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41. 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。

42. 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。

43. 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。

44. 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。

45. 发明申请

WO2005067460A2 EPHA2 VACCINES 审中-公开
标题翻译： EPHA2疫苗
公开(公告)号：WO2005067460A2
公开(公告)日：2005-07-28
申请号：PCT/US2004/034693
申请日：2004-10-15
申请人： MEDIMMUNE, INC. , KINCH, Michael, S.
发明人： KINCH, Michael, S.
IPC分类号： A61K39/00
CPC分类号： A61K39/0011 , A61K47/6425 , A61K47/644 , A61K47/6901 , A61K2035/122 , A61K2039/52 , A61K2039/523 , A61K2039/5256 , A61K2039/53 , A61K2039/6043 , A61K2039/6056
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly metastatic cancer, and hyperproliferative diseases involving EphA2-expressing cells. In one embodiment, the methods of the invention comprise the administration of an effective amount of an EphA2 antigenic peptide to elicit an immune response against the EphA2-expressing cells. In other embodiments, the methods of the invention entail the use of an EphA2 expression vehicle, such as a naked nucleic acid or viral vector. In yet other embodiments, the methods of the invention comprise the use of adoptive immunotherapy with autologous or non-autologous antigen presenting cells that are sensitized with one or more EphA2 antigenic peptides. The invention also provides pharmaceutical compositions comprising one or more EphA2 antigenic peptides, expression vehicles or antigen-presenting cells 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，特别是转移性癌症和涉及EphA2表达细胞的过度增殖性疾病的方法和组合物。在一个实施方案中，本发明的方法包括施用有效量的EphA2抗原肽以引发针对EphA2表达细胞的免疫应答。在其它实施方案中，本发明的方法需要使用EphA2表达载体，例如裸核酸或病毒载体。在其它实施方案中，本发明的方法包括使用与一种或多种EphA2抗原肽致敏的自体或非自体抗原呈递细胞的过继免疫治疗。本发明还提供包含本发明的一种或多种EphA2抗原肽，表达载体或抗原呈递细胞的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

46. 发明申请

WO2004091375A2 EPHA2 AND HYPERPROLIFERATIVE CELL DISORDERS 审中-公开
标题翻译： EPHA2和高增殖性细胞病变
公开(公告)号：WO2004091375A2
公开(公告)日：2004-10-28
申请号：PCT/US2004/011482
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： A61B
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 K off 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。

47. 发明申请

WO2011091395A1 ANTIBODIES FOR DIAGNOSIS AND THERAPEUTIC TREATMENT OF PROSTATE CANCER 审中-公开
标题翻译：用于诊断和治疗前列腺癌的抗体
公开(公告)号：WO2011091395A1
公开(公告)日：2011-07-28
申请号：PCT/US2011/022338
申请日：2011-01-25
申请人： FUNCTIONAL GENETICS, INC. , KOHLI, Manu , GOLDBLATT, Michael , KINCH, Michael
发明人： KOHLI, Manu , GOLDBLATT, Michael , KINCH, Michael
IPC分类号： C12Q1/70
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。

48. 发明申请

WO2011078937A1 PROTEASE INHIBITORS AND BROAD-SPECTRUM ANTIVIRAL 审中-公开
标题翻译：蛋白酶抑制剂和广谱抗病毒药物
公开(公告)号：WO2011078937A1
公开(公告)日：2011-06-30
申请号：PCT/US2010/058253
申请日：2010-11-30
申请人： FUNCTIONAL GENETICS, INC. , AMAN, M. Javad , KINCH, Michael , ENTERLEIN, Sven , ABDUL, Yunus
发明人： AMAN, M. Javad , KINCH, Michael , ENTERLEIN, Sven , ABDUL, Yunus
IPC分类号： A01N25/00
CPC分类号： A61K31/343 , A61K31/381 , Y02A50/397
摘要： Caspace inhibition provides inhibition of viral infection across a wide collection of caspaces and viruses. Caspace inhibition, the prevention of the formation of active caspaces, can be achieved either through gene therapy, protein binding an inhibition, or through small molecule administration. Examples for small molecule inhibition allow the formation of a pharmacaphore to identify more and more active small molecules.
摘要翻译： Cas空间抑制提供了对广泛的caspaces和病毒集合的病毒感染的抑制。通过基因治疗，蛋白结合抑制或通过小分子给药可以实现Cas空间抑制，预防活性胱天蛋白形成。小分子抑制的实例允许形成药物标记来鉴定越来越多的活性小分子。

49. 发明申请

WO2009055524A8 METHODS OF INHIBITING VIRAL INFECTION 审中-公开
标题翻译：抑制病毒感染的方法
公开(公告)号：WO2009055524A8
公开(公告)日：2010-08-26
申请号：PCT/US2008080867
申请日：2008-10-23
申请人： FUNCTIONAL GENETICS INC , KINCH MICHAEL , GOLDBLATT MICHAEL
发明人： KINCH MICHAEL , GOLDBLATT MICHAEL
IPC分类号： C07K16/00
CPC分类号： A61K31/4745 , A61K31/131 , A61K31/155 , A61K31/4184
摘要： A method of inhibiting viral infection in a mammal in need of same, includes administering an effective amount of at least one of the compounds of FGI- 103 which are represented by 273, 365 and 510 either prophylactically to prevent viral infection, or therapeutically following viral infection. These compounds appear to selectively inhibit Caspase 8 as a method of preventing infective viral particle release. They can be administered IV, IP, orally or via other conventional administration routes. The compounds are highly effective, requiring relatively low dosages on the order of 1 ng/kg - 200 mg/kg of body weight.
摘要翻译：在需要相同的哺乳动物中抑制病毒感染的方法包括施用有效量的至少一种由273,355和510表示的FGI-103化合物，以防止病毒感染，或治疗性病毒感染感染。这些化合物似乎选择性地抑制胱天蛋白酶8作为预防感染性病毒颗粒释放的方法。它们可以IV，IP，口服或其他常规给药途径给药。这些化合物是非常有效的，需要相当低的剂量约1ng / kg-200mg / kg体重。

50. 发明申请

WO2010080782A2 RANDOM HOMOZYGOUS GENE PERBURBATION (RHGP) WITH THERMAL ASSYMETRIC INTERLACED (TAIL)-PCR 审中-公开
标题翻译：随机共生基因座（RHGP）与热组分互连（尾）-PCR
公开(公告)号：WO2010080782A2
公开(公告)日：2010-07-15
申请号：PCT/US2010020190
申请日：2010-01-06
申请人： FUNCTIONAL GENETICS INC , KINCH MICHAEL S , GOLDBLATT MICHAEL , LI WU-BO , BAMBA DOUTY , CHANG SHAOJING , CHEN HUOSHENG , FESSEHA ZENBEWORK , KOHLI MANU , MAO HANWEN , UNG-MEDOFF HEATHER THI THU , WENG KE
发明人： KINCH MICHAEL S , GOLDBLATT MICHAEL , LI WU-BO , BAMBA DOUTY , CHANG SHAOJING , CHEN HUOSHENG , FESSEHA ZENBEWORK , KOHLI MANU , MAO HANWEN , UNG-MEDOFF HEATHER THI THU , WENG KE
IPC分类号： A61K39/395 , A61P31/16 , A61P31/18 , C12Q1/70
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的基因，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，鉴定有希望的靶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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