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1. 发明申请

WO2007136585A3 IMMUNOTHERAPEUTIC COMPOSITIONS AND METHODS 审中-公开
公开(公告)号：WO2007136585A3
公开(公告)日：2007-11-29
申请号：PCT/US2007/011453
申请日：2007-05-11
申请人： THE BUCK INSTITUTE FOR AGE RESEARCH , BREDESEN, Dale, E. , RABIZADEH, Shahrooz , NIAZI, Kayvan, R.
发明人： BREDESEN, Dale, E. , RABIZADEH, Shahrooz , NIAZI, Kayvan, R.
IPC分类号： C12P21/04 , C12P15/00 , C12P3/00
摘要： A vaccine is described which provides protection against a broad spectrum of viral strains, including but not limited to influenza A strains such as HlNl, H3N2, and H5N1. Embodiments of the present invention offer a number of advantages over conventional vaccine, in that they are cheaper to synthesize, more stable, easily scalable, and amenable to further genetic manipulation. Most importantly, certain embodiments of the present invention contemplate features, including but not limited to endosomal targeting, which result in a more robust immune response.

2. 发明申请

WO2007126787A2 REAGENTS AND METHODS FOR CANCER TREATMENT AND PREVENTION 审中-公开
标题翻译：癌症治疗和预防的试剂和方法
公开(公告)号：WO2007126787A2
公开(公告)日：2007-11-08
申请号：PCT/US2007/007526
申请日：2007-03-27
申请人： THE BUCK INSTITUTE FOR AGE RESEARCH , NIAZI, Kayvan, R. , RABIZADEH, Shahrooz , BREDESEN, Dale, E.
发明人： NIAZI, Kayvan, R. , RABIZADEH, Shahrooz , BREDESEN, Dale, E.
IPC分类号： A61K39/00 , A61K31/365 , C12P21/06 , C12N5/06 , C07K16/30
CPC分类号： G01N33/5023 , A61K31/365 , A61K39/0011 , A61K2039/5154 , G01N2333/90241 , G01N2500/10
摘要： The invention generally relates to the prevention and/or treatment of cancer, and, more specifically, to the treatment of tumors, including solid tumors and their metastases, without radiation or standard chemotherapeutic agents. In one embodiment, the invention involves a method comprising: a) providing a subject with tumor cells, b) removing at least a portion of said tumor cells from said subject to create removed cells, c) treating at least a portion of said removed cells ex vivo, using stimulating agents, including thapsigargin and/or thapsigargin-related compounds, so as to create treated tumor cells; and d) introducing said treated tumor cells (or fragments thereof) in vivo into the same subject to generate anticancer therapeutic effects.
摘要翻译：本发明一般涉及癌症的预防和/或治疗，更具体地涉及治疗包括实体瘤及其转移瘤在内的肿瘤，无辐射或标准化学治疗剂。在一个实施方案中，本发明涉及一种方法，其包括：a）向受试者提供肿瘤细胞，b）从所述受试者中移除所述肿瘤细胞的至少一部分以产生去除的细胞，c）将至少一部分所述去除的细胞离体使用刺激剂，包括毒胡萝卜素和/或毒胡萝卜素相关化合物，以产生经处理的肿瘤细胞; 和d）将所述经处理的肿瘤细胞（或其片段）体内引入相同受试者以产生抗癌治疗效果。

3. 发明申请

WO2006023410A2 SMALL MOLECULES THAT REPLACE OR AGONIZE P53 FUNCTION 审中-公开
标题翻译：小分子，替换或激活P53功能
公开(公告)号：WO2006023410A2
公开(公告)日：2006-03-02
申请号：PCT/US2005/028857
申请日：2005-08-12
申请人： BUCK INSTITUTE FOR AGE RESEARCH , RABIZADEH, Shahrooz , NIAZI, Kayvan , BREDESEN, Dale, E.
发明人： RABIZADEH, Shahrooz , NIAZI, Kayvan , BREDESEN, Dale, E.
IPC分类号： A61K31/555
CPC分类号： A61K31/555 , A61K31/505 , C12N2503/02 , C12N2510/00 , G01N33/5011
摘要： This invention provides a novel screening system for identifying p53 mimetics/agonists. Also provided are small organic molecules that act as effective p53 mimetics/agonists.
摘要翻译：本发明提供了用于鉴定p53模拟物/激动剂的新型筛选系统。还提供了作为有效p53模拟物/激动剂的小有机分子。

