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1. 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，

2. 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。

3. 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。

4. 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。

5. 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。

6. 发明申请

WO2005051307A3 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：WO2005051307A3
公开(公告)日：2006-09-08
申请号：PCT/US2004039112
申请日：2004-11-19
申请人： MEDIMMUNE INC , PURDUE RESEARCH FOUNDATION , KINCH MICHAEL S , CARLES-KINCH KELLY , STEWART JANE C
发明人： KINCH MICHAEL S , CARLES-KINCH KELLY , STEWART JANE C
IPC分类号： A61K39/395 , A61K20060101 , C07H21/04 , C07K16/24 , C07K16/28 , C07K16/30 , C12P21/08
CPC分类号： C07K16/24 , A61K2039/505 , C07K16/2866 , C07K16/30 , C07K16/3015 , C07K16/3069 , 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：本发明涉及用于治疗，治疗或预防癌症，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结合并激动EphA2的一种或多种抗体，从而增加EphA2磷酸化并降低EphA2已被激动的细胞中的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。

7. 发明申请

WO2006047638A2 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：WO2006047638A2
公开(公告)日：2006-05-04
申请号：PCT/US2005038667
申请日：2005-10-27
申请人： MEDIMMUNE INC , KINCH MICHAEL S , CARLES-KINCH KELLY
发明人： KINCH MICHAEL S , CARLES-KINCH KELLY
IPC分类号： A61K48/00 , A61K39/00 , A61K39/395
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, EphrinAl. The invention also provides pharmaceutical compositions comprising one or more EphA2/EphrinAl Modulators of the invention either alone or in combination with one or more other agents useful for therapy for such nonneoplastic hyperproliferative epithelial and/or endothelial disorders. Diagnostic methods and methods for screening for EphA2/EphrinAl 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的药物EphrinA1。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增殖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。

8. 发明申请

WO2005012350A3 EPHA2 T-CELL EPITOPE AGONISTS AND USES THEREFOR 审中-公开
标题翻译： EPHA2 T细胞表位激动剂及其用途
公开(公告)号：WO2005012350A3
公开(公告)日：2005-07-14
申请号：PCT/US2004023931
申请日：2004-07-22
申请人： UNIV PITTSBURGH , MEDIMMUNE INC , STORKUS WALTER J , KINCH MICHAEL S
发明人： STORKUS WALTER J , KINCH MICHAEL S
IPC分类号： A61K38/17 , C07K14/47 , C07K14/705 , G01N33/50 , G01N33/569 , A61K38/08 , A61P35/00 , C12N15/12 , 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：本文提供了EphA2T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蛋白特定片段的肽及其保守衍生物。 EphA2T细胞表位激动剂可用于可用于确定和/或量化患者对EphA2的免疫应答性的测定，例如ELISPOT测定。激动剂还可用于调节患者对EphA2的免疫反应性的方法，其作为治疗过度表达EphA2的癌症的实质性用途，例如肾细胞癌（RCC）。 EphA2激动剂也可用于通过体内或体外方法针对EphA2疫苗接种患者。

