公开(公告)号：US08486402B2

公开(公告)日：2013-07-16

申请号：US13106280

申请日：2011-05-12

申请人： Tomoyuki Tahara ,  Yoshikatsu Kanai ,  Hitoshi Endou ,  Shiro Kataoka ,  Kazumasa Hasegawa ,  Tetsuya Yoshino

发明人： Tomoyuki Tahara ,  Yoshikatsu Kanai ,  Hitoshi Endou ,  Shiro Kataoka ,  Kazumasa Hasegawa ,  Tetsuya Yoshino

IPC分类号： A61K38/00

CPC分类号： C07K16/2896 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/30 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/76

摘要： A human antibody or a functional fragment thereof having specific binding ability to CD98 which is derived from the cell membrane of cancer cells and is in the form of a complex with a protein having an amino acid transporter activity (for example, LAT1) is disclosed. This antibody binds to CD98 in the form of a dimer with LAT1 on the surface of cancer cells, specifically attacks cancer cells expressing CD98 via the immune system by ADCC or CDC, and further inhibits amino acid uptake of the cancer cells via LAT1, to suppress growth of the cancer cells. Accordingly, a preventive and therapeutic agent for cancer comprising this antibody or a fragment thereof, which acts on various cancers, is specific to cancer, and causes no side effect, is provided.

摘要翻译： 公开了具有来自癌细胞的细胞膜的与CD98特异性结合能力并与具有氨基酸转运蛋白活性的蛋白质（例如LAT1）形成复合物的形式的人抗体或其功能片段。 该抗体以癌细胞表面的LAT1二聚体形式结合CD98，特异性地通过ADCC或CDC通过免疫系统侵袭表达CD98的癌细胞，并进一步通过LAT1抑制癌细胞的氨基酸摄取，抑制 癌细胞的生长。 因此，提供了作用于各种癌症的该抗体或其片段的癌症的预防和治疗剂，其对癌症是特异性的，并且不产生副作用。

公开(公告)号：US07666999B2

公开(公告)日：2010-02-23

申请号：US10913191

申请日：2004-08-05

申请人： Hitoshi Endou ,  Yoshikatsu Kanai

发明人： Hitoshi Endou ,  Yoshikatsu Kanai

IPC分类号： C07K16/00 ,  C07K16/28

CPC分类号： C07K14/705 ,  A01K2217/05 ,  A61K38/00

摘要： A novel amino acid transporter molecule mediating transportation of amino acids, which are nutrients essentially required in the survival and proliferation of various normal cells constituting a living body and various pathology-associated abnormal cells such as tumor cells, into cells and being expressed specifically in tumor cells compared with normal cells; and drugs for treating various pathogenic conditions such as tumor (cancer) which are obtained by identifying and isolating the above amino acid transporter molecule and identifying a substance capable of inhibiting the biological activity and/or expression of this molecule. Intensive studies were made to identify a tumor cell membrane surface molecule associating or interacting with a cell membrane surface 4F2hc molecule seemingly playing an important role in the activation of an unknown amino acid transporter. As a result, a gene encoding the novel amino acid transporter molecule, which mediates the incorporation of various neutral amino acids, various drugs or physiological substances into cells, has been found out and a substance capable of inhibiting the incorporation of amino acids via this molecule and thus inhibiting the proliferation of tumor cells has been also found out.

