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公开(公告)号：US09492508B2
公开(公告)日：2016-11-15
申请号：US13697249
申请日：2011-05-12
IPC分类号： A61K38/29 , C07K14/635
CPC分类号： A61K38/29 , C07K14/635
摘要： Disclosed are two PTH analog ligands, SP-PTH-AAK and Aib-SP-PTH-AAK, that have long-acting activity at the PTH receptor, as demonstrated both in vitro and in vivo. These polypeptides are thus particularly useful in the treatment of diseases, such as hypoparathyroidism, in which long-acting activity is desired. The method of making the analog polypeptides is also disclosed.
摘要翻译： 公开了在体外和体内证明在PTH受体具有长效活性的两个PTH类似物配体SP-PTH-AAK和Aib-SP-PTH-AAK。 因此，这些多肽特别可用于治疗需要长效活性的疾病，如甲状旁腺功能减退。 还公开了制备类似物多肽的方法。
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公开(公告)号：US08568737B2
公开(公告)日：2013-10-29
申请号：US12671429
申请日：2008-08-01
申请人： Thomas J. Gardella , John T. Potts, Jr. , Masaru Shimizu , Fumihiko Ichikawa , Harald Juppner , Makoto Okazaki
发明人： Thomas J. Gardella , John T. Potts, Jr. , Masaru Shimizu , Fumihiko Ichikawa , Harald Juppner , Makoto Okazaki
IPC分类号： A61K38/22 , C07K14/575
CPC分类号： G01N33/56966 , A61K38/00 , A61K49/00 , C07K14/635 , C07K14/723 , G01N33/74 , G01N2333/645 , G01N2333/726
摘要： The present invention provides screening methods for GPCRs based on the discovery that the affinity of a receptor agonist for a GPCR (such as the parathyroid hormone receptor) when not bound to a G-protein is correlated with the length of time over which the agonist is effective, independently of its pharmacokinetic properties. The invention also provides PTH- and PTHrP-derived polypeptides.
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公开(公告)号：US20130116180A1
公开(公告)日：2013-05-09
申请号：US13697249
申请日：2011-05-12
IPC分类号： A61K38/29 , C07K14/635
CPC分类号： A61K38/29 , C07K14/635
摘要： Disclosed are two PTH analog ligands, SP-PTH-AAK and Aib-SP-PTH-AAK, that have long-acting activity at the PTH receptor, as demonstrated both in vitro and in vivo. These polypeptides are thus particularly useful in the treatment of diseases, such as hypoparathyroidism, in which long-acting activity is desired. The method of making the analog polypeptides is also disclosed.
摘要翻译： 公开了在体外和体内证明在PTH受体具有长效活性的两个PTH类似物配体SP-PTH-AAK和Aib-SP-PTH-AAK。 因此，这些多肽特别可用于治疗需要长效活性的疾病，如甲状旁腺功能减退。 还公开了制备类似物多肽的方法。
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4.发明申请SCREENING METHODS USING G-PROTEIN COUPLED RECEPTORS AND RELATED COMPOSITIONS 有权使用G蛋白偶联受体的筛选方法及相关组合物公开(公告)号：US20110172153A1
公开(公告)日：2011-07-14
申请号：US12671429
申请日：2008-08-01
申请人： Thomas J. Gardella , John T. Potts, JR. , Masaru Shimizu , Fumihiko Ichikawa , Harald Juppner , Makoto Okazaki
发明人： Thomas J. Gardella , John T. Potts, JR. , Masaru Shimizu , Fumihiko Ichikawa , Harald Juppner , Makoto Okazaki
IPC分类号： A61K38/02 , G01N33/68 , C40B30/04 , C07K14/635 , C07K7/08 , C07K7/06 , A61P19/10 , A61P19/08 , A61P19/02 , A61P5/18 , A61P17/00 , A61K38/16 , A61P3/00 , A61P43/00 , C07H21/00
CPC分类号： G01N33/56966 , A61K38/00 , A61K49/00 , C07K14/635 , C07K14/723 , G01N33/74 , G01N2333/645 , G01N2333/726
摘要： The present invention provides screening methods for GPCRs based on the discovery that the affinity of a receptor agonist for a GPCR (such as the parathyroid hormone receptor) when not bound to a G-protein is correlated with the length of time over which the agonist is effective, independently of its pharmacokinetic properties. The invention also provides PTH- and PTHrP-derived polypeptides.
摘要翻译： 本发明提供了基于以下发现的GPCR的筛选方法，即当受体激动剂不与G蛋白结合时，受体激动剂对GPCR（例如甲状旁腺激素受体）的亲和力与激动剂的时间长度相关 有效，独立于其药代动力学性质。 本发明还提供了PTH-和PTHrP衍生的多肽。
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公开(公告)号：US07910544B2
公开(公告)日：2011-03-22
申请号：US10564744
申请日：2004-07-16
IPC分类号： A61K38/29
CPC分类号： C07K14/635 , A61K38/00
摘要： The invention provides novel P1R polypeptide antagonists. These antagonists contain amino acid substitutions at selected positions in truncated PTH and PRHrP polypeptides and function by binding selectively to the juxtamembrane (“J”) domain of the receptor. The J domain is the region of the receptor that spans the seven transmembrane domain and the extracellular loops.
