公开(公告)号：EP2045253A4

公开(公告)日：2013-01-23

申请号：EP07767879

申请日：2007-06-29

申请人： NISSAN CHEMICAL IND LTD ,  CHUGAI PHARMACEUTICAL CO LTD

发明人： OHRAI KAZUHIKO ,  ADACHI MICHIAKI ,  TOYAMA KOJI ,  SHIMIZU TAKANORI ,  HAYASHI KEISHI ,  MINAMI MASATAKA ,  SUZUKI YOSHIYUKI ,  SUGIYAMA MASAKAZU ,  OHTA MASATERU ,  KADONO SHOJIRO ,  SHIRAISHI TAKUYA ,  SATO HARUHIKO ,  WATANABE YOSHIAKI ,  ISHII NOBUYA ,  SAKAITANI MASAHIRO ,  HASEGAWA MASAMI

IPC分类号： C07D513/04 ,  A61K31/429 ,  A61K31/4439 ,  A61P9/04 ,  A61P35/00 ,  A61P43/00

CPC分类号： C07D513/04

公开(公告)号：EP2889377A4

公开(公告)日：2016-08-03

申请号：EP13831250

申请日：2013-08-23

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： KATADA HITOSHI ,  KADONO SHOJIRO ,  MIMOTO FUTA ,  IGAWA TOMOYUKI

IPC分类号： A61K39/00 ,  C07K16/00 ,  C07K16/28 ,  C07K16/30

CPC分类号： C07K16/00 ,  A61K9/0019 ,  A61K2039/505 ,  C07K16/28 ,  C07K16/2866 ,  C07K16/303 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/53 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/30

摘要： An objective of the present invention is to provide an Fc region variant with enhanced Fc³RIIb-binding activity, and/or enhanced binding selectivity to Fc³RIIb compared to Fc³RIIa (type R), as compared to those of a polypeptide containing an Fc region to which an amino acid alteration(s) has not been introduced; a polypeptide which includes the Fc region variant; a pharmaceutical composition containing the polypeptide; preventing therapeutic or preventive agent for immunological inflammatory diseases that includes the pharmaceutical composition; a production method thereof; and a method of enhancing Fc³RIIb-binding activity and also enhancing binding selectivity to Fc³RIIb compared to Fc³RIIa (type R). It was found that a polypeptide containing an antibody Fc region variant that contains an amino acid sequence in which an amino-acid alteration at position 238 (EU numbering) is combined with other specific amino-acid alterations enhances Fc³RIIb-binding activity, and/or enhances binding selectivity to Fc³RIIb compared to Fc³RIIa (type R).

摘要翻译： 本发明的目的是提供与FcαRIIa（R型）相比具有增强的Fc3RIIb结合活性和/或增强的对Fc3RIIb的结合选择性的Fc区变体，与含有Fc区的多肽相比， 氨基酸改变尚未引入; 包括Fc区变体的多肽; 含有多肽的药物组合物; 预防包括该药物组合物的免疫性炎性疾病的治疗或预防剂; 其制造方法; 以及增强Fc3RIIb结合活性的方法，并且与FcγRIIa（R型）相比，增强与Fc3RIIb的结合选择性。 发现含有含有氨基酸序列的抗体Fc区变体的多肽，其中238位氨基酸改变（EU编号）与其他特异性氨基酸改变组合增强Fc3RIIb结合活性，和/或 与FcγRIIa（R型）相比，增强与Fc3RIIb的结合选择性。

公开(公告)号：EP1364960A4

公开(公告)日：2005-05-18

申请号：EP02711294

申请日：2002-02-04

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： SHIRAISHI TAKUYA ,  KADONO SHOJIRO ,  HARAMURA MASAYUKI ,  SATO HARUHIKO ,  KOZONO TOSHIRO ,  KOGA TAKAKI ,  SAKAMOTO AKIHISA

IPC分类号： A61K38/00 ,  C07K5/06 ,  C07K5/065 ,  C07K5/078 ,  G01N33/68 ,  C07K5/062 ,  C07K14/745 ,  G01N33/15 ,  G06F17/50

