公开(公告)号：US20090162933A1

公开(公告)日：2009-06-25

申请号：US12177722

申请日：2008-07-22

申请人： Peter A. Kiener ,  Michael S. Kinch ,  Solomon Langermann ,  Jennifer L. Reed

发明人： Peter A. Kiener ,  Michael S. Kinch ,  Solomon Langermann ,  Jennifer L. Reed

IPC分类号： C12N5/02

CPC分类号： C07K16/28 ,  A61K2039/505 ,  C07K16/32

摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of a non-neoplastic hyperproliferative cell or excessive cell accumulation disorders, particularly those involving hyperproliferation of epithelial or endothelial cells. In one embodiment, the methods of the invention comprise the administration of an effective amount of one or more EphA2 agonistic agents that bind to EphA2 and increase EphA2 cytoplasmic tail phosphorylation and/or increase EphA2 autophosphorylation, in cells which EphA2 has been agonized. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more EphA2 agonistic agents that bind to EphA2 and reduce EphA2 activity (other than autophosphorylation). In another embodiment, the methods of the invention comprise administration of an effective amount of one or more EphA2 agonistic agents that bind to EphA2 and decrease a pathology-causing cell phenotype (e.g., a pathology-causing epithelial cell phenotype or a pathology-causing endothelial cell phenotype). In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more EphA2 agonistic agents that are EphA2 antibodies that bind to EphA2 with a very low Koff rate. In preferred embodiments, agents of the invention are monoclonal antibodies. The invention also provides pharmaceutical compositions comprising one or more EphA2 agonistic agents of the invention either alone or in combination with one or more other agents useful in therapy for non-neoplastic hyperproliferative cell or excessive cell accumulation disorders.

摘要翻译： 本发明涉及设计用于治疗，管理或预防非肿瘤性过度增殖性细胞或过度细胞累积障碍，特别是涉及上皮细胞或内皮细胞过度增殖的方法和组合物。 在一个实施方案中，本发明的方法包括在EphA2已经被激动的细胞中施用有效量的结合EphA2并增加EphA2胞质尾磷酸化和/或增加EphA2自磷酸化的EphA2激动剂。 在另一个实施方案中，本发明的方法包括施用有效量的一种或多种EphA2激动剂，其结合EphA2并降低EphA2活性（除了自磷酸化）。 在另一个实施方案中，本发明的方法包括施用有效量的一种或多种结合EphA2的EphA2激动剂并减少病理学引起的细胞表型（例如，导致病理的上皮细胞表型或致病性病因的内皮 细胞表型）。 在另一个实施方案中，本发明的方法包括施用有效量的一种或多种EphA2激动剂，其是以非常低的Koff率与EphA2结合的EphA2抗体。 在优选的实施方案中，本发明的试剂是单克隆抗体。 本发明还提供包含本发明的一种或多种EphA2激动剂的药物组合物，其单独或与一种或多种其它可用于治疗非肿瘤性过度增殖性细胞或过度细胞累积障碍的其它药物组合。

公开(公告)号：US20110059100A1

公开(公告)日：2011-03-10

申请号：US12351145

申请日：2009-01-09

申请人： Jennifer L. Reed ,  Wendy I. White ,  Anthony Coyle ,  Alexander Kozhich ,  Jack Elias ,  Nanci Donacki ,  Changshou Gao ,  Herren Wu

发明人： Jennifer L. Reed ,  Wendy I. White ,  Anthony Coyle ,  Alexander Kozhich ,  Jack Elias ,  Nanci Donacki ,  Changshou Gao ,  Herren Wu

IPC分类号： A61K39/395 ,  C07K16/00 ,  A61P11/00

CPC分类号： C07K16/40 ,  A61K48/00 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/52 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2319/00 ,  C12N9/2442 ,  C12N15/86 ,  C12N2710/10343 ,  C12Y302/01014

摘要： The invention relates to the novel discovery that antagonizing a C/CLP can be useful for the treatment of diseases associated with the upregulation of one or more C/CLP such as Th2-driven and/or IL-13 mediated inflammatory diseases. Accordingly the present invention provides C/CLP antagonists and also provides compositions and methods for the prevention, management, treatment or amelioration of an inflammatory condition associated with the upregulation of a C/CLP or one or more symptoms thereof and/or the inhibition of IL-13 mediated inflammation.

摘要翻译： 本发明涉及拮抗C / CLP的新发现，可用于治疗与上调一种或多种C / CLP如Th2驱动和/或IL-13介导的炎性疾病相关的疾病。 因此，本发明提供了C / CLP拮抗剂，并且还提供了用于预防，治疗，改善与C / CLP或其一种或多种症状的上调相关的炎性病症和/或抑制IL的组合物和方法 -13介导的炎症。