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    EphA2 and hyperproliferative cell disorders
    1.
    发明申请
    EphA2 and hyperproliferative cell disorders 审中-公开
    EphA2和过度增殖性细胞病变

    公开(公告)号：US20050059592A1

    公开(公告)日：2005-03-17

    申请号：US10823254

    申请日：2004-04-12

    申请人： Peter Kiener ,  Michael Kinch ,  Solomon Langermann ,  Jennifer Reed

    发明人： Peter Kiener ,  Michael Kinch ,  Solomon Langermann ,  Jennifer Reed

    IPC分类号： A61B20060101 ,  A61K39/00 ,  A61K39/395 ,  A61K49/00 ,  C07K16/28 ,  C07K16/32

    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，本发明的方法包括施用有效量的一种或多种EphA2激动剂，其结合EphA2并增加EphA2细胞质尾磷酸化和/或增加EphA2已被激动的细胞中的EphA2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。

    EpA2 monoclonal antibodies and methods of use thereof
    3.
    发明申请
    EpA2 monoclonal antibodies and methods of use thereof 审中-公开
    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。

    EphA2, hypoproliferative cell disorders and epithelial and endothelial reconstitution
    4.
    发明申请
    EphA2, hypoproliferative cell disorders and epithelial and endothelial reconstitution 审中-公开
    EphA2，低增殖细胞疾病和上皮和内皮重建

    公开(公告)号：US20050049176A1

    公开(公告)日：2005-03-03

    申请号：US10823259

    申请日：2004-04-12

    申请人： Peter Kiener ,  Michael Kinch ,  Solomon Langermann

    发明人： Peter Kiener ,  Michael Kinch ,  Solomon Langermann

    IPC分类号： A61K38/00 ,  A61K38/19 ,  A61K39/395 ,  A61K48/00 ,  C07K14/715 ,  C07K16/28 ,  C12N20060101

    CPC分类号： C07K16/2866 ,  A61K38/19 ,  C07K14/715

    摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of a hypoproliferative cell disorder, especially those disorders relating to the destruction, shedding, or inadequate proliferation of epithelial and/or endothelial cells, particularly interstitial cystitis (IC) and lesions associated with inflammatory bowel disease (IBD). The methods of the invention comprise the administration of an effective amount of one or more agents that are antagonists of EphA2. In certain embodiments, the EphA2 antagonistic agent of the invention decreases EphA2-endogenous ligand binding, upregulates EphA2 gene expression and/or translation, increases EphA2 protein stability or protein accumulation, decreases EphA2 cytoplasmic tail phosphorylation, promotes EphA2 kinase activity (other than autophosphorylation or ligand-mediated EphA2 signaling), increases proliferation of EphA2 expressing cells, increases survival of EphA2 expressing cells, and/or maintains/reconstitutes epithelial and/or endothelial cell layer integrity. The invention also provides pharmaceutical compositions comprising one or more EphA2 antagonistic agents of the invention either alone or in combination with one or more other agents useful for therapy for a hypoproliferative cell disorder. Diagnostic methods and methods for screening for therapeutically useful agents are also provided.

    摘要翻译： 本发明涉及设计用于治疗，治疗或预防低增殖性细胞病症的方法和组合物，特别是与上皮和/或内皮细胞，特别是间质性膀胱炎（IC）的破坏，脱落或不充分增殖有关的那些疾病， 和与炎症性肠病（IBD）相关的损伤。 本发明的方法包括施用有效量的一种或多种作为EphA2拮抗剂的试剂。 在某些实施方案中，本发明的EphA2拮抗剂降低EphA2-内源性配体结合，上调EphA2基因表达和/或翻译，增加EphA2蛋白稳定性或蛋白质积累，降低EphA2胞质尾磷酸化，促进EphA2激酶活性（除了自磷酸化或 配体介导的EphA2信号传导）增加EphA2表达细胞的增殖，增加EphA2表达细胞的存活，和/或保持/重建上皮和/或内皮细胞层完整性。 本发明还提供包含本发明的一种或多种EphA2拮抗剂的药物组合物，其单独或与一种或多种其它用于治疗低增殖性细胞病症的其它药剂组合。 还提供了用于筛选治疗有用的试剂的诊断方法和方法。

    EphA2 BiTE molecules and uses thereof
    5.
    发明申请
    EphA2 BiTE molecules and uses thereof 审中-公开
    EphA2 BiTE分子及其用途

    公开(公告)号：US20080044413A1

    公开(公告)日：2008-02-21

    申请号：US11645290

    申请日：2006-12-21

    申请人： Scott Hammond ,  Peter Kiener ,  Elizabeth Bruckheimer ,  Michael Kinch ,  Shannon Roff ,  Ralf Lutterbuese ,  Petra Lutterbuese ,  Bernd Schlereth ,  Patrick Baeuerle ,  Peter Kufer

    发明人： Scott Hammond ,  Peter Kiener ,  Elizabeth Bruckheimer ,  Michael Kinch ,  Shannon Roff ,  Ralf Lutterbuese ,  Petra Lutterbuese ,  Bernd Schlereth ,  Patrick Baeuerle ,  Peter Kufer

    IPC分类号： A61K39/395 ,  A61P31/00 ,  A61P35/00 ,  A61P43/00 ,  C07K16/28

    CPC分类号： C07K16/2866 ,  C07K16/2809 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/92 ,  C07K2319/30

    摘要： The present invention relates to bispecific single chain antibodies comprising a first binding domain that immunospecifically binds to the T-cell antigen CD3 and a second binding domain that immunospecifically binds to the EphA2 receptor. Such bispecific single chain antibodies are encompassed by the term “EphA2-BiTEs.” The present invention further relates to methods and compositions designed for the treatment, prevention and/or management of disorders associated with aberrant expression and/or activity of EphA2. Such disorders include, but are not limited to, cancer, non-cancer hyperproliferative cell disorders, and infections. The invention further relates to vectors comprising polynucleotides encoding the EphA2-BiTEs of the invention, host cells transformed therewith, and their use in the production of said EphA2-BiTEs. The invention also provides compositions, including pharmaceutical compositions, comprising any of the aforementioned EphA2-BiTEs, polynucleotides or vectors either alone or in combination with one or more prophylactic or therapeutic agents. Also disclosed are methods of screening for said EphA2-BiTEs and kits comprising any of the aforementioned compositions and diagnostic reagents.

