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。

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。

公开(公告)号：US5132408A

公开(公告)日：1992-07-21

申请号：US270225

申请日：1988-11-14

申请人： Andrew J. Baird ,  Nicholas C. Ling

发明人： Andrew J. Baird ,  Nicholas C. Ling

IPC分类号： C12N15/09 ,  A61K38/00 ,  C07K14/00 ,  C07K14/50 ,  C12N15/00 ,  C12P21/02 ,  C12R1/19 ,  C12R1/865

CPC分类号： C07K14/503 ,  A61K38/00

摘要： Antagonists to basic fibroblast growth factor, a 146 amino acid residue polypeptide, are produced. These antagonists are generally between 4 and 45 residues in length and are characterized by their ability to interact with the FGF receptor and/or inhibit and therefore modulate endothelial and other cell growth. One group of these antagonists includes the four residue sequence which forms basic FGF(36-39), namely Pro-Asp-Gly-Arg. Another of these antagonists includes the sequence of bovine basic FGF(106-115), namely Tyr-Arg-Ser-Arg-Lys-Tyr-Ser-Ser-Trp-Tyr. These peptides are also antagonistic to acidic FGF and other members of the family of FGF peptides. They are effective to combat FGF-promoted mitosis in melanomas and the like.

摘要翻译： 产生碱性成纤维细胞生长因子（146个氨基酸残基多肽）的拮抗剂。 这些拮抗剂的长度通常为4至45个残基，其特征在于它们与FGF受体相互作用和/或抑制和因此调节内皮细胞和其它细胞生长的能力。 一组这些拮抗剂包括形成碱性FGF（36-39）的四个残基序列，即Pro-Asp-Gly-Arg。 这些拮抗剂中的另一种包括牛碱性FGF（106-115）的序列，即Tyr-Arg-Ser-Arg-Lys-Tyr-Ser-Ser-Trp-Tyr。 这些肽也与酸性FGF和FGF家族的其他成员拮抗。 它们有效地对抗FGF促进黑素瘤等有丝分裂。

公开(公告)号：US5478804A

公开(公告)日：1995-12-26

申请号：US250097

申请日：1994-05-26

申请人： Paul Calabresi ,  Julie G. Beitz ,  Jeffrey W. Clark ,  A. Raymond Frackelton, Jr. ,  Douglas A. Lappi ,  Andrew J. Baird

发明人： Paul Calabresi ,  Julie G. Beitz ,  Jeffrey W. Clark ,  A. Raymond Frackelton, Jr. ,  Douglas A. Lappi ,  Andrew J. Baird

IPC分类号： A61K47/48 ,  A61K38/18 ,  A61K38/43

CPC分类号： A61K47/48261

摘要： Conjugates comprising bFGF or other FGF polypeptides and a cytotoxic agent are prepared. The cytotoxic agent can be a ribosome-inactivating protein (RIP), such as saporin, which is attached to bFGF through a chemical bond, or the composition can be prepared as a recombinant DNA chimera. The conjugates are used to specifically target cells, in vivo and in vitro, which express FGF receptors. The cytotoxicity of the conjugates is proportional to the number of receptors expressed by a cell type. The conjugate is useful to effectively treat mammals, and in particular human patients, afflicted with tumorigenic conditions, such as human melanomas, human ovarian carcinomas, teratocarcinomas and neuroblastomas, and other FGF-mediated tumors caused by a proliferation of cells which express FGF receptors.

摘要翻译： 制备包含bFGF或其他FGF多肽和细胞毒性剂的缀合物。 细胞毒性剂可以是通过化学键连接到bFGF的核糖体失活蛋白（RIP），例如皂草素，或者该组合物可以制备成重组DNA嵌合体。 缀合物用于特异性靶向体内和体外表达FGF受体的细胞。 缀合物的细胞毒性与细胞类型表达的受体数成正比。 缀合物可有效治疗哺乳动物，特别是患有致瘤性疾病如人黑素瘤，人卵巢癌，畸胎癌和神经母细胞瘤的人类患者，以及由表达FGF受体的细胞增殖引起的其他FGF介导的肿瘤。