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公开(公告)号:US09517264B2
公开(公告)日:2016-12-13
申请号:US13641041
申请日:2011-04-13
申请人: Roger Fachini , Ian Foltz , Seog Joon Han , Susie Miki Harris , Shaw-Fen Sylvia Hu , Chadwick Terence King , Yang Li , Ji Lu , Mark Leo Michaels , Jeonghoon Sun
发明人: Roger Fachini , Ian Foltz , Seog Joon Han , Susie Miki Harris , Shaw-Fen Sylvia Hu , Chadwick Terence King , Yang Li , Ji Lu , Mark Leo Michaels , Jeonghoon Sun
IPC分类号: A61K39/395 , C07K16/28 , C07K16/40
CPC分类号: A61K39/3955 , C07K16/2863 , C07K16/40 , C07K2317/21 , C07K2317/31 , C07K2317/32 , C07K2317/75 , C07K2317/92 , C07K2319/75
摘要: The present invention provides compositions and methods relating to or derived from antigen binding proteins and antigen binding protein-FGF21 fusions that specifically bind to β-Klotho, or β-Klotho and one or more of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins and antigen binding protein-FGF21 fusions induce FGF21-like signaling. In some embodiments, an antigen binding protein or antigen binding protein-FGF21 fusion antigen binding component is a fully human, humanized, or chimeric antibody, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to β-Klotho, or β-Klotho and one or more of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins and antigen binding protein-FGF21 fusions, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins and antigen binding protein-FGF21 fusions, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins and antigen binding protein-FGF21 fusions, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.
摘要翻译: 本发明提供与抗原结合蛋白和特异性结合β-Klotho或β-Klotho以及FGFR1c,FGFR2c,FGFR3c和FGFR4中的一种或多种的抗原结合蛋白和抗原结合蛋白-FGF21融合相关或衍生的组合物和方法。 在一些实施方案中,抗原结合蛋白和抗原结合蛋白FGF21融合物诱导FGF21样信号传导。 在一些实施方案中,抗原结合蛋白或抗原结合蛋白FGF21融合抗原结合组分是完全人,人源化或嵌合抗体,所述抗体的结合片段和衍生物,以及特异性结合β-Klotho或β- Klotho和FGFR1c,FGFR2c,FGFR3c和FGFR4中的一种或多种。 其他实施方案提供编码这种抗原结合蛋白和抗原结合蛋白-FGF21融合体的核酸,及其片段和衍生物,以及多肽,包含这种多核苷酸的细胞,制备这种抗原结合蛋白的方法和抗原结合蛋白-FGF21融合物, 其衍生物和多肽,以及使用这种抗原结合蛋白和抗原结合蛋白-FGF21融合体,其片段和衍生物和多肽的方法,包括治疗或诊断患有2型糖尿病,肥胖症,NASH,代谢综合征和 相关疾病或病症。
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公开(公告)号:US08642546B2
公开(公告)日:2014-02-04
申请号:US13327504
申请日:2011-12-15
申请人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
发明人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
IPC分类号: A61K38/18 , C07K14/50 , A61K39/395 , C07K16/00
CPC分类号: C07K14/50 , A61K38/00 , A61K38/1825 , A61K2039/505 , C07K16/18 , C07K2319/30
摘要: The invention provides nucleic acid molecules encoding FGF21 mutant fusion polypeptides comprising mutations at positions 98, 171, 179, 180 or 181, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
摘要翻译: 本发明提供编码FGF21突变融合多肽的核酸分子,其包含位置98,171,179,180或181,FGF21突变体多肽,包含FGF21突变体多肽的药物组合物的突变,以及使用此类核酸,多肽或 药物组合物。
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公开(公告)号:US08410051B2
公开(公告)日:2013-04-02
申请号:US13196544
申请日:2011-08-02
申请人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
发明人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
CPC分类号: C07K14/50 , A61K38/00 , A61K38/1825 , A61K2039/505 , C07K16/18 , C07K2319/30
摘要: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
摘要翻译: 本发明提供编码FGF21突变体多肽,FGF21突变体多肽,包含FGF21突变体多肽的药物组合物的核酸分子,以及使用此类核酸,多肽或药物组合物治疗代谢紊乱的方法。
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公开(公告)号:US08361963B2
公开(公告)日:2013-01-29
申请号:US13328028
申请日:2011-12-16
申请人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
发明人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
CPC分类号: C07K14/50 , A61K38/00 , A61K38/1825 , A61K2039/505 , C07K16/18 , C07K2319/30
摘要: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
摘要翻译: 本发明提供编码FGF21突变体多肽,FGF21突变体多肽,包含FGF21突变体多肽的药物组合物的核酸分子,以及使用此类核酸,多肽或药物组合物治疗代谢紊乱的方法。
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公开(公告)号:US20120003216A1
公开(公告)日:2012-01-05
申请号:US13196544
申请日:2011-08-02
申请人: EDWARD JOHN BELOUSKI , MURIELLE MARIE ELLISON , AGNES EVA HAMBURGER , RANDY IRA HECHT , YUE-SHENG LI , MARK LEO MICHAELS , JEONGHOON SUN , JING XU
发明人: EDWARD JOHN BELOUSKI , MURIELLE MARIE ELLISON , AGNES EVA HAMBURGER , RANDY IRA HECHT , YUE-SHENG LI , MARK LEO MICHAELS , JEONGHOON SUN , JING XU