    摘要翻译： 本发明涉及双特异性单链抗体，其包含免疫特异性结合T细胞抗原CD3的第一结合结构域和免疫特异性结合EphA2受体的第二结合结构域。 这种双特异性单链抗体包括在术语“EphA2-BiTEs”中。 本发明还涉及设计用于治疗，预防和/或控制与EphA2的异常表达和/或活性相关的病症的方法和组合物。 这些疾病包括但不限于癌症，非癌症过度增殖性细胞病症和感染。 本发明还涉及包含编码本发明的EphA2-BiTE的多核苷酸，转化的宿主细胞的载体及其在所述EphA2-BiTE的生产中的用途。 本发明还提供包含单独或与一种或多种预防或治疗剂组合的任何上述EphA2-BiTE，多核苷酸或载体的组合物，包括药物组合物。 还公开了筛选所述EphA2-BiTE和包含任何上述组合物和诊断试剂的试剂盒的方法。

    Listeria-based EphA2 vaccines
    6.
    发明申请
    Listeria-based EphA2 vaccines 审中-公开
    基于李斯特菌的EphA2疫苗

    公开(公告)号：US20050281783A1

    公开(公告)日：2005-12-22

    申请号：US10966483

    申请日：2004-10-15

    申请人： Michael Kinch ,  Peter Kiener ,  Elizabeth Bruckheimer ,  Thomas Dubensky ,  David Cook

    发明人： Michael Kinch ,  Peter Kiener ,  Elizabeth Bruckheimer ,  Thomas Dubensky ,  David Cook

    IPC分类号： A61K20060101 ,  A61K39/00 ,  A61K48/00 ,  C12N1/21

    CPC分类号： A61K39/0011 ,  A61K2039/522 ,  A61K2039/523

    摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly metastatic cancer and cancers of T cell origin, and hyperproliferative diseases involving EphA2-expressing cells. The methods of the invention entail the use of a Listeria-based EphA2 vaccine. The invention also provides pharmaceutical compositions comprising one or more Listeria-based vaccines of the invention either alone or in combination with one or more other agents useful for cancer therapy. In certain aspects of the invention, the methods entail eliciting both CD4+ and CD8+ T-cell responses against EphA2 and/or EphA2-expressing cells.

    摘要翻译： 本发明涉及设计用于治疗，治疗或预防癌症，特别是转移性癌症和T细胞来源的癌症以及涉及EphA2表达细胞的过度增殖性疾病的方法和组合物。 本发明的方法需要使用基于李斯特菌的EphA2疫苗。 本发明还提供包含本发明的一种或多种基于李斯特菌的疫苗的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。 在本发明的某些方面，所述方法需要引起针对EphA2和/或EphA2表达细胞的CD4 +和/或CD8 + T细胞应答。

    Use of modulators of EphA2 and EphrinA1 for the treatment and prevention of infections
    8.
    发明申请
    Use of modulators of EphA2 and EphrinA1 for the treatment and prevention of infections 审中-公开
    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）。

    ANTIBODIES FOR DIAGNOSIS AND THERAPEUTIC TREATMENT OF PROSTATE CANCER
    10.
    发明申请
    ANTIBODIES FOR DIAGNOSIS AND THERAPEUTIC TREATMENT OF PROSTATE CANCER 审中-公开
    用于诊断和治疗前列腺癌的抗体

    公开(公告)号：US20110206695A1

    公开(公告)日：2011-08-25

    申请号：US13013002

    申请日：2011-01-25

    申请人： Manu Kohli ,  Michael Goldblatt ,  Michael Kinch

    发明人： Manu Kohli ,  Michael Goldblatt ,  Michael Kinch

    IPC分类号： A61K39/395 ,  C12Q1/70 ,  A61P35/00

    CPC分类号： C07K16/18 ,  A61K2039/505 ,  C07K16/28 ,  G01N33/57434 ,  G01N2333/15

    摘要： XMRV appears to be related to both prostate cancer if it infects a male germ cell and chronic fatigue syndrome in both sexes. (If the virus does not infect a germ cell). Prostate cancer cells exhibit TSG101 on the surface only upon infection with a virus like XMRV. Antibodies to TSG101 can be effective diagnostics to identify individuals with a predisposition to prostate. They can also be used in place of current diagnostics to confirm the presence of prostate cancer. TSG101 antibodies, when administered in vivo, exhibit the ability to reduce tumor size, suppress metastatic transformation and extend survival.

    摘要翻译： XMRV似乎与前列腺癌相关，如果它感染男性生殖细胞和慢性疲劳综合征两性。 （如果病毒不感染生殖细胞）。 前列腺癌细胞只有在感染了像XMRV这样的病毒时才在表面上显示TSG101。 对TSG101的抗体可以有效地诊断以鉴别具有前列腺炎倾向的个体。 它们也可以用于代替目前的诊断以确认前列腺癌的存在。 TSG101抗体在体内施用时，具有减少肿瘤大小，抑制转移转化和延长存活的能力。