公开(公告)号：US20080305102A1

公开(公告)日：2008-12-11

申请号：US11993774

申请日：2006-06-23

申请人： Toshihiro Nakajima ,  Yukihiro Kato ,  Tadayuki Yamadera ,  Tetsuya Amano

发明人： Toshihiro Nakajima ,  Yukihiro Kato ,  Tadayuki Yamadera ,  Tetsuya Amano

IPC分类号： A61K39/395 ,  C07H21/00 ,  C07K16/18 ,  C07K2/00 ,  C12Q1/68 ,  G01N33/50 ,  A61K31/53 ,  C07D403/04 ,  C07D251/54 ,  A61P35/00 ,  A61K38/00 ,  A61K48/00

CPC分类号： G01N33/5011 ,  A01K2267/0325 ,  A61K31/53 ,  A61K31/7088 ,  A61K38/1709 ,  A61K38/53 ,  C12N9/93 ,  C12N15/1135 ,  C12N2310/11 ,  C12N2310/14 ,  G01N2500/00 ,  G01N2800/102

摘要： Inhibition of synoviolin function was found to activate the cancer-suppressing protein p53. Substances inhibiting the function of synoviolin are useful as cancer therapeutic agents. The inhibition of synoviolin function was also found to lead to the inhibition of p53 ubiquitination, increased activity of p53 phosphorylation proteins, and the like. Based on these findings, the present invention provides methods capable of efficiently screening for cancer therapeutic agents. Further, it was also found that regulation of the autoubiquitination of synoviolin protein suppresses the proliferation of rheumatoid arthritis synovial cells. Substances regulating the autoubiquitination of synoviolin protein are useful as anti-rheumatic agents. Moreover, the present invention provides methods of efficiently screening for anti-rheumatic agents.

摘要翻译： 发现滑膜蛋白功能的抑制活化了癌症抑制蛋白p53。 抑制滑膜素功能的物质可用作癌症治疗剂。 还发现滑膜蛋白功能的抑制导致p53泛素化的抑制，p53磷酸化蛋白的活性增加等。 基于这些发现，本发明提供能够有效筛选癌症治疗剂的方法。 此外，还发现调节滑膜蛋白自身泛素化抑制类风湿性关节炎滑膜细胞的增殖。 调节滑膜蛋白自身泛素化的物质可用作抗风湿药。 此外，本发明提供了有效筛选抗风湿剂的方法。

公开(公告)号：US20080274479A1

公开(公告)日：2008-11-06

申请号：US11628412

申请日：2005-06-02

申请人： Toshihiro Nakajima ,  Sayumi Toriyama ,  Tadayuki Yamadera ,  Tomohiko Ohta ,  Satoshi Yamasaki ,  Naoko Yagishita ,  Lei Zhang ,  Rie Ikeda ,  Takeshi Sasaki ,  Tetsuya Amano

发明人： Toshihiro Nakajima ,  Sayumi Toriyama ,  Tadayuki Yamadera ,  Tomohiko Ohta ,  Satoshi Yamasaki ,  Naoko Yagishita ,  Lei Zhang ,  Rie Ikeda ,  Takeshi Sasaki ,  Tetsuya Amano

IPC分类号： G01N33/53

CPC分类号： C12Q1/25 ,  G01N2333/9015 ,  G01N2500/02

摘要： The present invention relates to an assay method for determining a auto-ubiquitination activity of synoviolin, comprising reacting synoviolin and ubiquitin in a reaction system containing them and determining an amount of ubiquitin binding to synoviolin, to a method of screening a substance capable of regulating such an activity, and to a kit for auto-ubiquitination assay of synoviolin.

摘要翻译： 本发明涉及一种用于测定滑膜蛋白的自身泛素化活性的测定方法，包括使滑膜蛋白和泛素在含有它们的反应体系中反应并确定与滑膜蛋白结合的泛素的量，以筛选能够调节这种蛋白质的物质的方法 一种活性，以及​​用于滑膜蛋白自动泛素化测定的试剂盒。

公开(公告)号：US20090029929A1

公开(公告)日：2009-01-29

申请号：US10594146

申请日：2005-03-28

申请人： Toshihiro Nakajima ,  Kaneyuki Tsuchimochi ,  Naoko Yagishita ,  Satoshi Yamasaki ,  Yukihiro Kato ,  Tetsuya Amano ,  Kaori Tamitsu

发明人： Toshihiro Nakajima ,  Kaneyuki Tsuchimochi ,  Naoko Yagishita ,  Satoshi Yamasaki ,  Yukihiro Kato ,  Tetsuya Amano ,  Kaori Tamitsu

