公开(公告)号：US09156912B2

公开(公告)日：2015-10-13

申请号：US13139089

申请日：2009-11-04

申请人： Kouji Matsushima ,  Satoshi Ueha ,  Yusuke Shono

发明人： Kouji Matsushima ,  Satoshi Ueha ,  Yusuke Shono

IPC分类号： A61K39/395 ,  A61K35/28 ,  C07K16/28 ,  A61K45/06 ,  A61K39/00

CPC分类号： C07K16/2812 ,  A61K39/395 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/2815 ,  A61K2300/00

摘要： The object of the invention is to provide an immunological reconstitution promoter or a prophylactic agent for infections for use in allogeneic hematopoietic stem cell transplantation therapy for tumors. The promoter or prophylactic agent enables the amelioration of delayed immune reconstitution or the prevention of infection following transplantation, while maintaining the GVT effect of allogeneic hematopoietic stem cell transplantation. Specifically, in a transplant patient in whom immune reconstitution is delayed, such reconstitution can be promoted by administering, at an early stage following transplantation, a substance capable of depleting CD4+ cells. Early completion of infection management in the patient and improvement in the survival rate are anticipated as a result. In addition, the risk of complications associated with allogeneic hematopoietic stem cell transplantation is reduced, enabling more widespread use of this therapy.

摘要翻译： 本发明的目的是提供用于肿瘤的同种异体造血干细胞移植治疗的免疫重建促进剂或用于感染的预防剂。 促进剂或预防剂能够改善延迟免疫重建或移植后预防感染，同时保持同种异体造血干细胞移植的GVT作用。 具体地说，在免疫重建延迟的移植患者中，可以通过在移植后的早期施用能够消耗CD4 +细胞的物质来促进这种重建。 因此预计早期完成患者感染管理，提高生存率。 此外，与同种异体造血干细胞移植相关的并发症的风险降低，可以更广泛地使用该疗法。

公开(公告)号：US20090117538A1

公开(公告)日：2009-05-07

申请号：US10581211

申请日：2004-06-04

申请人： Shin-ichi Hashimoto ,  Kouji Matsushima ,  Sumio Sugano

发明人： Shin-ichi Hashimoto ,  Kouji Matsushima ,  Sumio Sugano

IPC分类号： C12Q1/68 ,  C07H21/04 ,  C12N15/79 ,  C12N5/10 ,  C12P21/02 ,  C12P19/34 ,  C07K14/00 ,  C07K16/00

CPC分类号： C12Q1/6855 ,  C12N15/1096

摘要： The present invention provides methods for providing as tags the nucleotide sequences at the 5′ end of mRNA. The method of the present invention comprises the step of synthesizing cDNA using, as a template, mRNA whose CAP structure is linked with a IIs linker having a type IIs endonuclease recognition sequence. Tags including the nucleotide sequence from the 5′ end of mRNA are generated by reacting the type IIs endonuclease to cDNA. Tags can be generated from all mRNA, independently of their nucleotide sequences. Methods for identifying transcriptional start sites and primers for full-length cDNA synthesis are provided based on the nucleotide sequence information of tags of the present invention.

摘要翻译： 本发明提供了在mRNA的5'末端提供核苷酸序列作为标签的方法。 本发明的方法包括使用CAP结构与具有II型内切核酸酶识别序列的IIs连接子连接的mRNA作为模板来合成cDNA的步骤。 通过将II型核酸内切酶与cDNA反应产生包括mRNA的5'末端的核苷酸序列的标签。 标签可以从所有mRNA生成，与其核苷酸序列无关。 基于本发明的标签的核苷酸序列信息提供用于鉴定全长cDNA合成的转录起始位点和引物的方法。

公开(公告)号：US06998407B2

公开(公告)日：2006-02-14

申请号：US10716652

申请日：2003-11-18

申请人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

发明人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

IPC分类号： A61K31/36 ,  A61K31/343 ,  C07D307/79 ,  C07D317/60

CPC分类号： C07D235/06 ,  C07D209/08 ,  C07D249/18 ,  C07D263/56 ,  C07D307/79 ,  C07D317/68 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D417/12

摘要： Chemical compounds which are antagonists of Monocyte Chemoattractant Protein-1 (MCP-1) function, pharmaceutical compositions comprising these compounds, methods of treatment employing these compounds and compositions, and processes for preparing these compounds. The compounds are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection.

