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1. 发明申请

US20050152899A1 EphA2 agonistic monoclonal antibodies and methods of use thereof 审中-公开
标题翻译： EphA2激动单克隆抗体及其使用方法
公开(公告)号：US20050152899A1
公开(公告)日：2005-07-14
申请号：US10994129
申请日：2004-11-19
申请人： Michael Kinch , Kelly Carles-Kinch , Jane Stewart
发明人： Michael Kinch , Kelly Carles-Kinch , Jane Stewart
IPC分类号： A61K39/395 , C07K16/30 , C12N5/06
CPC分类号： C07K16/30 , A61K2039/505 , C07K16/24 , C07K16/2866 , C07K16/3015 , C07K16/3069 , C07K16/3076 , C07K2317/56 , C07K2317/565 , C07K2317/75
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. The methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to and agonize EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels in cells which EphA2 has been agonized. The invention also encompasses antibodies that preferentially bind an EphA2 epitope exposed on cancer cells but not non-cancer cells. The invention also provides pharmaceutical compositions comprising one or more EphA2 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.
摘要翻译：本发明涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。本发明的方法包括施用有效量的一种或多种与EphA2结合并激动EphA2的抗体，从而增加EphA2被激动的细胞中的EphA2磷酸化和降低EphA2水平。本发明还包括优先结合暴露于癌细胞但不是非癌细胞的EphA2表位的抗体。本发明还提供包含本发明的一种或多种EphA2抗体的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

2. 发明申请

US20070134254A1 EphA2 agonistic monoclonal antibodies and methods of use thereof 审中-公开
公开(公告)号：US20070134254A1
公开(公告)日：2007-06-14
申请号：US11650287
申请日：2007-01-05
申请人： Michael Kinch , Kelly Carles-Kinch , Jane Stewart
发明人： Michael Kinch , Kelly Carles-Kinch , Jane Stewart
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C12N5/06
CPC分类号： C07K16/30 , A61K2039/505 , C07K16/24 , C07K16/2866 , C07K16/3015 , C07K16/3069 , C07K16/3076 , C07K2317/56 , C07K2317/565 , C07K2317/75
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. The methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to and agonize EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels in cells which EphA2 has been agonized. The invention also encompasses antibodies that preferentially bind an EphA2 epitope exposed on cancer cells but not non-cancer cells. The invention also provides pharmaceutical compositions comprising one or more EphA2 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.

3. 发明申请

US20070086943A1 EphA2 agonistic monoclonal antibodies and methods of use thereof 审中-公开
标题翻译： EphA2激动单克隆抗体及其使用方法
公开(公告)号：US20070086943A1
公开(公告)日：2007-04-19
申请号：US11544332
申请日：2006-10-06
申请人： Michael Kinch , Kelly Carles-Kinch , Jane Stewart
发明人： Michael Kinch , Kelly Carles-Kinch , Jane Stewart
IPC分类号： A61K51/00 , A61K39/395
CPC分类号： C07K16/2866 , A61K2039/505 , C07K16/24 , C07K16/30 , C07K16/3015 , C07K16/3069 , C07K16/3076 , C07K2317/565 , C07K2317/73 , C07K2317/75
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. The methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to and agonize EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels in cells which EphA2 has been agonized. The invention also encompasses antibodies that preferentially bind an EphA2 epitope exposed on cancer cells but not non-cancer cells. The invention also provides pharmaceutical compositions comprising one or more EphA2 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.
摘要翻译：本发明涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。本发明的方法包括施用有效量的一种或多种与EphA2结合并激动EphA2的抗体，从而增加EphA2被激动的细胞中的EphA2磷酸化和降低EphA2水平。本发明还包括优先结合暴露于癌细胞但不是非癌细胞的EphA2表位的抗体。本发明还提供包含本发明的一种或多种EphA2抗体的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