CPC分类号： G06F19/16 ,  A61K38/00 ,  C07K5/06078 ,  C07K5/06139 ,  C07K5/06156 ,  G01N33/68

摘要： Compounds represented by the following general formula (1): (1) wherein R1 represents amidinophenyl, etc.; R2 represents hydrogen, etc.; R3 represents carbamoylalkyl, etc.; R4 represents hydrogen, etc.; R5 represents benzyl, etc.; R6 represents hydrogen, etc.; and R7 represents alkylsulfonyl, etc. Crystals of a complex of VIIa factor/human soluble tissue factor with a low-molecular weight reversible VIIa factor inhibitor. A medium carrying the whole or a part of the coordinate data of the stereostructure of the complex of human VIIa factor/human soluble tissue factor with a low-molecular weight reversible VIIa factor inhibitor obtained by X-ray crystal structure analysis of the above crystals recorded thereon. A method of designing a low-molecular weight reversible VIIa factor inhibitor by using the above data.

公开(公告)号：EP3078744A4

公开(公告)日：2017-06-07

申请号：EP14867380

申请日：2014-12-04

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： IGAWA TOMOYUKI ,  TAMBA SHIGERO ,  SHIMIZU SHUN ,  TATSUMI KANAKO ,  KADONO SHOJIRO ,  KAWAUCHI HIROKI ,  OHARA KAZUHIRO ,  MATSUSHITA MASAYUKI ,  EMURA TAKASHI ,  KAMIMURA MASAKI

IPC分类号： C12N15/09 ,  A61K39/00 ,  C07K16/00 ,  C07K19/00 ,  C12P21/08 ,  C40B40/08 ,  C40B40/10

CPC分类号： C12N15/1093 ,  C07K16/00 ,  C07K16/005 ,  C07K16/248 ,  C07K16/2809 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/30 ,  C07K16/4283 ,  C07K16/44 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/92

摘要： An objective of the present invention is to provide target tissue-specific antigen-binding molecules, antigen-binding molecules whose antigen-binding activity varies depending on the concentration of an unnatural compound, libraries comprising a plurality of the antigen-binding molecules which are different from one another, pharmaceutical compositions comprising the antigen-binding molecules, methods of screening for the antigen-binding molecules, and methods for producing the antigen-binding molecules. The present inventors created antigen-binding domains whose antigen-binding activity varies depending on the concentration of a small molecule compound or antigen-binding molecules containing an antigen-binding domain, and libraries comprising a plurality of the antigen-binding domains which are different from one another or antigen-binding domains, and demonstrated that the above-noted objective could be achieved by using the libraries. Various diseases originating from target tissues can be treated in a target tissue-specific manner by using the antigen-binding molecules of the present invention.

摘要翻译： 本发明的一个目的是提供靶组织特异性的抗原结合分子的抗原结合分子，其抗原结合活性的变化取决于非天然化合物的浓度，库包括抗原结合分子，其是不同的多元 彼此，药物组合物包含抗原结合分子，筛选的抗原结合分子的方法，以及用于制备抗原结合分子。 本发明人创建的抗原结合结构域是谁的抗原结合活性的变化取决于小分子化合物或抗原结合分子包含抗原结合结构域的的浓度，和库包含抗原结合结构域哪些是从不同的多元 彼此或抗原结合结构域，和实例阐述没有上面提到的目的可以通过使用的库来实现。 各种疾病从靶组织源自可在靶组织特异性方式通过使用本发明的抗原结合分子进行处理。

公开(公告)号：EP2857420A4

公开(公告)日：2015-12-30

申请号：EP13797450

申请日：2013-05-30

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： IGAWA TOMOYUKI ,  TAMBA SHIGERO ,  TATSUMI KANAKO ,  SHIMIZU SHUN ,  KADONO SHOJIRO

IPC分类号： C07K16/28

CPC分类号： C07K16/248 ,  A61K2039/505 ,  C07K16/00 ,  C07K16/005 ,  C07K16/18 ,  C07K16/2866 ,  C07K16/30 ,  C07K16/44 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/55 ,  C07K2317/732 ,  C07K2317/92 ,  G01N33/6845 ,  G01N33/6869 ,  G01N2333/5412 ,  G01N2500/00 ,  G01N2500/20

摘要： The present inventors discovered that the above-mentioned problems can be solved by producing antigen-binding molecules that contain an antigen-binding domain whose antigen-binding activity varies depending on the concentration of a target tissue-specific compound. Use of antigen-binding molecules of the present invention enables various diseases that originate from a target tissue to be treated in a manner specific to the target tissue.

