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1. 发明申请

US20060025577A1 Endothelial cell growth factor methods of isolation and expression 审中-公开
标题翻译：内皮细胞生长因子分离和表达方法
公开(公告)号：US20060025577A1
公开(公告)日：2006-02-02
申请号：US11210001
申请日：2005-08-22
申请人： Napoleone Ferrara , Denis Gospodarowicz , Jean Plouet
发明人： Napoleone Ferrara , Denis Gospodarowicz , Jean Plouet
IPC分类号： A61K38/18 , C07K14/59
CPC分类号： C07K14/52 , A61K38/1866
摘要： A novel growth factor specific for vascular endothelial cells has been identified in conditioned medium of bovine pituitary derived folliculo stellate cells. This factor, named folliculo stellate derived growth facto (FSdGF) or vascular endothelial growth factor (VEGF), was purified to homogeneity by a combination of heparin sepharose affinity chromatography, Bio Gel P-60 exclusion chromatography, Mono S ion exchange chromatography and hydrophobic chromatography on a C4 reverse phase HPLC column. The factor is also found in the murine AtT-20 cell line. Alternatively, the growth factor is purified by a first reverse phase HPLC using acetonitrile gradient followed by a second reverse phase HPLC using an isopropanol gradient. FSdGF, having a molecular weight of about 43,000 da, was characterized as a glycoprotein composed of two homologous sub units with MW of about 23 kDa. FSdGF was a potent mitogen for vascular endothelial cells with activity detectable at 10 pg/ml and saturation at 500 pg/ml. It did not stimulate the proliferation of other cell types such as bovine corneal endothelial cells, adrenal cortex cells, granulosa cells, BALB/MK cells or BHK-21 cells. Microsequencing revealed an amino terminal sequence containing no significant homology to any known protein. The release of FSdGF by pituitary cells and its unique target cell specificity indicate that FSdGF is useful in angiogenesis.
摘要翻译：已经在牛垂体衍生的卵泡星状细胞的条件培养基中鉴定了对血管内皮细胞特异性的新型生长因子。通过肝素琼脂糖亲和层析，Bio Gel P-60排除色谱法，Mono S离子交换色谱法和疏水色谱法的组合，将这一命名为卵泡星状衍生生长因子（FSdGF）或血管内皮生长因子（VEGF）的因子纯化至均质在C4反相HPLC柱上。该因子也在鼠AtT-20细胞系中发现。或者，通过使用乙腈梯度的第一反相HPLC纯化生长因子，然后使用异丙醇梯度进行第二反相HPLC纯化生长因子。具有约43,000Da分子量的FSdGF被表征为由具有约23kDa的MW的两个同源亚单位组成的糖蛋白。 FSdGF是血管内皮细胞的有效促分裂原，其活性可检测为10 pg / ml，饱和度为500 pg / ml。它不刺激其他细胞类型的增殖，如牛角膜内皮细胞，肾上腺皮质细胞，颗粒细胞，BALB / MK细胞或BHK-21细胞。微测序显示与任何已知蛋白质没有显着同源性的氨基末端序列。垂体细胞释放FSdGF及其独特的靶细胞特异性表明FSdGF可用于血管发生。

2. 发明授权

US06899882B1 Endothelial cell growth factor methods of isolation and expression 失效
标题翻译：内皮细胞生长因子分离和表达方法
公开(公告)号：US06899882B1
公开(公告)日：2005-05-31
申请号：US08473276
申请日：1995-06-06
申请人： Napoleone Ferrara , Denis Gospodarowicz , Jean Plouet
发明人： Napoleone Ferrara , Denis Gospodarowicz , Jean Plouet
IPC分类号： A61K38/00 , C07K14/52 , A61K38/18
CPC分类号： C07K14/52 , A61K38/1866
摘要： A novel growth factor specific for vascular endothelial cells has been identified in conditioned medium of bovine pituitary derived folliculo stellate cells. This factor, named folliculo stellate derived growth facto (FSdGF) or vascular endothelial growth factor (VEGF), was purified to homogeneity by a combination of heparin sepharose affinity chromatography, Bio Gel P-60 exclusion chromatography, Mono S ion exchange chromatography and hydrophobic chromatography on a C4 reverse phase HPLC column. The factor is also found in the murine AtT-20 cell line.
摘要翻译：已经在牛垂体衍生的滤泡星状细胞的条件培养基中鉴定了对血管内皮细胞特异性的新型生长因子。通过肝素琼脂糖亲和层析，Bio Gel P-60排除色谱法，Mono S离子交换色谱法和疏水色谱法的组合，将这一命名为卵泡星状衍生生长因子（FSdGF）或血管内皮生长因子（VEGF）的因子纯化至均质在C4反相HPLC柱上。该因子也在鼠AtT-20细胞系中发现。

