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1.发明授权公开(公告)号：US09428568B2
公开(公告)日：2016-08-30
申请号：US13128290
申请日：2009-11-10
申请人： Jun Li , Agnès Vignery
发明人： Jun Li , Agnès Vignery
IPC分类号： G01N33/53 , C07K14/705
CPC分类号： C07K14/705
摘要： Compositions and methods are provided for modulating cell-cell fusion by using agents that modulate expression, activity, or function of intermediate-conductance calcium-activated potassium (SK4) channel. In some embodiments, the compositions and methods of the invention provide for inhibition of multi-nucleated osteoclastogenesis and cell-cell fusion, especially cell fusion involving macrophages. In such embodiments, the compositions can comprise inhibitory nucleic acids, monoclonal antibodies or small molecule inhibitors of the SK4 channels and find use in preventing and/or treating various diseases or disorders including bone loss, autoimmune and inflammatory diseases or disorders, implant and transplant rejection, and cancer metastasis. In other embodiments, the compositions and methods of the invention provide for activation of cell-cell fusion. Also provided are methods to screen for SK4 channel modulators (inhibitors or activators) that modulate cell-cell fusion, particularly macrophage cell fusion.
摘要翻译： 提供了通过使用调节中间电导钙激活钾（SK4）通道的表达，活性或功能的试剂来调节细胞 - 细胞融合的组合物和方法。 在一些实施方案中，本发明的组合物和方法提供了抑制多核破骨细胞发生和细胞 - 细胞融合，特别是涉及巨噬细胞的细胞融合。 在这样的实施方案中，组合物可以包含SK4通道的抑制性核酸，单克隆抗体或小分子抑制剂，并且可用于预防和/或治疗各种疾病或病症，包括骨丢失，自身免疫和炎性疾病或病症，植入物和移植排斥 ，和癌转移。 在其它实施方案中，本发明的组合物和方法提供细胞 - 细胞融合的活化。 还提供了筛选调节细胞融合，特别是巨噬细胞融合的SK4通道调节剂（抑制剂或活化剂）的方法。
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公开(公告)号：US08852240B2
公开(公告)日：2014-10-07
申请号：US11796439
申请日：2007-04-27
CPC分类号： A61B17/58 , A61B2017/564 , A61L27/12 , A61L27/54 , A61L2300/112 , A61L2300/252 , A61L2300/414 , A61L2300/43
摘要： A method for augmenting bone in a subject in need thereof including installing within an interior portion of a bone located in the subject a sufficient amount of a biocompatible material to form a scaffold within the bone interior, wherein the scaffold serves as a support for the formation of new bone within the bone interior portion, and administering to the subject a sufficient amount of at least one bone augmentation agent to elevate blood concentration of at least one anabolic agent in the subject. The method may further include administering at least one anti-resorptive agent to the subject in an amount sufficient to substantially prevent resorption of new bone growth. In another embodiment, the method may further include a step of mechanically inducing an increase in osteoblast activity in the subject, wherein the elevation in blood concentration of the anabolic agent and the increase in osteoblast activity at least partially overlap in time.
摘要翻译： 一种用于在有需要的受试者中增加骨的方法，包括在位于受试者内的骨的内部部分内安装足够量的生物相容性材料以在骨内部形成支架，其中所述支架用作所述形成的支撑体 的骨内部部分中的新骨，并且向受试者施用足够量的至少一种骨增强剂以提高受试者中至少一种合成代谢物的血液浓度。 该方法还可以包括以足以基本上防止新骨生长再吸收的量向受试者施用至少一种抗吸收剂。 在另一个实施方案中，该方法还可以包括机械诱导受试者中成骨细胞活性增加的步骤，其中合成代谢剂的血液浓度升高和成骨细胞活性的增加在时间上至少部分重叠。
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公开(公告)号：US07648965B2
公开(公告)日：2010-01-19
申请号：US11267987
申请日：2005-11-07
申请人： Agnès Vignery , Nozer M. Mehta , James P. Gilligan
发明人： Agnès Vignery , Nozer M. Mehta , James P. Gilligan
CPC分类号： A61K38/1825 , A61F2002/2817 , A61K38/1833 , A61K38/1841 , A61K38/1875 , A61K38/225 , A61K38/29 , A61K38/30 , Y10S435/81
摘要： A method of inducing bone formation in a subject in need of such inducement comprises the steps of mechanically inducing an increase in osteoblast activity in the subject and elevating blood concentration of at least one bone anabolic agent in the subject. The method steps may be performed in any order, but in sufficient time proximity that the elevated concentration of the anabolic agent and the mechanically induced increase in osteoblast activity overlaps. The method may additionally comprise providing the subject with an elevated blood concentration of at least one antiresorptive agent, wherein the elevated concentration is sufficient to prevent resorption of new bone growth produced due to the osteoblast activity. Use of the method permits targeting of specific bones of the subject for bone production and preservation, faster bone production and earlier discontinuation of bone anabolic pharmaceuticals. Kits adapted for performing the method are provided.
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公开(公告)号：US07531518B2
公开(公告)日：2009-05-12
申请号：US11128095
申请日：2005-05-11
申请人： Agnès Vignery , Nozer M. Mehta , James P. Gilligan
发明人： Agnès Vignery , Nozer M. Mehta , James P. Gilligan
CPC分类号： A61K38/1833 , A61K38/1825 , A61K38/1841 , A61K38/1875 , A61K38/225 , A61K38/29 , A61K38/30 , Y10S435/81
摘要： A method of inducing bone formation in a subject in need of such inducement comprises the steps of mechanically inducing an increase in osteoblast activity in the subject and elevating blood concentration of at least one bone anabolic agent in the subject. The method steps may be performed in any order, but in sufficient time proximity that the elevated concentration of the anabolic agent and the mechanically induced increase in osteoblast activity overlaps. The method may additionally comprise providing the subject with an elevated blood concentration of at least one antiresorptive agent, wherein the elevated concentration is sufficient to prevent resorption of new bone growth produced due to the osteoblast activity. Use of the method permits targeting of specific bones of the subject for bone production and preservation, faster bone production and earlier discontinuation of bone anabolic pharmaceuticals. Kits adapted for performing the method are provided.
摘要翻译： 在需要这种诱导的受试者中诱导骨形成的方法包括以下步骤：机械诱导受试者中成骨细胞活性的增加并提高受试者中至少一种骨合成代谢物的血液浓度。 方法步骤可以以任何顺序进行，但是在足够的时间接近度下，合成代谢剂的升高浓度和机械诱导的成骨细胞活性增加重叠。 该方法可另外包括向受试者提供至少一种抗再吸收剂的升高的血液浓度，其中提高的浓度足以防止由于成骨细胞活性而产生的新骨生长的再吸收。 使用该方法允许靶向受试者的特定骨骼用于骨生产和保存，更快的骨生产和早期停止骨合成代谢药物。 提供适用于执行该方法的套件。
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