摘要翻译： 作为单核细胞趋化蛋白-1（MCP-1）功能拮抗剂的化合物，包含这些化合物的药物组合物，使用这些化合物和组合物的治疗方法，以及制备这些化合物的方法。 该化合物可用于预防或治疗慢性或急性炎性或自身免疫疾病，特别是与异常淋巴细胞或单核细胞积累相关的疾病，如关节炎，哮喘，动脉粥样硬化，糖尿病性肾病，炎性肠病，克罗恩病，多发性硬化，肾炎， 胰腺炎，肺纤维化，牛皮癣，再狭窄和移植排斥。

公开(公告)号：US06992086B2

公开(公告)日：2006-01-31

申请号：US10716363

申请日：2003-11-17

申请人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

发明人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

IPC分类号： A61K31/496 ,  A61K31/437 ,  C07D498/04 ,  C07D471/04 ,  A61P37/00

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5513 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention relates to chemical compounds, pharmaceutical compositions comprising said compounds, uses of said compounds and compositions, methods of treatment employing said compounds and compositions, and processes for preparing said compounds. Specifically, this invention relates to novel compounds which are antagonists of MCP-1 function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection. More specifically, the invention is related to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases.

公开(公告)号：US06677365B2

公开(公告)日：2004-01-13

申请号：US10106881

申请日：2002-03-25

申请人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

发明人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

IPC分类号： A61K3142

CPC分类号： C07D235/06 ,  C07D209/08 ,  C07D249/18 ,  C07D263/56 ,  C07D307/79 ,  C07D317/68 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D417/12

摘要： Chemical compounds which are antagonists of Monocyte Chemoattractant Protein-1 (MCP-1) function, pharmaceutical compositions comprising these compounds, methods of treatment employing these compounds and compositions, and processes for preparing these compounds. The compounds are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection.

公开(公告)号：US06475741B1

公开(公告)日：2002-11-05

申请号：US10037218

申请日：2001-11-09

申请人： Kouji Matsushima ,  Teizo Yoshimura ,  Edward J. Leonard ,  Joost Oppenheim ,  Ettore Appella ,  Stephen D. Showalter

发明人： Kouji Matsushima ,  Teizo Yoshimura ,  Edward J. Leonard ,  Joost Oppenheim ,  Ettore Appella ,  Stephen D. Showalter

IPC分类号： C12Q168

CPC分类号： C07K14/5421 ,  A61K38/00 ,  C07K16/244 ,  Y10S435/81 ,  Y10S514/885 ,  Y10S930/12

摘要： An isolated, synthetic preparation of a novel neutrophil-specific chemotactic factor (NCF), monoclonal antibodies having specific binding affinity for NCF and a clone containing the complete cDNA coding sequence for NCF are disclosed.

摘要翻译： 公开了一种新型嗜中性粒细胞特异性趋化因子（NCF）的分离合成制剂，对NCF具有特异性结合亲和力的单克隆抗体和含NCF完整cDNA编码序列的克隆。

公开(公告)号：US5646117A

公开(公告)日：1997-07-08

申请号：US433519

申请日：1995-07-12

申请人： Kouji Matsushima ,  Masanobu Naruto

发明人： Kouji Matsushima ,  Masanobu Naruto

IPC分类号： A61K38/00 ,  A61P1/00 ,  A61P1/04 ,  A61P17/00 ,  C07K14/52 ,  A61K38/19

CPC分类号： C07K14/523 ,  A61K38/00

摘要： A therapeutic agent for treating wounds having properties and actions different from those of growth factors and proteins inducing growth factors, which have strong therapeutic effect is disclosed. The therapeutic agent for treating wounds according to the present invention comprises monocyte chemotactic and activating factor or a variation thereof having a monocyte-attracting property or a derivative of said monocyte chemotactic and activating factor or said variation thereof.

摘要翻译： PCT No.PCT / JP94 / 01512 Sec。 371日期：1995年7月12日 102（e）日期1995年7月12日PCT 1994年9月13日PCT PCT。 公开号WO95 / 07710 日期：1995年3月23日公开了具有强效治疗作用的具有不同于生长因子和诱导生长因子的蛋白质的性质和作用的伤口的治疗剂。 根据本发明的治疗伤口的治疗剂包含单核细胞趋化性和活化因子或其单核细胞吸引性的变体或所述单核细胞趋化性和激活因子的衍生物或其变化。