IPC分类号： A61K31/711 ,  A61K48/00 ,  A61P19/02 ,  A61P21/00 ,  A61P25/00 ,  A61P25/16 ,  A61P25/28 ,  A61P29/00 ,  A61P35/00 ,  C12N15/12 ,  C12N5/10

CPC分类号： C12N15/113 ,  A61K31/7088 ,  A61K48/00 ,  C12N2310/13

摘要： The present invention provides a decoy nucleic acid for the Synoviolin gene promoter. Also provided is the decoy nucleic acid can inhibit the promoter activity by binding to the transcription factor of the Synoviolin gene promoter. It also provides a decoy nucleic acid as expressed in (a) a decoy nucleic acid consisting of a nucleotide sequence as shown in SEQ ID NO: 11 or 12; and it also provides (b) a decoy nucleic acid consisting of a nucleotide sequence as shown in SEQ ID NO: 11 or 12 having deletion, substitution or addition of one or several nucleotides and has the function of inhibiting Synoviolin gene promoter activity.

摘要翻译： 本发明提供了用于滑膜炎基因启动子的诱饵核酸。 还提供了诱饵核酸可以通过与滑膜素基因启动子的转录因子结合来抑制启动子活性。 它还提供如（a）由如SEQ ID NO：11或12所示的核苷酸序列组成的诱饵核酸所表达的诱饵核酸; 并且还提供（b）由SEQ ID NO：11或12所示的具有缺失，取代或添加一个或几个核苷酸的核苷酸序列组成的具有抑制滑膜素基因启动子活性的功能的诱饵核酸。

公开(公告)号：US20070238677A1

公开(公告)日：2007-10-11

申请号：US10592918

申请日：2005-03-16

申请人： Toshihiro Nakajima ,  Tetsuya Amano ,  Satoshi Yamasaki ,  Naoko Yagishita ,  Takeshi Sasaki ,  Yukihiro Kato ,  Lei Zhang

发明人： Toshihiro Nakajima ,  Tetsuya Amano ,  Satoshi Yamasaki ,  Naoko Yagishita ,  Takeshi Sasaki ,  Yukihiro Kato ,  Lei Zhang

IPC分类号： A61K31/7088 ,  A61K45/00 ,  A61K48/00 ,  A61P19/02 ,  A61P29/00 ,  A61P35/00 ,  C12N15/09 ,  C12N5/00

CPC分类号： C12N15/113 ,  A61K48/00 ,  C12N2310/14

摘要： The present invention provides a pharmaceutical composition containing a substance which inhibits the proliferation of synovial tissue or synovial cells and the interleukin-6 production. It also provides a pharmaceutical composition for inhibiting the proliferation of synovial tissue or synovial cells and the interleukin-6 production, which is useful for diagnosing and treating at least one selected from the group consisting of rheumatoid arthritis, fibrosis, arthritis, cancers, and cerebral neural diseases. In addition, it provides a method for inhibiting the proliferation of synovial cells and the interleukin-6 production by inhibiting the expression of hsHRD3 in synovial cells.

摘要翻译： 本发明提供含有抑制滑膜组织或滑膜细胞增殖的物质和白细胞介素-6产生的药物组合物。 它还提供用于抑制滑膜组织或滑膜细胞增殖的药物组合物和白细胞介素-6产生，其可用于诊断和治疗选自以下的至少一种：类风湿性关节炎，纤维化，关节炎，癌症和脑 神经疾病 另外，通过抑制滑膜细胞中hsHRD3的表达，提供了抑制滑膜细胞增殖和白细胞介素-6产生的方法。

公开(公告)号：US07632507B2

公开(公告)日：2009-12-15

申请号：US10275602

申请日：2001-12-21

申请人： Toshihiro Nakajima ,  Tetsuya Amano

发明人： Toshihiro Nakajima ,  Tetsuya Amano

IPC分类号： A61K39/00 ,  A61K38/00 ,  A01N37/18 ,  C07K1/00 ,  C07K14/00 ,  C07K17/00

CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K67/0276 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0325 ,  A61K38/00 ,  C12N9/104 ,  C12N9/93 ,  C12Y203/02 ,  C12Y603/02 ,  G01N33/564 ,  G01N33/574 ,  G01N2500/00

摘要： The present invention discloses a novel protein called Synoviolin and a gene that encodes it. This protein is expressed specifically by synovial tissue and also accompanies the presence of an auto-antibody that recognizes this protein in rheumatoid arthritis (RA) patients. The protein according to the present invention and its antibody can be expected to be used as specific diagnostic markers for RA. In addition, the gene or protein according to the present invention may be used to permit the screening of drugs to treat RA. Moreover, the present invention provides synoviolin gene transgenic animals. The transgenic animals according to the present invention can be used as RA model animals in the development of pharmaceuticals to treat RA.

