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1. 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。

2. 发明申请

US20120121582A1 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：US20120121582A1
公开(公告)日：2012-05-17
申请号：US13014005
申请日：2011-01-26
申请人： Michael S. Kinch , Kelly Carles-Kinch
发明人： Michael S. Kinch , Kelly Carles-Kinch
IPC分类号： A61K39/395 , A61K48/00 , A61K31/7088 , A61P13/12 , A61P1/16 , A61P11/00 , A61P9/00 , A61P27/02 , A61K38/17 , A61P29/00
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。

3. 发明申请

US20100298545A1 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：US20100298545A1
公开(公告)日：2010-11-25
申请号：US12626016
申请日：2009-11-25
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： C07K16/32 , C07H21/04 , C07K16/00 , C12N15/63 , C12N5/10
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

US20100278838A1 EPHA2 MONOCLONAL ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译： EPHA2单克隆抗体及其使用方法
公开(公告)号：US20100278838A1
公开(公告)日：2010-11-04
申请号：US12755468
申请日：2010-04-07
申请人： Michael S. Kinch , Kelly Carles-Kinch , Peter Kiener , Solomon Langermann
发明人： Michael S. Kinch , Kelly Carles-Kinch , Peter Kiener , Solomon Langermann
IPC分类号： A61K39/395 , C07K16/00 , C12N15/13 , C12N15/63 , C12N5/00 , G01N33/567 , A61P35/00
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Koff，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。

5. 发明申请

US20100166657A1 USE OF EphA4 AND MODULATOR OF EphA4 FOR DIAGNOSIS, TREATMENT AND PREVENTION OF CANCER 审中-公开
标题翻译： EphA4的使用和EphA4的调节剂用于诊断，治疗和预防癌症
公开(公告)号：US20100166657A1
公开(公告)日：2010-07-01
申请号：US12558052
申请日：2009-09-11
申请人： Michael S. Kinch , Kelly Carles-Kinch
发明人： Michael S. Kinch , Kelly Carles-Kinch
IPC分类号： A61K49/00 , C07K16/18 , G01N33/53 , C12N5/071
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。

6. 发明申请

US20100260749A1 Modulators of EphA2 and Ephrin-A1 for the treatment of fibrosis-related disease 审中-公开
标题翻译：用于治疗纤维化相关疾病的EphA2和Ephrin-A1的调节剂
公开(公告)号：US20100260749A1
公开(公告)日：2010-10-14
申请号：US12185568
申请日：2008-08-04
申请人： Michael S. Kinch , Kelly Carles-Kinch
发明人： Michael S. Kinch , Kelly Carles-Kinch
IPC分类号： A61K39/395 , A61K38/45 , A61K31/7088 , A61K39/00 , A61P1/16 , A61P29/00 , A61P9/10 , A61P11/00 , A61P13/12
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，隐性营养不良的大疱性表皮松解症，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. 发明授权

US07604799B2 EphA4 Antibodies 失效
标题翻译： EphA4抗体
公开(公告)号：US07604799B2
公开(公告)日：2009-10-20
申请号：US10863729
申请日：2004-06-07
申请人： Michael S. Kinch , Kelly Carles-Kinch
发明人： Michael S. Kinch , Kelly Carles-Kinch
IPC分类号： A61K39/395 , C07K16/30
CPC分类号： C07K16/2866 , A61K2039/505 , C07K14/52 , C07K16/24 , C07K2317/622 , C07K2317/73 , C07K2319/30
摘要： The invention provides agonistic anti-EphA4 antibodies.
摘要翻译：本发明提供激动性抗EphA4抗体。