4. 发明申请

WO2007120912A2 COMPOSITIONS AND METHODS FOR SUPPRESSION OF AMYLOID PLAQUE FORMATION ASSOCIATED WITH NEURODEGENERATIVE DISORDERS. 审中-公开
标题翻译：用于抑制与神经变性障碍相关的淀粉样蛋白形成的组合物和方法。
公开(公告)号：WO2007120912A2
公开(公告)日：2007-10-25
申请号：PCT/US2007/009394
申请日：2007-04-16
申请人： BUCK INSTITUTE FOR AGE RESEARCH , CENTRE LEON-BERARD , MEHLEN, Patrick , CALHEIROS-LOURENCO, Felipe , GALVAN, Veronica , BREDESEN, Dale, E.
发明人： MEHLEN, Patrick , CALHEIROS-LOURENCO, Felipe , GALVAN, Veronica , BREDESEN, Dale, E.
CPC分类号： A61K38/18 , A61K9/0019 , A61K9/5123 , A61K47/542 , A61K47/549 , A61K47/64 , A61K47/6929
摘要： The invention provides a method for reducing or inhibiting net beta-amyloid peptide production and amyloid plaque formation associated with Alzheimer's Disease by administering to a subject an amount of a netrin-1 polypeptide, wherein the netrin-1 polypeptide comprises an amino acid sequence that a) binds to a naturally occurring APP protein and b) inhibits Aβ peptide production. A netrin-1 polypeptide has an amino acid sequence sufficient for specific binding of the netrin-1 polypeptide to the APP protein. A netrin-1 polypeptide can mimic netrin-1 -mediated signal transduction by altering the localization, protein-protein binding and/or enzymatic activity of an intracellular protein involved in an APP signal pathway. The invention also provides a method for reducing or inhibiting amyloid plaque formation associated with Alzheimer's Disease by administering to a subject an amount of a netrin-1 therapeutic, wherein the netrin-1 therapeutic comprises an amino acid sequence that a) binds to a naturally occurring APP protein and b) inhibits Aβ peptide production.
摘要翻译：本发明提供了一种通过向受试者施用一定量的netrin-1多肽来减少或抑制与β-阿尔茨海默病相关的β-淀粉样蛋白肽产生和淀粉样蛋白斑形成的方法，其中所述netrin-1多肽包含氨基酸序列，）与天然存在的APP蛋白结合，b）抑制Aβ肽的产生。 netrin-1多肽具有足以使netrin-1多肽与APP蛋白特异性结合的氨基酸序列。 netrin-1多肽可通过改变涉及APP信号途径的细胞内蛋白质的定位，蛋白质 - 蛋白质结合和/或酶活性来模拟netrin-1介导的信号转导。本发明还提供了通过向受试者施用一定量的netrin-1治疗剂来减少或抑制与阿尔茨海默氏病有关的淀粉样蛋白斑形成的方法，其中所述netrin-1治疗剂包含氨基酸序列，所述氨基酸序列a）结合天然存在的 APP蛋白和b）抑制AββI肽生产。

5. 发明申请

WO2003070971A3 MODULATORS OF PARAPTOSIS AND RELATED METHODS 审中-公开
公开(公告)号：WO2003070971A3
公开(公告)日：2003-08-28
申请号：PCT/US2003/005221
申请日：2003-02-19
申请人： BUCK INSTITUTE , SPERANDIO, Sabina , CASTRO-OBREGON, Susana , BREDESEN, Dale, E.
发明人： SPERANDIO, Sabina , CASTRO-OBREGON, Susana , BREDESEN, Dale, E.
IPC分类号： A61K38/00
摘要： The invention is directed to a method of identifying a compound that modulates SP-induced paraptosis by (a) contacting a population of cells with an effective amount of substance P to induce SP-induced paraptosis; (b) contacting a first sub-population of the cells with a test-compound, and a second sub-population of the cells with a control-compound; and (c) comparing the amount of cell death between the first and second sub-populations of cells, where a difference in he amount of cell death between the first and second sub-populations of cells indicates that the test-compound is a compound that modulates SP-induced paraptosis. The invention is also directed to a method of modulating paraptotic cell death in a cell by contacting the cell with an effective amount of a compound selected from the group consisting of ceramide, Tumor Necrosis Factor (TNF), caspase-7, caspase-8, α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA), kainic acid and glutamic acid, wherein the effective amount of the compound induces paraptotic death of the cell.

