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21. 发明授权

US5438121A Brain derived neurotrophic factor 失效
标题翻译：脑源性神经营养因子
公开(公告)号：US5438121A
公开(公告)日：1995-08-01
申请号：US691612
申请日：1991-04-25
申请人： Yves-Alain Barde , Joachim Leibrock , Friedrich Lottspeich , David Edgar , George Yancopoulos , Hans Thoenen
发明人： Yves-Alain Barde , Joachim Leibrock , Friedrich Lottspeich , David Edgar , George Yancopoulos , Hans Thoenen
IPC分类号： A61K38/00 , C07K14/475 , C07K14/48 , C07K14/71 , C07K16/22 , C07K16/28 , F02B75/02 , A61K38/22 , A23J1/00 , C07K1/00 , C12P21/06
CPC分类号： C07K14/71 , C07K14/475 , C07K14/48 , C07K16/22 , C07K16/2863 , A61K38/00 , F02B2075/027 , G01N2333/4709 , G01N2333/475
摘要： The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), as well as BDNF protein produced in quantity using these nucleic acid sequences, as well as fragments and derivatives thereof. In addition, the invention relates to pharmacologic compositions and therapeutic uses of BDNF, having provided, for the first time, the means to generate sufficient quantities of substantially pure BDNF for clinical use. In a specific embodiment, BDNF may be used to promote the survival of substantia nigra dopaminergic neurons and basal forebrain cholinergic neurons, thereby providing a method for treating, respectively, Parkinson's disease and Alzheimer's disease. The invention also relates to antibodies directed toward BDNF or fragments thereof, having provided a method for generating sufficient immunogen. Further, by permitting a comparison of the nucleic acid sequences of BDNF and NGF, the present invention provides for the identification of homologous regions of nucleic acid sequence between BDNF and NGF, thereby defining a BDNF/NGF gene family; the invention provides a method for identifying and isolating additional members of this gene family.
摘要翻译：本发明涉及编码脑源性神经营养因子（BDNF）的核酸序列，以及使用这些核酸序列量产生的BDNF蛋白质，以及其片段和衍生物。此外，本发明涉及BDNF的药物组合物和治疗用途，其首次提供了产生足够量的用于临床使用的基本上纯的BDNF的方法。在一个具体实施方案中，BDNF可用于促进黑质多巴胺能神经元和基础前脑胆碱能神经元的存活，从而提供分别治疗帕金森病和阿尔茨海默氏病的方法。本发明还涉及针对BDNF或其片段的抗体，其提供了产生足够免疫原的方法。此外，通过比较BDNF和NGF的核酸序列，本发明提供了鉴定BDNF和NGF之间的核酸序列的同源区，从而限定BDNF / NGF基因家族; 本发明提供了鉴定和分离该基因家族的其他成员的方法。