摘要翻译： 介导氨基酸运输的新型氨基酸转运蛋白分子，其是构成活体的各种正常细胞的存活和增殖以及各种病理学相关异常细胞如肿瘤细胞基本上需要的营养素，并且在肿瘤中特异性表达 细胞与正常细胞相比; 以及用于治疗通过鉴定和分离上述氨基酸转运蛋白分子并鉴定能够抑制该分子的生物活性和/或表达的物质而获得的各种病原性病症如肿瘤（癌症）的药物。 进行了深入研究，以确定与细胞膜表面缔合或相互作用的肿瘤细胞膜表面分子4F2hc分子在未知氨基酸转运蛋白的活化中似乎起着重要作用。 结果，已经发现了编码新的氨基酸转运蛋白分子的基因，其介导各种中性氨基酸，各种药物或生理物质掺入细胞中，并且能够通过该分子抑制氨基酸的掺入的物质 从而也发现抑制肿瘤细胞的增殖。

公开(公告)号：US07335482B2

公开(公告)日：2008-02-26

申请号：US10913263

申请日：2004-08-05

申请人： Hitoshi Endou ,  Yoshikatsu Kanai

发明人： Hitoshi Endou ,  Yoshikatsu Kanai

IPC分类号： G01N33/53

CPC分类号： C07K14/705 ,  A01K2217/05 ,  A61K38/00

摘要： A novel amino acid transporter molecule mediating transportation of amino acids, which are nutrients essentially required in the survival and proliferation of various normal cells constituting a living body and various pathology-associated abnormal cells such as tumor cells, into cells and being expressed specifically in tumor cells compared with normal cells; and drugs for treating various pathogenic conditions such as tumor (cancer) which are obtained by identifying and isolating the above amino acid transporter molecule and identifying a substance capable of inhibiting the biological activity and/or expression of this molecule. Intensive studies were made to identify a tumor cell membrane surface molecule associating or interacting with a cell membrane surface 4F2hc molecule seemingly playing an important role in the activation of an unknown amino acid transporter. As a result, a gene encoding the novel amino acid transporter molecule, which mediates the incorporation of various neutral amino acids, various drugs or physiological substances into cells, has been found out and a substance capable of inhibiting the incorporation of amino acids via this molecule and thus inhibiting the proliferation of tumor cells has been also found out.

摘要翻译： 介导氨基酸运输的新型氨基酸转运蛋白分子，其是构成活体的各种正常细胞的存活和增殖以及各种病理学相关异常细胞如肿瘤细胞基本上需要的营养素，并且在肿瘤中特异性表达 细胞与正常细胞相比; 以及用于治疗通过鉴定和分离上述氨基酸转运蛋白分子并鉴定能够抑制该分子的生物活性和/或表达的物质而获得的各种病原性病症如肿瘤（癌症）的药物。 进行了深入研究，以确定与细胞膜表面缔合或相互作用的肿瘤细胞膜表面分子4F2hc分子在未知氨基酸转运蛋白的活化中似乎起着重要作用。 结果，已经发现了编码新的氨基酸转运蛋白分子的基因，其介导各种中性氨基酸，各种药物或生理物质掺入细胞中，并且能够通过该分子抑制氨基酸的掺入的物质 从而也发现抑制肿瘤细胞的增殖。

公开(公告)号：US20050019868A1

公开(公告)日：2005-01-27

申请号：US10913073

申请日：2004-08-05

申请人： Hitoshi Endou ,  Yoshikatsu Kanai

发明人： Hitoshi Endou ,  Yoshikatsu Kanai

IPC分类号： A61K38/00 ,  C07K14/705 ,  G01N33/567 ,  C07H21/04

CPC分类号： C07K14/705 ,  A01K2217/05 ,  A61K38/00

摘要： A novel amino acid transporter molecule mediating transportation of amino acids, which are nutrients essentially required in the survival and proliferation of various normal cells constituting a living body and various pathology-associated abnormal cells such as tumor cells, into cells and being expressed specifically in tumor cells compared with normal cells; and drugs for treating various pathogenic conditions such as tumor (cancer) which are obtained by identifying and isolating the above amino acid transporter molecule and identifying a substance capable of inhibiting the biological activity and/or expression of this molecule. Intensive studies were made to identify a tumor cell membrane surface molecule associating or interacting with a cell membrane surface 4F2hc molecule seemingly playing an important role in the activation of an unknown amino acid transporter. As a result, a gene encoding the novel amino acid transporter molecule, which mediates the incorporation of various neutral amino acids, various drugs or physiological substances into cells, has been found out and a substance capable of inhibiting the incorporation of amino acids via this molecule and thus inhibiting the proliferation of tumor cells has been also found out.

