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    Alpha-galactosyl ceramide analogs and their use as immunotherapies
    1.
    发明授权
    Alpha-galactosyl ceramide analogs and their use as immunotherapies 有权
    α-半乳糖基神经酰胺类似物及其作为免疫治疗的用途

    公开(公告)号：US07928077B2

    公开(公告)日：2011-04-19

    申请号：US12218082

    申请日：2008-07-11

    申请人： Chi-Huey Wong ,  Alice Yu ,  Ya-Jen Chang ,  Kun-Hsien Lin ,  Jung-Tung Hung

    发明人： Chi-Huey Wong ,  Alice Yu ,  Ya-Jen Chang ,  Kun-Hsien Lin ,  Jung-Tung Hung

    IPC分类号： A61K31/7032 ,  C07H15/18

    CPC分类号： C07H15/18 ,  A61K31/7034 ,  A61K39/0011 ,  A61K2039/57 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/48

    摘要： The present disclosure relates to synthetic alpha-galactosyl ceramide (α-GalCer) analogs, and their use as immunotherapies. In one aspect. a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula 1: or a pharmaceutically acceptable salt thereof; forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte; and activating the lymphocyte to produce the cytokine response.

    摘要翻译： 本公开涉及合成的α-半乳糖神经酰胺（α-GalCer）类似物，以及它们作为免疫治疗的用途。 在一个方面 在受试者中激活细胞因子应答的方法包括向受试者施用有效量的化合物，其中受试者具有包括细胞群的适应性免疫系统，所述群体包括至少一种淋巴细胞和至少一种抗原 - 呈递细胞，并且其中所述化合物由式1的结构表示：或其药学上可接受的盐; 在化合物和抗原呈递细胞之间形成复合物，其中复合物的形成导致淋巴细胞上受体的活化; 并激活淋巴细胞以产生细胞因子反应。

    Alpha-galactosyl ceramide analogs and their use as immunotherapies
    2.
    发明申请
    Alpha-galactosyl ceramide analogs and their use as immunotherapies 有权
    α-半乳糖基神经酰胺类似物及其作为免疫治疗的用途

    公开(公告)号：US20100008954A1

    公开(公告)日：2010-01-14

    申请号：US12218082

    申请日：2008-07-11

    申请人： Chi-Huey Wong ,  Alice Yu ,  Ya-Jen Chang ,  Kun-Hsien Lin ,  Jung-Tung Hung

    发明人： Chi-Huey Wong ,  Alice Yu ,  Ya-Jen Chang ,  Kun-Hsien Lin ,  Jung-Tung Hung

    IPC分类号： A61K39/02 ,  A61K31/7034 ,  C07H15/18 ,  A61K39/00

    CPC分类号： C07H15/18 ,  A61K31/7034 ,  A61K39/0011 ,  A61K2039/57 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/48

    摘要： The present disclosure relates to synthetic alpha-galactosyl ceramide (α-GalCer) analogs, and their use as immunotherapies. In one aspect. a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula 1: or a pharmaceutically acceptable salt thereof; forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte; and activating the lymphocyte to produce the cytokine response.

    摘要翻译： 本公开涉及合成的α-半乳糖神经酰胺（α-GalCer）类似物，以及它们作为免疫治疗的用途。 在一个方面 在受试者中激活细胞因子应答的方法包括向受试者施用有效量的化合物，其中受试者具有包括细胞群的适应性免疫系统，所述群体包括至少一种淋巴细胞和至少一种抗原 - 呈递细胞，并且其中所述化合物由式1的结构表示：或其药学上可接受的盐; 在化合物和抗原呈递细胞之间形成复合物，其中复合物的形成导致淋巴细胞上受体的活化; 并激活淋巴细胞以产生细胞因子反应。

    METHODS FOR THE TREATMENT AND PREVENTION OF INFLAMMATORY DISEASES
    3.
    发明申请
    METHODS FOR THE TREATMENT AND PREVENTION OF INFLAMMATORY DISEASES 有权
    治疗和预防感染性疾病的方法

    公开(公告)号：US20140301996A1

    公开(公告)日：2014-10-09

    申请号：US13699436

    申请日：2011-05-24

    申请人： Dale T. Umetsu ,  Rosemarie Helena De Kruyff ,  Ya-Jen Chang ,  Petr Illarionov

    发明人： Dale T. Umetsu ,  Rosemarie Helena De Kruyff ,  Ya-Jen Chang ,  Petr Illarionov