4. 发明申请

US20060121042A1 Modulation of antibody specificity by tailoring the affinity to cognate antigens 审中-公开
标题翻译：通过调整对同源抗原的亲和力来调节抗体特异性
公开(公告)号：US20060121042A1
公开(公告)日：2006-06-08
申请号：US11259133
申请日：2005-10-27
申请人： William Dall'Acqua , Melissa Damschroder , Michael Kinch , Kelly Carles-Kinch
发明人： William Dall'Acqua , Melissa Damschroder , Michael Kinch , Kelly Carles-Kinch
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C12N5/06 , C07K16/30
CPC分类号： C07K16/2866 , C07K16/005 , C07K2317/21 , C07K2317/55 , C07K2317/565 , C07K2317/92
摘要： The present invention relates to methods and compositions designed for the treatment, management, prevention and/or amelioration of various disorders associated with aberrant expression and/or activity of one or more Eph receptor tyrosine kinase family members and/or one or more Eph receptor ligands, particularly the Ephrins. In particular, the invention provides methods for the treatment, management, prevention and/or amelioration of a disorder associated with aberrant expression and/or activity(ies) of one or more Eph receptors and/or one or more Ephrins, the method comprising administering to a subject in need thereof an effective amount of one or more Eph/Ephrin Modulators. The present invention further relates to methods of modulating antibody specificity by tailoring the affinity to cognate antigens.
摘要翻译：本发明涉及设计用于治疗，管理，预防和/或改善与一种或多种Eph受体酪氨酸激酶家族成员和/或一种或多种Eph受体配体的异常表达和/或活性相关的各种疾病的方法和组合物，特别是Ephrins。特别地，本发明提供了治疗，管理，预防和/或改善与一种或多种Eph受体和/或一种或多种Ephrins的异常表达和/或活性相关的病症的方法，所述方法包括施用对有需要的受试者有效量的一种或多种Eph / Ephrin调节剂。本发明还涉及通过调整对同源抗原的亲和力来调节抗体特异性的方法。

5. 发明申请

US20060121043A1 Use of modulators of EphA2 and EphrinA1 for the treatment and prevention of infections 审中-公开
标题翻译：使用EphA2和EphrinA1调节剂治疗和预防感染
公开(公告)号：US20060121043A1
公开(公告)日：2006-06-08
申请号：US11259266
申请日：2005-10-27
申请人： Michael Kinch , Kelly Carles-Kinch
发明人： Michael Kinch , Kelly Carles-Kinch
IPC分类号： A61K39/395
CPC分类号： C07K16/2866 , A61K2039/505 , Y02A50/403 , Y02A50/41
摘要： The present invention provides methods and compositions designed for the treatment, management, and/or amelioration of an infection, in particular an intracellular pathogen infection, such as a viral, bacterial, protozoa or fungal infection. In particular, the present invention provides methods for treating, managing, preventing and/or ameliorating an infection where the expression of EphA2 is upregulated in infected cells (e.g., infected epithelial cells), said methods comprising administering to a subject an effective amount of one or more EphA2/EphrinA1 Modulators. In accordance with the present invention, such methods may also comprise the administration of one or more therapies other than an EphA2/EphrinA1 Modulator. The present invention also provides pharmaceutical compositions comprising EphA2/EphrinA1 Modulators, and optionally, one or more prophylactic or therapeutic agents other than an EphA2/EphrinA1 Modulator, and the use of such compositions in the treating, management, prevention and/or amelioration of an infection. Further provided by the invention are articles of manufacture and kits comprising an EphA2/EphrinA1 Modulator of the invention, and, optionally, other prophylactic or therapeutic agents (e.g., immunomodulatory agents, anti-viral agents, anti-inflammatory agents, anti-bacterial agents, anti-fungal agents, etc.).
摘要翻译：本发明提供了用于治疗，管理和/或改善感染，特别是细胞内病原体感染如病毒，细菌，原生动物或真菌感染的方法和组合物。特别地，本发明提供了用于治疗，控制，预防和/或改善感染的方法，其中EphA2的表达在受感染的细胞（例如感染的上皮细胞）中被上调，所述方法包括向受试者施用有效量的一种或更多的EphA2 / EphrinA1调节剂。根据本发明，这些方法还可以包括施用除EphA2 / EphrinA1调节剂之外的一种或多种治疗。本发明还提供包含EphA2 / EphrinA1调节剂的药物组合物，以及任选的除EphA2 / EphrinA1调节剂之外的一种或多种预防或治疗剂，以及这些组合物在治疗，管理，预防和/或改善感染。本发明进一步提供的是包含本发明的EphA2 / EphrinA1调节剂和任选的其它预防或治疗剂（例如免疫调节剂，抗病毒剂，抗炎剂，抗菌剂，抗真菌剂等）。

