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    Cell Death Inducing Agents
    1.
    发明申请
    Cell Death Inducing Agents 审中-公开
    细胞死亡诱导剂

    公开(公告)号：US20070280951A1

    公开(公告)日：2007-12-06

    申请号：US10582304

    申请日：2004-12-10

    申请人： Naoki Kimura ,  Masayuki Tsuchiya ,  Masahiko Nanami ,  Takashi Tomimatsu ,  Shigeto Kawai

    发明人： Naoki Kimura ,  Masayuki Tsuchiya ,  Masahiko Nanami ,  Takashi Tomimatsu ,  Shigeto Kawai

    IPC分类号： A61K39/395 ,  A61P35/00 ,  A61P37/00 ,  C07H21/00 ,  C07K16/00 ,  C12N1/00 ,  C12N15/63 ,  C12N5/00 ,  C12P21/00

    CPC分类号： C07K16/00 ,  C07K2317/622 ,  C07K2317/73

    摘要： The present inventors constructed a DNA expression vector encoding 2D7sc(Fv)2 in which the heavy chain variable region sequence (VH) and the light chain variable region sequence (VL) of the 2D7 antibody is arranged in the order of VH-VL-VH-VL, and these sequences are linked by a 15-mer linker. The vector was introduced into CHO cells and a 2D7sc(Fv)2-producing expression cell line was established. When 2D7sc(Fv)2 was expressed in this cell line, purified, and cell death-inducing experiments performed, 2D7sc(Fv)2 was found to have a concentration-dependent cell death-inducing activity.

    摘要翻译： 本发明人构建了编码2D7sc（Fv）2的DNA表达载体，其中2D7抗体的重链可变区序列（VH）和轻链可变区序列（VL）以VH-VL-VH -VL，并且这些序列通过15聚体连接子连接。 将载体导入CHO细胞，并建立产生2D7sc（Fv）2的表达细胞系。 当在该细胞系中表达2D7sc（Fv）2时，发现2D7sc（Fv）2的纯化和细胞死亡诱导实验具有浓度依赖性细胞死亡诱导活性。

    Cell death-inducing agent
    2.
    发明申请
    Cell death-inducing agent 失效
    细胞死亡诱导剂

    公开(公告)号：US20060275301A1

    公开(公告)日：2006-12-07

    申请号：US10530696

    申请日：2003-10-10

    申请人： Shuji Ozaki ,  Masahiro Abe ,  Masayuki Tsuchiya ,  Naoki Kimura ,  Shigeto Kawai

    发明人： Shuji Ozaki ,  Masahiro Abe ,  Masayuki Tsuchiya ,  Naoki Kimura ,  Shigeto Kawai

    IPC分类号： A61K39/395 ,  C07K16/30

    CPC分类号： C07K16/2833 ,  A61K2039/505 ,  C07K14/70539 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/626 ,  C07K2317/73

    摘要： To identify antigens of the 2D7 antibody, the present inventors cloned the 2D7 antigen. The results suggested that the 2D7 antigen is an HLA class I molecule. Based on this finding, the present inventors examined whether the 2D7 antibody has cell death-inducing activity. Nuclei fragmentation was observed when the 2D7 antibody was cross-linked with another antibody, indicating that cell-death was induced. Further, diabodies of the 2D7 antibody were found to have very strong cell death-inducing activities, even without the addition of another antibody. These results indicate that minibodies of an HLA-recognizing antibody can be used as cell death-inducing agents.

    摘要翻译： 为了鉴定2D7抗体的抗原，本发明人克隆了2D7抗原。 结果表明，2D7抗原是HLA I类分子。 基于该发现，本发明人检查了2D7抗体是否具有细胞死亡诱导活性。 当2D7抗体与另一种抗体交联时，观察到细胞核碎裂，表明诱导细胞死亡。 此外，发现2D7抗体的双抗体具有非常强的细胞死亡诱导活性，即使没有添加另一种抗体。 这些结果表明HLA识别抗体的小体抗体可以用作细胞死亡诱导剂。