22. 发明授权

US5229500A Brain derived neurotrophic factor 失效
标题翻译：脑源性神经营养因子
公开(公告)号：US5229500A
公开(公告)日：1993-07-20
申请号：US570657
申请日：1990-08-20
申请人： Yves-Alain Barde , Joachim Leibrock , Friedrich Lottspeich , David Edgar , George Yancopoulos , Hans Thoenen
发明人： Yves-Alain Barde , Joachim Leibrock , Friedrich Lottspeich , David Edgar , George Yancopoulos , Hans Thoenen
IPC分类号： A61K38/00 , C07K14/475 , C07K14/48 , C07K14/71 , C07K16/22 , C07K16/28 , F02B75/02
CPC分类号： C07K14/71 , C07K14/475 , C07K14/48 , C07K16/22 , C07K16/2863 , A61K38/00 , F02B2075/027 , G01N2333/4709 , G01N2333/475
摘要： The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), as well as BDNF protein produced in quantity using these nucleic acid sequences, as well as fragments and derivatives thereof. In addition, the invention relates to pharmacologic compositions and therapeutic uses of BDNF, having provided, for the first time, the means to generate sufficient quantities of substantially pure BDNF for clinical use. In a specific embodiment, BDNF may be used to promote the survival of substantia nigra dopaminergic neurons and basal forebrain cholinergic neurons, thereby providing a method for treating, respectively, Parkinson's disease and Alzheimer's disease. The invention also relates to antibodies directed toward BDNF or fragments thereof, having provided a method for generating sufficient immunogen. Further, by permitting a comparison of the nucleic acid sequences of BDNF and NGF, the present invention provides for the identification of homologous regions of nucleic acid sequence between BDNF and NGF, thereby defining a BDNF/NGF gene family; the invention provides a method for identifying and isolating additional members of this gene family.
摘要翻译：本发明涉及编码脑源性神经营养因子（BDNF）的核酸序列，以及使用这些核酸序列量产生的BDNF蛋白质，以及其片段和衍生物。此外，本发明涉及BDNF的药物组合物和治疗用途，其首次提供了产生足够量的用于临床使用的基本上纯的BDNF的方法。在一个具体实施方案中，BDNF可用于促进黑质多巴胺能神经元和基础前脑胆碱能神经元的存活，从而提供分别治疗帕金森病和阿尔茨海默氏病的方法。本发明还涉及针对BDNF或其片段的抗体，其提供了产生足够免疫原的方法。此外，通过比较BDNF和NGF的核酸序列，本发明提供了鉴定BDNF和NGF之间的核酸序列的同源区，从而限定BDNF / NGF基因家族; 本发明提供了鉴定和分离该基因家族的其他成员的方法。

23. 发明授权

US07205148B2 Genome mutation by intron insertion into an embryonic stem cell genome 有权
标题翻译：通过内含子插入到胚胎干细胞基因组中的基因组突变
公开(公告)号：US07205148B2
公开(公告)日：2007-04-17
申请号：US10865424
申请日：2004-06-10
申请人： Aris N. Economides , David M. Valenzuela , Samuel Davis , George Yancopoulos
发明人： Aris N. Economides , David M. Valenzuela , Samuel Davis , George Yancopoulos
IPC分类号： C12N15/87 , C12N15/05 , C12N15/00
CPC分类号： C12N15/85 , A01K67/0275 , A01K2217/05 , A01K2217/075 , A61D19/04 , C12N15/907 , C12N2800/30 , C12N2830/42 , C12N2840/44
摘要： Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.
摘要翻译：通过将内含子通过同源重组插入到基因组外显子中而在基因组外显子中产生突变的方法。此外，提供了通过将内含子通过同源重组插入到基因组外显子中而将修饰引入基因组外显子的方法，从而提供了从包含基因组外显子的基因组的基因组区域产生的成熟mRNA转录物不含修饰。所述方法提供了用于将任何类型的突变和/或修饰引入哺乳动物细胞基因组的快速方法。

24. 发明申请

US20050272655A1 Methods of using IL-1 antagonists to treat autoinflammatory disease 有权
标题翻译：使用IL-1拮抗剂治疗自身炎症性疾病的方法
公开(公告)号：US20050272655A1
公开(公告)日：2005-12-08
申请号：US11144987
申请日：2005-06-03
申请人： Scott Mellis , Margaret Karow , George Yancopoulos , Joanne Papadopoulos
发明人： Scott Mellis , Margaret Karow , George Yancopoulos , Joanne Papadopoulos
IPC分类号： A61K38/17 , C07K14/715
CPC分类号： C07K14/7155 , A61K38/00 , A61K38/177 , A61K45/06 , A61K2300/00
摘要： Methods of treating, inhibiting, or ameliorating an autoinflammatory disorder, disease, or condition in a subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the autoinflammatory disorder, disease, or condition is treated, inhibited, or ameliorated. The IL-1 antagonist is a molecule capable of binding and inhibiting IL-1. The therapeutic methods are useful for treating a human adult or child suffering from Neonatal Onset Multisystem Inflammatory Disorder (NOMID/CINCA), Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory Syndrome (FCAS), familial mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), or systemic onset juvenile idiopathic arthritis (Still's Disease).
摘要翻译：在有需要的受试者中治疗，抑制或改善自身炎性疾病，疾病或病症的方法，包括向需要治疗的受试者施用治疗量的白细胞介素1（IL-1）拮抗剂，其中所述自身炎性疾病，疾病，或条件得到治疗，抑制或改善。 IL-1拮抗剂是能够结合和抑制IL-1的分子。治疗方法可用于治疗患有新生儿起始多系统炎症性疾病（NOMID / CINCA），Muckle-Wells综合征（MWS），家族性冷自身炎症综合征（FCAS），家族性地中海热（FMF），肿瘤坏死的成人或儿童因子受体相关的周期性发热综合征（TRAPS）或全身性发作的幼年特发性关节炎（Still氏病）。

