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公开(公告)号：US08338569B2
公开(公告)日：2012-12-25
申请号：US12535479
申请日：2009-08-04
申请人： Shannon Marshall , Deborah H. Charych , Ali Sadra
发明人： Shannon Marshall , Deborah H. Charych , Ali Sadra
IPC分类号： C07K14/50 , C07K14/705 , C07H21/04
CPC分类号： C07K14/71 , A61K38/177 , A61K38/179 , C07K14/705 , C07K2319/30 , C07K2319/31
摘要： Fibroblast growth factor receptor (FGFR) extracellular domain (ECD) acidic region muteins that have been engineered to exhibit decreased tissue binding by increasing the number of acidic amino acid residues within the D1-D2 linker region are provided. Polynucleotides encoding FGFR ECD acidic region muteins are also provided. Methods of making FGFR ECD acidic region muteins, and methods of using such molecules to treat proliferative disorders, including cancers, disorders of angiogenesis, and macular degeneration, are also provided.
摘要翻译： 提供了通过增加D1-D2接头区域内的酸性氨基酸残基的数目而被改造以显示减少的组织结合的成纤维细胞生长因子受体（FGFR）胞外结构域（ECD）酸性区突变蛋白。 还提供了编码FGFR ECD酸性区突变蛋白的多核苷酸。 还提供了制备FGFR ECD酸性区突变蛋白的方法，以及使用这些分子治疗增殖性疾病，包括癌症，血管生成障碍和黄斑变性的方法。
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公开(公告)号：US09175065B2
公开(公告)日：2015-11-03
申请号：US13612044
申请日：2012-09-12
申请人： Shannon Marshall , Deborah H. Charych , Ali Sadra
发明人： Shannon Marshall , Deborah H. Charych , Ali Sadra
IPC分类号： A61K38/02 , C07K14/71 , C07K14/74 , A61P35/00 , C07K19/00 , C07K2/00 , A61K38/17 , C07K14/705
CPC分类号： C07K14/71 , A61K38/177 , A61K38/179 , C07K14/705 , C07K2319/30 , C07K2319/31
摘要： Fibroblast growth factor receptor (FGFR) extracellular domain (ECD) acidic region muteins that have been engineered to exhibit decreased tissue binding by increasing the number of acidic amino acid residues within the D1-D2 linker region are provided. Polynucleotides encoding FGFR ECD acidic region muteins are also provided. Methods of making FGFR ECD acidic region muteins, and methods of using such molecules to treat proliferative disorders, including cancers, disorders of angiogenesis, and macular degeneration, are also provided.
摘要翻译： 提供了通过增加D1-D2接头区域内的酸性氨基酸残基的数目而被改造以显示减少的组织结合的成纤维细胞生长因子受体（FGFR）胞外结构域（ECD）酸性区突变蛋白。 还提供了编码FGFR ECD酸性区突变蛋白的多核苷酸。 还提供了制备FGFR ECD酸性区突变蛋白的方法，以及使用这些分子治疗增殖性疾病，包括癌症，血管生成障碍和黄斑变性的方法。
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公开(公告)号：US20130004492A1
公开(公告)日：2013-01-03
申请号：US13612044
申请日：2012-09-12
申请人： Shannon Marshall , Deborah H. Charych , Ali Sadra
发明人： Shannon Marshall , Deborah H. Charych , Ali Sadra
IPC分类号： A61K39/395 , A61P35/00 , A61K38/02 , C07K2/00 , C07K19/00
CPC分类号： C07K14/71 , A61K38/177 , A61K38/179 , C07K14/705 , C07K2319/30 , C07K2319/31
摘要： Fibroblast growth factor receptor (FGFR) extracellular domain (ECD) acidic region muteins that have been engineered to exhibit decreased tissue binding by increasing the number of acidic amino acid residues within the D1-D2 linker region are provided. Polynucleotides encoding FGFR ECD acidic region muteins are also provided. Methods of making FGFR ECD acidic region muteins, and methods of using such molecules to treat proliferative disorders, including cancers, disorders of angiogenesis, and macular degeneration, are also provided.