    IPC分类号： A61K35/14 ,  C07H15/24 ,  A61K31/704

    CPC分类号： C07H15/24 ,  A61K31/56 ,  A61K31/70 ,  A61K31/704 ,  A61K35/15 ,  A61K35/17 ,  A61K2039/572 ,  A61K2300/00

    摘要： The inventors demonstrate that treatment of young, suckling mice with a glycolipid derived from Helicobacter pylori activates NKT cells in a CD1d-restricted fashion, and is protective against AHR in a model of allergen-induced asthma. The inventors further found that this protective effect can be transferred by NKT cells exposed to the glycolipid, and is associated with the expansion of a suppressive double-negative NKT cells and Foxp3+ TReg cells. The inventors also demonstrate herein that pre-treatment of adult mice with a glycolipid derived from Helicobacter pylori partially suppresses airway hyperreactivity and inhibits BAL inflammation in an ozone-exposure model. Accordingly, provided herein are compositions and methods for the treatment and prevention of inflammatory diseases, such as asthma or autoimmune diseases, in a subject in need thereof.

    摘要翻译： 本发明人证明用来自幽门螺杆菌的糖脂处理年轻的哺乳小鼠以CD1d限制的方式激活NKT细胞，并且在变应原诱发的哮喘模型中对AHR有保护作用。 本发明人进一步发现，这种保护作用可以通过暴露于糖脂的NKT细胞转移，并且与抑制性双阴性NKT细胞和Foxp3 + TReg细胞的扩增有关。 发明人还在本文中证实，用幽门螺杆菌衍生的糖脂预处理成年小鼠部分抑制气道高反应性并抑制臭氧暴露模型中的BAL炎症。 因此，本文提供了在有需要的受试者中治疗和预防炎性疾病如哮喘或自身免疫性疾病的组合物和方法。

    MAMMAL DEDICATED CELL LINE
    4.
    发明申请
    MAMMAL DEDICATED CELL LINE 审中-公开
    男士专用细胞系

    公开(公告)号：US20100216232A1

    公开(公告)日：2010-08-26

    申请号：US12506572

    申请日：2009-07-21

    申请人： TSUI-JUNG CHANG ,  CHIH-HSIEN CHANG ,  YA-JEN CHANG ,  TE-WEI LEE ,  TIN-YUN HO ,  CHIEN-YUN HSIANG

    发明人： TSUI-JUNG CHANG ,  CHIH-HSIEN CHANG ,  YA-JEN CHANG ,  TE-WEI LEE ,  TIN-YUN HO ,  CHIEN-YUN HSIANG

    IPC分类号： C12N5/10 ,  C12N5/071

    CPC分类号： G01N33/5008

    摘要： A mammal dedicated cell line is provided, which is a HepG2 hepatocellular carcinoma cell line (HepG2/NF-kB/Luc/sr39tk)1_18 obtained by co-transformation with NF-kB/Luc and NF-kB/sr39tk. Firstly, a successfully transformed pNF-kB/Luc HepG2 cell is obtained. Then, a dedicated cell line sensitive to TPA and MTX is generated by experimental screening Next, a plasmid construct carrying pNF-kB/sr39tk genome is introduced into the dedicated cell line by means of Superfect protocol. Finally, a HepG2 cell line co-expressing NF-kB/Luc and NF-kB/sr39tk is screened with G418 and ZEOCIN, and transformation result is confirmed by luminescence and radio activity. The (HepG2/NF-kB/Luc/sr39tk)1_18 obtained is suitable to screen drug for treating liver cancer and examine these cells by bioluminescence imaging and nuclear medicine imaging.

    摘要翻译： 提供哺乳动物专用细胞系，其是通过与NF-kB / Luc和NF-kB / sr39tk共转化获得的HepG2肝细胞癌细胞系（HepG2 / NF-kB / Luc / sr39tk）1-18。 首先，获得成功转化的pNF-kB / Luc HepG2细胞。 然后，通过实验筛选产生对TPA和MTX敏感的专用细胞系。接下来，通过Superfect方案将携带pNF-kB / sr39tk基因组的质粒构建体导入专用细胞系。 最后，用G418和ZEOCIN筛选共表达NF-kB / Luc和NF-kB / sr39tk的HepG2细胞株，通过发光和放射活性证实转化结果。 获得的（HepG2 / NF-kB / Luc / sr39tk）1_18适用于筛选药物治疗肝癌，并通过生物发光成像和核医学成像检查这些细胞。

    MAMMAL DEDICATED CELL LINE FROM HUMAN HEPATOCELLULAR CARCINOMA CELL
    5.
    发明申请
    MAMMAL DEDICATED CELL LINE FROM HUMAN HEPATOCELLULAR CARCINOMA CELL 审中-公开
    来自人肝细胞癌细胞的MAMMAL专用细胞系