25. 发明申请

US20050186623A1 Isolating cells expressing secreted proteins 审中-公开
公开(公告)号：US20050186623A1
公开(公告)日：2005-08-25
申请号：US11099158
申请日：2005-04-05
申请人： James Fandl , Neil Stahl , Gang Chen , George Yancopoulos
发明人： James Fandl , Neil Stahl , Gang Chen , George Yancopoulos
IPC分类号： A01K67/027 , C07K14/315 , C07K14/52 , C07K16/28 , C12N5/10 , C12N15/09 , C40B30/04 , G01N33/569 , G01N33/68 , C12Q1/68 , G01N33/53 , G01N33/567
CPC分类号： C40B30/04 , A01K2217/05 , A01K2267/01 , C07K14/315 , C07K14/52 , C07K16/2863 , C07K2317/77 , C07K2319/00 , C12N15/1051 , G01N33/56966 , G01N33/6845 , G01N2500/10
摘要： A method for identifying and isolating cells which produce secreted proteins. This method is based upon a specific characteristic or the expression level of the secreted protein by transiently capturing the secreted protein on the surface of an individual cell, allowing selection of rare cell clones from a heterogeneous population. Also provided is the use of this method to generate cells which produce a desired level of secreted protein or secreted protein of a particular characteristic(s), and organisms which possess such cells. In particular, the method allows rapid isolation of high expression recombinant antibody-producing cell lines, or may be applied directly to rapid isolation of specific hybridomas, or to the isolation of antibody-producing transgenic animals. This method is applicable for any cell which secretes protein.

26. 发明授权

US06933276B1 Methods of treating peripheral neuropathies using neurotrophin-3 失效
标题翻译：使用神经营养因子-3治疗周围神经病变的方法
公开(公告)号：US06933276B1
公开(公告)日：2005-08-23
申请号：US08342457
申请日：1994-11-18
申请人： Andreas Hohn , Yves-Alain Barde , Hans Thoenen , Ronald M. Lindsay , George Yancopoulos
发明人： Andreas Hohn , Yves-Alain Barde , Hans Thoenen , Ronald M. Lindsay , George Yancopoulos
IPC分类号： A61K38/00 , C07K14/475 , C07K14/48 , C07K14/71 , C07K16/22 , C07K16/28 , F02B75/02 , A61K38/18
CPC分类号： C07K16/2863 , A61K38/00 , C07K14/475 , C07K14/48 , C07K14/71 , C07K16/22 , F02B2075/027 , G01N2333/4709 , G01N2333/475 , Y10S514/866 , Y10S514/903
摘要： The present invention relates to neurotrophin-3 (NT-3), a newly discovered member of the BDNF gene family. It is based, in part, on the identification of regions of nucleic acid sequence homology shared by BDNF and NGF (U.S. patent application Ser. No. 07/400,591, filed Aug. 30, 1989, incorporated by reference herein). According to the present invention, these regions of homology may be used to identify new members of the BDNF/NGF gene family; such methodology was used to identify NT-3. The present invention provides for the genes and gene products of new BDNF/NGF related neurotrophic factors identified by these methods. According to the invention, NT-3 may be used in the diagnosis and/or treatment of neurologic disorders, including, but not limited to, Alzheimer's disease and Parkinson's disease. Because NT-3 has been observed to exhibit a spectrum of activity different from the spcificities of BDNF or NGF, NT-3 provides new and valuable options for enducing regrowth and repair in the central nervous system.
摘要翻译：本发明涉及新发现的BDNF基因家族的神经营养因子-3（NT-3）。它部分地基于由BDNF和NGF共享的核酸序列同源性的区域的鉴定（美国专利申请07 / 400,591，1989年8月30日提交，通过引用并入本文）。根据本发明，这些同源区域可用于鉴定BDNF / NGF基因家族的新成员; 这种方法用于鉴定NT-3。本发明提供了通过这些方法鉴定的新型BDNF / NGF相关神经营养因子的基因和基因产物。根据本发明，NT-3可用于诊断和/或治疗神经障碍，包括但不限于阿尔茨海默氏病和帕金森病。由于NT-3已经被观察到表现出与BDNF或NGF的特征不同的活性谱系，NT-3为在中枢神经系统中诱导再生和修复提供了新的有价值的选择。

