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1. 发明授权

US11066483B2 Cytotoxicity-inducing therapeutic agent 有权
公开(公告)号：US11066483B2
公开(公告)日：2021-07-20
申请号：US13990088
申请日：2011-11-30
申请人： Junichi Nezu , Takahiro Ishiguro , Atsushi Narita , Akihisa Sakamoto , Yumiko Kawai , Tomoyuki Igawa , Taichi Kuramochi
发明人： Junichi Nezu , Takahiro Ishiguro , Atsushi Narita , Akihisa Sakamoto , Yumiko Kawai , Tomoyuki Igawa , Taichi Kuramochi
IPC分类号： C07K16/46 , C07K16/30 , C07K16/28 , A61K39/00
摘要： By replacing the antigen-binding domain, the present inventors discovered novel polypeptide complexes that retain BiTE's strong anti-tumor activity and excellent safety properties, as well as have long half-life in blood and can damage various different target cells.

2. 发明申请

US20140112914A1 CYTOTOXICITY-INDUCING THERAPEUTIC AGENT 审中-公开
标题翻译：细胞毒性诱导治疗剂
公开(公告)号：US20140112914A1
公开(公告)日：2014-04-24
申请号：US13990088
申请日：2011-11-30
申请人： Junichi Nezu , Takahiro Ishiguro , Atsushi Narita , Akihisa Sakamoto , Yumiko Kawai , Tomoyuki Igawa , Taichi Kuramochi
发明人： Junichi Nezu , Takahiro Ishiguro , Atsushi Narita , Akihisa Sakamoto , Yumiko Kawai , Tomoyuki Igawa , Taichi Kuramochi
IPC分类号： C07K16/46
CPC分类号： C07K16/46 , A61K2039/505 , C07K16/2809 , C07K16/2863 , C07K16/30 , C07K16/303 , C07K2317/31 , C07K2317/35 , C07K2317/41 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/60 , C07K2317/622 , C07K2317/64 , C07K2317/71 , C07K2317/73 , C07K2317/94 , C07K2319/00 , C07K2319/30
摘要： By replacing the antigen-binding domain, the present inventors discovered novel polypeptide complexes that retain BiTE's strong anti-tumor activity and excellent safety properties, as well as have long half-life in blood and can damage various different target cells.
摘要翻译：通过替代抗原结合结构域，本发明人发现了保留BiTE强抗肿瘤活性和优异安全性能的新型多肽复合物，并且在血液中具有长的半衰期并且可以损伤各种不同的靶细胞。

3. 发明申请

US20140093496A1 Fc-gamma-RIIb-SPECIFIC Fc ANTIBODY 审中-公开
标题翻译： Fc-γ-RIIb-SPECIFIC Fc抗体
公开(公告)号：US20140093496A1
公开(公告)日：2014-04-03
申请号：US14001218
申请日：2012-02-24
申请人： Futa Mimoto , Taichi Kuramochi , Tomoyuki Igawa , Hitoshi Katada , Shojiro Kadono
发明人： Futa Mimoto , Taichi Kuramochi , Tomoyuki Igawa , Hitoshi Katada , Shojiro Kadono
IPC分类号： C07K16/18 , C07K16/08
CPC分类号： C07K16/2866 , C07K16/08 , C07K16/18 , C07K16/303 , C07K2317/524 , C07K2317/72
摘要： An objective of the present invention is to provide a polypeptide containing an Fc region having maintained or decreased binding activities towards both allotypes of FcγRIIa, types H and R, and having enhanced FcγRIIb-binding activity in comparison with a parent polypeptide; a pharmaceutical composition containing the polypeptide; an agent for treating or preventing immunological inflammatory diseases that includes the pharmaceutical composition; a production method thereof; and a method for maintaining or decreasing binding activities towards both allotypes of FcγRIIa and enhancing the FcγRIIb-binding activity. Specifically, it is found that a polypeptide containing an antibody Fc region that has an alteration of substituting Pro at position 238 (EU numbering) with Asp or Leu at position 328 (EU numbering) with Glu enhances FcγRIIb-binding activity, and maintains or decreases binding activities towards both allotypes of FcγRIIa, types H and R. It is also found that a polypeptide containing an antibody Fc region that contains an alteration of substituting Pro at position 238 (EU numbering) with Asp and several other alterations, enhances FcγRIIb-binding activity, and maintains or decreases binding activities towards both allotypes of FcγRIIa, types H and R.
摘要翻译：本发明的目的是提供一种多肽，其含有与亲本多肽相比具有增强的FcγRIIb结合活性的FcγRIIa，H型和R型两种的同种异型的具有维持或降低的结合活性的Fc区; 含有该多肽的药物组合物; 用于治疗或预防包括该药物组合物的免疫性炎性疾病的药剂; 其制造方法; 以及用于维持或减少对FcγRIIa的同种异型的结合活性并增强FcγRIIb结合活性的方法。具体地说，发现含有在位置238上用Asp或Leu取代第238位（EU编号）的抗体Fc区的多肽与Glu的EU编号增强FcγRIIb结合活性，维持或减少对H型和R型FcγRIIa的两种同种异型的结合活性。还发现含有抗体Fc区的多肽含有替换Pro位于第238位（EU编号）与Asp和其他几种改变增强FcγRIIb结合活动，并维持或减少对类型H和R的两种同种异型的结合活性。