公开(公告)号：US20110081370A1

公开(公告)日：2011-04-07

申请号：US11992880

申请日：2006-09-28

申请人： Arya Biragyn ,  Kouji Matsushima ,  Dolgor Bataar

发明人： Arya Biragyn ,  Kouji Matsushima ,  Dolgor Bataar

IPC分类号： A61K39/385 ,  A61K38/00 ,  A61P37/00 ,  A61P31/12 ,  A61P35/00

CPC分类号： A61K38/465 ,  A61K38/195 ,  A61K38/45 ,  A61K45/06 ,  A61K47/6415 ,  A61K47/642 ,  C07K14/521 ,  C07K14/523 ,  C07K14/7158 ,  C07K2319/55 ,  C12N9/1077 ,  C12N9/22 ,  C12Y204/02036 ,  C12Y301/27 ,  C12Y301/27005

摘要： The instant invention provides methods and compositions for modulation of the immune system. Specifically, the invention provides methods and compositions for increasing T cell mediated immune response useful in the treatment of cancer and chronic infection.

摘要翻译： 本发明提供了用于调节免疫系统的方法和组合物。 具体地，本发明提供了用于增加可用于治疗癌症和慢性感染的T细胞介导的免疫应答的方法和组合物。

公开(公告)号：US20090214587A1

公开(公告)日：2009-08-27

申请号：US11576829

申请日：2005-10-11

申请人： Michinori Kohara ,  Kyosuke Mizuno ,  Hisatoshi Shida ,  Kouji Matsushima ,  Koichi Morita ,  Minoru Kidokoro ,  Yukie Sameshima

发明人： Michinori Kohara ,  Kyosuke Mizuno ,  Hisatoshi Shida ,  Kouji Matsushima ,  Koichi Morita ,  Minoru Kidokoro ,  Yukie Sameshima

IPC分类号： A61K39/215 ,  C12N7/00

CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/215 ,  A61K2039/5256 ,  C07K14/005 ,  C12N7/00 ,  C12N2710/24143 ,  C12N2770/20022 ,  C12N2770/20034 ,  C12N2830/15

摘要： The present invention provides a recombinant virus which is efficacious and highly safe in preventing the onset of SARS infection and a vaccine for SARS coronavirus containing the same. The recombinant virus of the invention can express a SARS coronavirus gene.

摘要翻译： 本发明提供一种在预防SARS感染发作中有效和高度安全的重组病毒，以及含有该SARS冠状病毒的疫苗。 本发明的重组病毒可以表达SARS冠状病毒基因。

公开(公告)号：US20090081693A1

公开(公告)日：2009-03-26

申请号：US12191213

申请日：2008-08-13

申请人： Kouji MATSUSHIMA ,  Yuya Terashima

发明人： Kouji MATSUSHIMA ,  Yuya Terashima

IPC分类号： G01N33/53

CPC分类号： C07K14/521

摘要： Concerning intracellular signal transduction mechanism, there has been drawn a novel hypothesis that, even in the case where phosphorylation does not occur in the intracellular C-terminal domain of a receptor, an unknown molecule associates with the Pro-C terminal domain of a G protein-coupled receptor for each chemokine and thus leukocyte chemotaxis depending on the receptor is controlled. To examine this hypothesis and clarify therapeutic targets in inflammatory diseases as well as other various diseases, attempts are made to search for a CCR2-binding protein.As a result, a novel cytoplasmic protein associating directly and specifically with the Pro-12-C-terminal domain of CCR2 is found out and it is clarified that this protein forms clusters with CCR2 after stimulation with CCL2. Thus, it is confirmed that there is a novel signal transduction system in the G protein relating signal transduction in the CCL2-CCR2 pathway. It is also found out that this novel protein associates with the intracellular C-terminal domain of a receptor CCR5 too.

摘要翻译： 关于细胞内信号转导机制，已经出现了一种新颖的假说，即使在受体的细胞内C-末端结构域中不发生磷酸化的情况下，未知分子与G蛋白的Pro-C末端结构域相关联 每个趋化因子的偶联受体，因此取决于受体的白细胞趋化性被控制。 为了检查这一假设并阐明炎性疾病以及其他各种疾病的治疗靶点，尝试寻找CCR2结合蛋白。 结果发现与CCR2的Pro-12-C-末端结构域直接和特异性结合的新型细胞质蛋白，并且阐明了这种蛋白质在用CCL2刺激后与CCR2形成簇。 因此证实在G蛋白中有一个新的信号转导系统与CCL2-CCR2通路中的信号转导相关。 还发现这种新型蛋白质也与受体CCR5的胞内C末端结构域结合。