9. 发明申请

WO2005055948A3 EPHA2, EPHA4 AND LMW-PTP AND METHODS OF TREATMENT OF HYPERPROLIFERATIVE CELL DISORDERS 审中-公开
标题翻译： EPHA2，EPHA4和LMW-PTP及治疗高增殖性细胞病的方法
公开(公告)号：WO2005055948A3
公开(公告)日：2006-11-09
申请号：PCT/US2004041023
申请日：2004-12-06
申请人： MEDIMMUNE INC , KINCH MICHAEL S
发明人： KINCH MICHAEL S
IPC分类号： A61K38/00 , A61K20060101 , A61K9/127 , A61K39/395 , A61K48/00
CPC分类号： A61K38/1709 , A61K9/127 , A61K48/00 , A61K2039/505 , C07K16/2866 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C12N9/12 , C12N9/16 , C12Y301/03048
摘要： The present invention relates to methods and compositions designed for treatment, management, or prevention of a hyperproliferative cell disease, particular cancer. The methods of the invention comprise the administration of an effective amount of a composition that targets cells expressing low molecular weight protein tyrosine kinase ("LMW-PTP") in particular using moieties that bind an Eph family receptor tyrosine kinase, such as EphA2 or EphA4, and inhibits or reduces LMW-PTP expression and/or activity. In i 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 agents that inhibit LMW-PTP expression and/or activity 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 an agent that inhibits or reduces LMW-PTP expression and/or activity. 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 inhibits or reduces LMW-PTP expression and/or activity, where the nucleic acid is operatively associated with the delivery vehicle. Pharmaceutical compositions are also provided by the present invention.
摘要翻译：本发明涉及用于治疗，治疗或预防过度增殖性细胞疾病，特定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低分子量蛋白酪氨酸激酶（“LMW-PTP”）的细胞的组合物，特别是使用结合Eph家族受体酪氨酸激酶（例如EphA2或EphA4）的部分，并且抑制或降低LMW-PTP表达和/或活性。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，以及一种或多种抑制LMW-PTP表达和/或与递送有效相关的活性的试剂车辆。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抑制或降低LMW-PTP表达和/或活性的试剂。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抑制或降低LMW-PTP表达和/或活性的试剂的核苷酸序列的核酸，其中核酸与递送载体可操作地相关联。药物组合物也由本发明提供。

10. 发明申请

WO2005016381A3 COMBINATION THERAPY FOR THE TREATMENT AND PREVENTION OF CANCER USING EPHA2, PCDGF, AND HAAH 审中-公开
标题翻译：使用EPHA2，PCDGF和HAAH治疗和预防癌症的联合治疗
公开(公告)号：WO2005016381A3
公开(公告)日：2006-02-09
申请号：PCT/US2004023097
申请日：2004-07-16
申请人： MEDIMMUNE INC , KINCH MICHAEL S , CARLES-KINCH KELLY , KIENER PETER , LANGERMANN SOLOMON , MCCARTHY MICHAEL P , TICE DAVID , WOESSNER RICHARD
发明人： KINCH MICHAEL S , CARLES-KINCH KELLY , KIENER PETER , LANGERMANN SOLOMON , MCCARTHY MICHAEL P , TICE DAVID , WOESSNER RICHARD
IPC分类号： A61K39/395 , C07K16/28 , C07K16/30 , C07K16/40 , A61P35/04
CPC分类号： C07K16/40 , A61K39/39558 , A61K2039/505 , C07K16/3076 , C07K2317/73 , C07K2317/75 , C07K2317/80 , A61K2300/00
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of a hyperproliferative disorder, particularly cancer, more particularly metastatic cancer. The methods of the invention comprise the administration of an effective amount of one or more agents that decrease/inhibit EphA2 expression or activity in combination with one or more agents that decrease/inhibit PCDGF or HAAH expression or activity. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more EphA2, PCDGF, and/or HAAH agents of the invention that inhibit cancer cell colony formation in soft agar or tubular network formation in three-dimensional basement membrane or extracellular matrix preparation. The invention also provides pharmaceutical compositions comprising one or more EphA2 agents of the invention in combination with one or more PCDGF agents of the invention and/or one or more HAAH agents of the invention. In some embodiments, the agents of the invention can be administered with other cancer therapeutic agents that are not EphA2-, PCDGF-, or HAAH-based. Diagnostic methods and methods for screening for therapeutically useful agents of the invention are also provided.
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疾病，特别是癌症，特别是转移性癌症的方法和组合物。本发明的方法包括给予一种或多种降低/抑制EphA2表达或活性的一种或多种与减少/抑制PCDGF或HAAH表达或活性的一种或多种试剂组合的试剂。在另一个实施方案中，本发明的方法包括施用有效量的本发明的一种或多种EphA2，PCDGF和/或HAAH剂，其抑制在三维基底中的软琼脂或管状网络形成中的癌细胞集落形成膜或细胞外基质制剂。本发明还提供包含本发明的一种或多种EphA2试剂与本发明的一种或多种PCDGF试剂和/或本发明的一种或多种HAAH试剂组合的药物组合物。在一些实施方案中，本发明的药剂可以与不是EphA2-，PCDGF-或HAAH的其它癌症治疗剂一起施用。还提供了用于筛选本发明的治疗有用的药剂的诊断方法和方法。

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