6. 发明申请

WO2013026021A2 TRKA AS A TARGET FOR INHIBITING APP CLEAVAGE AND/OR PROGRESSION OF ALZHEIMER'S DISEASE 审中-公开
标题翻译： TRKA作为抑制阿尔茨海默病应用切割和/或进展的目标
公开(公告)号：WO2013026021A2
公开(公告)日：2013-02-21
申请号：PCT/US2012/051426
申请日：2012-08-17
申请人： BUCK INSTITUTE FOR RESEARCH ON AGING , JOHN, Varghese , ZHANG, Qiang , BREDESEN, Dale, E.
发明人： JOHN, Varghese , ZHANG, Qiang , BREDESEN, Dale, E.
IPC分类号： A61K48/00 , A61K38/43
CPC分类号： C07K14/71 , A61K31/433 , C07K14/4711 , C12N2999/005
摘要： In various embodiments method are provided for inhibiting (partially or fully) the C-terminal cleavage of APP resulting in the formation of APP-C31 peptide and APPneo (APP664) in a mammal. The methods typically involve administering or causing to be administered to the mammal a TrkA kinase inhibitor in an amount sufficient to reduce C-terminal cleavage of APP and production of a C31 peptide and/or APPneo. In certain embodiments the inhibitor comprises ADDN-1351 or a derivative thereof.
摘要翻译：在各种实施方案中，提供了用于抑制（部分或完全）APP的C末端切割从而导致在哺乳动物中形成APP-C31肽和APPneo（APP664）的方法。所述方法通常涉及以足以减少APP的C末端切割和产生C31肽和/或APPneo的量向哺乳动物施用或导致施用TrkA激酶抑制剂。在某些实施方案中，抑制剂包含ADDN-1351或其衍生物。

7. 发明申请

WO2005094383A2 HUNTER-KILLER PEPTIDES AND METHODS OF USE 审中-公开
标题翻译：杀戮剂及其使用方法
公开(公告)号：WO2005094383A2
公开(公告)日：2005-10-13
申请号：PCT/US2005/010951
申请日：2005-03-31
申请人： BUCK INSTITUTE , BREDESEN, Dale, E. , ELLERBY, Michael , ELLERBY, Lisa
发明人： BREDESEN, Dale, E. , ELLERBY, Michael , ELLERBY, Lisa
CPC分类号： A61K38/16 , A61K47/64
摘要： The present invention provides homing conjugates containing an antimicrobial peptide and a tumor homing molecule, wherein the tumor homing molecule comprises a dimer of two endothelium-homing peptide monomers, wherein the conjugate homes to and is internalized by a tumor cell type or tissue comprising angiogenic endothelial cells and exhibits high toxicity thereto, wherein the high toxicity is due to disruption of mitochondrial membranes, and wherein the antimicrobial peptide has low mammalian cell toxicity when not linked to said tumor homing molecule. The present invention is based, in part, on the discovery that dimerization of endothelium-homing peptide monomer confers greatly increased cytotoxic activity on the conjugate. Based on this discovery, the invention further provides methods of inducing selective toxicity in vivo in an angiogenic endothelial tissue or cell type as well as methods of treating an individual having cancer by administering an effective amount of a homing conjugate of the invention also are provided.
摘要翻译：本发明提供了含有抗微生物肽和肿瘤归巢分子的归巢缀合物，其中所述肿瘤归巢分子包含两个内皮归巢肽单体的二聚体，其中所述缀合物归因于包含血管生成内皮的肿瘤细胞类型或组织细胞并且对其呈现高毒性，其中高毒性是由于线粒体膜的破坏，并且其中当不与所述肿瘤归巢分子连接时，所述抗微生物肽具有低的哺乳动物细胞毒性。本发明部分地基于发现内皮归巢肽单体的二聚化大大提高了缀合物的细胞毒活性。基于该发现，本发明还提供了在血管生成内皮组织或细胞类型中诱导体内选择性毒性的方法以及通过施用有效量的本发明的归巢缀合物治疗患有癌症的个体的方法。

8. 发明申请

WO2003070971A2 MODULATORS OF PARAPTOSIS AND RELATED METHODS 审中-公开
标题翻译： PARAPTOSIS的调制器和相关方法
公开(公告)号：WO2003070971A2
公开(公告)日：2003-08-28
申请号：PCT/US2003/005221
申请日：2003-02-19
申请人： BUCK INSTITUTE , SPERANDIO, Sabina , CASTRO-OBREGON, Susana , BREDESEN, Dale, E.
发明人： SPERANDIO, Sabina , CASTRO-OBREGON, Susana , BREDESEN, Dale, E.
IPC分类号： C12Q
CPC分类号： G01N33/5058 , A61K31/00 , A61K31/198 , A61K31/40 , A61K31/421 , A61K31/739 , A61K38/046 , A61K38/1709 , A61K38/191 , A61K38/4873 , A61K45/06 , G01N33/5008 , G01N33/5041 , G01N2510/00
摘要： The invention is directed to a method of identifying a compound that modulates SP-induced paraptosis by (a) contacting a population of cells with an effective amount of substance P to induce SP-induced paraptosis; (b) contacting a first sub-population of the cells with a test-compound, and a second sub-population of the cells with a control-compound; and (c) comparing the amount of cell death between the first and second sub-populations of cells, where a difference in he amount of cell death between the first and second sub-populations of cells indicates that the test-compound is a compound that modulates SP-induced paraptosis. The invention is also directed to a method of modulating paraptotic cell death in a cell by contacting the cell with an effective amount of a compound selected from the group consisting of ceramide, Tumor Necrosis Factor (TNF), caspase-7, caspase-8, α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA), kainic acid and glutamic acid, wherein the effective amount of the compound induces paraptotic death of the cell.
摘要翻译：本发明涉及一种鉴定通过使一群细胞与有效量的物质P接触来诱导SP诱导的parapptosis b调节SP诱导的parapptosis的化合物的方法，以使细胞的第一个亚群与测试接触化合物和具有对照化合物的细胞的第二亚群，c比较细胞的第一和第二亚群之间的细胞死亡量，其中第一和第二细胞死亡量之间的差异细胞亚群表明测试化合物是调节SP诱导的parapptosis的化合物。本发明还涉及一种通过使细胞与有效量的选自神经酰胺，肿瘤坏死因子TNF，半胱天冬酶-7，半胱天冬酶-8，α-淀粉样蛋白的化合物接触来调节细胞中的旁分泌细胞死亡的方法。氨基-3-羟基-5-甲基-4-异恶唑丙酸AMPA，红藻氨酸和谷氨酸，其中该化合物的有效量诱导细胞的副作用死亡。