公开(公告)号：US20050019812A1

公开(公告)日：2005-01-27

申请号：US10913263

申请日：2004-08-05

申请人： Hitoshi Endou ,  Yoshikatsu Kanai

发明人： Hitoshi Endou ,  Yoshikatsu Kanai

IPC分类号： C12N15/09 ,  A01K67/027 ,  A61K31/711 ,  A61K38/00 ,  A61K39/395 ,  A61K48/00 ,  A61P35/00 ,  C07K14/705 ,  C07K16/28 ,  C12N5/10 ,  C12N15/12 ,  C12P21/08 ,  C12Q1/02 ,  C12Q1/68 ,  C12R1/91 ,  G01N33/53 ,  G01N33/566 ,  G01N33/577 ,  C07H21/04 ,  G01N33/567

CPC分类号： C07K14/705 ,  A01K2217/05 ,  A61K38/00

摘要： A novel amino acid transporter molecule mediating transportation of amino acids, which are nutrients essentially required in the survival and proliferation of various normal cells constituting a living body and various pathology-associated abnormal cells such as tumor cells, into cells and being expressed specifically in tumor cells compared with normal cells; and drugs for treating various pathogenic conditions such as tumor (cancer) which are obtained by identifying and isolating the above amino acid transporter molecule and identifying a substance capable of inhibiting the biological activity and/or expression of this molecule. Intensive studies were made to identify a tumor cell membrane surface molecule associating or interacting with a cell membrane surface 4F2hc molecule seemingly playing an important role in the activation of an unknown amino acid transporter. As a result, a gene encoding the novel amino acid transporter molecule, which mediates the incorporation of various neutral amino acids, various drugs or physiological substances into cells, has been found out and a substance capable of inhibiting the incorporation of amino acids via this molecule and thus inhibiting the proliferation of tumor cells has been also found out.

公开(公告)号：US20120083588A1

公开(公告)日：2012-04-05

申请号：US12658612

申请日：2010-02-08

申请人： Hitoshi Endou ,  Yoshikatsu Kanai

发明人： Hitoshi Endou ,  Yoshikatsu Kanai

IPC分类号： C07K16/46

CPC分类号： C07K14/705 ,  A01K2217/05 ,  A61K38/00

摘要： The present invention relates to an amino acid transporter protein having the ability to mediate the transport of amino acids into a cell, a gene encoding the protein, an antibody having a reactivity with the protein, a cell which produces the antibody, related kits and methods.

摘要翻译： 本发明涉及具有介导氨基酸向细胞转运的能力的氨基酸转运蛋白，编码该蛋白的基因，与该蛋白具有反应性的抗体，产生该抗体的细胞，相关试剂盒和方法 。

公开(公告)号：US07943745B2

公开(公告)日：2011-05-17

申请号：US12295991

申请日：2007-04-05

申请人： Tomoyuki Tahara ,  Yoshikatsu Kanai ,  Hitoshi Endou ,  Shiro Kataoka ,  Kazumasa Hasegawa ,  Tetsuya Yoshino

发明人： Tomoyuki Tahara ,  Yoshikatsu Kanai ,  Hitoshi Endou ,  Shiro Kataoka ,  Kazumasa Hasegawa ,  Tetsuya Yoshino

IPC分类号： C12P21/08 ,  C12P21/04 ,  C07K16/00 ,  C07K17/00 ,  C07K17/14 ,  A61K39/395 ,  A61K39/00

CPC分类号： C07K16/2896 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/30 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/76

摘要： A human antibody or a functional fragment thereof having specific binding ability to CD98 which is derived from the cell membrane of cancer cells and is in the form of a complex with a protein having an amino acid transporter activity (for example, LAT1) is disclosed. This antibody binds to CD98 in the form of a dimer with LAT1 on the surface of cancer cells, specifically attacks cancer cells expressing CD98 via the immune system by ADCC or CDC, and further inhibits amino acid uptake of the cancer cells via LAT1, to suppress growth of the cancer cells. Accordingly, a preventive and therapeutic agent for cancer comprising this antibody or a fragment thereof, which acts on various cancers, is specific to cancer, and causes no side effect, is provided.