摘要翻译： 提供了通过增加D1-D2接头区域内的酸性氨基酸残基的数目而被改造以显示减少的组织结合的成纤维细胞生长因子受体（FGFR）胞外结构域（ECD）酸性区突变蛋白。 还提供了编码FGFR ECD酸性区突变蛋白的多核苷酸。 还提供了制备FGFR ECD酸性区突变蛋白的方法，以及使用这些分子治疗增殖性疾病，包括癌症，血管生成障碍和黄斑变性的方法。
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公开(公告)号：US20100087627A1
公开(公告)日：2010-04-08
申请号：US12535479
申请日：2009-08-04
申请人： Shannon Marshall , Deborah H. Charych , Ali Sadra
发明人： Shannon Marshall , Deborah H. Charych , Ali Sadra
CPC分类号： C07K14/71 , A61K38/177 , A61K38/179 , C07K14/705 , C07K2319/30 , C07K2319/31
摘要： Fibroblast growth factor receptor (FGFR) extracellular domain (ECD) acidic region muteins that have been engineered to exhibit decreased tissue binding by increasing the number of acidic amino acid residues within the D1-D2 linker region are provided. Polynucleotides encoding FGFR ECD acidic region muteins are also provided. Methods of making FGFR ECD acidic region muteins, and methods of using such molecules to treat proliferative disorders, including cancers, disorders of angiogenesis, and macular degeneration, are also provided.
摘要翻译： 提供了通过增加D1-D2接头区域内的酸性氨基酸残基的数目而被改造以显示减少的组织结合的成纤维细胞生长因子受体（FGFR）胞外结构域（ECD）酸性区突变蛋白。 还提供了编码FGFR ECD酸性区突变蛋白的多核苷酸。 还提供了制备FGFR ECD酸性区突变蛋白的方法，以及使用这些分子治疗增殖性疾病，包括癌症，血管生成障碍和黄斑变性的方法。
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5.发明申请公开(公告)号：US20120301921A1
公开(公告)日：2012-11-29
申请号：US13438638
申请日：2012-04-03
申请人： Lewis T. Williams , Elizabeth Bosch , Stephen Doberstein , Kevin Hestir , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra , Justin Wong , Ge Wu , Hongbing Zhang
发明人： Lewis T. Williams , Elizabeth Bosch , Stephen Doberstein , Kevin Hestir , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra , Justin Wong , Ge Wu , Hongbing Zhang
CPC分类号： C07K14/71 , A61K45/06 , C07K14/765 , C07K16/2863 , C07K17/08 , C07K2319/30 , C07K2319/32
摘要： The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.
摘要翻译： 本发明提供了FGFR融合蛋白，其制备方法以及使用它们来治疗增殖性疾病（包括癌症和血管生成障碍）的方法。 FGFR融合分子可以在CHO细胞中制备，并且可以包含改善其稳定性的FGFRs的细胞外结构域中的缺失突变。 这些融合蛋白体外和体内抑制癌细胞的生长和活力。 这些受体对其配体FGF的相对高亲和力的组合以及这些诱饵受体抑制肿瘤生长的证明的能力是本文提供的组合物和方法的临床价值的指示。
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6.发明授权公开(公告)号：US07678890B2
公开(公告)日：2010-03-16
申请号：US11791889
申请日：2006-07-24
申请人： Elizabeth Bosch , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra
发明人： Elizabeth Bosch , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra
CPC分类号： C07K14/71 , A61K45/06 , C07K14/765 , C07K16/2863 , C07K17/08 , C07K2319/30 , C07K2319/32
摘要： The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.
摘要翻译： 本发明提供了FGFR融合蛋白，其制备方法以及使用它们来治疗增殖性疾病（包括癌症和血管生成障碍）的方法。 FGFR融合分子可以在CHO细胞中制备，并且可以包含改善其稳定性的FGFRs的细胞外结构域中的缺失突变。 这些融合蛋白体外和体内抑制癌细胞的生长和活力。 这些受体对其配体FGF的相对高亲和力的组合以及这些诱饵受体抑制肿瘤生长的证明的能力是本文提供的组合物和方法的临床价值的指示。
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7.发明申请公开(公告)号：US20080171689A1
公开(公告)日：2008-07-17
申请号：US11791889
申请日：2006-07-24
申请人： Lewis T. Williams , Elizabeth Bosch , Stephen Doberstein , Kevin Hestir , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra , Justin Wong , Ge Wu , Hongbing Zhang
发明人： Lewis T. Williams , Elizabeth Bosch , Stephen Doberstein , Kevin Hestir , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra , Justin Wong , Ge Wu , Hongbing Zhang
CPC分类号： C07K14/71 , A61K45/06 , C07K14/765 , C07K16/2863 , C07K17/08 , C07K2319/30 , C07K2319/32
摘要： The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.