27. 发明申请

US20050100906A1 TIE-2 ligands, methods of making and uses thereof 失效
标题翻译： TIE-2配体，其制备方法和用途
公开(公告)号：US20050100906A1
公开(公告)日：2005-05-12
申请号：US10603293
申请日：2003-06-25
申请人： Samuel Davis , George Yancopoulos
发明人： Samuel Davis , George Yancopoulos
IPC分类号： A61K31/00 , C07H21/04 , C07K14/705 , C12Q1/68
CPC分类号： A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0306
摘要： The present invention provides for an isolated nucleic acid molecule encoding a human TIE-2 ligand. In addition, the invention provides for a receptorbody which specifically binds a human TIE-2 ligand. The invention also provides an antibody which specifically binds a human TIE-2 ligand. The invention further provides for an antagonist of human TIE-2. The invention further provides for a ligandbody which specifically binds TIE-2 receptor. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth, differentiation or migration of cells expressing the TIE-2 receptor, including, but not limited to, hematopoietic precursor cells, a method of blocking the growth, differentiation or migration of cells expressing the TIE-2 receptor including, but not limited to, hematopoietic precursor cells, and a method of attenuating or preventing tumor growth in a human.
摘要翻译：本发明提供了编码人TIE-2配体的分离的核酸分子。此外，本发明提供了特异性结合人TIE-2配体的受体体。本发明还提供了特异性结合人TIE-2配体的抗体。本发明进一步提供人TIE-2的拮抗剂。本发明进一步提供了特异性结合TIE-2受体的配体体。本发明还提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法，促进表达TIE-2受体的细胞的生长，分化或迁移的方法，包括但不限于，造血前体细胞，阻断表达TIE-2受体的细胞的生长，分化或迁移的方法，包括但不限于造血前体细胞，以及减弱或预防人类肿瘤生长的方法。

28. 发明授权

US5180820A Brain-derived neurotrophic factor 失效
标题翻译：脑源性神经营养因子
公开(公告)号：US5180820A
公开(公告)日：1993-01-19
申请号：US400591
申请日：1989-08-30
申请人： Yves-Alain Barde , Joachim Leibrock , Friedrich Lottspeich , George Yancopoulos , Hans Thoenen
发明人： Yves-Alain Barde , Joachim Leibrock , Friedrich Lottspeich , George Yancopoulos , Hans Thoenen
IPC分类号： A61K38/00 , A61K38/18 , A61K38/27 , A61K39/395 , A61K49/00 , A61P25/00 , A61P25/02 , A61P25/28 , A61P35/00 , C07H15/12 , C07H21/04 , C07K14/00 , C07K14/18 , C07K14/47 , C07K14/475 , C07K14/48 , C07K14/52 , C07K14/71 , C07K16/00 , C07K16/22 , C07K16/28 , C12N1/19 , C12N1/21 , C12N5/00 , C12N5/10 , C12N15/00 , C12N15/09 , C12N15/12 , C12P21/00 , C12P21/02 , C12P21/08 , C12Q1/00 , C12Q1/68 , C12R1/01 , C12R1/645 , C12R1/91 , F02B75/02 , G01N33/53 , G01N33/577
CPC分类号： C07K14/48 , C07K14/475 , C07K14/71 , C07K16/22 , C07K16/2863 , A61K38/00 , F02B2075/027 , G01N2333/4709 , G01N2333/475
摘要： The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), as well as BDNF protein produced in quantity using these nucleic acid sequences, as well as fragments and derivatives thereof. In addition, the invention relates to pharmacologic compositions and therapeutic uses of BDNF, having provided, for the first time, the ability to generate sufficient quantities of substantially pure BDNF for clinical use. The invention also relates to antibodies directed toward BDNF or fragments thereof, having provided a method for generating sufficient immunogen. Further, by permitting a comparison of the nucleic acid sequences of BDNF and NGF, the present invention provides for the identification of homologous regions of nucleic acid sequence between BDNF and NGF, thereby defining a BDNF/NGF gene family; the invention provides a method for identifying an disolating additional members of this gene family.
摘要翻译：本发明涉及编码脑源性神经营养因子（BDNF）的核酸序列，以及使用这些核酸序列量产生的BDNF蛋白质，以及其片段和衍生物。此外，本发明涉及BDNF的药物组合物和治疗用途，BDNF首次提供产生足够量的基本上纯的BDNF用于临床应用的能力。本发明还涉及针对BDNF或其片段的抗体，其提供了产生足够免疫原的方法。此外，通过比较BDNF和NGF的核酸序列，本发明提供了鉴定BDNF和NGF之间的核酸序列的同源区，从而限定BDNF / NGF基因家族; 本发明提供了一种用于鉴定该基因家族的不成体的附加成员的方法。