摘要翻译： 本发明公开了一种称为Synoviolin的新型蛋白质及其编码基因。 该蛋白质通过滑膜组织特异性表达，并且还伴随着在类风湿性关节炎（RA）患者中识别该蛋白质的自身抗体的存在。 根据本发明的蛋白质及其抗体可以预期用作RA的特异性诊断标记物。 此外，根据本发明的基因或蛋白质可用于允许筛选药物以治疗RA。 此外，本发明提供滑膜素基因转基因动物。 根据本发明的转基因动物可用作RA模型动物，用于开发药物以治疗RA。

公开(公告)号：US20090276863A1

公开(公告)日：2009-11-05

申请号：US11631040

申请日：2005-07-01

申请人： Toshihiro Nakajima ,  Naoko Yagishita ,  Tetsuya Amano

发明人： Toshihiro Nakajima ,  Naoko Yagishita ,  Tetsuya Amano

IPC分类号： A61K49/00 ,  A01K67/027 ,  C12N5/10 ,  C12N15/09 ,  G01N33/567 ,  G01N33/00 ,  C07K14/00 ,  A61K38/16 ,  C07K16/00 ,  A61P35/00

CPC分类号： C07K14/475 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/035 ,  A61K38/00 ,  G01N33/5044

摘要： The present inventors discovered that knockout mice whose S1-5 gene function is lost develop age-related diseases or symptoms. Histological analysis in such knockout mice revealed that bone mineral content, bone mineral density, and bone strength were decreased, and the number of osteoclasts in bone tissues was increased. Analysis of osteoclast-forming ability using bone marrow cells derived from the knockout mice revealed that osteoclast-forming ability is enhanced and osteoclasts are larger in the knockout mice than in wildtype mice. When purified S1-5 protein was added to this in vitro system, osteoclast-forming ability was inhibited.

摘要翻译： 本发明人发现S1-5基因功能丧失的敲除小鼠发生与年龄相关的疾病或症状。 在这种敲除小鼠中的组织学分析显示，骨矿物质含量，骨矿物质密度和骨强度降低，骨组织中破骨细胞数量增加。 使用衍生自敲除小鼠的骨髓细胞破骨细胞形成能力的分析显示，在野生型小鼠中，敲除小鼠的破骨细胞形成能力增强，破骨细胞较大。 当纯化的S1-5蛋白加入体外时，破骨细胞形成能力受到抑制。

公开(公告)号：US20070275887A1

公开(公告)日：2007-11-29

申请号：US10576281

申请日：2004-10-20

申请人： Toshihiro Nakajima ,  Tetsuya Amano ,  Lei Zhang ,  Rie Ikeda ,  Satoshi Yamasaki ,  Naoko Yagishita

发明人： Toshihiro Nakajima ,  Tetsuya Amano ,  Lei Zhang ,  Rie Ikeda ,  Satoshi Yamasaki ,  Naoko Yagishita

IPC分类号： A61K38/55 ,  A61P25/28

CPC分类号： C12N15/1137 ,  A61K31/7088 ,  A61K45/06 ,  C12N2310/14 ,  A61K2300/00

摘要： The present invention provides a method for inhibiting secretase activity. A method for promoting the sensitivity of a secretase inhibitor, a method for binding synoviolin to Herp (homocysteine-inducible endoplasmic reticulum stress-inducible ubiquitin-like domain member 1), or the like is employed to inhibit secretase activity.

摘要翻译： 本发明提供抑制分泌酶活性的方法。 用于促进分泌酶抑制剂的敏感性的方法，将滑膜蛋白与Herp结合的方法（同型半胱氨酸诱导型内质网应激诱导型泛素样结构域成员1）等用于抑制分泌酶活性。

公开(公告)号：US20070134720A1

公开(公告)日：2007-06-14

申请号：US10568913

申请日：2004-08-20

申请人： Toshihiro Nakajima ,  Tetsuya Amano ,  Lei Zhang ,  Rie Ikeda ,  Satoshi Yamasaki ,  Naoko Yagishita ,  Hiromitsu Yokohama ,  Motoji Kogushi

发明人： Toshihiro Nakajima ,  Tetsuya Amano ,  Lei Zhang ,  Rie Ikeda ,  Satoshi Yamasaki ,  Naoko Yagishita ,  Hiromitsu Yokohama ,  Motoji Kogushi

IPC分类号： A61K38/48 ,  G01N33/53 ,  C12Q1/37

CPC分类号： A61K38/16 ,  A61K38/005 ,  C12Q1/25 ,  C12Q1/26 ,  G01N2333/90245 ,  G01N2500/00

摘要： The present invention provides methods for evaluating the regulation on prolyl 4-hydroxylase activity. The present invention also provides screening methods using the evaluation methods. Furthermore, the present invention provides methods of screening for compounds that are useful for treating or preventing fibrosis or rheumatoid arthritis. The present invention relates to methods for detecting regulatory activity on the synoviolin ubiquitination of prolyl 4-hydroxylase α subunit (P4HA1). It also relates to methods of screening for compounds with regulatory effect on the ubiquitination activity of synoviolin on P4HA1 based on these methods. Compounds discovered in the screening are useful for treating and/or preventing diseases caused by abnormalities in the prolyl 4-hydroxylase activity, such as fibrosis and rheumatoid arthritis.

