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    Novel curcuminoid-factor VIIa constructs as suppressors of tumor growth and angiogenesis
    1.
    发明申请
    Novel curcuminoid-factor VIIa constructs as suppressors of tumor growth and angiogenesis 审中-公开
    新型姜黄素因子VIIa构建成肿瘤生长和血管生成抑制因子

    公开(公告)号：US20060229239A9

    公开(公告)日：2006-10-12

    申请号：US10383898

    申请日：2003-03-07

    申请人： Mamoru Shoji ,  James Snyder ,  Dennis Liotta ,  Aiming Sun

    发明人： Mamoru Shoji ,  James Snyder ,  Dennis Liotta ,  Aiming Sun

    IPC分类号： A61K38/17

    CPC分类号： C12Y304/21021 ,  A61K47/64 ,  A61K47/6425 ,  C07D213/63 ,  C12N9/6437

    摘要： The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. The present invention provides methods to deliver a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors. The method involves tethering the drug to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage. The present invention further provides for the synthesis of novel curcuminoid-tether-linker-factor VIIa compositions and for methods of delivery of effective doses of the novel compositions to target tumor or endothelial cells in a patient

    摘要翻译： 氟化姜黄素（3,5-双 - （2-氟亚苄基） - 哌啶-4-酮乙酸酯在阻止肿瘤细胞生长方面比顺铂高约十倍。本发明提供递送细胞毒性化合物的方法， 例如姜黄素，特别是癌细胞和滋养实体瘤的血管内皮细胞，该方法涉及将药物系在蛋白质上，例如对表面蛋白组织因子保持高亲和力的因子VIIa，在复合后，产生 异二聚体被内吞，并且药物随后通过蛋白水解切割在靶细胞内释放。本发明还提供了新型姜黄素 - 连接子 - 连接因子VIIa组合物的合成和用于将有效剂量的新组合物递送至靶 肿瘤或内皮细胞

    PRODRUGS OF CURCUMIN ANALOGS
    2.
    发明申请
    PRODRUGS OF CURCUMIN ANALOGS 审中-公开
    曲霉素类似物的研究

    公开(公告)号：US20070270464A1

    公开(公告)日：2007-11-22

    申请号：US11678156

    申请日：2007-02-23

    申请人： Dennis Liotta ,  James Snyder ,  Mamoru Shoji ,  Yang Lu ,  Aiming Sun

    发明人： Dennis Liotta ,  James Snyder ,  Mamoru Shoji ,  Yang Lu ,  Aiming Sun

    IPC分类号： A61K38/10 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/4545 ,  A61P3/10 ,  C07D211/44 ,  C07D211/82 ,  C07D401/12 ,  C07D405/06 ,  C07D409/06 ,  A61K38/08 ,  A61K38/06 ,  A61K38/05

    CPC分类号： C07D211/74

    摘要： The invention provides sulfur-linked and nitrogen-linked peptidic conjugates of curcumin analogs that can provide increased water solubility and photostability as compared to the corresponding unmodified curcumin analogs without sacrificing therapeutic efficacy. The conjugates, which are believed to act as prodrugs, can be used therapeutically in the same manner as the unmodified curcumin analogs, such as in the treatment or prevention of cancer, diabetes, or inflammatory diseases. One conjugate comprises 3,5-Bis-(2-fluorobenzylidene)-piperidin-4-one, or a salt thereof, covalently attached through a sulfur linkage to a thiol-containing peptide such as glutathione.

    摘要翻译： 本发明提供与相应的未修饰的姜黄素类似物相比，可以提供增加的水溶性和光稳定性的姜黄素类似物的硫连接和氮连接的肽共轭物，而不牺牲治疗功效。 被认为用作前药的缀合物可以以与未修饰的姜黄素类似物相同的方式治疗地使用，例如在治疗或预防癌症，糖尿病或炎症性疾病中。 一个缀合物包含通过硫键共价连接到含硫醇的肽如谷胱甘肽的3,5-双 - （2-氟亚苄基） - 哌啶-4-酮或其盐。

    Cytotoxic compound-protein conjugates as suppressors of tumor growth and angiogenesis
    3.
    发明申请
    Cytotoxic compound-protein conjugates as suppressors of tumor growth and angiogenesis 审中-公开
    细胞毒性复合物 - 蛋​​白质缀合物作为肿瘤生长和血管发生的抑制剂