6. 发明申请

US20060122138A1 Modulators of EphA2 and EphrinA1 for the treatment of fibrosis-related disease 审中-公开
标题翻译： EphA2和EphrinA1的调节剂用于治疗纤维化相关疾病
公开(公告)号：US20060122138A1
公开(公告)日：2006-06-08
申请号：US11259267
申请日：2005-10-27
申请人： Michael Kinch , Kelly Carles-Kinch
发明人： Michael Kinch , Kelly Carles-Kinch
IPC分类号： A61K48/00 , A61K39/395 , A61K39/00
CPC分类号： C12N9/1205 , A61K48/00 , C07K16/24 , C07K16/2866
摘要： The present invention relates to methods and compositions designed for the treatment, management, prevention and/or amelioration of non-neoplastic hyperproliferative epithelial and/or endothelial cell disorders, including but not limited to disorders associated with increased deposition of extracellular matrix components (e.g., collagen, proteoglycans, tenascin and fibronectin) and/or aberrant angiogenesis. Non-limiting examples of such disorders include cirrhosis, fibrosis (e.g., fibrosis of the liver, kidney, lungs, heart, retina and other viscera), asthma, ischemia, atherosclerosis, diabetic retinopathy, retinopathy of prematurity, vascular restenosis, macular degeneration, rheumatoid arthritis, osteoarthritis, infantile hemangioma, verruca vulgaris, Kaposi's sarcoma, neurofibromatosis, recessive dystrophic epidermolysis bullosa, ankylosing spondylitis, systemic lupus, Reiter's syndrome, Sjogren's syndrome, endometriosis, preeclampsia, atherosclerosis, coronary artery disease, psoriatic arthropathy and psoriasis. The methods of the invention comprise the administration of an effective amount of one or more agents that are modulators of EphA2 and/or its endogenous ligand, EphrinA1. The invention also provides pharmaceutical compositions comprising one or more EphA2/EphrinA1 Modulators of the invention either alone or in combination with one or more other agents useful for therapy for such non-neoplastic hyperproliferative epithelial and/or endothelial disorders. Diagnostic methods and methods for screening for EphA2/EphrinA1 Modulators are also provided.
摘要翻译：本发明涉及设计用于治疗，管理，预防和/或改善非肿瘤性过度增殖性上皮细胞和/或内皮细胞病症的方法和组合物，包括但不限于与增加的细胞外基质组分沉积相关的病症（例如，胶原蛋白，蛋白聚糖，腱生蛋白和纤连蛋白）和/或异常血管生成。这种疾病的非限制性实例包括肝硬化，纤维化（例如肝脏，肾脏，肺，心脏，视网膜和其他内脏的纤维化），哮喘，局部缺血，动脉粥样硬化，糖尿病性视网膜病变，早产儿视网膜病变，血管再狭窄，黄斑变性，类风湿关节炎，骨关节炎，婴儿血管瘤，寻常疣状，卡波西肉瘤，神经纤维瘤病，隐性营养不良性表皮松解性大疱性，强直性脊柱炎，系统性红斑狼疮，赖特综合征，干燥综合征，子宫内膜异位症，先兆子痫，动脉粥样硬化，冠状动脉疾病，牛皮癣性关节病和牛皮癣。本发明的方法包括施用有效量的一种或多种作为EphA2和/或其内源性配体调节剂EphrinA1的试剂。本发明还提供包含本发明的一种或多种EphA2 / EphrinA1调节剂的药物组合物，其单独或与一种或多种其它可用于治疗这种非肿瘤性过度增殖性上皮和/或内皮病症的其它试剂组合。还提供了用于筛选EphA2 / EphrinA1调节剂的诊断方法和方法。

