350159
申请日：2009-01-07
申请人： ANDREW P. FEINBERG , LIORA STRICHMAN-ALMASHANU , SHAN JIANG
发明人： ANDREW P. FEINBERG , LIORA STRICHMAN-ALMASHANU , SHAN JIANG
IPC分类号： C40B20/00 , C12N5/073 , C12Q1/68 , C40B50/00
CPC分类号： C12N5/0611 , C12N2501/115 , C12N2501/125 , C12N2501/235 , C12N2501/385 , C12N2502/13 , C12N2503/00 , C12N2503/02 , C12N2510/00 , C12N2517/00 , C12Q1/6827 , C12Q1/6886 , C12Q2600/118 , C12Q2600/136 , C12Q2600/154
摘要： Genomic imprinting is a parent of origin-dependent gene silencing that involves marking of alleles in the germline and differential expression in somatic cells of the offspring. Imprinted genes and abnormal imprinting have been implicated in development, human disease, and embryonic stem cell transplantation. We have established a model system for genomic imprinting using pluripotent 8.5 d.p.c. mouse embryonic germ (EG) cell lines derived from an interspecific cross. We find that allele-specific imprinted gene expression has been lost in these cells. However, partial restoration of allele-specific silencing can occur for some imprinted genes after in vitro differentiation of EG cells into somatic cell lineages, indicating the presence of a gametic memory that is separable from allele-specific gene silencing. We have also generated a library containing most methylated CpG islands. A subset of these clones was analyzed and revealed a subdivision of methylated CpG islands into 4 distinct subtypes: CpG islands belonging to high copy number repeat families; unique CpG islands methylated in all tissues; unique methylated CpG islands that are unmethylated in the paternal germline; and unique CpG islands methylated in tumors. This approach identifies a methylome of methylated CpG islands throughout the genome.
摘要翻译：基因印记是起源依赖基因沉默的亲本，其涉及在种系中标记等位基因和在后代的体细胞中的差异表达。印迹基因和异常印记涉及发育，人类疾病和胚胎干细胞移植。我们已经建立了使用多能8.5 d.p.c的基因组印迹模型系统。来自种间交叉的小鼠胚胎胚芽（EG）细胞系。我们发现在这些细胞中已经丢失了等位基因特异性印记的基因表达。然而，在将EG细胞体外分化成体细胞谱系后，一些印迹基因可能发生等位基因特异性沉默的部分恢复，表明存在可与等位基因特异性基因沉默分离的配子记忆。我们还生成了一个包含大多数甲基化CpG岛的文库。分析了这些克隆的一个子集，并揭示了甲基化CpG岛分为4个不同的亚型：属于高拷贝数重复家族的CpG岛; 所有组织中独特的CpG岛甲基化; 在父系种系中未甲基化的独特的甲基化CpG岛; 和独特的CpG岛在肿瘤中甲基化。该方法鉴定了整个基因组中甲基化CpG岛的甲基化。