    公开(公告)号：US20050069551A1

    公开(公告)日：2005-03-31

    申请号：US10900490

    申请日：2004-07-28

    申请人： Mamoru Shoji ,  James Snyder ,  Dennis Liotta ,  Aiming Sun

    发明人： Mamoru Shoji ,  James Snyder ,  Dennis Liotta ,  Aiming Sun

    IPC分类号： A61K47/48 ,  C07D213/63 ,  C12N9/64 ,  A61K39/395 ,  C07K16/46

    CPC分类号： C12N9/6437 ,  A61K47/64 ,  A61K47/642 ,  A61K47/6849 ,  C07D213/63 ,  C12Y304/21021

    摘要： Compositions and methods are provided for delivering cytotoxic compounds, such as natural curcumoids and synthetic curcumin analogs, specifically to cancer cells and to blood vessels that nourish solid tumors. The compositions include a cytotoxic drug tethered to a protein, such as factor VIIa, which can bind with high affinity to a receptor, such as tissue factor, expressed on the surface of cancer cells and vascular endothelial cells within the tumor microenvironment. Upon binding, the drug-protein-receptor complex is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage. The compositions and methods may increase the efficacy of the cytotoxic agets and decrease their side effects by delivering the agents to specific target cells, such as cancer cells, vascular endothelial cells in a tumor, and metastatic foci anywhere in the body, providing the target cells express surface bound tissue factor. Additionally, methods of synthesis of cytotoxic compound-protein conjugates are provided, for example, curcuminoid-tether-linker-factor VIIa composition, as well as pharmaceutically acceptable compositions and methods for delivering a therapeutically-effective amount of a cytotoxic compound-protein conjugate together with one or more pharmaceutically acceptable carriers (additives) and/or diluents to an animal or human patient.

    摘要翻译： 提供组合物和方法用于递送细胞毒性化合物，例如天然的姜黄素和合成的姜黄素类似物，特别是癌细胞和滋养实体瘤的血管。 组合物包括与诸如因子VIIa结合的蛋白质的细胞毒性药物，其可以高度亲和力结合到在肿瘤微环境中在癌细胞表面和血管内皮细胞表面上的受体，例如组织因子。 结合后，药物 - 蛋​​白 - 受体复合物被内吞，并且药物随后通过蛋白水解切割在靶细胞内释放。 组合物和方法可以通过将药物递送到特定靶细胞，例如肿瘤中的癌细胞，血管内皮细胞和体内任何地方的转移灶，来增加细胞毒性作用的功效并降低其副作用，提供靶细胞 表达结合组织因子。 此外，提供了合成细胞毒性化合物 - 蛋​​白质缀合物的方法，例如，姜黄素 - 链 - 连接体 - 因子VIIa组合物，以及用于将治疗有效量的细胞毒性化合物 - 蛋​​白质缀合物一起递送的药学上可接受的组合物和方法 与动物或人类患者的一种或多种药学上可接受的载体（添加剂）和/或稀释剂。

    System and method of managing software product-line customizations
    7.
    发明申请
    System and method of managing software product-line customizations 失效
    管理软件产品线定制的系统和方法

    公开(公告)号：US20050267889A1

    公开(公告)日：2005-12-01

    申请号：US11053743

    申请日：2005-02-08

    申请人： James Snyder ,  Harry Lai ,  Shirish Reddy ,  Jimmy Wan

    发明人： James Snyder ,  Harry Lai ,  Shirish Reddy ,  Jimmy Wan

    IPC分类号： G06F7/00 ,  G06F17/30

    CPC分类号： G06F17/30592

    摘要： A method of managing application service provider product line variations is disclosed. The method includes receiving a client customization request, creating a configuration managed file tailored to the client customization request, binding the configuration managed file to at least one customizable resource, and deploying the customizable resource to a data store. The customizable resource is instantiated after disposition at the data store.