摘要翻译： 本发明提供了评估脯氨酰4-羟化酶活性调节的方法。 本发明还提供了使用评价方法的筛选方法。 此外，本发明提供筛选可用于治疗或预防纤维化或类风湿性关节炎的化合物的方法。 本发明涉及检测脯氨酰4-羟化酶α亚基（P4HA1）的滑膜蛋白泛素化的调节活性的方法。 它还涉及基于这些方法筛选对P4HA1上滑膜素泛素化活性具有调节作用的化合物的方法。 在筛选中发现的化合物可用于治疗和/或预防由脯氨酰4-羟化酶活性异常引起的疾病，例如纤维化和类风湿性关节炎。

公开(公告)号：US20100058488A1

公开(公告)日：2010-03-04

申请号：US11994327

申请日：2005-12-28

申请人： Toshihiro Nakajima ,  Naoko Yagishita ,  Tetsuya Amano

发明人： Toshihiro Nakajima ,  Naoko Yagishita ,  Tetsuya Amano

IPC分类号： A01K67/033 ,  C12N5/078 ,  C12N5/071 ,  A01K67/00 ,  G01N33/53 ,  C07K14/00 ,  C07K2/00 ,  A61K38/16 ,  C07K16/00 ,  A61P35/00 ,  A61P25/28

CPC分类号： C07K14/47 ,  A01K67/027 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0368 ,  A61K38/00 ,  C12N15/8509

摘要： The present inventors discovered that knockout mice whose S1-5 gene function is lost develop age-related diseases or symptoms. In such knockout mice, bone mineral content, bone mineral density, and bone strength were found to be decreased, and the number of osteoclasts in bone tissues was found to be increased. Analysis of osteoclast-forming ability using bone marrow cells derived from the knockout mice revealed that osteoclast-forming ability is enhanced and osteoclasts are larger in the knockout mice than in wildtype mice. When purified S1-5 protein was added to this in vitro system, osteoclast-forming ability was inhibited. Furthermore, administration of purified S1-5 protein to osteoporotic model mice showed that this protein has the effect of improving osteoporosis. The above findings demonstrate that S1-5 protein is useful for treating and preventing age-related diseases such as osteoporosis.

摘要翻译： 本发明人发现S1-5基因功能丧失的敲除小鼠发生与年龄相关的疾病或症状。 在这样的敲除小鼠中，发现骨矿物质含量，骨矿物质密度和骨强度降低，并且发现骨组织中破骨细胞的数量增加。 使用衍生自敲除小鼠的骨髓细胞破骨细胞形成能力的分析显示，在野生型小鼠中，敲除小鼠的破骨细胞形成能力增强，破骨细胞较大。 当纯化的S1-5蛋白加入体外时，破骨细胞形成能力受到抑制。 此外，将纯化的S1-5蛋白施用于骨质疏松模型小鼠显示该蛋白质具有改善骨质疏松症的作用。 以上研究结果表明，S1-5蛋白可用于治疗和预防年龄相关疾病如骨质疏松症。

公开(公告)号：US20080305499A1

公开(公告)日：2008-12-11

申请号：US11631283

申请日：2005-07-04

申请人： Toshihiro Nakajima ,  Satoshi Yamasaki ,  Lei Zhang ,  Tetsuya Amano

发明人： Toshihiro Nakajima ,  Satoshi Yamasaki ,  Lei Zhang ,  Tetsuya Amano

IPC分类号： G01N33/567 ,  C07K16/40 ,  C12N5/16 ,  C12P21/08 ,  C12N9/10

CPC分类号： C12Q1/25 ,  A61K2039/505 ,  C07K16/40 ,  C07K2317/76

摘要： The present invention relates to an antibody against synoviolin or a fragment thereof for providing a monoclonal antibody capable of recognizing a part of synoviolin, which monoclonal antibody is capable of inhibiting the auto-ubiquitination of synoviolin.

摘要翻译： 本发明涉及用于提供能够识别部分滑膜蛋白的单克隆抗体的抗滑膜炎抗体或其片段，该单克隆抗体能够抑制滑膜素的自身泛素化。