9. 发明申请

WO2005115136A2 TRANSGENIC MODELS OF ALZHEIMER’S DISEASE AND USES THEREOF IN THE TREATMENT OF A VARIETY OF NEURODEGENERATIVE DISEASES 审中-公开
标题翻译：阿尔茨海默病的转移模型及其在治疗多种神经损伤疾病中的应用
公开(公告)号：WO2005115136A2
公开(公告)日：2005-12-08
申请号：PCT/US2005/013761
申请日：2005-04-22
申请人： BUCK INSTITUTE , BREDESEN, Dale, E. , GALVAN, Veronica
发明人： BREDESEN, Dale, E. , GALVAN, Veronica
IPC分类号： A01K67/027
CPC分类号： C12Q1/37 , A01K67/0275 , A01K2207/15 , A01K2217/00 , A01K2227/105 , A01K2227/107 , A01K2227/108 , A01K2267/0312 , A61K48/00 , C12N15/8509 , G01N33/5088 , G01N33/6896 , G01N2333/4709 , G01N2333/96466 , G01N2500/02 , G01N2800/2814 , G01N2800/2821
摘要： In accordance with the present invention, it is demonstrated that selected mutations such as an Asp -> Ala (D664A) mutation in APP (which prevents cleavage at the caspase cleavage site) prevent both hippocampal synaptic loss and dentate gyral atrophy, even though such mutations do not interfere with the production of Aß or the formation of amyloid plaques in a transgenic model of Alzheimer's disease. Accordingly, in view of this finding, methods have been developed for the identification of agents which block cleavage at Asp664 of APP, including transgenic animals which are useful for such purpose, as well as methods for the use thereof for the treatment of neurodegenerative diseases.
摘要翻译：根据本发明，证明了APP中的选择性突变（例如防止胱天蛋白酶切割位点处的切割）的Asp - > Ala（D664A）突变阻止海马突触损失和齿状回缩萎缩，尽管这种突变不要干扰阿尔茨海默病转基因模型中Aβ的产生或淀粉样蛋白斑的形成。因此，鉴于这一发现，已经开发了用于鉴定在Asp的Asp664处阻断切割的试剂的方法，包括可用于此目的的转基因动物以及用于治疗神经变性疾病的方法。

10. 发明申请

WO2002054066A3 NON-APOPTOTIC FORMS OF CELL DEATH AND METHODS OF MODULATION 审中-公开
公开(公告)号：WO2002054066A3
公开(公告)日：2002-07-11
申请号：PCT/US2001/048261
申请日：2001-12-13
申请人： THE BURNHAM INSTITUTE , SPERANDIO, Sabina , DE BELLE, Ian , BREDESEN, Dale, E.
发明人： SPERANDIO, Sabina , DE BELLE, Ian , BREDESEN, Dale, E.
IPC分类号： G01N33/50
摘要： The invention is directed to methods for identifying molecules that modulate paraptosis, a newly identified nonapoptotic form of programmed cell death. The invention also provides a method of inhibiting paraptosis by preventing association of caspase-9 and an endogenous paraptosis-mediating molecule. In one embodiment, the invention provides a method of inhibiting paraptosis by preventing association of caspase-9 and the Insulin-Like Growth Factor I Receptor (IGFIR). The invention further is directed to therapeutic methods for treatment of pathologies associated with aberrant levels of paraptosis such as neural cell death disorders and neoplastic disorders. Also provided by the present invention are methods of identifying endogenous paraptosis-mediating molecules.

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