    摘要翻译： 公开了一种管理应用服务提供商产品线变化的方法。 该方法包括接收客户端定制请求，创建针对客户端定制请求定制的配置管理文件，将配置管理文件绑定到至少一个可定制资源，以及将可定制资源部署到数据存储。 可定制的资源在数据存储处理后实例化。

    Method for forming polymer materials utilizing modular die units
    9.
    发明申请
    Method for forming polymer materials utilizing modular die units 审中-公开
    使用模块化模具单元形成聚合物材料的方法

    公开(公告)号：US20050003035A1

    公开(公告)日：2005-01-06

    申请号：US10819698

    申请日：2004-04-07

    申请人： Jerry Zucker ,  James Schaeffer ,  Richard Ferencz ,  James Snyder ,  Tim Krause ,  Nick Carter

    发明人： Jerry Zucker ,  James Schaeffer ,  Richard Ferencz ,  James Snyder ,  Tim Krause ,  Nick Carter

    IPC分类号： B29C47/04 ,  B29C47/06 ,  B29C47/10 ,  B29C47/12 ,  B29C47/16 ,  B29C47/30 ,  D01D4/02 ,  D01D13/00

    CPC分类号： D01D4/02 ,  B29C48/05 ,  B29C48/08 ,  B29C48/16 ,  B29C48/18 ,  B29C48/285 ,  B29C48/30 ,  B29C48/304 ,  B29C48/31 ,  B29C48/345 ,  B29K2067/00 ,  B29K2077/00 ,  B29K2105/12 ,  B29K2311/10

    摘要： The present invention is directed to a modular die unit comprising a plurality of individually shaped plates wherein the shaped plates are stacked in face to face juxtaposition, and when placed into such a juxtaposition exhibit useful polymer forming attributes heretofore unattainable by prior art practices. Single die plates are formed such that the plates exhibit a finite geometric relationship, which in turn provides resistance to flexural deformation of the individually shaped die plates and conversely, improved resistance to variability of the modular die unit and enhanced and predictable formation characteristics of the polymer material formed therewith. Each of said single die plates within the stack forming the modular die unit exhibit an x-direction, a y-direction, and a z-direction, wherein any one of said single die plates exhibit in said x-direction and y-direction to have at least a 50% planar continuity of the total planar continuity.

    摘要翻译： 本发明涉及一种模块化模具单元，其包括多个单独成形的板，其中成形板以并列方式堆叠，并且当放置成这样并列时，显示出迄今为止由现有技术实践不可达到的有用的聚合物形成属性。 形成单模板，使得板呈现有限的几何关系，其又提供抵抗单独成型的模板的弯曲变形的阻力，反之，提高了模块化模具单元的变异性，并且增强了且可预测的聚合物的形成特性 形成的材料。 形成模块化单元的堆叠内的每个所述单模板呈现x方向，y方向和z方向，其中所述单模板中的任何一个在所述x方向和y方向上表现为 具有总平面连续性的至少50％的平面连续性。

    Single solvent process for preparing 2-methallyloxy-phenol from catechol
    10.
    发明授权
    Single solvent process for preparing 2-methallyloxy-phenol from catechol 失效
    用于从儿茶酚制备2-甲基烯丙氧基 - 苯酚的单一溶剂法

    公开(公告)号：US4851587A

    公开(公告)日：1989-07-25

    申请号：US200336

    申请日：1988-05-31

    申请人： Borivoj Franko-Filipasic ,  James Snyder

    发明人： Borivoj Franko-Filipasic ,  James Snyder

    IPC分类号： C07C41/16

    CPC分类号： C07C41/16

    摘要： 2-Methallyloxyphenol precursor to 2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuran is prepared selectively and in good yield in the etherification of an alkali metal catecholate by methallyl chloride in an improved process using the same solvent medium for both the precursor and the hydroxybenzofuran, the process characterized by a solvent medium comprising an aromatic hydrocarbon solvent, the medium also containing an amine selected from alkylamines and N-heterocyclic amines. The amine forms a quaternary salt with the methallyl chloride in situ to catalyze the etherification and the aromatic solvent permits rearrangement of the product and Claisen closure to a benzofuran intermediate without solvent exchange.

    摘要翻译： 对于2,3-二氢-2,2-二甲基-7-羟基苯并呋喃的2-甲基丙烯酰氧基苯酚前体是通过甲基烯丙基氯在碱金属儿茶酚酸的醚化中以良好的收率制备的，使用相同的溶剂介质， 前体和羟基苯并呋喃，该方法的特征在于包含芳族烃溶剂的溶剂介质，该介质还含有选自烷基胺和N-杂环胺的胺。 胺与甲代烯丙基氯原位形成季盐以催化醚化，并且芳族溶剂允许将产物重新排列并将Claisen封闭物重整至苯并呋喃中间体而无需溶剂交换。