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    Targeted drug delivery using EphA2 or EphA4 binding moieties
    14.
    发明申请
    Targeted drug delivery using EphA2 or EphA4 binding moieties 审中-公开
    使用EphA2或EphA4结合部分的靶向药物递送

    公开(公告)号：US20050153923A1

    公开(公告)日：2005-07-14

    申请号：US11004794

    申请日：2004-12-03

    申请人： Michael Kinch

    发明人： Michael Kinch

    IPC分类号： A61K9/127 ,  A61K39/395 ,  A61K48/00

    CPC分类号： C07K16/2866 ,  A61K39/395 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/545 ,  C07K14/52 ,  C07K14/715 ,  C07K2317/73 ,  C07K2317/75 ,  C07K2317/92 ,  C07K2319/30 ,  A61K2300/00

    摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of a hyperproliferative cell disease, particularly cancer. The methods of the invention comprise the administration of an effective amount of a composition that targets cells expressing an Eph family receptor tyrosine kinase, such as EphA2 or EphA4, for the treatment, management, or prevention of hyperproliferative diseases, particularly cancer. In one embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety attached to a delivery vehicle, and one or more therapeutic or prophylactic agents that treat or prevent a hyperproliferative disease, where the therapeutic or prophylactic agents are operatively associated with the delivery vehicle. In another embodiment, the method of the invention comprises administering to a subject a composition comprising a nucleic acid comprising a nucleotide sequence encoding an EphA2 or EphA4 targeting moiety and a therapeutic or prophylactic agent that treats or prevents a hyperproliferative disease. In yet another embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety and a nucleic acid comprising a nucleotide sequence encoding an agent that treats or prevents a hyperproliferative disease, where the nucleic acid is operatively associated with the delivery vehicle. Pharmaceutical compositions are also provided by the present invention.

    摘要翻译： 本发明涉及设计用于治疗，控制或预防过度增殖性细胞疾病，特别是癌症的方法和组合物。 本发明的方法包括施用有效量的靶向表达Eph家族受体酪氨酸激酶（例如EphA2或EphA4）的细胞的组合物，用于治疗，控制或预防过度增殖性疾病，特别是癌症。 在一个实施方案中，本发明的方法包括向受试者施用包含与递送载体​​连接的EphA2或EphA4靶向部分的组合物，以及治疗或预防过度增殖性疾病的一种或多种治疗或预​​防剂，其中所述治疗或预防 试剂与输送载体可操作地相关联。 在另一个实施方案中，本发明的方法包括向受试者施用包含核酸的组合物，所述核酸包含编码EphA2或EphA4靶向部分的核苷酸序列和治疗或预防过度增殖性疾病的治疗或预防剂。 在另一个实施方案中，本发明的方法包括对受试者施用包含EphA2或EphA4靶向部分的组合物和包含编码治疗或预防过度增殖性疾病的药物的核苷酸序列的核酸，其中所述核酸可操作地相关联 与送货车。 药物组合物也由本发明提供。

    EphA2 T-cell epitope agonists and uses therefor
    15.
    发明申请
    EphA2 T-cell epitope agonists and uses therefor 审中-公开
    EphA2 T细胞表位激动剂及其用途

    公开(公告)号：US20050048550A1

    公开(公告)日：2005-03-03

    申请号：US10897711

    申请日：2004-07-22

    申请人： Walter Storkus ,  Michael Kinch

    发明人： Walter Storkus ,  Michael Kinch

    IPC分类号： A61K38/17 ,  C07K14/47 ,  C07K14/705 ,  G01N33/50 ,  G01N33/569 ,  C12Q1/68 ,  G01N33/574

    CPC分类号： C07K14/4748 ,  A61K38/1793 ,  A61K39/0011 ,  A61K2039/55566 ,  C07K7/06 ,  C07K7/08 ,  C07K14/47 ,  C07K14/705 ,  G01N33/505 ,  G01N33/5091 ,  G01N33/56966 ,  G01N33/56972 ,  G01N2333/5409 ,  G01N2333/57

    摘要： EphA2 T-cell epitope agonists are provided herein. The agonists include peptides corresponding to specific fragments of human EphA2 protein containing one or more T-cell epitopes, and conservative derivatives thereof. The EphA2 T-cell epitope agonists are useful in an assay, such as an ELISPOT assay, that may be used to determine and/or quantify a patient's immune responsiveness to EphA2. The agonists also are useful in methods of modulating a patient's immune reactivity to EphA2, which has substantial utility as a treatment for cancers that overexpress EphA2, such as renal cell carcinoma (RCC). The EphA2 agonists also can be used to vaccinate a patient against EphA2, by in vivo or ex vivo methods.

    摘要翻译： 本文提供EphA2 T细胞表位激动剂。 激动剂包括对应于含有一个或多个T细胞表位的人EphA2蛋白的特异性片段的肽及其保守衍生物。 EphA2 T细胞表位激动剂可用于可用于确定和/或定量患者对EphA2的免疫反应性的测定中，例如ELISPOT测定。 激动剂也可用于调节患者对EphA2的免疫反应性的方法，其对于过表达EphA2的癌症如肾细胞癌（RCC）具有实际作用。 EphA2激动剂也可用于通过体内或离体方法对EphA2接种患者。

    Modulators of EphA2 and EphrinA1 for the treatment of fibrosis-related disease
    19.
    发明申请
    Modulators of EphA2 and EphrinA1 for the treatment of fibrosis-related disease 审中-公开
    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。

    Use of EphA4 and modulator of EphA4 for diagnosis, treatment and prevention of cancer
    20.
    发明申请
    Use of EphA4 and modulator of EphA4 for diagnosis, treatment and prevention of cancer 失效
    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。