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1. 发明申请

US20060275301A1 Cell death-inducing agent 失效
标题翻译：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。

2. 发明申请

US20080274110A1 Cell Death-Inducing Agents 审中-公开
标题翻译：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。

3. 发明授权

US08158385B2 Cell death-inducing agent 失效
标题翻译：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。

4. 发明申请

US20070280951A1 Cell Death Inducing Agents 审中-公开
标题翻译：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。

5. 发明申请

US20100150927A1 CELL DEATH INDUCER 审中-公开
标题翻译：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。

6. 发明授权

US08846870B2 Anti-HS6ST2 antibodies and uses thereof 有权
标题翻译：抗HS6ST2抗体及其用途
公开(公告)号：US08846870B2
公开(公告)日：2014-09-30
申请号：US12998988
申请日：2009-12-22
申请人： Shigeto Kawai , Naoki Kimura
发明人： Shigeto Kawai , Naoki Kimura
IPC分类号： C07K16/00 , G01N33/574 , C07K16/30 , C07K16/40 , C07K16/28
CPC分类号： C07K16/30 , C07K16/28 , C07K16/40 , C07K2317/73 , C07K2317/732 , G01N33/57423 , G01N33/57438 , G01N33/57449
摘要： The present invention provides antibodies that bind to HS6ST2 proteins, pharmaceutical compositions comprising the antibodies as active ingredients, methods for diagnosing cancer using the antibodies, HS6ST2 proteins conjugated to cytotoxic agents and pharmaceutical compositions comprising the HS6ST2 proteins as active ingredients.
摘要翻译：本发明提供结合HS6ST2蛋白的抗体，包含抗体作为活性成分的药物组合物，使用抗体诊断癌症的方法，与细胞毒性剂缀合的HS6ST2蛋白和包含HS6ST2蛋白作为活性成分的药物组合物。

7. 发明申请

US20110262929A1 ANTI-HS6ST2 ANTIBODIES AND USES THEREOF 有权
标题翻译：抗HS6ST2抗体及其用途
公开(公告)号：US20110262929A1
公开(公告)日：2011-10-27
申请号：US12998988
申请日：2009-12-22
申请人： Shigeto Kawai , Naoki Kimura
发明人： Shigeto Kawai , Naoki Kimura
IPC分类号： C12Q1/68 , A61P35/00 , C12N9/96 , C07K16/40 , C12Q1/48
CPC分类号： C07K16/30 , C07K16/28 , C07K16/40 , C07K2317/73 , C07K2317/732 , G01N33/57423 , G01N33/57438 , G01N33/57449
摘要： The present invention provides antibodies that bind to HS6ST2 proteins, pharmaceutical compositions comprising the antibodies as active ingredients, methods for diagnosing cancer using the antibodies, HS6ST2 proteins conjugated to cytotoxic agents and pharmaceutical compositions comprising the HS6ST2 proteins as active ingredients.
摘要翻译：本发明提供结合HS6ST2蛋白的抗体，包含抗体作为活性成分的药物组合物，使用抗体诊断癌症的方法，与细胞毒性剂缀合的HS6ST2蛋白和包含HS6ST2蛋白作为活性成分的药物组合物。

8. 发明申请

US20100035280A1 Chimeric Fc-gamma Receptor and Method for Determination of ADCC Activity by Using the Receptor 有权
标题翻译：嵌合Fc-γ受体和使用受体测定ADCC活性的方法
公开(公告)号：US20100035280A1
公开(公告)日：2010-02-11
申请号：US12525031
申请日：2008-01-30
申请人： Shigeto Kawai
发明人： Shigeto Kawai
IPC分类号： G01N33/567 , C07K14/705 , C07H21/04 , C12N15/63 , C12N5/10
CPC分类号： G01N33/566 , C07K14/70535 , C07K16/18 , C07K2317/24 , C07K2317/41 , C07K2317/52 , C07K2317/732 , C07K2319/00 , G01N33/5014 , G01N2500/04 , G01N2500/10
摘要： An objective of the present invention is to provide chimeric receptors containing a mouse Fcγ receptor extracellular domain and a human Fcγ receptor transmembrane domain, or chimeric receptors containing a mouse Fcγ receptor extracellular domain and a human γ chain transmembrane domain. Another objective of the present invention is to provide methods for measuring the ADCC activity of mouse antibodies and methods of screening for mouse antibodies having ADCC activity, using the chimeric receptors.To accomplish the above-mentioned objectives, the present inventors produced chimeric molecules by fusing the extracellular domain of mouse FcγR3 or mouse FcγR4 with the transmembrane domain/intracellular domain of human γ chain or human FcγR3, and expressed the chimeric molecules in human NK92 cells. It was revealed that the ADCC activity can be induced by the chimeric receptors produced by any combination of the domains, and that the ADCC activity of mouse antibodies can be measured using the chimeric receptors of the present invention.
摘要翻译：本发明的目的是提供含有小鼠Fcγ受体细胞外结构域和人Fcγ受体跨膜结构域的嵌合受体或含有小鼠Fcγ受体细胞外结构域和人γ链跨膜结构域的嵌合受体。本发明的另一个目的是提供使用嵌合受体测量小鼠抗体的ADCC活性的方法和筛选具有ADCC活性的小鼠抗体的方法。为了实现上述目的，本发明人通过将小鼠FcgammaR3或小鼠FcγR4的细胞外结构域与人γ链或人FcγR3的跨膜结构域/细胞内结构域融合而产生嵌合分子，并在人NK92细胞中表达嵌合分子。显示ADCC活性可以由通过结构域的任何组合产生的嵌合受体诱导，并且可以使用本发明的嵌合受体来测量小鼠抗体的ADCC活性。