摘要翻译： 公开了具有来自癌细胞的细胞膜的与CD98特异性结合能力并与具有氨基酸转运蛋白活性的蛋白质（例如LAT1）形成复合物的形式的人抗体或其功能片段。 该抗体以癌细胞表面的LAT1二聚体形式结合CD98，特异性地通过ADCC或CDC通过免疫系统侵袭表达CD98的癌细胞，并进一步通过LAT1抑制癌细胞的氨基酸摄取，抑制 癌细胞的生长。 因此，提供了作用于各种癌症的该抗体或其片段的癌症的预防和治疗剂，其对癌症是特异性的，并且不产生副作用。

公开(公告)号：US20090312415A1

公开(公告)日：2009-12-17

申请号：US10579173

申请日：2004-11-11

申请人： Hitoshi Endou ,  Yoshikatsu Kanai ,  Richard J. Johnson ,  Karen Leigh Price

发明人： Hitoshi Endou ,  Yoshikatsu Kanai ,  Richard J. Johnson ,  Karen Leigh Price

IPC分类号： A61K31/343 ,  C12Q1/62 ,  C12Q1/02 ,  C12Q1/68 ,  A61K31/18

CPC分类号： G01N33/5061 ,  A61K31/00 ,  G01N33/5008 ,  G01N2500/00 ,  Y10T436/103332

摘要： It is intended to clarify a transportation system participating in the uric acid uptake in vascular smooth muscle cells (VSMCs) and provide a novel remedy, a preventive or a treating agent for vascular disorders, hypertension and renal disorders with the use of a drug participating in this transportation system. It is also intended to provide a novel screening system for a remedy, a preventive or a treating agent for vascular disorders, hypertension and renal disorders with the use of such a transportation system. Namely, a medicinal composition for healing, preventing or treating vascular disorders, hypertension and renal disorders which comprises a drug having an effect of inhibiting the uric acid uptake by a uric acid transporter URAT1 and a pharmaceutically acceptable carrier; and a method of screening a substance efficacious for healing, preventing or treating vascular disorders, hypertension and renal disorders which comprises using a cell line expressing URAT1 in the presence or absence of a test compound and assaying the uric acid uptake level, cell proliferation ability or the amount of a monocyte chemotactic factor produced by the cells.

摘要翻译： 旨在澄清参与血管平滑肌细胞（VSMC）中尿酸摄取的运输系统，并提供新的治疗方法，血管疾病，高血压和肾脏疾病的预防或治疗剂，使用药物参与 这个运输系统。 还旨在提供一种用于治疗的新型筛选系统，用于血管疾病，高血压和肾脏疾病的预防或治疗剂，其使用这种运输系统。 即，用于治疗，预防或治疗血管疾病，高血压和肾脏疾病的药物组合物，其包含具有抑制尿酸转运蛋白URAT1和药学上可接受的载体的尿酸摄取的作用的药物; 以及筛选对于治疗，预防或治疗血管疾病，高血压和肾脏疾病有效的物质的方法，其包括在存在或不存在测试化合物的情况下使用表达URAT1的细胞系，并测定尿酸摄取水平，细胞增殖能力或 由细胞产生的单核细胞趋化因子的量。