摘要翻译： 本发明提供了FGFR融合蛋白，其制备方法以及使用它们来治疗增殖性疾病（包括癌症和血管生成障碍）的方法。 FGFR融合分子可以在CHO细胞中制备，并且可以包含改善其稳定性的FGFRs的细胞外结构域中的缺失突变。 这些融合蛋白体外和体内抑制癌细胞的生长和活力。 这些受体对其配体FGF的相对高亲和力的组合以及这些诱饵受体抑制肿瘤生长的证明的能力是本文提供的组合物和方法的临床价值的指示。
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公开(公告)号：US08501191B2
公开(公告)日：2013-08-06
申请号：US13438638
申请日：2012-04-03
申请人： Elizabeth Bosch , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra
发明人： Elizabeth Bosch , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra
CPC分类号： C07K14/71 , A61K45/06 , C07K14/765 , C07K16/2863 , C07K17/08 , C07K2319/30 , C07K2319/32
摘要： The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.
摘要翻译： 本发明提供了FGFR融合蛋白，其制备方法以及使用它们来治疗增殖性疾病（包括癌症和血管生成障碍）的方法。 FGFR融合分子可以在CHO细胞中制备，并且可以包含改善其稳定性的FGFRs的细胞外结构域中的缺失突变。 这些融合蛋白体外和体内抑制癌细胞的生长和活力。 这些受体对其配体FGF的相对高亲和力的组合以及这些诱饵受体抑制肿瘤生长的证明的能力是本文提供的组合物和方法的临床价值的指示。
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公开(公告)号：US20130065276A1
公开(公告)日：2013-03-14
申请号：US13227398
申请日：2011-09-07
申请人： Lewis T. WILLIAMS , Elizabeth Bosch , Stephen Doberstein , Kevin Hestir , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra , Justin Wong , Ge Wu , Hongbing Zhang
发明人： Lewis T. WILLIAMS , Elizabeth Bosch , Stephen Doberstein , Kevin Hestir , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra , Justin Wong , Ge Wu , Hongbing Zhang
CPC分类号： C07K14/71 , A61K45/06 , C07K14/765 , C07K16/2863 , C07K17/08 , C07K2319/30 , C07K2319/32
摘要： The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.
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10.发明申请公开(公告)号：US20110281302A1
公开(公告)日：2011-11-17
申请号：US13157712
申请日：2011-06-10
申请人： Lewis T. WILLIAMS , Elizabeth Bosch , Stephen Doberstein , Kevin Hestir , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra , Justin Wong , Ge Wu , Hongbing Zhang
发明人： Lewis T. WILLIAMS , Elizabeth Bosch , Stephen Doberstein , Kevin Hestir , Diane Hollenbaugh , Ernestine Lee , Minmin Qin , Ali Sadra , Justin Wong , Ge Wu , Hongbing Zhang
CPC分类号： C07K14/71 , A61K45/06 , C07K14/765 , C07K16/2863 , C07K17/08 , C07K2319/30 , C07K2319/32
摘要： The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.
摘要翻译： 本发明提供了FGFR融合蛋白，其制备方法以及使用它们来治疗增殖性疾病（包括癌症和血管生成障碍）的方法。 FGFR融合分子可以在CHO细胞中制备，并且可以包含改善其稳定性的FGFRs的细胞外结构域中的缺失突变。 这些融合蛋白体外和体内抑制癌细胞的生长和活力。 这些受体对其配体FGF的相对高亲和力的组合以及这些诱饵受体抑制肿瘤生长的证明的能力是本文提供的组合物和方法的临床价值的指示。
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