    Cell Death-Inducing Agents
    3.
    发明申请
    Cell Death-Inducing Agents 审中-公开
    细胞死亡诱导剂

    公开(公告)号：US20080274110A1

    公开(公告)日：2008-11-06

    申请号：US11547747

    申请日：2004-04-09

    申请人： Shuji Ozaki ,  Masahiro Abe ,  Masayuki Tsuchiya ,  Naoki Kimura ,  Shigeto Kawai

    发明人： Shuji Ozaki ,  Masahiro Abe ,  Masayuki Tsuchiya ,  Naoki Kimura ,  Shigeto Kawai

    IPC分类号： A61K39/395 ,  C07K16/00 ,  A61P35/04 ,  C12N5/02

    CPC分类号： C07K16/2833 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/626 ,  C07K2317/73

    摘要： To identify antigens of the 2D7 antibody, the present inventors cloned the 2D7 antigen. As a result, the 2D7 antibody was found to recognize HLA class IA. In addition, the present inventors examined whether the 2D7 antibody has cell death-inducing activity. Nuclei fragmentation was observed when the 2D7 antibody was cross-linked with another antibody, indicating that cell-death was induced. Further, diabodies of the 2D7 antibody were found to have very strong cell death-inducing activities, even without the addition of another antibody. These results indicate that minibodies of an HLA-recognizing antibody can be used as cell death-inducing agents.

    摘要翻译： 为了鉴定2D7抗体的抗原，本发明人克隆了2D7抗原。 结果发现2D7抗体识别HLA类别IA。 此外，本发明人检查了2D7抗体是否具有细胞死亡诱导活性。 当2D7抗体与另一种抗体交联时，观察到细胞核碎裂，表明诱导细胞死亡。 此外，发现2D7抗体的双抗体具有非常强的细胞死亡诱导活性，即使没有添加另一种抗体。 这些结果表明HLA识别抗体的小体抗体可以用作细胞死亡诱导剂。

    Cell death-inducing agent
    4.
    发明授权
    Cell death-inducing agent 失效
    细胞死亡诱导剂

    公开(公告)号：US08158385B2

    公开(公告)日：2012-04-17

    申请号：US10530696

    申请日：2003-10-10

    申请人： Shuji Ozaki ,  Masahiro Abe ,  Masayuki Tsuchiya ,  Naoki Kimura ,  Shigeto Kawai

    发明人： Shuji Ozaki ,  Masahiro Abe ,  Masayuki Tsuchiya ,  Naoki Kimura ,  Shigeto Kawai

    IPC分类号： C12P21/04 ,  C12P21/08

    CPC分类号： C07K16/2833 ,  A61K2039/505 ,  C07K14/70539 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/626 ,  C07K2317/73

    摘要： To identify antigens of the 2D7 antibody, the present inventors cloned the 2D7 antigen. The results suggested that the 2D7 antigen is an HLA class I molecule. Based on this finding, the present inventors examined whether the 2D7 antibody has cell death-inducing activity. Nuclei fragmentation was observed when the 2D7 antibody was cross-linked with another antibody, indicating that cell-death was induced. Further, diabodies of the 2D7 antibody were found to have very strong cell death-inducing activities, even without the addition of another antibody. These results indicate that minibodies of an HLA-recognizing antibody can be used as cell death-inducing agents.

    摘要翻译： 为了鉴定2D7抗体的抗原，本发明人克隆了2D7抗原。 结果表明，2D7抗原是HLA I类分子。 基于该发现，本发明人检查了2D7抗体是否具有细胞死亡诱导活性。 当2D7抗体与另一种抗体交联时，观察到细胞核碎裂，表明诱导细胞死亡。 此外，发现2D7抗体的双抗体具有非常强的细胞死亡诱导活性，即使没有添加另一种抗体。 这些结果表明HLA识别抗体的小体抗体可以用作细胞死亡诱导剂。