29. 发明授权

US07354578B2 Method of tumor regression with VEGF inhibitors 有权
标题翻译： VEGF抑制剂肿瘤消退的方法
公开(公告)号：US07354578B2
公开(公告)日：2008-04-08
申请号：US10860958
申请日：2004-06-04
申请人： Jessica Kandel , Jocelyn Holash , Darrell Yamashiro , Jianzhong Huang , George Yancopoulos , John Rudge
发明人： Jessica Kandel , Jocelyn Holash , Darrell Yamashiro , Jianzhong Huang , George Yancopoulos , John Rudge
IPC分类号： A61K38/18 , C07K14/71 , C12N15/62
CPC分类号： A61K38/179 , A61K2039/505 , C07K2319/30
摘要： Methods of regressing or inhibiting a tumor in a subject by administering an agent capable of blocking, inhibiting, or ameliorating vascular endothelial growth factor (VEGF)-mediated activity to a subject in need thereof such that the tumor is regressed or inhibited. The method of the invention results in a reduction of tumor size and inhibition of tumor metastases. This method is particularly useful for patients suffering from bulky, metastatic cancers.
摘要翻译：通过给予有需要的受试者能够阻断，抑制或改善血管内皮生长因子（VEGF）介导的活性的试剂使得肿瘤被退化或抑制，从而使受试者的肿瘤回归或抑制肿瘤的方法。本发明的方法导致肿瘤大小的减小和肿瘤转移的抑制。该方法对于患有体积大，转移性癌症的患者特别有用。

30. 发明申请

US20070275466A1 Methods of modifying genes in eukaryotic cells 审中-公开
标题翻译：在真核细胞中修饰基因的方法
公开(公告)号：US20070275466A1
公开(公告)日：2007-11-29
申请号：US11787969
申请日：2007-04-17
申请人： Aris Economides , David Valenzuela , Samuel Davis , George Yancopoulos
发明人： Aris Economides , David Valenzuela , Samuel Davis , George Yancopoulos
IPC分类号： C12N15/89
CPC分类号： C12N15/85 , A01K67/0275 , A01K2217/05 , A01K2217/075 , A61D19/04 , C12N15/907 , C12N2800/30 , C12N2830/42 , C12N2840/44
摘要： Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.
摘要翻译：通过将内含子通过同源重组插入到基因组外显子中而在基因组外显子中产生突变的方法。此外，提供了通过将内含子通过同源重组插入到基因组外显子中而将修饰引入基因组外显子的方法，从而提供了从包含基因组外显子的基因组的基因组区域产生的成熟mRNA转录物不含修饰。所述方法提供了用于将任何类型的突变和/或修饰引入哺乳动物细胞基因组的快速方法。

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