3. 发明授权

US5155214A Basic fibroblast growth factor 失效
标题翻译：碱性成纤维细胞生长因子
公开(公告)号：US5155214A
公开(公告)日：1992-10-13
申请号：US462126
申请日：1990-01-08
申请人： Andrew J. Baird , Frederick S. Esch , Denis Gospodarowicz , Peter Bohlen , Nicholas C. Ling
发明人： Andrew J. Baird , Frederick S. Esch , Denis Gospodarowicz , Peter Bohlen , Nicholas C. Ling
IPC分类号： A61K38/00 , C07K14/50
CPC分类号： C07K14/503 , A61K38/00
摘要： Substantially pure mammalian basic fibroblast growth factors are produced. The amino acid residue sequences of bovine and human bFGF are disclosed as well as a DNA chain encoding the polypeptide of the bovine species. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.
摘要翻译：产生基本纯化的哺乳动物碱性成纤维细胞生长因子。公开了牛和人bFGF的氨基酸残基序列以及编码牛种多肽的DNA链。通过将合成的DNA链适当地插入到克隆载体中并使用克隆载体来转化细胞，可以从原核和真核的转化细胞系获得合成的bFGF。

4. 发明授权

US4902782A Isolation of fibroblast growth factor 失效
标题翻译：分离成纤维细胞生长因子
公开(公告)号：US4902782A
公开(公告)日：1990-02-20
申请号：US268000
申请日：1988-11-07
申请人： Denis Gospodarowicz , Andrew Baird , Peter Bohlen
发明人： Denis Gospodarowicz , Andrew Baird , Peter Bohlen
IPC分类号： C07K14/50
CPC分类号： C07K14/503 , Y10S530/827 , Y10S530/829 , Y10S530/837 , Y10S530/849
摘要： Basic Fibroblast Growth Factor (FGF) is substantially purified by the employment of affinity chromatography using heparin-linked support material. Described is a simplified three step procedure for extracting basic FGF from either mammalian brain or mammalian pituitary tissue. Salt precipitation, e.g., with ammonium sulfate is used to provide a partially purified precipitate that is then subjected to ion-exchange chromatography, e.g., using a Carboxymethyl-Sephadex column. Substantially pure basic FGF fractions are then obtained by fractionating the further partially purified fractions using affinity chromatography on a heparin-linked support e.g., Heparin-Sepharose.
摘要翻译：碱性成纤维细胞生长因子（FGF）通过使用与肝素连接的支持材料的亲和层析基本上纯化。描述了从哺乳动物脑或哺乳动物垂体组织中提取碱性FGF的简化三步法。盐沉淀，例如用硫酸铵，用于提供部分纯化的沉淀，然后进行离子交换层析，例如使用羧甲基Sephadex柱。然后通过使用肝素连接的载体例如肝素 - 琼脂糖凝胶上的亲和层析分离进一步部分纯化的级分来获得基本上纯的碱性FGF级分。

5. 发明授权

US5464774A Bovine basic fibroblast growth factor 失效
标题翻译：牛碱性成纤维细胞生长因子
公开(公告)号：US5464774A
公开(公告)日：1995-11-07
申请号：US139953
申请日：1987-12-31
申请人： Andrew J. Baird , Frederick S. Esch , Denis Gospodarowicz , Peter Bohlen , Nicholas C. Ling
发明人： Andrew J. Baird , Frederick S. Esch , Denis Gospodarowicz , Peter Bohlen , Nicholas C. Ling
IPC分类号： A61K38/00 , C07K14/50 , C12N15/18
CPC分类号： C07K14/503 , A61K38/00
摘要： Substantially pure mammalian basic fibroblast growth factors are produced. The amino acid residue sequences of bovine and human bFGF are disclosed as well as a DNA chain encoding the polypeptide of the bovine species. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bovin bFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.
摘要翻译：产生基本纯化的哺乳动物碱性成纤维细胞生长因子。公开了牛和人bFGF的氨基酸残基序列以及编码牛种多肽的DNA链。通过将合成的DNA链适当地插入到克隆载体中并使用克隆载体来转化细胞，可以从原核和真核的转化细胞系获得合成的bovin bFGF。

