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公开(公告)号:US20070280951A1
公开(公告)日:2007-12-06
申请号:US10582304
申请日:2004-12-10
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。
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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。
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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。
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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
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。
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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。
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公开(公告)号:US08946386B2
公开(公告)日:2015-02-03
申请号:US10574045
申请日:2004-09-29
申请人: Kouji Matsushima , Shinichi Hashimoto , Masayuki Tsuchiya , Yuichi Hirata , Kenji Yoshida , Kazuyuki Ojima
发明人: Kouji Matsushima , Shinichi Hashimoto , Masayuki Tsuchiya , Yuichi Hirata , Kenji Yoshida , Kazuyuki Ojima
IPC分类号: A61K38/17 , C07K14/705 , A61K31/00 , G01N33/564 , G01N33/566
CPC分类号: C07K14/705 , A61K31/00 , G01N33/564 , G01N33/566 , G01N2500/00
摘要: Purified immunocytes were analyzed for expression frequencies, and the NKIR gene expressed specifically in natural killer (NK) cells was successfully identified. The NKIR gene encodes a receptor. Agonists and antagonists for the receptor can be identified by using the receptor.
摘要翻译: 分析纯化的免疫细胞的表达频率,并且成功鉴定了在自然杀伤(NK)细胞中特异表达的NKIR基因。 NKIR基因编码受体。 用于受体的激动剂和拮抗剂可以通过使用受体来鉴定。
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公开(公告)号:US08257703B2
公开(公告)日:2012-09-04
申请号:US12727162
申请日:2010-03-18
IPC分类号: A61K39/395
CPC分类号: C07K16/3084 , C07K16/00 , C07K2317/21 , C07K2317/52 , C07K2317/734 , G01N33/6854 , G01N33/686
摘要: IgM can be obtained in the form of a pentamer by placing the genes encoding the H, L, and J chains on the same vector to transform appropriate host cells. The gene encoding the J chain may be introduced by co-transfection. When no J chain is expressed, the IgM is produced as a hexamer. The transformants obtained according to the present invention achieve a high yield of IgM. The present invention also provides methods which enable separation and quantification of polymeric IgM.
摘要翻译: 通过将编码H,L和J链的基因置于相同载体上以转化合适的宿主细胞,可以以五聚体的形式获得IgM。 编码J链的基因可以通过共转染来引入。 当没有J链表达时,IgM作为六聚体产生。 根据本发明获得的转化体获得高产量的IgM。 本发明还提供能够分离和定量聚合物IgM的方法。
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公开(公告)号:US20120156724A1
公开(公告)日:2012-06-21
申请号:US13329658
申请日:2011-12-19
申请人: Yasufumi Kikuchi , Shinsuke Uno , Yasuko Kinoshita , Shigeyuki Iijima , Naoshi Fukushima , Masayuki Tsuchiya
发明人: Yasufumi Kikuchi , Shinsuke Uno , Yasuko Kinoshita , Shigeyuki Iijima , Naoshi Fukushima , Masayuki Tsuchiya
CPC分类号: C07K16/2803 , C07K2317/24 , C07K2317/50 , C07K2317/73
摘要: The present invention relates to humanized antibodies binding to CD47; diabodies binding to human CD47, characterized in that a disulfide bond exists between diabody-forming fragments; genes encoding any one of said antibodies; vectors containing said genes; host cells containing said vectors; processes for preparing antibodies comprising the step of culturing said host cells; and therapeutic agents for hematological disorders comprising said antibodies.
摘要翻译: 本发明涉及与CD47结合的人源化抗体; 结合人CD47的双抗体,其特征在于二糖键存在于形成双抗体的片段之间; 编码任何一种所述抗体的基因; 含有所述基因的载体; 含有所述载体的宿主细胞; 制备抗体的方法包括培养所述宿主细胞的步骤; 和包含所述抗体的血液病症治疗剂。
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公开(公告)号:US08008076B2
公开(公告)日:2011-08-30
申请号:US11587701
申请日:2005-04-27
申请人: Masayuki Tsuchiya , Masami Suzuki , Kenji Yoshida , Etsuko Fujii , Miho Watanabe , Koichi Matsubara , Yu Jau Chen , Juliana Sim
发明人: Masayuki Tsuchiya , Masami Suzuki , Kenji Yoshida , Etsuko Fujii , Miho Watanabe , Koichi Matsubara , Yu Jau Chen , Juliana Sim
CPC分类号: A01K67/027 , A01K2267/01 , A61K35/16 , C07K16/00 , C07K16/30
摘要: An objective of the present invention is to facilitate the acquisition of antibody-producing cells that are infiltrating virus-infected cells, cancer cells, abnormal cells forming a benign hyperplasia, and the like, and to improve the efficiency of the production of antibodies as well as nucleic acids encoding them from the antibody-producing cells.The present inventors discovered that, when cancer tissues comprising infiltrating lymphocytes are transplanted into highly immunodeficient animals that do not have T cells, B cells, and NK cells and further exhibit a low IFN production ability, the differentiation and proliferation of infiltrating lymphocytes are unexpectedly promoted, and the number of plasma cells that produce antibodies recognizing cancer tissues increases dramatically, plasma cells can be separated easily, and antibodies or nucleic acids encoding them can be easily prepared from the plasma cells.
摘要翻译: 本发明的目的是便于获得渗透病毒感染细胞的抗体产生细胞,癌细胞,形成良性增生的异常细胞等,以及提高抗体生产的效率 作为从抗体产生细胞编码它们的核酸。 本发明人发现,当将包含浸润性淋巴细胞的癌组织移植到不具有T细胞,B细胞和NK细胞的高度免疫缺陷的动物中并且进一步表现出低的IFN产生能力时,意外地促进了浸润性淋巴细胞的分化和增殖 并且产生识别癌组织的抗体的浆细胞的数量急剧增加,可以容易地分离浆细胞,并且可以容易地从浆细胞制备抗体或编码它们的核酸。
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公开(公告)号:US08008073B2
公开(公告)日:2011-08-30
申请号:US12874872
申请日:2010-09-02
CPC分类号: C07K16/28 , C07K2317/24 , C07K2317/34 , C07K2317/565 , C07K2317/622 , C07K2317/626 , C07K2317/75
摘要: Anti-human Mpl antibodies were isolated and purified. Anti-human Mpl diabodies and anti-human Mpl sc(Fv)2 were prepared using genetic engineering techniques and anti-human Mpl sc(Fv)2 was also humanized. The diabodies and sc(Fv)2 were assayed for TPO-like agonistic activity, and were found to have activities higher than those of anti-human Mpl antibodies, or activities equivalent to or higher than those of naturally-occurring human TPO ligand.
摘要翻译: 分离纯化抗人Mpl抗体。 使用遗传工程技术制备抗人Mpl双抗体和抗人Mpl sc(Fv)2,抗人Mpl sc(Fv)2也被人源化。 测定双抗体和sc(Fv)2的TPO样激动活性,发现其活性高于抗人Mpl抗体的活性,或与天然存在的人TPO配体相当或更高的活性。
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