4. 发明申请

US20120071634A1 Antibody Constant Region Variant 审中-公开
标题翻译：抗体恒定区变体
公开(公告)号：US20120071634A1
公开(公告)日：2012-03-22
申请号：US13257145
申请日：2010-03-19
申请人： Tomoyuki Igawa , Taichi Kuramochi , Atsuhiko Maeda , Hirotake Shiraiwa
发明人： Tomoyuki Igawa , Taichi Kuramochi , Atsuhiko Maeda , Hirotake Shiraiwa
IPC分类号： C07K16/18
CPC分类号： C07K16/00 , C07K16/2866 , C07K16/2875 , C07K2317/515 , C07K2317/52 , C07K2317/522 , C07K2317/524 , C07K2317/526 , C07K2317/528 , C07K2317/53 , C07K2317/71 , C07K2317/72 , C07K2317/76 , C07K2317/92 , C07K2317/94
摘要： By altering amino acid sequences, the present inventors successfully produced constant regions that can confer antibodies with particularly favorable properties for pharmaceutical agents. When used to produce antibodies, the altered constant regions produced according to the present invention significantly reduce heterogeneity. Specifically, the antibody homogeneity can be achieved by using antibody heavy chain and light chain constant regions introduced with alterations provided by the present invention. More specifically, the alterations can prevent the loss of homogeneity of antibody molecules due to disulfide bond differences in the heavy chain. Furthermore, in a preferred embodiment, the present invention can improve antibody pharmacokinetics as well as prevent the loss of homogeneity due to C-terminal deletion in antibody constant region.
摘要翻译：通过改变氨基酸序列，本发明人成功地制备了可赋予具有特别有利于药剂特性的抗体的恒定区域。当用于产生抗体时，根据本发明产生的改变的恒定区域显着降低异质性。具体而言，抗体均一性可以通过使用由本发明提供的改变引入的抗体重链和轻链恒定区来实现。更具体地，改变可以防止由于重链中的二硫键差异导致的抗体分子的均匀性的丧失。此外，在优选的实施方案中，本发明可以改善抗体药代动力学，并且可以防止由于抗体恒定区域中的C-末端缺失导致的均一性丧失。

5. 发明申请

US20110076275A1 Method of Modifying Isoelectric Point of Antibody Via Amino Acid Substitution in CDR 有权
标题翻译：通过CDR中氨基酸取代修饰抗体等电点的方法
公开(公告)号：US20110076275A1
公开(公告)日：2011-03-31
申请号：US12679922
申请日：2008-09-26
申请人： Tomoyuki Igawa , Hiroyuki Tsunoda , Tatsuhiko Tachibana , Taichi Kuramochi
发明人： Tomoyuki Igawa , Hiroyuki Tsunoda , Tatsuhiko Tachibana , Taichi Kuramochi
IPC分类号： A61K39/395 , C07K16/00 , C12P21/00 , C07H21/00 , C12N5/10 , A61P43/00
CPC分类号： C07K16/2866 , A61K39/39591 , C07K16/00 , C07K16/28 , C07K2317/24 , C07K2317/565 , C07K2317/732 , G01N33/6854
摘要： The present inventors provide methods for modifying the isoelectric point of an antibody while retaining its antigen-binding activity, comprising modifying the charge of at least one exposable amino acid residue on the surface of the complementarity determining region (CDR). The present invention also provides methods for purifying multispecific antibodies, comprising modifying isoelectric point, and methods for improving the plasma pharmacokinetics of antibodies, comprising modifying isoelectric point. The present invention further provides antibodies with a modified isoelectric point, pharmaceutical compositions comprising the antibodies as an active ingredient, and methods for producing the antibodies and compositions.
摘要翻译：描述了用于修饰抗体的等电点同时保留其抗原结合活性的方法，包括修饰互补决定区（CDR）表面上至少一个可暴露氨基酸残基的电荷。本公开还提供了用于纯化多特异性抗体的方法，包括修饰等电点，以及用于改进具有修饰的等电点的抗体的血浆药代动力学的方法。本公开进一步提供具有修饰的等电点的抗体，包含抗体作为活性成分的药物组合物，以及用于产生抗体和组合物的方法。