6. 发明授权

US4785079A Isolation of fibroblast growth factor 失效
公开(公告)号：US4785079A
公开(公告)日：1988-11-15
申请号：US940524
申请日：1986-12-10
申请人： Denis Gospodarowicz , Andrew Baird , Peter Bohlen
发明人： Denis Gospodarowicz , Andrew Baird , Peter Bohlen
IPC分类号： C07K14/50 , C07K3/28
CPC分类号： C07K14/503
摘要： Basic Fibroblast Growth Factor (FGF) is substantially purified by the employment of affinity chromatography using heparin-linked support material. Described is a simplified three step procedure for extracting basic FGF from either mammalian brain or mammalian pituitary tissue. Salt precipitation, e.g., with ammonium sulfate is used to provide a partially purified precipitate that is then subjected to ion-exchange chromatography, e.g., using a Carboxymethyl-Sephadex column. Substantially pure basic FGF fractions are then obtained by fractionating the further partially purified fractions using affinity chromatography on a heparin-linked support e.g., Heparin-Sepharose.

7. 发明申请

US20050090445A1 Truncated keratinocyte growth factor (KGF) having increased biological activity 失效
标题翻译：截短的角质形成细胞生长因子（KGF）具有增加的生物活性
公开(公告)号：US20050090445A1
公开(公告)日：2005-04-28
申请号：US10998425
申请日：2004-11-29
申请人： Denis Gospodarowicz , Frank Masiarz
发明人： Denis Gospodarowicz , Frank Masiarz
IPC分类号： A61K38/00 , A61K47/48 , C07K14/50 , A61K38/18 , A61K39/02 , C07K14/415 , C07K14/475
CPC分类号： C07K14/50 , A61K38/00 , A61K47/6415 , A61K47/642
摘要： The present invention relates to a keratinocyte growth factor fragment, KGFdes1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGF163 N-terminus. The present invention also relates to a DNA molecule encoding KGFdes1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGFdes1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGFdes1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidernis. Moreover, the present invention relates to a therapeutic composition containing KGFdes1-23 and a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.
摘要翻译：本发明涉及由成熟的全长角质形成细胞生长因子的一部分氨基酸序列组成的角质形成细胞生长因子片段，KGF 或其类似物，KGF _{163 。与成熟的重组角质形成细胞生长因子rKGF相比，该片段显示出促有丝分裂活性的至少2倍的增加，但是缺少包含前23个氨基酸残基的序列CNDMTPEQMATNVNCSSPERH-TR-（SEQ ID NO：2） KGF 163 N末端。本发明还涉及编码KGF Sub1-23的DNA分子，表达载体和含有该DNA分子的转化宿主，以及生产KGF 通过培养转化的宿主。本发明进一步涉及一种KGF des 1>>>>>>。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。此外，本发明涉及含有KGF和其药学上可接受的载体的治疗组合物及其用于伤口愈合目的的用途。}

8. 发明授权

US4956455A Bovine fibroblast growth factor 失效
标题翻译：牛成纤维细胞生长因子
公开(公告)号：US4956455A
公开(公告)日：1990-09-11
申请号：US747154
申请日：1985-06-20
申请人： Andrew Baird , Frederick S. Esch , Peter Bohlen , Denis Gospodarowicz , Nicholas C. Ling
发明人： Andrew Baird , Frederick S. Esch , Peter Bohlen , Denis Gospodarowicz , Nicholas C. Ling
IPC分类号： C12N15/00 , A61K38/00 , C07K14/00 , C07K14/50 , C12N1/16 , C12N1/19 , C12N1/20 , C12N1/21 , C12N15/09 , C12N15/12 , C12P21/02 , C12R1/19 , C12R1/865 , C12R1/91
CPC分类号： C07K14/503 , A61K38/00 , Y10S530/82 , Y10S530/827 , Y10S530/839
摘要： Substantially pure bovine pituitary fibroblast growth factor, a 146 amino acid residue polypeptide, is produced. The amino acid residue sequence of bpFGF is disclosed as well as a DNA chain encoding the polypeptide. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bpFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.
摘要翻译：产生基本上纯的牛垂体成纤维细胞生长因子146个氨基酸残基多肽。公开了bpFGF的氨基酸残基序列以及编码该多肽的DNA链。通过将合成的DNA链适当地插入到克隆载体中并使用克隆载体来转化细胞，可以从原核和真核的转化细胞系获得合成的bpFGF。

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