IPC分类号: A61K39/395 , A61K38/16 , C07H21/00 , A61P3/04 , C12N5/10 , C07K16/00 , A61P3/10 , C07K14/00 , C12N15/63
CPC分类号: C07K14/50 , A61K38/00 , A61K38/1825 , A61K2039/505 , C07K16/18 , C07K2319/30
摘要: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
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公开(公告)号:US08618053B2
公开(公告)日:2013-12-31
申请号:US13463731
申请日:2012-05-03
申请人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
发明人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
IPC分类号: A61K38/18 , A61K39/395 , C07K14/50 , C07K16/00
摘要: The invention provides a multimer comprising at least a first and a second chain, the first chain comprising the polypeptide of SEQ ID NO:4, wherein the leucine at position 98 is substituted with an arginine; the proline at position 171 is substituted with glycine; and the alanine at position 180 is substituted with glutamic acid; a linker sequence comprising SEQ ID NO:31; and an Fe domain comprising SEQ NO:11; and a second chain comprising the polypeptide of SEQ ID NO:4, wherein the leucine at position 98 is substituted with an arginine; the proline at position 171 is substituted with glycine; and the alanine at position 180 is substituted with glutamic acid; a linker sequence comprising SEQ ID NO:31; and an Fe domain comprising SEQ ID NO:11, nucleic acids encoding the multimer, pharmaceutical compositions comprising the multimer and methods for treating metabolic disorders using such nucleic acids, multimers or pharmaceutical compositions.
摘要翻译: 本发明提供包含至少第一和第二链的多聚体,所述第一链包含SEQ ID NO:4的多肽,其中98位的亮氨酸被精氨酸取代; 位置171的脯氨酸被甘氨酸取代; 位置180处的丙氨酸被谷氨酸取代; 包含SEQ ID NO:31的接头序列; 和包含SEQ ID NO:11的Fe结构域; 和包含SEQ ID NO:4的多肽的第二链,其中98位的亮氨酸被精氨酸取代; 位置171的脯氨酸被甘氨酸取代; 位置180处的丙氨酸被谷氨酸取代; 包含SEQ ID NO:31的接头序列; 和包含SEQ ID NO:11的Fe结构域,编码多聚体的核酸,包含多聚体的药物组合物和使用这种核酸,多聚体或药物组合物治疗代谢紊乱的方法。
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公开(公告)号:US20120178685A1
公开(公告)日:2012-07-12
申请号:US13427249
申请日:2012-03-22
申请人: EDWARD JOHN BELOUSKI , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
发明人: EDWARD JOHN BELOUSKI , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
IPC分类号: A61K38/18 , C07K19/00 , C12N15/12 , C12N15/63 , C12N1/21 , A61P9/10 , A61P3/10 , A61P3/04 , A61P9/12 , A61P1/16 , A61P9/00 , C07K14/50 , A61P3/00
摘要: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
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公开(公告)号:US08034770B2
公开(公告)日:2011-10-11
申请号:US12455610
申请日:2009-06-03
申请人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
发明人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
CPC分类号: C07K14/50 , A61K38/00 , A61K38/1825 , A61K2039/505 , C07K16/18 , C07K2319/30
摘要: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
摘要翻译: 本发明提供编码FGF21突变体多肽,FGF21突变体多肽,包含FGF21突变体多肽的药物组合物的核酸分子,以及使用此类核酸,多肽或药物组合物治疗代谢紊乱的方法。
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公开(公告)号:US20100285131A1
公开(公告)日:2010-11-11
申请号:US12773266
申请日:2010-05-04
申请人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
发明人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
IPC分类号: A61K38/18 , C07K14/47 , C07K19/00 , C07H21/04 , C07K17/02 , A61K9/00 , A61P3/04 , A61P3/10 , A61P3/00 , C12N15/63 , C12N5/00
摘要: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
摘要翻译: 本发明提供编码FGF21突变体多肽,FGF21突变体多肽,包含FGF21突变体多肽的药物组合物的核酸分子,以及使用此类核酸,多肽或药物组合物治疗代谢紊乱的方法。
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公开(公告)号:US08835385B2
公开(公告)日:2014-09-16
申请号:US13426460
申请日:2012-03-21
申请人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
发明人: Edward John Belouski , Murielle Marie Ellison , Agnes Eva Hamburger , Randy Ira Hecht , Yue-Sheng Li , Mark Leo Michaels , Jeonghoon Sun , Jing Xu
摘要: The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides, pharmaceutical compositions comprising FGF21 mutant polypeptides, wherein the FGF 21 mutant polypeptides comprise two or more mutations, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
摘要翻译: 本发明提供编码FGF21突变体多肽,FGF21突变体多肽,包含FGF21突变体多肽的药物组合物的核酸分子,其中FGF21突变体多肽包含两个或多个突变,以及使用此类核酸,多肽或药物组合物治疗代谢紊乱的方法 。
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