    CELL DEATH INDUCER
    5.
    发明申请
    CELL DEATH INDUCER 审中-公开
    细胞死亡诱导因子

    公开(公告)号：US20100150927A1

    公开(公告)日：2010-06-17

    申请号：US12307042

    申请日：2007-07-13

    申请人： Naoki Kimura ,  Shigeto Kawai

    发明人： Naoki Kimura ,  Shigeto Kawai

    IPC分类号： A61K39/395 ,  C07K16/28 ,  C12N5/0781 ,  C12N5/0783 ,  A61P35/00 ,  A61P37/06

    CPC分类号： C07K16/18 ,  A61K2039/505 ,  C07K16/2833 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73

    摘要： An objective of the present invention is to provide an antibody having a high cell death-inducing activity. To solve the above-described problems, the present inventors immunized mice with cells expressing human HLA class IA and human β2 microglobulin (β2M) to obtain monoclonal antibodies. Screening of the obtained antibodies was performed to obtain ten clones of antibodies having a cell death-inducing activity. Analyses of these clones revealed that three of the clones (antibodies C3B3, C11B9, and C17D11), which have the α2 domain of the HLA class I antigen as an epitope, showed a stronger cytotoxic activity when crosslinked with an anti-mouse IgG antibody. Furthermore, when a C3B3 diabody was generated, this diabody was revealed to show a stronger anti-tumor effect compared with conventional diabodies of the 2D7 antibody, which is an HLA class IA antibody.

    摘要翻译： 本发明的目的是提供具有高细胞死亡诱导活性的抗体。 为了解决上述问题，本发明人用表达人类HLAⅠA型和人类2微球蛋白（＆amp; 2M）的细胞免疫小鼠以获得单克隆抗体。 进行所得抗体的筛选，得到10个具有细胞死亡诱导活性的抗体克隆。 这些克隆的分析显示，当用抗小鼠IgG抗体交联时，具有HLA I类抗原的α2结构域作为表位的三个克隆（抗体C3B3，C11B9和C17D11）显示出更强的细胞毒性活性。 此外，当产生C3B3双抗体时，与作为HLA 1A类抗体的2D7抗体的常规双抗体相比，该双抗体显示出更强的抗肿瘤效果。

    Modified antibodies against cd22 and utilization thereof
    8.
    发明申请
    Modified antibodies against cd22 and utilization thereof 审中-公开
    针对cd22的修饰抗体及其应用

    公开(公告)号：US20070003556A1

    公开(公告)日：2007-01-04

    申请号：US10550934

    申请日：2004-03-31

    申请人： Masayuki Tsuchiya ,  Naoki Kimura ,  Tatsuya Fukuda

    发明人： Masayuki Tsuchiya ,  Naoki Kimura ,  Tatsuya Fukuda

    IPC分类号： A61K39/395 ,  C07K16/30

    CPC分类号： C07K16/2803 ,  C07K2317/622 ,  C07K2317/73

    摘要： CD22 diabodies, in which heavy-chain and light-chain variable regions are linked by a 5-mer linker, were produced based on known sequence information for two types of anti-CD22 antibodies. The two diabodies produced were analyzed for their activity of binding to lymphoma cells and inducing lymphoma cell death (apoptosis). As a result, both diabodies were revealed to bind to the B-lymphoma cell line, “Raji”, and to have apoptosis-inducing activity towards Raji cells as well as towards another B-lymphoma cell line: Daudi cells. These results show that minibodies of antibodies that recognize CD22 can be used as apoptosis-inducing agents for tumor cells such as lymphoma cells.

    摘要翻译： 基于两种类型的抗-CD22抗体的已知序列信息产生CD22双抗体，其中重链和轻链可变区通过5-聚体连接子连接。 分析所产生的两种双抗体与淋巴瘤细胞结合的活性，诱导淋巴瘤细胞死亡（凋亡）。 结果，双抗体被揭示结合到B淋巴瘤细胞系“Raji”，并且对Raji细胞以及另一B淋巴瘤细胞系具有凋亡诱导活性：Daudi细胞。 这些结果表明识别CD22的抗体的小体抗体可以用作肿瘤细胞如淋巴瘤细胞的凋亡诱导剂。

    Photodiode carrier and photo sensor using the same
    9.
    发明授权
    Photodiode carrier and photo sensor using the same 有权
    光电二极管载体和光电传感器使用相同