8. 发明申请

US20080226665A1 EphA2 T-cell epitopes and uses therefor 有权
标题翻译： EphA2 T细胞表位及其用途
公开(公告)号：US20080226665A1
公开(公告)日：2008-09-18
申请号：US11977179
申请日：2007-10-22
申请人： Walter J. Storkus , Michael S. Kinch
发明人： Walter J. Storkus , Michael S. Kinch
IPC分类号： A61K39/00 , C07K4/00 , C07K14/00 , C07K7/06 , A61P37/00 , G01N33/567 , A61P35/04 , C07K7/08 , A61K38/08 , A61K38/10
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 are provided herein. The epitopes 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 epitopes 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 epitopes 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 epitopes 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。表位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细胞表位可用于可用于测定和/或定量患者对EphA2的免疫反应性的测定中，例如ELISPOT测定。表位也可用于调节患者对EphA2的免疫反应性的方法，EphA2具有作为过表达EphA2的癌症如肾细胞癌（RCC）的治疗的实用性。 EphA2表位也可用于通过体内或体外方法对EphA2接种患者。

9. 发明申请

US20120201840A1 EphA2 T-Cell Epitopes and Uses Therefor 有权
标题翻译： EphA2 T细胞表位及其用途
公开(公告)号：US20120201840A1
公开(公告)日：2012-08-09
申请号：US13355343
申请日：2012-01-20
申请人： Walter J. Storkus , Michael S. Kinch
发明人： Walter J. Storkus , Michael S. Kinch
IPC分类号： A61K39/00 , C07K14/00 , A61P37/04 , C07K7/08
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 are provided herein. The epitopes 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 epitopes 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 epitopes 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 epitopes 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。表位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细胞表位可用于可用于测定和/或定量患者对EphA2的免疫反应性的测定中，例如ELISPOT测定。表位也可用于调节患者对EphA2的免疫反应性的方法，EphA2具有作为过表达EphA2的癌症如肾细胞癌（RCC）的治疗的实用性。 EphA2表位也可用于通过体内或体外方法对EphA2接种患者。

10. 发明申请

US20100183628A1 RANDOM HOMOZYGOUS GENE PERTURBATION (RHGP) WITH THERMAL ASSYMETRIC INTERLACED (TAIL)-PCR 失效
标题翻译：随机共生基因突变（RHGP）与热组分互连（尾）-PCR
公开(公告)号：US20100183628A1
公开(公告)日：2010-07-22
申请号：US12652877
申请日：2010-01-06
申请人： Michael S. Kinch , Michael Goldblatt , Wu-Bo Li , Douty Bamba , Shaojing Chang , Huosheng Chen , Zenbework Fesseha , Manu Kohli , Hanwen Mao , Heather Thi Thu Ung-Medoff , Ke Weng
发明人： Michael S. Kinch , Michael Goldblatt , Wu-Bo Li , Douty Bamba , Shaojing Chang , Huosheng Chen , Zenbework Fesseha , Manu Kohli , Hanwen Mao , Heather Thi Thu Ung-Medoff , Ke Weng
IPC分类号： A61K39/395 , C12Q1/70 , A61P31/16 , A61P31/18
CPC分类号： C07K16/28 , C12N15/1082
摘要： A method for identifying host genes and encoded proteins for potential targets for therapeutic intervention employs a Gene Search Vector that is either lentivirus or MMLV-based, and can be used to interrogate an entire cell genome without prior knowledge of the genomic sequence. This Random Homozygous Gene Perturbation (RUGP) technique is rapidly verifiable and is used to identify potential host targets for intervention for influenza, HIV and other viral infections. Using Thermal Assymetric Interlaced (TAIL)-PCR, the period for identification of promising targets is reduced from months to weeks or less. Specific targets including PTCH1, Robo1 and Nedd4 are reviewed in detail.
摘要翻译：用于鉴定用于治疗性干预的潜在靶标的宿主基因和编码的蛋白质的方法使用基因搜索载体，其是慢病毒或基于MMLV的，并且可用于询问整个细胞基因组，而无需基因组序列的先验知识。这种随机纯合基因扰动（RUGP）技术可以快速验证，并用于识别潜在的宿主对流感，艾滋病病毒和其他病毒感染的干预目标。使用热分析交错（TAIL）-PCR，鉴定有希望的目标的时间从几个月减少到几周。具体目标包括PTCH1，Robo1和Nedd4。

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