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    Surface loop structural analogues of fibroblast growth factors
    4.
    发明授权
    Surface loop structural analogues of fibroblast growth factors 失效
    成纤维细胞生长因子的表面环结构类似物

    公开(公告)号：US5491220A

    公开(公告)日：1996-02-13

    申请号：US290373

    申请日：1994-08-15

    申请人： Andrew P. Seddon ,  Luyuan Li ,  Peter Bohlen ,  Magdalena Eisinger ,  Avner Yayon

    发明人： Andrew P. Seddon ,  Luyuan Li ,  Peter Bohlen ,  Magdalena Eisinger ,  Avner Yayon

    IPC分类号： A61K38/00 ,  C07K14/50 ,  C07K14/545 ,  C12N15/18

    CPC分类号： C07K14/501 ,  C07K14/50 ,  C07K14/503 ,  C07K14/545 ,  A61K38/00

    摘要： Structural analogues of fibroblast growth factors have an amino acid sequence replacement in the ninth or tenth .beta.-strand of the factor, or the sequence that corresponds to the surface loop that connects the ninth and tenth .beta.-strands, such that the folding of the molecule is not significantly perturbed. Preferred analogues have the amino acid sequence replacement in the surface loop that extends from the ninth .beta.-strand to the tenth .beta.-strand and have the overall secondary and tertiary structure of the original factor, and bind to heparin and a member or members of the fibroblast growth factor receptor family with high affinity. In some embodiments, the analogues are prepared by replacing the surface loop sequence that connects the ninth and tenth .beta.-strand with another amino acid sequence such as a loop sequence from another structurally related fibroblast growth factor or an interleukin. Preferred analogues exhibit different biological properties and/or receptor binding specificity profiles from native factors.

    摘要翻译： 成纤维细胞生长因子的结构类似物在该因子的第9或第10个β链中具有氨基酸序列替换，或者对应于连接第9和第10个β链的表面环的序列，使得分子的折叠 没有明显的扰动。 优选的类似物在表面循环中具有从第九个β链延伸到第十个β链的氨基酸序列替代物，并具有原始因子的总体二级结构和三级结构，并且结合肝素和成员 成纤维细胞生长因子受体家族具有高亲和力。 在一些实施方案中，通过将来自另一结构相关的成纤维细胞生长因子或白介素的另一个氨基酸序列例如环序列替换连接第九和第十个β链的表面环序列来制备类似物。 优选的类似物表现出与天然因素不同的生物学特性和/或受体结合特异性谱。

    DNA encoding chimeric fibroblast growth factors
    5.
    发明授权
    DNA encoding chimeric fibroblast growth factors 失效
    编码嵌合成纤维细胞生长因子的DNA

    公开(公告)号：US5371206A

    公开(公告)日：1994-12-06

    申请号：US177502

    申请日：1994-01-05

    申请人： Andrew P. Seddon ,  Peter Bohlen ,  Yakov Gluzman

    发明人： Andrew P. Seddon ,  Peter Bohlen ,  Yakov Gluzman

    IPC分类号： A61K38/22 ,  A61P17/00 ,  C07K1/00 ,  C07K1/22 ,  C07K14/50 ,  C12N1/21 ,  C12N5/10 ,  C12N7/00 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12R1/19 ,  C12R1/92 ,  C12V15/01 ,  C12V15/18

    CPC分类号： C07K14/503

    摘要： The present invention relates to novel chimeric fibroblast growth factors (FGF) wherein the alanine at amino acid 3 and serine 5 of native human recombinant basic fibroblast growth factor are replaced with glutamic acid. The N-terminus sequence of the present chimeric FGFs identify homology with that of human acidic fibroblast growth factor. The mitogenic properties of the native human recombinant basic FGF are exhibited by the present chimeric FGFs, and they are efficiently expressed in E. coli at significantly greater yields that previously reported. Novel variants of this new glu.sup.3,5 basic fibroblast growth factor, such as those in which cysteine 78 and cysteine 96 are replaced, e.g., with serine or other amino acids, to produce stabilized versions of the glu.sup.3,5 basic FGF and eliminate disulfide scrambled forms, are also described.