7. 发明申请

US20050282147A1 Methods for assaying gene imprinting and methylated CpG islands 失效
标题翻译：测定基因印迹和甲基化CpG岛的方法
公开(公告)号：US20050282147A1
公开(公告)日：2005-12-22
申请号：US11084085
申请日：2005-03-17
申请人： Andrew Feinberg , Liora Strichman-Almashanu , Shan Jiang
发明人： Andrew Feinberg , Liora Strichman-Almashanu , Shan Jiang
IPC分类号： A01K67/027 , A61P35/00 , C12N5/074 , C12N5/10 , C12N15/09 , C12Q1/02 , C12Q1/68 , C12Q1/00 , C12N5/08
CPC分类号： C12N5/0611 , C12N2501/115 , C12N2501/125 , C12N2501/235 , C12N2501/385 , C12N2502/13 , C12N2503/00 , C12N2503/02 , C12N2510/00 , C12N2517/00 , C12Q1/6827 , C12Q1/6886 , C12Q2600/118 , C12Q2600/136 , C12Q2600/154
摘要： Genomic imprinting is a parent of origin-dependent gene silencing that involves marking of alleles in the germline and differential expression in somatic cells of the offspring. Imprinted genes and abnormal imprinting have been implicated in development, human disease, and embryonic stem cell transplantation. We have established a model system for genomic imprinting using pluripotent 8.5 d.p.c. mouse embryonic germ (EG) cell lines derived from an interspecific cross. We find that allele-specific imprinted gene expression has been lost in these cells. However, partial restoration of allele-specific silencing can occur for some imprinted genes after in vitro differentiation of EG cells into somatic cell lineages, indicating the presence of a gametic memory that is separable from allele-specific gene silencing. We have also generated a library containing most methylated CpG islands. A subset of these clones was analyzed and revealed a subdivision of methylated CpG islands into 4 distinct subtypes: CpG islands belonging to high copy number repeat families; unique CpG islands methylated in all tissues; unique methylated CpG islands that are unmethylated in the paternal germline; and unique CpG islands methylated in tumors. This approach identifies a methylome of methylated CpG islands throughout the genome.
摘要翻译：基因印记是起源依赖基因沉默的亲本，其涉及在种系中标记等位基因和在后代的体细胞中的差异表达。印迹基因和异常印记涉及发育，人类疾病和胚胎干细胞移植。我们已经建立了使用多能8.5 d.p.c的基因组印迹模型系统。来自种间交叉的小鼠胚胎胚芽（EG）细胞系。我们发现在这些细胞中已经丢失了等位基因特异性印记的基因表达。然而，在将EG细胞体外分化成体细胞谱系后，一些印迹基因可能发生等位基因特异性沉默的部分恢复，表明存在可与等位基因特异性基因沉默分离的配子记忆。我们还生成了一个包含大多数甲基化CpG岛的文库。分析了这些克隆的一个子集，并揭示了甲基化CpG岛分为4个不同的亚型：属于高拷贝数重复家族的CpG岛; 所有组织中独特的CpG岛甲基化; 在父系种系中未甲基化的独特的甲基化CpG岛; 和独特的CpG岛在肿瘤中甲基化。该方法鉴定了整个基因组中甲基化CpG岛的甲基化。

8. 发明申请

US20020045257A1 Methods for assaying gene imprinting and methylated CpG islands 失效
标题翻译：测定基因印记和甲基化CpG岛的方法
公开(公告)号：US20020045257A1
公开(公告)日：2002-04-18
申请号：US09861893
申请日：2001-05-22
发明人： Andrew P. Feinberg , Liora Strichman-almashanu
IPC分类号： C12N005/06
CPC分类号： C12N5/0611 , C12N2501/115 , C12N2501/125 , C12N2501/235 , C12N2501/385 , C12N2502/13 , C12N2503/00 , C12N2503/02 , C12N2510/00 , C12N2517/00 , C12Q1/6827 , C12Q1/6886 , C12Q2600/118 , C12Q2600/136 , C12Q2600/154
摘要： Genomic imprinting is a parent of origin-dependent gene silencing that involves marking of alleles in the germline and differential expression in somatic cells of the offspring. Imprinted genes and abnormal imprinting have been implicated in development, human disease, and embryonic stem cell transplantation. We have established a model system for genomic imprinting using pluripotent 8.5 d.p.c. mouse embryonic germ (EG) cell lines derived from an interspecific cross. We find that allele-specific imprinted gene expression has been lost in these cells. However, partial restoration of allele-specific silencing can occur for some imprinted genes after in vitro differentiation of EG cells into somatic cell lineages, indicating the presence of a gametic memory that is separable from allele-specific gene silencing. We have also generated a library containing most methylated CpG islands. A subset of these clones was analyzed and revealed a subdivision of methylated CpG islands into 4 distinct subtypes: CpG islands belonging to high copy number repeat families; unique CpG islands methylated in all tissues; unique methylated CpG islands that are unmethylated in the paternal germline; and unique CpG islands methylated in tumors. This approach identifies a methylome of methylated CpG islands throughout the genome.
摘要翻译：基因印记是起源依赖基因沉默的亲本，其涉及在种系中标记等位基因和在后代的体细胞中的差异表达。印迹基因和异常印记涉及发育，人类疾病和胚胎干细胞移植。我们已经建立了使用多能8.5 d.p.c的基因组印迹模型系统。来自种间交叉的小鼠胚胎胚芽（EG）细胞系。我们发现在这些细胞中已经丢失了等位基因特异性印记的基因表达。然而，在将EG细胞体外分化成体细胞谱系后，一些印迹基因可能发生等位基因特异性沉默的部分恢复，表明存在可与等位基因特异性基因沉默分离的配子记忆。我们还生成了一个包含大多数甲基化CpG岛的文库。分析了这些克隆的一个子集，并揭示了甲基化CpG岛分为4个不同的亚型：属于高拷贝数重复家族的CpG岛; 所有组织中独特的CpG岛甲基化; 在父系种系中未甲基化的独特的甲基化CpG岛; 和独特的CpG岛在肿瘤中甲基化。该方法鉴定了整个基因组中甲基化CpG岛的甲基化。

