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公开(公告)号：US20070202501A1
公开(公告)日：2007-08-30
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
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：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：US07993642B2
公开(公告)日：2011-08-09
申请号：US10551504
申请日：2004-12-10
IPC分类号： A61K39/395 , C12P21/08 , C07K16/00
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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公开(公告)号：US5856135A
公开(公告)日：1999-01-05
申请号：US553501
申请日：1996-02-20
申请人： Masayuki Tsuchiya , Koh Sato , Yuichi Hirata
发明人： Masayuki Tsuchiya , Koh Sato , Yuichi Hirata
CPC分类号： C07K16/00 , C07K16/248 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2319/00
摘要： A reshaped antibody comprising:(A) L chains comprising:(1) a human C region, and(2) an L chain V region comprising human L chain FRs and L chain CDRs of a mouse monoclonal antibody; and(B) H chains comprising:(1) a human H chain C region, and(2) an H chain V region comprising human H chain FRs, and H chain cDRs of a mouse monoclonal antibody to human IL-6. Since the major portions of the reshaped human antibody are derived from human, and the mouse CDRs are less immunogenic, then the present reshaped human antibody is less immunogenic, and therefore inhibits information transfer by IL-6, and is promising as a therapeutic agent for diseases caused by IL-6.
摘要翻译： PCT No.PCT / JP94 / 00859 Sec。 371日期1996年2月20日 102（e）日期1996年2月20日PCT 1994年5月30日PCT PCT。 公开号WO94 / 28159 日期：1994年12月8日一种重整抗体，其包含：（A）L链，其包含：（1）人C区，和（2）包含小鼠单克隆抗体的人L链FR和L链CDR的L链V区; 和（B）H链，其包含：（1）人H链C区，和（2）包含人H链FR的H链V区和对人IL-6的小鼠单克隆抗体的H链cR。 由于重构人抗体的主要部分来自人，小鼠CDR的免疫原性较小，因此本发明的重组人抗体免疫原性较小，因此抑制IL-6的信息传递，并且作为治疗剂是有希望的 IL-6引起的疾病。
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公开(公告)号：US20110059488A1
公开(公告)日：2011-03-10
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, and then anti-human Mpl diabodies and anti-human Mpl sc(Fv)2 were purified using genetic engineering techniques. Furthermore, the present inventors succeeded in humanizing anti-human Mpl sc(Fv)2.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： 分离和纯化抗人Mpl抗体，然后使用遗传工程技术纯化抗人Mpl双抗体和抗人Mpl sc（Fv）2。 此外，本发明人成功地将抗人Mpl sc（Fv）2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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公开(公告)号：US07691588B2
公开(公告)日：2010-04-06
申请号：US10548727
申请日：2004-03-12
申请人： Masayuki Tsuchiya , Yuichi Hirata
发明人： Masayuki Tsuchiya , Yuichi Hirata
IPC分类号： G01N33/53 , G01N33/574 , G01N33/576 , C12P21/08 , C07K16/00
CPC分类号： C09K11/7733 , G21K4/00
摘要： The present inventors used antibody engineering techniques to prepare functional antibodies that correspond to individual mutations in causative genes of diseases, and discovered that such antibodies enable the treatment of the diseases. Specifically, the inventors succeeded in preparing ligands, particularly minibodies, which have agonistic activity to receptors that have almost completely lost responsiveness to their natural ligands because of gene mutations (for example, a thrombopoietin (TPO) receptor whose reactivity to TPO has been markedly impaired), and which can transduce signals by interacting with these mutant receptors at levels comparable to normal.
摘要翻译： 本发明人使用抗体工程技术来制备与疾病的致病基因中的个体突变相对应的功能性抗体，并发现这种抗体能够治疗疾病。 具体地，本发明人成功地制备了由于基因突变（例如，其对TPO的反应性已被显着损伤的血小板生成素（TPO）受体）而对几乎完全丧失对其天然配体的反应性的受体具有激动作用的配体，特别是微型抗体 ），并且其可以通过与这些突变体受体的相互作用来转导信号，其水平与正常水平相当。
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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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公开(公告)号：US20060222643A1
公开(公告)日：2006-10-05
申请号：US10551504
申请日：2004-12-10
IPC分类号： A61K39/395 , C07K16/44 , C07K16/28
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, and then anti-human Mpl diabodies and anti-human Mpl sc(Fv)2 were purified using genetic engineering techniques. Furthermore, the present inventors succeeded in humanizing anti-human Mpl sc(Fv)2. 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： 分离和纯化抗人Mpl抗体，然后使用遗传工程技术纯化抗人Mpl双抗体和抗人Mpl sc（Fv）2。 此外，本发明人成功地将抗人Mpl sc（Fv）2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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公开(公告)号：US20060189794A1
公开(公告)日：2006-08-24
申请号：US10548727
申请日：2004-03-12
申请人： Masayuki Tsuchiya , Yuichi Hirata
发明人： Masayuki Tsuchiya , Yuichi Hirata
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C09K11/7733 , G21K4/00
摘要： The present inventors used antibody engineering techniques to prepare functional antibodies that correspond to individual mutations in causative genes of diseases, and discovered that such antibodies enable the treatment of the diseases. Specifically, the inventors succeeded in preparing ligands, particularly minibodies, which have agonistic activity to receptors that have almost completely lost responsiveness to their natural ligands because of gene mutations (for example, a thrombopoietin (TPO) receptor whose reactivity to TPO has been markedly impaired), and which can transduce signals by interacting with these mutant receptors at levels comparable to normal.
摘要翻译： 本发明人使用抗体工程技术来制备与疾病的致病基因中的个体突变相对应的功能性抗体，并发现这种抗体能够治疗疾病。 具体地，本发明人成功地制备了由于基因突变（例如，其对TPO的反应性已被显着损伤的血小板生成素（TPO）受体）而对几乎完全丧失对其天然配体的反应性的受体具有激动作用的配体，特别是微型抗体 ），并且其可以通过与这些突变体受体的相互作用来转导信号，其水平与正常水平相当。
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公开(公告)号：US06121423A
公开(公告)日：2000-09-19
申请号：US205231
申请日：1998-12-04
申请人： Masayuki Tsuchiya , Koh Sato , Yuichi Hirata
发明人： Masayuki Tsuchiya , Koh Sato , Yuichi Hirata
CPC分类号： C07K16/00 , C07K16/248 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2319/00
摘要： A reshaped antibody comprising:(A) L chains comprising:(1) a human C region, and(2) an L chain V region comprising human L chain FRs and L chain CDRs of a mouse monoclonal antibody; and(B) H chains comprising:(1) a human H chain C region, and(2) an H chain V region comprising human H chain FRs, and H chain CDRs of a mouse monoclonal antibody to human IL-6. Since the major portions of the reshaped human antibody are derived from human, and the mouse CDRs are less immunogenic, then the present reshaped human antibody is less immunogenic, and therefore inhibits information transfer by IL-6, and is promising as a therapeutic agent for diseases caused by IL-6.
摘要翻译： 重组抗体，其包含：（A）L链，其包含：（1）人C区，和（2）包含小鼠单克隆抗体的人L链FR和L链CDR的L链V区; 和（B）H链，其包含：（1）人H链C区，和（2）包含人H链FR的H链V区和针对人IL-6的小鼠单克隆抗体的H链CDR。 由于重构人抗体的主要部分来自人，小鼠CDR的免疫原性较小，因此本发明的重组人抗体免疫原性较小，因此抑制IL-6的信息传递，并且作为治疗剂是有希望的 IL-6引起的疾病。
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