    公开(公告)号：US20120295349A1

    公开(公告)日：2012-11-22

    申请号：US13555495

    申请日：2012-07-23

    申请人： TSUI-JUNG CHANG ,  Chih-Hsien Chang ,  Ya-Jen Chang ,  Te-Wei Lee ,  Tin-Yun Ho ,  Chien-yun Hsiang

    发明人： TSUI-JUNG CHANG ,  Chih-Hsien Chang ,  Ya-Jen Chang ,  Te-Wei Lee ,  Tin-Yun Ho ,  Chien-yun Hsiang

    IPC分类号： C12N5/10

    CPC分类号： G01N33/5008

    摘要： A mammal dedicated cell line is provided, which is a HepG2 hepatocellular carcinoma cell line (HepG2/NF-kB/Luc/sr39tk)1_18 obtained by co-transformation with NF-kB/Luc and NF-kB/sr39tk. Firstly, a successfully transformed pNF-kB/Luc HepG2 cell is obtained. Then, a dedicated cell line sensitive to TPA and MTX is generated by experimental screening Next, a plasmid construct carrying pNF-kB/sr39tk genome is introduced into the dedicated cell line by means of Superfect protocol. Finally, a HepG2 cell line co-expressing NF-kB/Luc and NF-kB/sr39tk is screened with G418 and ZEOCIN, and transformation result is confirmed by luminescence and radio activity. The (HepG2/NF-kB/Luc/sr39tk)1_18 obtained is suitable to screen drug for treating liver cancer and examine these cells by bioluminescence imaging and nuclear medicine imaging.

    摘要翻译： 提供哺乳动物专用细胞系，其是通过与NF-kB / Luc和NF-kB / sr39tk共转化获得的HepG2肝细胞癌细胞系（HepG2 / NF-kB / Luc / sr39tk）1-18。 首先，获得成功转化的pNF-kB / Luc HepG2细胞。 然后，通过实验筛选产生对TPA和MTX敏感的专用细胞系。接下来，通过Superfect方案将携带pNF-kB / sr39tk基因组的质粒构建体导入专用细胞系。 最后，用G418和ZEOCIN筛选共表达NF-kB / Luc和NF-kB / sr39tk的HepG2细胞株，通过发光和放射活性证实转化结果。 获得的（HepG2 / NF-kB / Luc / sr39tk）1_18适用于筛选药物治疗肝癌，并通过生物发光成像和核医学成像检查这些细胞。

    Alpha-galactosyl ceramide analogs and their use as immunotherapies
    7.
    发明申请
    Alpha-galactosyl ceramide analogs and their use as immunotherapies 审中-公开
    α-半乳糖基神经酰胺类似物及其作为免疫治疗的用途

    公开(公告)号：US20080260774A1

    公开(公告)日：2008-10-23

    申请号：US12082751

    申请日：2008-04-14

    申请人： Chi-Huey Wong ,  Alice Yu ,  Ya-Jen Chang

    发明人： Chi-Huey Wong ,  Alice Yu ,  Ya-Jen Chang

    IPC分类号： A61K39/00 ,  A61K31/35 ,  C07D315/00 ,  A61P37/00

    CPC分类号： C07H15/26 ,  A61K8/68 ,  A61K2800/91 ,  A61Q17/005 ,  C07H15/06 ,  C07H15/18

    摘要： The present disclosure relates to synthetic alpha-galactosyl ceramide (α-GalCer) analogs, and their use as immunotherapies. In one aspect, a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula 1: wherein, n is 0 to 25; X is selected from O and S; R1 is selected from H, CH3, and phenyl, where phenyl is optionally substituted with H, OH, OCH3, F, CF3, phenyl, phenyl-F, C1-C6 alkyl, or C2-C6 branched alkyl; R2 is selected from OH and H; R3 is selected from C1-C15 alkyl, and phenyl, where phenyl is optionally substituted with H, OH, OCH3, F, CF3, phenyl, C1-C6 alkyl, or C2-C6 branched alkyl; R4 is selected from OH, OSO3H, OSO3Na, and OSO3K; and R5 is selected from CH2OH and CO2H; or a pharmaceutically acceptable salt thereof; forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte; and activating the lymphocyte to produce the cytokine response.

