公开(公告)号：US06756480B2

公开(公告)日：2004-06-29

申请号：US09843221

申请日：2001-04-26

申请人： Paul Kostenuik ,  Chuan-Fa Liu ,  David Lee Lacey

发明人： Paul Kostenuik ,  Chuan-Fa Liu ,  David Lee Lacey

IPC分类号： C07K1600

CPC分类号： C07K14/635 ,  A61K38/00 ,  A61K47/60 ,  A61K47/61 ,  A61K47/6425 ,  C07K2319/00

摘要： The present invention concerns therapeutic agents that modulate the activity of PTH and PTHrP. In accordance with the present invention, modulators of PTH and PTHrP comprise: (a) a PTH/PTHrP modulating domain; and (b) a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the C-terminus of the PTH/PTHrP modulating domain. The vehicle and the PTH/PTHrP modulating domain may be linked through the N- or C-terminus of the PTH/PTHrP modulating domain, as described further below. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain. Preferred PTH/PTHrP modulating domains comprise the PTH and PTHrP-derived amino acid sequences described hereinafter. Other PTH/PTHrP modulating domains can be generated by phage display, RNA-peptide screening and the other techniques mentioned herein. Such peptides typically will be modulators of both PTH activity and PTHrP activity, although such techniques can be used to generate peptide sequences that serve as selective modulators (e.g., agonists of PTH activity but not PTHrP activity).

摘要翻译： 本发明涉及调节PTH和PTHrP活性的治疗剂。 根据本发明，PTH和PTHrP的调节剂包括：（a）PTH / PTHrP调节结构域; 和（b）优选的载体，例如聚合物（例如PEG或葡聚糖）或Fc结构域;其中载体共价连接到PTH / PTHrP调节结构域的C末端。 载体和PTH / PTHrP调节结构域可以通过PTH / PTHrP调节结构域的N末端或C末端连接，如下文进一步描述的。 优选的载体是Fc结构域，优选的Fc结构域是IgG Fc结构域。 优选的PTH / PTHrP调节结构域包含下文描述的PTH和PTHrP衍生的氨基酸序列。 其他PTH / PTHrP调节结构域可以通过噬菌体展示，RNA-肽筛选和本文提及的其他技术产生。 尽管这样的技术可用于产生用作选择性调节剂的肽序列（例如，PTH活性的激动剂但不是PTHrP活性），但是这些肽通常将是PTH活性和PTHrP活性的调节剂。

公开(公告)号：US07005413B1

公开(公告)日：2006-02-28

申请号：US09613591

申请日：2000-07-10

申请人： William J. Boyle ,  David Lee Lacey ,  Frank J. Calzone ,  Ming-Shi Chang

发明人： William J. Boyle ,  David Lee Lacey ,  Frank J. Calzone ,  Ming-Shi Chang

IPC分类号： A61K38/00 ,  C07K14/51 ,  C07K14/525 ,  C07K14/54 ,  C07K16/46

CPC分类号： A61K38/1793 ,  A61K38/00 ,  C07K14/70578 ,  C07K2319/30

摘要： The present invention discloses a novel secreted polypeptide, termed osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind OPG, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis. Methods of treatment are described using the polypeptides in conjunction with various agents, including IL-1 inhibitors, TNF-α inhibitors, and serine protease inhibitors.

摘要翻译： 本发明公开了一种称为骨保护素的新型分泌多肽，其是肿瘤坏死因子受体超家族的成员，并且参与骨代谢的调节。 还公开了编码骨保护素，多肽，重组载体和表达宿主细胞，结合OPG的抗体和药物组合物的核酸。 多肽用于治疗以增加再吸收为特征的骨疾病，例如骨质疏松症。 使用多种结合多种试剂（包括IL-1抑制剂，TNF-α抑制剂和丝氨酸蛋白酶抑制剂）描述治疗方法。