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1. 发明授权

US6010999A Stabilization of fibroblast growth factors by modification of cysteine residues 失效
标题翻译：通过修饰半胱氨酸残基稳定成纤维细胞生长因子
公开(公告)号：US6010999A
公开(公告)日：2000-01-04
申请号：US459906
申请日：1995-06-02
申请人： Michael Joseph Daley , Brian Lee Buckwalter , Susan Mancini Cady , Hong-Ming Shieh , Peter Bohlen , Andrew P. Seddon
发明人： Michael Joseph Daley , Brian Lee Buckwalter , Susan Mancini Cady , Hong-Ming Shieh , Peter Bohlen , Andrew P. Seddon
IPC分类号： A61K47/48 , C07K14/50 , A01N61/00 , A01N37/18
CPC分类号： A61K47/48215 , C07K14/50 , C07K14/503
摘要： The present invention relates to physiologically-active derivatized natural and recombinant mammalian and human proteins and polypeptides. The invention provides chemical methods for derivatizing natural and recombinantly-derived proteins or polypeptides containing cysteine residues, either naturally or through site specific mutageneses. The pharmaceutical compositions containing said derivatized proteins and/or polypeptides are formulated to provide stable, long-acting compositions of such proteins and/or polypeptides, previously difficult to achieve.
摘要翻译：本发明涉及生理活性衍生的天然和重组哺乳动物和人类蛋白质和多肽。本发明提供用于衍生自然和重组衍生的蛋白质或含有半胱氨酸残基的多肽的化学方法，天然或通过位点特异性突变体。将含有所述衍生化蛋白质和/或多肽的药物组合物配制成提供以前难以实现的这种蛋白质和/或多肽的稳定的长效组合物。

2. 发明授权

US5951972A Stabilization of somatotropins and other proteins by modification of cysteine residues 失效
标题翻译：通过修饰半胱氨酸残基稳定生长激素和其他蛋白质
公开(公告)号：US5951972A
公开(公告)日：1999-09-14
申请号：US383621
申请日：1995-02-06
申请人： Michael Joseph Daley , Brian Lee Buckwalter , Susan Mancini Cady , Hong-Ming Shieh , Peter Bohlen , Andrew P. Seddon
发明人： Michael Joseph Daley , Brian Lee Buckwalter , Susan Mancini Cady , Hong-Ming Shieh , Peter Bohlen , Andrew P. Seddon
IPC分类号： A61K47/48 , C07K14/50 , A61K38/19 , A61K38/18 , A61K38/27
CPC分类号： A61K47/48215 , C07K14/50 , C07K14/503
摘要： The present invention relates to physiologically-active derivatized natural and recombinant mammalian and human proteins and polypeptides. The invention provides chemical methods for derivatizing natural and recombinantly-derived proteins or polypeptides containing cysteine residues, either naturally or through site specific mutageneses. The pharmaceutical compositions containing the derivatized proteins and/or polypeptides are formulated to provide stable, long-acting compositions of such proteins and/or polypeptides, previously difficult to achieve.
摘要翻译：本发明涉及生理活性衍生的天然和重组哺乳动物和人类蛋白质和多肽。本发明提供用于衍生自然和重组衍生的蛋白质或含有半胱氨酸残基的多肽的化学方法，天然或通过位点特异性突变体。配制含有衍生化蛋白质和/或多肽的药物组合物被配制以提供以前难以实现的这种蛋白质和/或多肽的稳定的长效组合物。

3. 发明授权

US5310883A Chimeric fibroblast growth factors 失效
公开(公告)号：US5310883A
公开(公告)日：1994-05-10
申请号：US783694
申请日：1991-11-04
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.

4. 发明授权

US5206354A DNA sequence encoding active fragment of fibroblast growth factor, HBF-2 失效
标题翻译： DNA序列编码成纤维细胞生长因子HBF-2的活性片段
公开(公告)号：US5206354A
公开(公告)日：1993-04-27
申请号：US615207
申请日：1990-11-23
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
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.

5. 发明授权

US5371206A DNA encoding chimeric fibroblast growth factors 失效
标题翻译：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。

6. 发明授权

US5491220A Surface loop structural analogues of fibroblast growth factors 失效
标题翻译：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。

7. 发明授权

US5387673A Active fragments of fibroblast growth factor 失效
标题翻译：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。

8. 发明授权

US5302702A Chimeric fibroblast growth factors 失效
标题翻译：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。

9. 发明授权

US07972596B2 Antibodies against vascular endothelial growth factor receptor-1 有权
标题翻译：抗血管内皮生长因子受体-1的抗体
公开(公告)号：US07972596B2
公开(公告)日：2011-07-05
申请号：US11719677
申请日：2005-11-18
申请人： Yan Wu , Danny J. Hicklin , Peter Bohlen
发明人： Yan Wu , Danny J. Hicklin , Peter Bohlen
IPC分类号： A61K39/395 , C12P21/08 , C07K16/18 , C07K16/28
CPC分类号： C07K16/2863 , A61K39/39541 , A61K2039/505 , C07K2317/21 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , A61K2300/00
摘要： Monoclonal antibodies that are specific for vascular endothelial growth factor receptor 1 (VEGFR-I). This invention also provides nucleotide sequences encoding and amino acid sequences comprising variable heavy and light chain immunoglobulin molecules, including sequences corresponding to the complementarity determining regions of CDR1, CDR2, and CDR3. The invention also provides methods for generation and expression of anti -VEGFR-I antibodies and methods of treating angiogenic-related disorders and reducing tumor growth by administering anti-VEGFR-I antibodies.
摘要翻译：对血管内皮生长因子受体1（VEGFR-1）特异的单克隆抗体。本发明还提供编码核苷酸序列和包含可变重链和轻链免疫球蛋白分子的氨基酸序列，其包括对应于CDR1，CDR2和CDR3的互补决定区的序列。本发明还提供了产生和表达抗-VEGFR-1抗体的方法以及通过施用抗VEGFR-1抗体治疗血管生成相关病症并降低肿瘤生长的方法。

10. 发明授权

US5210026A Human MK gene and method of expression 失效
标题翻译：人MK基因和表达方法
公开(公告)号：US5210026A
公开(公告)日：1993-05-11
申请号：US650795
申请日：1991-02-05
申请人： Imre Kovesdi , Peter Bohlen
发明人： Imre Kovesdi , Peter Bohlen
IPC分类号： A61K35/14 , A61K38/00 , A61P25/00 , C07K14/00 , C07K14/475 , C12N1/21 , C12N15/09 , C12N15/18 , C12P21/02 , C12R1/19
CPC分类号： C07K14/475 , A61K38/00
摘要： The invention relates to novel DNA and amino sequences for a human MK protein. Also described are expression vectors and host cells useful in a method for production of the MK protein.

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