9. 发明申请

US20070190599A1 Anti-glypican 3 antibody 有权
标题翻译：抗磷脂酰肌醇蛋白聚糖3抗体
公开(公告)号：US20070190599A1
公开(公告)日：2007-08-16
申请号：US10583795
申请日：2005-07-08
申请人： Kiyotaka Nakano , Takeshi Yoshino , Jun-Ichi Nezu , Hiroyuki Tsunoda , Tomoyuki Igawa , Hiroko Konishi , Megumi Tanaka , Izumi Sugo , Shigeto Kawai , Takahiro Ishiguro , Yasuko Kinoshita
发明人： Kiyotaka Nakano , Takeshi Yoshino , Jun-Ichi Nezu , Hiroyuki Tsunoda , Tomoyuki Igawa , Hiroko Konishi , Megumi Tanaka , Izumi Sugo , Shigeto Kawai , Takahiro Ishiguro , Yasuko Kinoshita
IPC分类号： C07K16/28 , C07H21/04 , C12P21/06 , C12N5/06
CPC分类号： C07K16/28 , C07K7/06 , C07K14/47 , C07K16/303 , C07K2317/24 , C07K2317/34 , C07K2317/565 , C07K2317/732 , C07K2317/734 , C07K2317/92
摘要： An antibody capable of binding to a specific region of glypican 3, as well as a humanized antibody created based on that antibody are disclosed. The anti-GPC3 antibody of the invention has a higher ADCC activity and CDC activity compared with those of a conventional antibody. The antibody of the present invention is useful as a cell growth inhibitor, an anticancer agent and an agent for diagnosis of cancers.
摘要翻译：公开了能够结合磷脂酰肌醇蛋白聚糖3的特定区域的抗体以及基于该抗体产生的人源化抗体。本发明的抗GPC3抗体与常规抗体相比具有较高的ADCC活性和CDC活性。本发明的抗体可用作细胞生长抑制剂，抗癌剂和癌症诊断剂。

10. 发明授权

US09139647B2 Diagnosis and treatment of cancer using anti-TM4SF20 antibody 有权
标题翻译：使用抗TM4SF20抗体诊断和治疗癌症
公开(公告)号：US09139647B2
公开(公告)日：2015-09-22
申请号：US13138014
申请日：2009-12-25
申请人： Hiroyuki Aburatani , Shunpei Ishikawa , Shigeto Kawai
发明人： Hiroyuki Aburatani , Shunpei Ishikawa , Shigeto Kawai
IPC分类号： C12P21/08 , C07K16/00 , C07K16/28 , C07K16/30 , G01N33/574 , A61K39/00
CPC分类号： C07K16/28 , A61K2039/505 , C07K16/30 , C07K2317/34 , C07K2317/56 , C07K2317/732 , C07K2317/734 , C07K2317/77 , G01N33/57423 , G01N33/57438 , G01N33/57446 , G01N33/57492
摘要： The present invention relates to an antibody binding to a TM4SF20 protein and the diagnosis and treatment of cancer using the antibody. Specifically, the present invention provides an anti-TM4SF20 antibody and a pharmaceutical composition (e.g., an anticancer agent and a diagnostic drug for cancer) comprising the antibody as an active ingredient.
摘要翻译：本发明涉及与TM4SF20蛋白结合的抗体以及使用该抗体诊断和治疗癌症。具体地说，本发明提供抗TM4SF20抗体和包含该抗体作为有效成分的药物组合物（例如抗癌剂和癌症诊断药）。

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