9. 发明申请

US20010007153A1 SOLID CHIMERIC ORGANS, ANIMAL MODELS HAVING SAME, PROCESS FOR PREPARING SAME, NON-TUMORIGENIC IMMORTALIZED HUMAN CELL LINES, SUSCEPTIBLE CELLS AND CYTOPATHIC MAMMALIAN VIRUSES 无效
标题翻译：固体动物器官，具有其的动物模型，制备它们的方法，非重组人免疫细胞系，可疑细胞和CYPOPATHIC MAMMALIAN病毒
公开(公告)号：US20010007153A1
公开(公告)日：2001-07-05
申请号：US08876635
申请日：1997-06-16
发明人： JENNIFER JUNE BROWN , ELAZAR RABBANI , JAMES J. DONEGAN , JAYANTA ROY-CHOWDHURY
IPC分类号： A01K067/00 , A01K067/033 , A01K067/027
CPC分类号： A01K67/0271 , A61K2035/122 , C12N2503/04 , C12N2510/04 , C12N2517/00 , C12N2517/02
摘要： This invention provides useful solid chimeric organs as well as animal models having such solid chimeric organs and processes for their preparation. Such organs find significant value and use in developing new models for disease, drug and therapeutic investigations and monitoring, and in studying storage functions and processes. The solid chimeric organs are comprised of recipient cells and donor cells, the latter themselves comprising allogeneic or xenogeneic cells which are unmodified or modified to contain one or more nucleic acid segments capable of exhibiting at least one biological property, e.g. DNA synthesis, replication, promoter function, transcription, translation, reverse transcription, and the like, non-native to the donor cell. The solid chimeric organs can be prepared from recipient organs using recipient cells and implanted allogeneic or xenogeneic donor cells from non-homologous organs or tissues. Also provided by this invention are non-tumorigenic immortalized human cell lines modified by having sequences derived from hepatotrophic viruses introduced into the cells. Susceptible cells, cytopathic mammalian viruses, target cells rendered susceptible to cytopathic events, and human cells infected or transfected by noncytopathic viruses are also provided.
摘要翻译：本发明提供了有用的固体嵌合器官以及具有这种固体嵌合器官的动物模型及其制备方法。这些器官在开发疾病，药物和治疗调查和监测的新模型以及研究储存功能和过程方面发现了重要的价值和用途。固体嵌合器官由受体细胞和供体细胞组成，后者本身包含未修饰或修饰以含有一个或多个能够表现出至少一种生物学特性的核酸区段的同种异体或异种细胞。 DNA合成，复制，启动子功能，转录，翻译，逆转录等，对供体细胞是非天然的。固体嵌合器官可以使用受体细胞和来自非同源器官或组织的植入的同种异体或异种供体细胞从受体器官制备。本发明还提供非致瘤性永生化人细胞系，其通过将源自引入细胞的肝细胞病毒的序列修饰。还提供易感细胞，致细胞病毒性哺乳动物病毒，对细胞病变事件变得敏感的靶细胞，以及非细胞病变病毒感染或转染的人类细胞。

10. 发明授权

US5612018A Drug screening and treatment for HIV thymocyte depletion 失效
标题翻译：药物筛选和治疗HIV胸腺细胞消耗
公开(公告)号：US5612018A
公开(公告)日：1997-03-18
申请号：US183178
申请日：1994-01-18
申请人： Mark L. Bonyhadi , Hideto Kaneshima , Joseph M. McCune , Reiko Namikawa , Lishan Su
发明人： Mark L. Bonyhadi , Hideto Kaneshima , Joseph M. McCune , Reiko Namikawa , Lishan Su
IPC分类号： A01K67/027 , A61K49/00 , C12N15/85
CPC分类号： A61K49/0004 , A01K67/0271 , C12N2517/00
摘要： A method is provided for screening compounds for the ability to supress thymocyte depletion in thymuses of HIV-infected individuals, particularly enhancing the CD4.sup.+ -expressing population as compared to an untreated individual. Particularly, drugs are provided which allow for this result, cyclosporine A being exemplary.
摘要翻译：提供了一种筛选化合物以抑制HIV感染个体的胸腺中胸腺细胞消耗的能力的方法，特别是与未处理的个体相比增强了CD4 +表达的群体。特别地，提供了允许该结果的药物，环孢菌素A是示例性的。

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