    公开(公告)号：US09013020B2

    公开(公告)日：2015-04-21

    申请号：US13982063

    申请日：2012-03-09

    申请人： Takeshi Takeuchi ,  Naoki Kimura

    发明人： Takeshi Takeuchi ,  Naoki Kimura

    IPC分类号： H01L27/144 ,  G01J1/04 ,  H01L31/0203 ,  H05K1/18 ,  H01L31/02 ,  H05K1/03

    CPC分类号： H01L27/1446 ,  G01J1/0403 ,  H01L31/02005 ,  H01L31/0203 ,  H01L2224/48091 ,  H01L2224/48137 ,  H05K1/0313 ,  H05K1/181 ,  H05K2201/10015 ,  H05K2201/10121 ,  Y02P70/611 ,  H01L2924/00014

    摘要： Disclosed is a photodiode carrier which can equalize the frequency response characteristics of a plurality of mounted photodiodes. A photodiode carrier as disclosed includes a diode array connection region, first and second signal side electrodes connected to the diode array connection region, first and second bias side electrodes connected to the diode array connection region, and first and second condensers connected between the electrode disposed on the way of the first and the second bias side electrodes and the ground electrode, wherein the electrodes disposed on the way of the first and the second bias side electrodes are located in the about equal distance from the diode array connection region 7 as a start point.

    摘要翻译： 公开了可以使多个安装的光电二极管的频率响应特性相等的光电二极管载体。 所公开的光电二极管载体包括二极管阵列连接区域，连接到二极管阵列连接区域的第一和第二信号侧电极，连接到二极管阵列连接区域的第一和第二偏置侧电极以及连接在所设置的电极之间的第一和第二电容器 在第一和第二偏置侧电极和接地电极的路径上，其中设置在第一和第二偏置侧电极途中的电极位于与二极管阵列连接区域7大致相等的距离处，作为起始点 点。

    PHARMACEUTICAL COMPOSITION COMPRISING ANTI-HB-EGF ANTIBODY AS ACTIVE INGREDIENT
    10.
    发明申请
    PHARMACEUTICAL COMPOSITION COMPRISING ANTI-HB-EGF ANTIBODY AS ACTIVE INGREDIENT 审中-公开
    作为活性成分包含抗HB-EGF抗体的药物组合物

    公开(公告)号：US20120282173A1

    公开(公告)日：2012-11-08

    申请号：US13391171

    申请日：2010-08-17

    申请人： Naoki Kimura

    发明人： Naoki Kimura

    IPC分类号： A61K39/395 ,  A61P35/00 ,  G01N33/574 ,  C12N5/09 ,  C07K1/107 ,  C07K16/22 ,  A61K51/10

    CPC分类号： C07K16/22 ,  C07K2317/24 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  G01N33/57407 ,  G01N33/577

    摘要： An anti-HB-EGF antibody having an internalizing activity is disclosed. A cytotoxic substance is preferably bound to the anti-HB-EGF antibody of the present invention. Also provided are an anti-cancer agent and a cell proliferation inhibitor, which comprise the antibody of the present invention as an active ingredient, a method of treating cancer and a method of diagnosing cancer, which comprise the administration of the antibody of the present invention. Cancers that can be treated by the anti-cancer agent of the present invention include pancreatic cancer, liver cancer, esophageal cancer, melanoma, colorectal cancer, gastric cancer, ovarian cancer, uterine cervical cancer, breast cancer, bladder cancer, brain tumors, and hematological cancers.

    摘要翻译： 公开了具有内在活性的抗HB-EGF抗体。 细胞毒性物质优选与本发明的抗HB-EGF抗体结合。 还提供了包含本发明的抗体作为活性成分的抗癌剂和细胞增殖抑制剂，治疗癌症的方法和诊断癌症的方法，其包括施用本发明的抗体 。 可以用本发明的抗癌剂治疗的癌症包括胰腺癌，肝癌，食管癌，黑素瘤，结肠直肠癌，胃癌，卵巢癌，子宫颈癌，乳腺癌，膀胱癌，脑肿瘤和 血液癌。