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1. 发明申请

WO2004091375A3 EPHA2 AND NON-NEOPLASTIC HYPERPROLIFERATIVE CELL DISORDERS 审中-公开
标题翻译： EPHA2和非神经性高增殖性细胞病变
公开(公告)号：WO2004091375A3
公开(公告)日：2005-07-14
申请号：PCT/US2004011482
申请日：2004-04-12
申请人： MEDIMMUNE INC , KIENER PETER A , KINCH MICHAEL S , LANGERMANN SOLOMON , REED JENNIFER L
发明人： KIENER PETER A , KINCH MICHAEL S , LANGERMANN SOLOMON , REED JENNIFER L
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 prefer-red embodiments, agents of the invention are inonoclonal 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结合EphA2并增加EphA2细胞质尾磷酸化和/或增加EphA2自磷酸化的EphA2激动剂。在EphA2被激活的细胞中。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，本发明的试剂是异源抗体。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。

2. 发明申请

WO2004092343A3 EPHA2, HYPOPROLIFERATIVE CELL DISORDERS AND EPITHELIAL AND ENDOTHELIAL RECONSTITUTION 审中-公开
标题翻译： EPHA2，HYPOPROLIFERATIVE CELL DISORDERS AND EPITHELIAL AND ENDOTHELIAL RECONSTITUTION
公开(公告)号：WO2004092343A3
公开(公告)日：2005-12-01
申请号：PCT/US2004011481
申请日：2004-04-12
申请人： MEDIMMUNE INC , KIENER PETER A , KINCH MICHAEL S , LANGERMANN SOLOMON
发明人： KIENER PETER A , KINCH MICHAEL S , LANGERMANN SOLOMON
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 EphA2endogenous 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 ligandmediated 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 增加EphA2表达细胞的增殖，增加EphA2表达细胞的存活，和/或维持/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药剂的诊断方法和方法。

3. 发明申请

WO2007103261A2 LISTERIA-BASED EPHA2 IMMUNOGENIC COMPOSITIONS 审中-公开
标题翻译：基于LISTERIA的EPHA2免疫组化
公开(公告)号：WO2007103261A2
公开(公告)日：2007-09-13
申请号：PCT/US2007005512
申请日：2007-03-01
申请人： MEDIMMUNE INC , CERUS CORP , BRUCKHEIMER ELIZABETH , KINCH MICHAEL S , KIENER PETER A , DUBENSKY THOMAS W JR , COOK DAVID N
发明人： BRUCKHEIMER ELIZABETH , KINCH MICHAEL S , KIENER PETER A , DUBENSKY THOMAS W JR , COOK DAVID N
IPC分类号： C07H21/04
CPC分类号： C12N9/1205 , C12N15/74 , C12Y207/10001
摘要： The present invention provides nucleic acid constructs comprising a nucleotide sequence encoding an EphA2 antigenic peptide andListeria comprising such constructs. In particular, the present invention provides Listeria engineered to express a plurality of EphA2 antigenic peptides and immunogenic compositions comprising such Listeria. The invention encompasses, inter alia,
摘要翻译：本发明提供了包含编码EphA2抗原肽的核苷酸序列和包含这种构建体的李斯特菌的核酸构建体。特别地，本发明提供了工程化表达多种EphA2抗原肽的李斯特菌和包含这种李斯特菌的免疫原性组合物。本发明尤其包括，

4. 发明申请

WO2005037233A3 LISTERIA-BASED EPHA2 VACCINES 审中-公开
标题翻译：基于LISTERIA的EPHA2疫苗
公开(公告)号：WO2005037233A3
公开(公告)日：2006-01-26
申请号：PCT/US2004034694
申请日：2004-10-15
申请人： MEDIMMUNE INC , CERUS CORP , KINCH MICHAEL S , KIENER PETER A , BRUCKHEIMER ELISABETH , DUBENSKY THOMAS W JR , COOK DAVID N
发明人： KINCH MICHAEL S , KIENER PETER A , BRUCKHEIMER ELISABETH , DUBENSKY THOMAS W JR , COOK DAVID N
IPC分类号： A61K20060101 , A61K39/00 , A61K48/00 , C12N1/21 , A61K39/102 , C12N1/20 , C07K1/100
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 in combination with one or more other agents useful for cancer therapy. In certain aspects of the invention, the method 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，管理或预防癌症，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，该方法需要引起针对EphA2和/或EphA2表达细胞的CD4 +和/或CD8 + T细胞应答。