    摘要翻译： 本发明涉及新型嵌合成纤维细胞生长因子（FGF），其中天然人重组碱性成纤维细胞生长因子的氨基酸3和丝氨酸5的丙氨酸被谷氨酸替代。 本发明嵌合FGFs的N-末端序列与人酸性成纤维细胞生长因子的N末端序列具有同源性。 天然人重组碱性FGF的促有丝分裂特性由本发明的嵌合FGF表现出来，并且在大肠杆菌中以以前报道的显着更高的产量有效地表达。 这种新的glu3,5碱性成纤维细胞生长因子的新变体，例如用半胱氨酸78和半胱氨酸96被替换的那些，例如用丝氨酸或其他氨基酸，以产生glu3,5碱性FGF的稳定化形式并消除二硫键扰乱 形式也被描述。

    Active fragments of fibroblast growth factor
    7.
    发明授权
    Active fragments of fibroblast growth factor 失效
    成纤维细胞生长因子的活性片段

    公开(公告)号：US5387673A

    公开(公告)日：1995-02-07

    申请号：US054650

    申请日：1993-04-26

    申请人： Andrew P. Seddon ,  Peter Bohlen

    发明人： Andrew P. Seddon ,  Peter Bohlen

    IPC分类号： C07K7/00 ,  A61K38/00 ,  C07K14/50 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12R1/19 ,  C12N15/00 ,  C07H7/00 ,  C07H13/00

    CPC分类号： C07K14/503 ,  A61K38/00

    摘要： The present invention relates to novel fragments of basic fibroblast growth factor (bFGF). The mitogenic potency of one of these bFGF fragments, identified as HBF-2 is about 25-50 fold less than that of native bFGF but at least 10.sup.3 -10.sup.4 fold more active than that of previously reported synthetic fragments of bFGF. Therefore, the present invention provides the shortest fragment of bFGF that retains substantial biologic activity.

    摘要翻译： 本发明涉及碱性成纤维细胞生长因子（bFGF）的新片段。 鉴定为HBF-2的这些bFGF片段之一的促有丝分裂能力比天然bFGF小约25-50倍，但比以前报道的bFGF合成片段活性高至少103-104倍。 因此，本发明提供了保留显着生物活性的bFGF的最短片段。

    Chimeric fibroblast growth factors
    8.
    发明授权
    Chimeric fibroblast growth factors 失效
    嵌合成纤维细胞生长因子

    公开(公告)号：US5302702A

    公开(公告)日：1994-04-12

    申请号：US23757

    申请日：1993-02-26

    申请人： Andrew P. Seddon ,  Peter Bohlen ,  Yakov Gluzman

    发明人： Andrew P. Seddon ,  Peter Bohlen ,  Yakov Gluzman

    IPC分类号： A61K38/22 ,  A61P17/00 ,  C07K1/00 ,  C07K1/22 ,  C07K14/50 ,  C12N1/21 ,  C12N5/10 ,  C12N7/00 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12R1/19 ,  C12R1/92 ,  C07K13/00

    CPC分类号： C07K14/503

    摘要： The present invention relates to novel chimeric fibroblast growth factors (FGF) wherein the alanine at amino acid 3 and serine 5 of native human recombinant basic fibroblast growth factor are replaced with glutamic acid. The N-terminus sequence of the present chimeric FGFs identify homology with that of human acidic fibroblast growth factor. The mitogenic properties of the native human recombinant basic FGF are exhibited by the present chimeric FGFs, and they are efficiently expressed in E. coli at significantly greater yields that previously reported. Novel variants of this new glu.sup.3,5 basic fibroblast growth factor, such as those in which cysteine 78 and cysteine 96 are replaced, e.g., with serine or other amino acids, to produce stabilized versions of the glu.sup.3,5 basic FGF and eliminate disulfide scrambled forms, are also described.

    摘要翻译： 本发明涉及新型嵌合成纤维细胞生长因子（FGF），其中天然人重组碱性成纤维细胞生长因子的氨基酸3和丝氨酸5的丙氨酸被谷氨酸替代。 本发明嵌合FGFs的N-末端序列与人酸性成纤维细胞生长因子的N末端序列具有同源性。 天然人重组碱性FGF的促有丝分裂特性由本发明的嵌合FGF表现出来，并且在大肠杆菌中以以前报道的显着更高的产量有效地表达。 这种新的glu3,5碱性成纤维细胞生长因子的新变体，例如用半胱氨酸78和半胱氨酸96被替换的那些，例如用丝氨酸或其他氨基酸，以产生glu3,5碱性FGF的稳定化形式并消除二硫键扰乱 形式也被描述。