公开(公告)号：US07553642B2

公开(公告)日：2009-06-30

申请号：US10547975

申请日：2004-03-05

申请人： Hitoshi Endou ,  Yoshikatsu Kanai

发明人： Hitoshi Endou ,  Yoshikatsu Kanai

IPC分类号： G01N33/00 ,  C12P21/06 ,  C07K14/00

CPC分类号： C07K14/705

摘要： It is intended to provide amino acid transporters which act as a single molecule and transport neutral amino acids typified by branched amino acids, and genes thereof. A protein consisting of an amino acid sequence represented by SEQ ID NO:2, 4, 6 or 8 or an amino acid sequence derived from an amino acid sequence represented by SEQ ID NO:2, 4, 6 or 8 by deletion, substitution or addition of one to several amino acids, and being capable of sodium-independently transporting neutral amino acids typified by branched amino acids and analogs thereof as a single molecule. A gene which is a DNA consisting of a base sequence represented by SEQ ID NO:1, 3, 5 or 7 or a DNA hybridizable with it and encodes a protein capable of sodium-independently transporting branched amino acids as a single molecule.

摘要翻译： 本发明提供氨基酸转运体，其作为单一分子并以支链氨基酸为代表的中性氨基酸及其基因。 由SEQ ID NO：2,4,6或8所示的氨基酸序列组成的蛋白质或由SEQ ID NO：2,4,6或8所示的氨基酸序列衍生的氨基酸序列的缺失，取代或 加入一至几个氨基酸，并且能够以单独的分子将以支链氨基酸为代表的中性氨基酸和其类似物单独运输。 作为由SEQ ID NO：1,3,5或7所示的碱基序列组成的DNA的基因，或与其可杂交的DNA，并编码能够单独输送支链氨基酸作为单一分子的蛋白质。

公开(公告)号：US07332293B2

公开(公告)日：2008-02-19

申请号：US10912983

申请日：2004-08-05

申请人： Hitoshi Endou ,  Yoshikatsu Kanai

发明人： Hitoshi Endou ,  Yoshikatsu Kanai

IPC分类号： G01N33/53

CPC分类号： C07K14/705 ,  A01K2217/05 ,  A61K38/00

摘要： A novel amino acid transporter molecule mediating transportation of amino acids, which are nutrients essentially required in the survival and proliferation of various normal cells constituting a living body and various pathology-associated abnormal cells such as tumor cells, into cells and being expressed specifically in tumor cells compared with normal cells; and drugs for treating various pathogenic conditions such as tumor (cancer) which are obtained by identifying and isolating the above amino acid transporter molecule and identifying a substance capable of inhibiting the biological activity and/or expression of this molecule. Intensive studies were made to identify a tumor cell membrane surface molecule associating or interacting with a cell membrane surface 4F2hc molecule seemingly playing an important role in the activation of an unknown amino acid transporter. As a result, a gene encoding the novel amino acid transporter molecule, which mediates the incorporation of various neutral amino acids, various drugs or physiological substances into cells, has been found out and a substance capable of inhibiting the incorporation of amino acids via this molecule and thus inhibiting the proliferation of tumor cells has been also found out.

摘要翻译： 介导氨基酸运输的新型氨基酸转运蛋白分子，其是构成活体的各种正常细胞的存活和增殖以及各种病理学相关异常细胞如肿瘤细胞基本上需要的营养素，并且在肿瘤中特异性表达 细胞与正常细胞相比; 以及用于治疗通过鉴定和分离上述氨基酸转运蛋白分子并鉴定能够抑制该分子的生物活性和/或表达的物质而获得的各种病原性病症如肿瘤（癌症）的药物。 进行了深入研究，以确定与细胞膜表面缔合或相互作用的肿瘤细胞膜表面分子4F2hc分子在未知氨基酸转运蛋白的活化中似乎起着重要作用。 结果，已经发现了编码新的氨基酸转运蛋白分子的基因，其介导各种中性氨基酸，各种药物或生理物质掺入细胞中，并且能够通过该分子抑制氨基酸的掺入的物质 从而也发现抑制肿瘤细胞的增殖。