    摘要翻译： 本公开涉及合成的α-半乳糖神经酰胺（α-GalCer）类似物，以及它们作为免疫治疗的用途。 一方面，在受试者中激活细胞因子应答的方法包括向受试者施用有效量的化合物，其中所述受试者具有包括细胞群的适应性免疫系统，所述群体包括至少一种淋巴细胞，并且在 至少一种抗原呈递细胞，并且其中所述化合物由式1的结构表示：其中n为0至25; X选自O和S; R 1选自H，CH 3和苯基，其中苯基任选被H，OH，OCH 3，F，CF 苯基，苯基-F，C 1 -C 6烷基或C 2 -C 6亚烷基 >支链烷基; R 2选自OH和H; R 3选自C 1 -C 15烷基和苯基，其中苯基任选被H，OH，OCH 3取代， 3，F，CF 3，苯基，C 1 -C 6烷基或C 2 H 2 -C 6 -C 6支链烷基; R 4选自OH，OSO 3 H，OSO 3 Na和OSO 3 K; 和R 5选自CH 2 OH和CO 2 H; 或其药学上可接受的盐; 在化合物和抗原呈递细胞之间形成复合物，其中复合物的形成导致淋巴细胞上受体的活化; 并激活淋巴细胞以产生细胞因子反应。

    Kit for preparation of nano-targeted liposome drug in combined radionuclide therapy and chemotherapy
    10.
    发明申请
    Kit for preparation of nano-targeted liposome drug in combined radionuclide therapy and chemotherapy 审中-公开
    用于在联合放射​​性核素治疗和化疗中制备纳米靶向脂质体药物的试剂盒

    公开(公告)号：US20080226546A1

    公开(公告)日：2008-09-18

    申请号：US11687650

    申请日：2007-03-18

    申请人： Te-Wei Lee ,  Ya-Jen Chang ,  Liang-Cheng Chen ,  Chia-Yu Yu ,  Shu-Pei Chiu ,  Shu-Ling Chen ,  Tsai-Yueh Luo ,  Chih-Hsien Chang ,  Gann Ting

    发明人： Te-Wei Lee ,  Ya-Jen Chang ,  Liang-Cheng Chen ,  Chia-Yu Yu ,  Shu-Pei Chiu ,  Shu-Ling Chen ,  Tsai-Yueh Luo ,  Chih-Hsien Chang ,  Gann Ting

    IPC分类号： A61K51/12 ,  A61K51/00 ,  A61P35/00 ,  A61K51/04

    CPC分类号： A61K31/704 ,  A61K47/6911 ,  A61K51/0478 ,  A61K51/1234 ,  A61K2300/00

    摘要： This invention is to manufacture a kit for preparation of nano-targeted liposome drugs in combined chemotherapy and radionuclide therapy. It is a kit consisting of three components: (1) A 10 ml vial A which contains BMEDA, gluconate acetate, SnCl2. (2) A 10 ml vial B which contains DSPC, cholesterol, DSPE-PEG, and Doxorubicin(DXR) (or Daunorubicin, Vinolbine). (3) A 10 ml vial C which contains 188ReO4− (or 186ReO4−) solution. The procedure of using the kit is as follows: (1) Remove the contents of the 188ReO4− (or 186ReO4−) solution from vial C. (2) Inject the 188ReO4− (or 186ReO4−) solution into the vial A, and the mixtures react in appropriate temperature. (3) Remove the contents of the 188Re-BMEDA (or 186Re-BMEDA) solution from vial A. (4) Inject the 188Re-BMEDA (or 186Re-BMEDA) solution into the vial B, and the mixtures react in appropriate temperature. The reconstituted solution in the vial B is applied to combine bimodality radiochemotherapy for treatment of tumor and ascites.

    摘要翻译： 本发明是在联合化疗和放射性核素治疗中制备用于制备纳米靶向脂质体药物的试剂盒。 它是由三个组分组成的试剂盒：（1）含有BMEDA，葡萄糖酸乙酯，SnCl 2 2的10ml小瓶A. （2）含有DSPC，胆固醇，DSPE-PEG和多柔比星（DXR）（或柔红霉素，维罗非因）的10ml小瓶B。 （3）将含有<！ - SIPO - >反应物（或<！ - SIPO - > - ）解决方案。 使用试剂盒的步骤如下：（1）除去 188 - （或 186 < 来自小瓶C的溶液。（2）注射<！ - SIPO - >反应物 > - （或 186 ）溶液加入到小瓶A中，并且混合物在合适的温度下反应。 （3）从小瓶A中取出 188 Re-BMEDA（或<186> 重BMEDA）溶液的内容物。（4）注入 188 Re-BMEDA）溶液加入小瓶B中，混合物在合适的温度下反应。 将小瓶B中的重构溶液应用于结合双功能放射化学疗法治疗肿瘤和腹水。