公开(公告)号：EP0482623B1

公开(公告)日：1995-05-10

申请号：EP91118120.4

申请日：1991-10-24

申请人： CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Folkman, Moses Judah ,  Shing, Yuen

IPC分类号： C07K14/475

CPC分类号： C07K14/475 ,  A61K38/00

公开(公告)号：EP0482623A2

公开(公告)日：1992-04-29

申请号：EP91118120.4

申请日：1991-10-24

申请人： CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Folkman, Moses Judah ,  Shing, Yuen

IPC分类号： C07K14/475

CPC分类号： C07K14/475 ,  A61K38/00

摘要： A novel growth factor (BTC-CG) was purified from the conditioned medium of pancreatic beta tumor cells initially derived from transgenic mice (RIP1-Tag2). The purification scheme included BioRex 70 chromatography, phenyl-Sepharose chromatography, TSL-GEL heparin FPLC and C4 reverse phase HPLC. The peptide also stimulated proliferation of bovine smooth muscle cells. It was not inactivated by boiling, by 10 mM dithiothreitol or by exposure to 1 M acetic acid. Biological activity of BTC-GF was recovered from a single band of protein which had a molecular weight of 32,000 on SDS-PAGE. The partial N-terminal amino acid sequence of this protein from BTC-3 and BTC-J10 cells was determined with an ABI 470A protein sequencer to be:

摘要翻译： 从最初衍生自转基因小鼠（RIP1-Tag2）的胰腺β细胞的细胞培养基中纯化出新的生长因子（BTC-CG）。 纯化方案包括BioRex 70色谱，苯基琼脂糖层析，TSL-GEL肝素FPLC和C4反相HPLC。 该肽还刺激了牛平滑肌细胞的增殖。 通过煮沸，10mM二硫苏糖醇或通过暴露于1M乙酸不灭活。 从SDS-PAGE上分子量为32,000的单一蛋白质带中回收BTC-GF的生物活性。 使用ABI 470A蛋白质测序仪测定来自BTC-3和BTC-J10细胞的该蛋白质的部分N-末端氨基酸序列：

公开(公告)号：EP0555785B1

公开(公告)日：1996-12-04

申请号：EP93101871.7

申请日：1993-02-06

申请人： Takeda Chemical Industries, Ltd. ,  CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Folkmann, Moses Judah ,  Shing, Yuen ,  Igarashi, Koichi

IPC分类号： C12N15/18 ,  C07K14/475

CPC分类号： C07K14/475 ,  A61K38/00

公开(公告)号：EP0555785A1

公开(公告)日：1993-08-18

申请号：EP93101871.7

申请日：1993-02-06

申请人： Takeda Chemical Industries, Ltd. ,  CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Folkmann, Moses Judah ,  Shing, Yuen ,  Igarashi, Koichi

IPC分类号： C12N15/18 ,  C07K15/06

CPC分类号： C07K14/475 ,  A61K38/00

摘要： A recombinant non-glycosylated mammalian growth factor (BTC-GF) stimulates proliferation of human smooth muscle cells. Especially, the amino acid sequence of the protein deduced from the nucleotide sequence coding for human BTC-GF is as that comprising the amino acids No. 1 to No. 147 of Figure 10 or the amino acids No. 1 to 80 of Figure 10, and the amino acid sequence of the protein deduced from the nucleotide sequence coding for mouse BTC-GF is as that comprising the amino acids No. 1 to No. 146 of Figure 9.

摘要翻译： 重组非糖基化哺乳动物生长因子（BTC-GF）刺激人平滑肌细胞的增殖。 特别地，从编码人BTC-GF的核苷酸序列推测的蛋白质的氨基酸序列是包含图10的氨基酸No.1至No.147或图10的氨基酸No.1至80， 并且从编码小鼠BTC-GF的核苷酸序列推测的蛋白质的氨基酸序列是包含图9的第1至第146号氨基酸的氨基酸序列。

公开(公告)号：EP0482623A3

公开(公告)日：1993-01-13

申请号：EP91118120.4

申请日：1991-10-24

申请人： CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Folkman, Moses Judah ,  Shing, Yuen

IPC分类号： C07K14/475

CPC分类号： C07K14/475 ,  A61K38/00

摘要： A novel growth factor (BTC-CG) was purified from the conditioned medium of pancreatic beta tumor cells initially derived from transgenic mice (RIP1-Tag2). The purification scheme included BioRex 70 chromatography, phenyl-Sepharose chromatography, TSL-GEL heparin FPLC and C4 reverse phase HPLC. The peptide also stimulated proliferation of bovine smooth muscle cells. It was not inactivated by boiling, by 10 mM dithiothreitol or by exposure to 1 M acetic acid. Biological activity of BTC-GF was recovered from a single band of protein which had a molecular weight of 32,000 on SDS-PAGE. The partial N-terminal amino acid sequence of this protein from BTC-3 and BTC-J10 cells was determined with an ABI 470A protein sequencer to be:

公开(公告)号：EP0457223A1

公开(公告)日：1991-11-21

申请号：EP91107682.6

申请日：1991-05-11

申请人： CHILDREN'S MEDICAL CENTER CORPORATION ,  THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

发明人： Folkman, Moses Judah ,  Shing, Yuen ,  Szabo, Sandor

IPC分类号： C07K15/00 ,  A61K37/02 ,  A61K31/70

CPC分类号： A61K9/0019 ,  A61K38/1825 ,  A61K47/26 ,  A61K47/36 ,  C07K14/501 ,  C07K14/503 ,  A61K2300/00

摘要： Methods for stabilizing fibroblast growth factor (FGF) in heat, acid and/or proteolytic environments are provided. Such methods comprise combining or otherwise complexing FGF with a salt of sucrose octasulfate (SOS) and in particular with the aluminum (sucralfate) or potassium salts thereof. The present invention also provides FGF-stable compositions comprising SOS and FGF. Such compositions can be used in the treatment of FGF-responsive diseases including the treatment of wounds and ulcerative conditions of the gastrointestinal tract. The present invention also provides various diagnostic protocols employing SOS as well as diagnostic kits with SOS as a component thereof. Finally, the present invention provides methods of purifying FGF with SOS.

摘要翻译： 提供了在热，酸和/或蛋白水解环境中稳定成纤维细胞生长因子（FGF）的方法。 这样的方法包括将FGF与蔗糖八硫酸盐（SOS）的盐，特别是与铝（硫糖铝）或其钾盐组合或以其它方式络合。 本发明还提供包含SOS和FGF的FGF稳定组合物。 这些组合物可用于治疗FGF反应性疾病，包括治疗伤口和溃疡性胃肠道疾病。 本发明还提供使用SOS的各种诊断方案以及具有SOS作为其组分的诊断试剂盒。 最后，本发明提供了用SOS纯化FGF的方法。