6. 发明授权

US10435458B2 Antibody constant region variants with reduced Fcgammar binding 有权
公开(公告)号：US10435458B2
公开(公告)日：2019-10-08
申请号：US13582073
申请日：2011-03-04
申请人： Taichi Kuramochi , Tomoyuki Igawa , Atsuhiko Maeda , Futa Mimoto
发明人： Taichi Kuramochi , Tomoyuki Igawa , Atsuhiko Maeda , Futa Mimoto
IPC分类号： C07K16/30 , C07K16/28 , C07K16/18 , C07K19/00 , C07K16/00
摘要： The present inventors carried out dedicated research to generate antibody constant regions with reduced Fcγ receptor-binding activity by altering amino acid sequences in the antibody constant region. As a result, the present inventors successfully identified novel constant region sequences with reduced Fcγ receptor-binding activity compared to conventional antibody constant regions.

7. 发明申请

US20140105889A1 METHOD FOR ALTERING PLASMA RETENTION AND IMMUNOGENICITY OF ANTIGEN-BINDING MOLECULE 审中-公开
标题翻译：改变抗原结合分子的等离子体保持和免疫原性的方法
公开(公告)号：US20140105889A1
公开(公告)日：2014-04-17
申请号：US14007947
申请日：2012-03-30
申请人： Tomoyuki Igawa , Atsuhiko Maeda , Kenta Haraya , Yuki Iwayanagi , Tatsuhiko Tachibana , Futa Mimoto , Taichi Kuramochi , Hitoshi Katada , Shojiro Kadono
发明人： Tomoyuki Igawa , Atsuhiko Maeda , Kenta Haraya , Yuki Iwayanagi , Tatsuhiko Tachibana , Futa Mimoto , Taichi Kuramochi , Hitoshi Katada , Shojiro Kadono
IPC分类号： C07K16/28
CPC分类号： C07K16/2866 , C07K16/08 , C07K16/18 , C07K16/303 , C07K2317/524 , C07K2317/72
摘要： The present invention demonstrated that the modification of the Fc region of an antigen-binding molecule into an Fc region that does not form in a neutral pH range a heterotetramer complex containing two molecules of FcRn and an active Fcγ receptor improved the pharmacokinetics of the antigen-binding molecule and reduced the immune response to the antigen-binding molecule. The present invention also revealed methods for producing antigen-binding molecules having the properties described above, and successfully demonstrated that pharmaceutical compositions containing as an active ingredient such an antigen-binding molecule or an antigen-binding molecule produced by a production method of the present invention have excellent features over conventional antigen-binding molecules in that when administered, they exhibit improved pharmacokinetics and reduced in vivo immune response.
摘要翻译：本发明证明，将抗原结合分子的Fc区修饰成在中性pH范围内不形成的Fc区，含有两分子FcRn和活性Fcγ受体的异四聚体复合物改善了抗原结合分子的药代动力学，并降低对抗原结合分子的免疫应答。本发明还公开了具有上述性质的抗原结合分子的制造方法，成功地证明了通过本发明的制造方法制造的含有作为活性成分的抗原结合分子或抗原结合分子的药物组合物与常规抗原结合分子相比，具有优异的特征，因为当其施用时，它们表现出改善的药代动力学和体内免疫应答降低。