5. 发明申请

WO2007073499A3 EPHA2 BITE MOLECULES AND USES THEREOF 审中-公开
标题翻译： EPHA2 BITE分子及其用途
公开(公告)号：WO2007073499A3
公开(公告)日：2008-10-02
申请号：PCT/US2006048995
申请日：2006-12-21
申请人： MEDIMMUNE INC , MICROMET AG , KINCH MICHAEL S , ROFF SHANNON , KUFER PETER , BRUCKHEIMER ELIZABETH , SCHLERETH BERND , HAMMOND SCOTT A , LUTTERBUESE RALF , KIENER PETER A , BAEURELE PATRICK , LUTTERBUESE PETRA
发明人： KINCH MICHAEL S , ROFF SHANNON , KUFER PETER , BRUCKHEIMER ELIZABETH , SCHLERETH BERND , HAMMOND SCOTT A , LUTTERBUESE RALF , KIENER PETER A , BAEURELE PATRICK , LUTTERBUESE PETRA
IPC分类号： A61K39/00 , C12P21/08
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 irnmunospecifÊcally 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，其包含与T细胞抗原CD3不相关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EphA2BiTE的多核苷酸，转化的宿主细胞及其在所述EphA2-BiTE的生产中的用途的载体。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 -BiTEs和包含任何上述组合物和诊断试剂的试剂盒的方法。

6. 发明申请

WO03027231A3 POLYNUCLEOTIDE ENCODING ADAPTER PROTEIN, PMN29 审中-公开
标题翻译：多核苷酸编码适配蛋白，PMN29
公开(公告)号：WO03027231A3
公开(公告)日：2003-10-16
申请号：PCT/US0228235
申请日：2002-09-04
申请人： SQUIBB BRISTOL MYERS CO , FINGER JOSHUA N , PEREZ-VILLAR JUAN J , RAJASHEKAR K REDDY , YANG GUCHEN , KIENER PETER A
发明人： FINGER JOSHUA N , PEREZ-VILLAR JUAN J , RAJASHEKAR K REDDY , YANG GUCHEN , KIENER PETER A
IPC分类号： C07K14/705 , C12N15/12 , A61K38/16 , A61K38/17 , C07K14/00 , C07K14/47 , C07K16/00 , C07K16/18 , C12N1/00 , C12N5/10 , C12N15/11 , C12N15/63 , C12Q1/68
CPC分类号： C07K14/705
摘要： The present invention provides novel polynucleotides encoding PMN29 polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel PMN29 polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.
摘要翻译：本发明提供编码PMN29多肽的新型多核苷酸，其片段及其同源物。还提供了载体，宿主细胞，抗体以及用于产生所述多肽的重组和合成方法。本发明还涉及将这些新型PMN29多肽应用于诊断，治疗和/或预防与这些多肽相关的各种疾病和/或病症的诊断和治疗方法。本发明还涉及用于鉴定本发明的多核苷酸和多肽的激动剂和拮抗剂的筛选方法。

7. 发明公开

EP1617864A4 EPHA2 AND NON-NEOPLASTIC HYPERPROLIFERATIVE CELL DISORDERS 审中-公开
标题翻译： EphA2和非肿瘤性增殖性细胞紊乱
公开(公告)号：EP1617864A4
公开(公告)日：2006-06-21
申请号：EP04759523
申请日：2004-04-12
申请人： MEDIMMUNE INC
发明人： KIENER PETER A , KINCH MICHAEL S , LANGERMANN SOLOMON , REED JENNIFER L
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

8. 发明公开

EP1618184A4 EPHA2, HYPOPROLIFERATIVE CELL DISORDERS AND EPITHELIAL AND ENDOTHELIAL RECONSTITUTION 审中-公开
标题翻译： EPHA2，促进细胞增殖，上皮细胞再生和内皮细胞重新构建
公开(公告)号：EP1618184A4
公开(公告)日：2006-06-21
申请号：EP04759522
申请日：2004-04-12
申请人： MEDIMMUNE INC
发明人： KIENER PETER A , KINCH MICHAEL S , LANGERMANN SOLOMON
IPC分类号： A61K39/00 , A61K38/00 , A61K38/19 , A61K39/395 , A61K48/00 , A61K49/00 , C07K14/715 , C07K16/28 , C12N20060101
CPC分类号： C07K16/2866 , A61K38/19 , C07K14/715

9. 发明公开

EP1682173A4 LISTERIA-BASED EPHA2 VACCINES 审中-公开
标题翻译： EPHA2疫苗李斯特菌BASE
公开(公告)号：EP1682173A4
公开(公告)日：2007-10-31
申请号：EP04795804
申请日：2004-10-15
申请人： MEDIMMUNE INC , CERUS CORP
发明人： KINCH MICHAEL S , KIENER PETER A , BRUCKHEIMER ELISABETH , DUBENSKY THOMAS W JR , COOK DAVID N
IPC分类号： A61K39/02 , A61K20060101 , A61K39/00 , A61K48/00 , C12N1/20 , C12N1/21
CPC分类号： A61K39/0011 , A61K2039/522 , A61K2039/523

10. 发明专利

BRPI0620639A2 未知
公开(公告)号：BRPI0620639A2
公开(公告)日：2011-11-22
申请号：BRPI0620639
申请日：2006-12-21
申请人： MICROMET AG , MEDIMMUNE INC
发明人： KINCH MICHAEL , ROFF SHANNON , KUFER PETER , BRUCKHEIMER ELIZABETH , SCHLERETH BERND , HAMMOND SCOTT A , LUTTERBUESE RALF , KIENER PETER A , BAEURELE PATRICK , LUTTERBUESE PETRA
IPC分类号： A61K39/00 , C12P21/08

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