7. 发明申请

US20050013819A1 Use of EphA4 and modulator of EphA4 for diagnosis, treatment and prevention of cancer 失效
标题翻译：使用EphA4和EphA4调节剂进行诊断，治疗和预防癌症
公开(公告)号：US20050013819A1
公开(公告)日：2005-01-20
申请号：US10863729
申请日：2004-06-07
申请人： Michael Kinch , Kelly Carles-Kinch
发明人： Michael Kinch , Kelly Carles-Kinch
IPC分类号： C07K16/24 , A61K39/395
CPC分类号： C07K16/2866 , A61K2039/505 , C07K14/52 , C07K16/24 , C07K2317/622 , C07K2317/73 , C07K2319/30
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. In one embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to EphA4 and agonize EphA4. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to EphA4 and inhibit cancer cell colony formation in soft agar or tubular network formation in three-dimensional basement membrane or extracellular matrix preparation. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that preferentially binds to an EphA4 epitope that is exposed on cancer cells but not non-cancer cells. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to EphA4 with a very low Koff to reduce EphA4 expression and, thereby, inhibit tumor cell growth and/or metastasis. The invention also provides pharmaceutical compositions comprising one or more EphA4 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.
摘要翻译：本发明涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。在一个实施方案中，本发明的方法包括施用有效量的一种或多种结合EphA4并激动EphA4的抗体。在另一个实施方案中，本发明的方法包括施用有效量的结合EphA4的一种或多种抗体并抑制在三维基底膜或细胞外基质制剂中的软琼脂或管状网络形成中的癌细胞集落形成。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优先结合暴露于癌细胞但不暴露于非癌细胞的EphA4表位的抗体。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与非常低Koff结合EphA4的抗体以减少EphA4表达，从而抑制肿瘤细胞生长和/或转移。本发明还提供包含本发明的一种或多种EphA4抗体的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

8. 发明申请

US20070166314A1 EpA2 monoclonal antibodies and methods of use thereof 审中-公开
标题翻译： EpA2单克隆抗体及其使用方法
公开(公告)号：US20070166314A1
公开(公告)日：2007-07-19
申请号：US11717799
申请日：2007-03-12
申请人： Michael Kinch , Kelly Carles-Kinch , Peter Kiener , Solomon Langermann
发明人： Michael Kinch , Kelly Carles-Kinch , Peter Kiener , Solomon Langermann
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C12N5/06 , C07K16/30
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/56 , C07K2317/73 , C07K2317/75 , C07K2317/92
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. In one embodiment, the methods of the invention comprise the administration of an effective amount of an antibody that binds to EphA2 and agonizes EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels. In other embodiments, the methods of the invention comprise the administration of an effective amount of an antibody that binds to EphA2 and inhibits cancer cell colony formation in soft agar, inhibits tubular network formation in three-dimensional basement membrane or extracellular matrix preparation, preferentially binds to an EphA2 epitope that is exposed on cancer cells but not non-cancer cells, and/or has a low Koff, thereby, inhibiting tumor cell growth and/or metastasis. The invention also provides pharmaceutical compositions comprising one or more EphA2 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.
摘要翻译：本发明涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。在一个实施方案中，本发明的方法包括施用有效量的结合EphA2并激动EphA2的抗体，从而增加EphA2磷酸化并降低EphA2水平。在其它实施方案中，本发明的方法包括施用有效量的结合EphA2的抗体并抑制软琼脂中的癌细胞集落形成，抑制三维基底膜或细胞外基质制剂中的管状网络形成，优先结合涉及暴露于癌细胞但不暴露于非癌细胞的EphA2表位，和/或具有低K off，从而抑制肿瘤细胞生长和/或转移。本发明还提供包含本发明的一种或多种EphA2抗体的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