8. 发明申请

US20130101581A1 ANTIBODY CONSTANT REGION VARIANT 审中-公开
标题翻译：抗体恒定区变异
公开(公告)号：US20130101581A1
公开(公告)日：2013-04-25
申请号：US13582073
申请日：2011-03-04
申请人： Taichi Kuramochi , Tomoyuki Igawa , Atsuhiko Maeda , Futa Mimoto
发明人： Taichi Kuramochi , Tomoyuki Igawa , Atsuhiko Maeda , Futa Mimoto
IPC分类号： C07K16/00
CPC分类号： C07K16/00 , C07K2317/522 , C07K2317/524 , C07K2317/71 , C07K2317/72
摘要： The present inventors carried out dedicated research to generate antibody constant regions with reduced Fcγ receptor-binding activity by altering amino acid sequences in the antibody constant region. As a result, the present inventors successfully identified novel constant region sequences with reduced Fcγ receptor-binding activity compared to conventional antibody constant regions.
摘要翻译：本发明人进行了专门的研究，通过改变抗体恒定区中的氨基酸序列来产生具有降低的Fcγ受体结合活性的抗体恒定区。结果，与常规抗体恒定区相比，本发明人成功地鉴定了具有降低的Fcγ受体结合活性的新型恒定区序列。

9. 发明授权

US09340615B2 Anti-AXL antibody 有权
标题翻译：抗AXL抗体
公开(公告)号：US09340615B2
公开(公告)日：2016-05-17
申请号：US13320317
申请日：2010-05-14
申请人： Atsuhiko Maeda , Hajime Miyamoto , Taichi Kuramochi , Atsushi Matsuo , Tomoyuki Igawa , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana
发明人： Atsuhiko Maeda , Hajime Miyamoto , Taichi Kuramochi , Atsushi Matsuo , Tomoyuki Igawa , Hirotake Shiraiwa , Hiroyuki Tsunoda , Tatsuhiko Tachibana
IPC分类号： C07K16/00 , C07K16/28 , C07K16/30 , A61K39/00
CPC分类号： C07K16/2863 , A61K2039/505 , C07K16/303 , C07K2317/24 , C07K2317/30 , C07K2317/76 , C07K2317/92
摘要： An objective of the present invention is to decrease the immunogenicity of mouse-derived anti-AXL antibodies in humans by humanizing them. The present invention provides antibodies that can bind to a specific region in Anexelekto (AXL) and humanized antibodies that are produced based on such antibodies. The anti-AXL antibodies of the present invention have high antitumor activity, and are useful as agents for decreasing the AXL expression level, antitumor agents, and diagnostic agents for cancer.
摘要翻译：本发明的目的是通过人源化来降低小鼠来源的抗AXL抗体在人体中的免疫原性。本发明提供可以结合Anexelekto（AXL）中的特定区域的抗体和基于此类抗体产生的人源化抗体。本发明的抗AXL抗体具有高抗肿瘤活性，可用作降低AXL表达水平的药剂，抗肿瘤剂和癌症诊断剂。

10. 发明授权

US08575317B2 Anti-NR10 antibody and use thereof 有权
标题翻译：抗NR10抗体及其用途
公开(公告)号：US08575317B2
公开(公告)日：2013-11-05
申请号：US12809138
申请日：2009-12-04
申请人： Taichi Kuramochi , Keiko Kasutani , Souhei Ohyama , Hiroyuki Tsunoda , Tomoyuki Igawa , Tatsuhiko Tachibana , Hirotake Shiraiwa , Keiko Esaki
发明人： Taichi Kuramochi , Keiko Kasutani , Souhei Ohyama , Hiroyuki Tsunoda , Tomoyuki Igawa , Tatsuhiko Tachibana , Hirotake Shiraiwa , Keiko Esaki
IPC分类号： C07K16/28 , A61K39/00
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , G01N33/6869 , G01N2333/7155
摘要： The present inventors successfully obtained anti-NR10 antibodies having an effective neutralizing activity against NR10. The anti-NR10 antibodies provided by the present invention are useful as, for example, pharmaceuticals for treating or preventing inflammatory diseases.
摘要翻译：本发明人成功获得了抗NR10抗体的抗NR10抗体。本发明提供的抗NR10抗体可用作例如用于治疗或预防炎性疾病的药物。

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