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公开(公告)号：US06933276B1
公开(公告)日：2005-08-23
申请号：US08342457
申请日：1994-11-18
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。
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2.发明授权Method for producing biologically active human brain derived neurotrophic factor 失效生物活性人脑源性神经营养因子的制备方法
公开(公告)号：US5453361A
公开(公告)日：1995-09-26
申请号：US823117
申请日：1992-01-21
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 , C12P21/06 , C07H17/00
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 means 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 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。 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。
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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。
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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
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。
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公开(公告)号：US5180820A
公开(公告)日：1993-01-19
申请号：US400591
申请日：1989-08-30
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。
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公开(公告)号：US20050260203A1
公开(公告)日：2005-11-24
申请号：US11089803
申请日：2005-03-25
IPC分类号： A61K38/00 , A61K38/17 , A61K39/395 , C07K14/47 , C07K14/71
CPC分类号： C07K14/71 , A61K38/00 , A61K38/179 , C07K14/47 , C07K2319/00 , C07K2319/30
摘要： Modified chimeric polypeptides with improved pharmacokinetics and improved tissue penetration are disclosed useful for treating eye disorders, including age-related macular degeneration and diabetic retinopathy.
摘要翻译： 公开了具有改善的药物动力学和改善的组织穿透的修饰的嵌合多肽，其可用于治疗眼睛疾病，包括年龄相关性黄斑变性和糖尿病性视网膜病变。
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7.发明申请Modified chimeric polypeptides with improved pharmacokinetic properties and methods of making and using thereof 有权具有改善的药代动力学性质的修饰的嵌合多肽及其制备和使用方法公开(公告)号：US20050175610A1
公开(公告)日：2005-08-11
申请号：US10988243
申请日：2004-11-12
IPC分类号： A61K38/00 , C07K14/71 , A61K39/395 , A61K38/17
CPC分类号： C07K14/71 , A61K38/00 , C07K2319/00
摘要： Modified chimeric polypeptides with improved pharmacokinetics are disclosed useful for treating eye disorders, including age-related macular degeneration and diabetic retinopathy.
摘要翻译： 公开了具有改善的药代动力学的修饰的嵌合多肽可用于治疗眼睛疾病，包括年龄相关性黄斑变性和糖尿病性视网膜病变。
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公开(公告)号：US20050003543A1
公开(公告)日：2005-01-06
申请号：US10865424
申请日：2004-06-10
IPC分类号： A01K67/027 , C12N5/08 , C12N15/90 , C12N5/06 , C12N15/85
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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公开(公告)号：US20070037748A1
公开(公告)日：2007-02-15
申请号：US11502736
申请日：2006-08-11
申请人： Neil Stahl , George Yancopoulos , Eric Furfine , Jesse Cedarbaum
发明人： Neil Stahl , George Yancopoulos , Eric Furfine , Jesse Cedarbaum
IPC分类号： A61K38/17
CPC分类号： A61K38/179
摘要： A method of reducing or preventing hypertension associated with administration of a vascular endothelial growth factor (VEGF) antagonist in a human subjects suffering from a disease or condition treatable with a VEGF antagonist in which is it desirable to reduce or prevent hypertension. The method is particularly useful for treatment of patients unresponsive to treatment with a VEGF inhibitor administered intravenously.
摘要翻译： 在患有可用VEGF拮抗剂治疗的疾病或病症的人类受试者中降低或预防与血管内皮生长因子（VEGF）拮抗剂的给药相关的高血压的方法，其中希望减少或预防高血压。 该方法对于治疗对用静脉内施用的VEGF抑制剂治疗无反应的患者特别有用。
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公开(公告)号：US20060234311A1
公开(公告)日：2006-10-19
申请号：US11434403
申请日：2006-05-15
申请人： James Fandl , Neil Stahl , Gang Chen , George Yancopoulos
发明人： James Fandl , Neil Stahl , Gang Chen , George Yancopoulos
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 of detecting and isolating cells that produce any secreted protein of interest (POI), comprising: a) constructing a cell line transiently or stably expressing a cell surface capture molecule, which binds the POI, by transfecting the cell line with a nucleic acid that encodes such cell surface capture molecule; b) transfecting said cell simultaneously or subsequently with a second nucleic acid that encodes a POI wherein such POI is secreted; c) detecting the surface-displayed POI by contacting the cells with a detection molecule, which binds the POI; and d) isolating cells based on the detection molecule.
摘要翻译： 一种检测和分离产生任何分泌的感兴趣蛋白质（POI）的细胞的方法，包括：a）通过用核酸转染细胞系来构建瞬时或稳定表达结合POI的细胞表面捕获分子的细胞系 编码这种细胞表面捕获分子; b）同时或随后用编码POI的第二核酸同时转染所述细胞，其中所述POI被分泌; c）通过使细胞与结合POI的检测分子接触来检测表面显示的POI; 和d）基于检测分子分离细胞。
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