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31. 发明申请

US20090170890A1 METHOHDS OF INHIBITING VIRAL INFECTION 失效
标题翻译：抑制病毒感染的甲基化
公开(公告)号：US20090170890A1
公开(公告)日：2009-07-02
申请号：US12256571
申请日：2008-10-23
申请人： Michael Kinch , Michael Goldblatt
发明人： Michael Kinch , Michael Goldblatt
IPC分类号： A61K31/4745 , A61P31/12
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以预防方式施用有效量的至少一种由273,355和510表示的FGI-103化合物，以预防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。

32. 发明申请

US20080044413A1 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：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。

33. 发明申请

US20070166314A1 EpA2 monoclonal antibodies and methods of use thereof 审中-公开
标题翻译： 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。

34. 发明申请

US20070086943A1 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：US20070086943A1
公开(公告)日：2007-04-19
申请号：US11544332
申请日：2006-10-06
申请人： Michael Kinch , Kelly Carles-Kinch , Jane Stewart
发明人： Michael Kinch , Kelly Carles-Kinch , Jane Stewart
IPC分类号： A61K51/00 , A61K39/395
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。

35. 发明申请

US20070065887A1 Diagnosis of pre-cancerous conditions using pcdgf agents 审中-公开
标题翻译：使用pcdgf试剂诊断癌前病情
公开(公告)号：US20070065887A1
公开(公告)日：2007-03-22
申请号：US10565771
申请日：2004-07-16
申请人： Michael Kinch
发明人： Michael Kinch
IPC分类号： G01N33/574
CPC分类号： G01N33/574 , G01N33/5011 , G01N33/5082 , G01N33/5091 , G01N33/57407 , G01N33/57484 , G01N33/74 , G01N2500/00 , G01N2800/52
摘要： The present invention relates to methods and compositions designed for the treatment or management of pre-cancerous conditions, especially in order to prevent, delay, or decrease the likelihood that the pre-cancerous condition will progress to malignant cancer. The methods of the invention comprise the administration of an effective amount of one or more agents that decrease/inhibit PCDGF expression, secretion, and/or activity. The invention also provides pharmaceutical compositions comprising one or more PCDGF agents. In some embodiments, the PCDGF agents can be administered with other therapeutic agents for treatment or management of a pre-cancerous condition that are not PCDGF-based. Diagnostic methods and methods for screening for therapeutically useful PCDGF agents are also provided.
摘要翻译：本发明涉及设计用于治疗或治疗癌前病症的方法和组合物，特别是为了预防，延缓或降低癌前病情进展为恶性癌症的可能性。本发明的方法包括施用有效量的一种或多种降低/抑制PCDGF表达，分泌和/或活性的试剂。本发明还提供包含一种或多种PCDGF试剂的药物组合物。在一些实施方案中，PCDGF剂可以与其它治疗剂一起施用，用于治疗或治疗不是基于PCDGF的癌前病状。还提供了用于筛选治疗有用的PCDGF试剂的诊断方法和方法。

36. 发明申请

US20060093608A1 Low molecular weight protein tyrosine phosphatase (lmw-ptp) as a diagnostic and therapeutic target 失效
标题翻译：低分子量蛋白酪氨酸磷酸酶（lmw-ptp）作为诊断和治疗靶点
公开(公告)号：US20060093608A1
公开(公告)日：2006-05-04
申请号：US10515358
申请日：2003-05-22
申请人： Michael Kinch
发明人： Michael Kinch
IPC分类号： C12Q1/68 , G01N33/574 , A61K39/395
CPC分类号： C07K16/22 , A61K38/1709 , A61K2039/505 , C07K16/32 , C12N9/16 , C12Q1/42 , C12Y301/03048 , G01N33/5091 , G01N33/573 , G01N33/574 , G01N2333/91215
摘要： Low molecular weight protein tyrosine phosphatase (LMW-PTP) is identified as a novel diagnostic and therapeutic target in cancer diagnosis, prognosis and treatment. The invention provides diagnostic and treatment methods useful in connection with cancers expressing LMW-PTP and, optionally, EphA2 receptor. Also provided is a screening method that utilizes changes in the amount and/or activity of LMW-PTP to identify candidate cancer therapeutic agents that effectively target the oncoprotein EphA2.
摘要翻译：低分子量蛋白酪氨酸磷酸酶（LMW-PTP）被认为是癌症诊断，预后和治疗中的新型诊断和治疗靶点。本发明提供了与表达LMW-PTP的癌症和任选的EphA2受体有关的诊断和治疗方法。还提供了利用LMW-PTP的量和/或活性的变化来鉴定有效靶向癌蛋白EphA2的候选癌症治疗剂的筛选方法。

37. 发明申请

US20050281783A1 Listeria-based EphA2 vaccines 审中-公开
标题翻译：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。

38. 发明申请

US20050147593A1 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以及治疗过度增殖性细胞疾病的方法
公开(公告)号：US20050147593A1
公开(公告)日：2005-07-07
申请号：US11004795
申请日：2004-12-03
申请人： Michael Kinch
发明人： Michael Kinch
IPC分类号： 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 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/或与递送载体可操作地相关的活性的试剂。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，本发明的方法包括向受试者施用包含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。

39. 发明申请

US20050049176A1 EphA2, hypoproliferative cell disorders and epithelial and endothelial reconstitution 审中-公开
标题翻译： 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。

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