9. 发明申请

US20100143345A1 EPHA2 AGONISTIC MONOCLONAL ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译： EPHA2 AGONISTIC MONOCLONAL ANTIBODIES及其使用方法
公开(公告)号：US20100143345A1
公开(公告)日：2010-06-10
申请号：US12479559
申请日：2009-06-05
申请人： Michael S. Kinch , Kelly Carles-Kinch , Jane C. Stewart
发明人： Michael S. Kinch , Kelly Carles-Kinch , Jane C. Stewart
IPC分类号： A61K39/395 , A61P35/04
CPC分类号： C07K16/30 , A61K2039/505 , C07K16/24 , C07K16/2866 , C07K16/3015 , C07K16/3069 , C07K16/3076 , C07K2317/56 , C07K2317/565 , C07K2317/75
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. The methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to and agonize EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels in cells which EphA2 has been agonized. The invention also encompasses antibodies that preferentially bind an EphA2 epitope exposed on cancer cells but not non-cancer cells. The invention also provides pharmaceutical compositions comprising one or more EphA2 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.
摘要翻译：本发明涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。本发明的方法包括施用有效量的一种或多种与EphA2结合并激动EphA2的抗体，从而增加EphA2被激动的细胞中的EphA2磷酸化和降低EphA2水平。本发明还包括优先结合暴露于癌细胞但不是非癌细胞的EphA2表位的抗体。本发明还提供包含本发明的一种或多种EphA2抗体的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

10. 发明授权

US07402298B1 EphA2 monoclonal antibodies and methods of making and using same 失效
标题翻译： EphA2单克隆抗体及其制备和使用方法
公开(公告)号：US07402298B1
公开(公告)日：2008-07-22
申请号：US11004005
申请日：2004-12-02
申请人： Michael Scott Kinch , Kelly Carles-Kinch , Katherine E Kilpatrick
发明人： Michael Scott Kinch , Kelly Carles-Kinch , Katherine E Kilpatrick
IPC分类号： A61B5/055
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/73 , C07K2317/75
摘要： The invention provides a monoclonal antibody, a fragment thereof, or a molecular complex thereof that binds to an extracellular domain of an EphA2 receptor molecule, wherein binding of the monoclonal antibody or fragment thereof to the EphA2 receptor molecule present in the membrane of a cancer cell favorably alters activity of the EphA2 receptor molecule. The invention further relates to methods of making and using the monoclonal antibodies, fragments, and molecular complexes regarding the same. The monoclonal antibodies of the present invention target the extracellular domain of EphA2 and operate to redirect the function of EphA2 to selectively block the growth and invasiveness of metastatic cells. The invention thus makes possible therapeutic strategies that optimally target metastatic cells while preventing collateral damage to normal tissues.
摘要翻译：本发明提供了结合EphA2受体分子的细胞外结构域的单克隆抗体，其片段或其分子复合物，其中单克隆抗体或其片段与存在于癌细胞膜中的EphA2受体分子的结合有利地改变EphA2受体分子的活性。本发明还涉及制备和使用单克隆抗体，片段和分子复合物的方法。本发明的单克隆抗体靶向EphA2的细胞外结构域，并且用于重定向EphA2的功能以选择性阻断转移细胞的生长和侵袭。因此，本发明使得可以最佳地靶向转移细胞同时防止对正常组织的附带损伤的治疗策略。

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