摘要翻译： 本发明提供了新的P1R多肽拮抗剂。 这些拮抗剂在截短的PTH和PRHrP多肽中的选定位置含有氨基酸取代，并且通过选择性地结合受体的近红外（“J”）结构域起作用。 J结构域是跨越七个跨膜结构域和细胞外环的受体区域。
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公开(公告)号：US07479478B2
公开(公告)日：2009-01-20
申请号：US10959605
申请日：2004-10-07
CPC分类号： C07K14/635 , A61K38/00
摘要： The present invention is related to synthetic and/or recombinant biologically active peptide derivatives of PTH(1-28). Some of the peptides of the invention are at least 90% identical to a peptide consisting essentially of the amino acid sequence X01ValSerGluIleGlnLeuMetHis AsnLeuGlyLysHisLeuAsnSer MetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1), wherein X01 is Ser, Ala or Gly; and X02 is Glu or Arg.
摘要翻译： 本发明涉及PTH（1-28）的合成和/或重组生物活性肽衍生物。 本发明的一些肽与基本上由氨基酸序列X01ValSerGluIleGlnLeuMetHis AsnLeuGlyLysHisLeuAsnSer MetX02ArgValGluTrpLeuArgLysLysLeu（SEQ ID NO：1）组成的肽至少90％相同，其中X01是Ser，Ala或Gly; X02是Glu或Arg。
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公开(公告)号：US07244834B2
公开(公告)日：2007-07-17
申请号：US11366391
申请日：2006-03-03
IPC分类号： C07H21/04 , C07K14/635
CPC分类号： C07K14/635 , A61K38/00
摘要： Novel parathyroid hormone (PTH) peptides and analogs thereof of the PTH(1–34) fragment are disclosed that combine the N-terminal signaling domain (residues 1–9) and the C-terminal binding domain (residues 15–31) via a linker. Nucleic acid molecules and peptides for PTH(1–9)-(Gly)5-PTH(15–31) (PG5) and PTH(1–9)-(Gly)7-PTH(15–31) and a novel PTH receptor are disclosed. Additionally, methods of screening for PTH agonists, pharmaceutical compositions and methods of treatment are disclosed.
摘要翻译： 公开了PTH（1-34）片段的新型甲状旁腺激素（PTH）肽及其类似物，其通过以下方式组合N末端信号结构域（残基1-9）和C-末端结合结构域（残基15-31） 接头。 用于PTH（1-9） - （Gly）5-PTH（15-31）（PG5）和PTH（1-9） - （Gly）7-PTH（15-31）的核酸分子和肽和新型PTH 受体。 此外，公开了筛选PTH激动剂，药物组合物和治疗方法的方法。
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公开(公告)号：US06803213B2
公开(公告)日：2004-10-12
申请号：US10157076
申请日：2002-05-30
IPC分类号： C12N1500
CPC分类号： C07K14/635 , A61K38/00
摘要： The present invention is related to a synthetic and/or recombinant biologically active peptide derivatives of PTH(1-28). Some of the peptides of the invention are at least 90% identical to a peptide consisting essentially of the amino acid sequence X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsnSerMetX02ArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1), wherein X01 is Ser, Ala or Gly; and X02 is Glu or Arg.
摘要翻译： 本发明涉及PTH（1-28）的合成和/或重组生物活性肽衍生物。 一些本发明的肽与基本上由氨基酸序列X01ValSerGluIleGlnLeuMetHisAsnLeuGlyLysHisLeuAsnSerMetX02ArgValGluTrpLeuArgLysLysLeu（SEQ ID NO：1）组成的肽至少90％相同，其中X01是Ser，Ala或Gly; X02是Glu或Arg。
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9.发明授权Bioactive peptides and peptide derivatives of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) 有权甲状旁腺激素（PTH）和甲状旁腺激素相关肽（PTHrP）的生物活性肽和肽衍生物公开(公告)号：US06495662B1
公开(公告)日：2002-12-17
申请号：US09421379
申请日：1999-10-20
IPC分类号： C07K500
CPC分类号： C07K7/08 , A61K38/00 , C07K14/635
摘要： Novel parathyroid hormone peptide (PTH) and parathyroid hormone related peptide (PTHrP) or derivatives thereof which are biologically active are disclosed, as are pharmaceutical compositions containing said peptides, and synthetic and recombinant methods for producing said peptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing said peptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of said compounds.
摘要翻译： 公开了具有生物活性的新型甲状旁腺激素肽（PTH）和甲状旁腺激素相关肽（PTHrP）或其衍生物，以及含有所述肽的药物组合物以及用于产生所述肽的合成和重组方法。 还公开了使用含有所述肽的治疗有效的药物组合物治疗哺乳动物状况的方法，其特征在于骨量减少。 还公开了用于筛选本发明的候选化合物对甲状旁腺激素受体作用的拮抗作用或激动作用的方法。 还公开了所述化合物的诊断和治疗方法。
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公开(公告)号：US07022815B1
公开(公告)日：2006-04-04
申请号：US09672020
申请日：2000-09-29
CPC分类号： C07K14/635 , A61K38/00
摘要： Novel parathyroid hormone(PTH) polypeptide derivatives are disclosed, as are pharmaceutical compositions containing said polypeptides, and synthetic and recombinant methods for producing said polypeptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing said polypeptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of said compounds.
摘要翻译： 公开了新型甲状旁腺激素（PTH）多肽衍生物，含有所述多肽的药物组合物以及用于产生所述多肽的合成和重组方法。 还公开了使用含有所述多肽的治疗有效的药物组合物治疗哺乳动物状况的方法，其特征在于骨量减少。 还公开了用于筛选本发明的候选化合物对甲状旁腺激素受体作用的拮抗作用或激动作用的方法。 还公开了所述化合物的诊断和治疗方法。
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