摘要翻译： 本发明人发现上述问题可以通过产生含抗原结合结构域的抗原结合分子来解决，其抗原结合活性随目标组织特异性化合物的浓度而变化。 使用本发明的抗原结合分子可以以对目标组织特异性的方式来源于待处理的靶组织的各种疾病。

公开(公告)号：EP2818183A4

公开(公告)日：2015-11-04

申请号：EP13751098

申请日：2013-02-22

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： IGAWA TOMOYUKI ,  MAEDA ATSUHIKO ,  IWAYANAGI YUKI ,  HARAYA KENTA ,  KATADA HITOSHI ,  KADONO SHOJIRO ,  MIMOTO FUTA

IPC分类号： C07K16/00

CPC分类号： C07K16/00 ,  A61K2039/505 ,  C07K16/2866 ,  C07K16/303 ,  C07K2317/41 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2317/94

摘要： The present invention provides antigen-binding molecules containing (i) an antigen-binding domain whose antigen-binding activity varies depending on ion concentration conditions, (ii) an Fc³-binding domain having Fc³ RIIb-selective binding activity, and (iii) an FcRn-binding domain having FcRn-binding activity under an acidic pH range condition, and methods of decreasing plasma antigen concentration as compared to before administering the molecule, which include the step of administering the molecule.

摘要翻译： 本发明提供了抗原结合分子，其含有（i）其抗原结合活性随离子浓度条件而变化的抗原结合结构域，（ii）具有Fc 3 RIIb选择性结合活性的Fc 3结合结构域，和（iii） 在酸性pH范围条件下具有FcRn结合活性的FcRn结合结构域，以及与施用分子前相比降低血浆抗原浓度的方法，包括给予该分子的步骤。

公开(公告)号：EP2679681A4

公开(公告)日：2015-01-28

申请号：EP12749420

申请日：2012-02-24

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： MIMOTO FUTA ,  KURAMOCHI TAICHI ,  IGAWA TOMOYUKI ,  KATADA HITOSHI ,  KADONO SHOJIRO

IPC分类号： C07K16/00 ,  A61K39/395 ,  A61P35/00 ,  C07K16/28

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 Fc³RIIa, types H and R, and having enhanced Fc³RIIb-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 Fc³RIIa and enhancing the Fc³RIIb-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 Fc³RIIb-binding activity, and maintains or decreases binding activities towards both allotypes of Fc³RIIa, 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 Fc³RIIb-binding activity, and maintains or decreases binding activities towards both allotypes of Fc³RIIa, types H and R.

公开(公告)号：EP3070168A4

公开(公告)日：2017-06-28

申请号：EP14859814

申请日：2014-11-11

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： IGAWA TOMOYUKI ,  KADONO SHOJIRO ,  HIRONIWA NAOKA ,  SAKURAI MIKA

IPC分类号： C07K16/28 ,  A61K39/395 ,  A61P35/00 ,  C07K16/30 ,  C07K16/42 ,  C07K16/46 ,  C12N15/09

CPC分类号： C07K16/2809 ,  C07K16/2848 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/2875 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/4283 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2319/00 ,  C07K2319/70

摘要： The present inventors have successfully prepared an antigen-binding molecule comprising an antibody variable region that has binding activity against a molecule expressed on the surface of a T cell and a molecule expressed on the surface of any other immunocyte, but does not bind to these molecules at the same time. The present invention allows the preparation of an antigen-binding molecule capable of circumventing adverse reactions that may be caused by the cross-linking of T cells to other immunocytes, and provides an antigen-binding molecule suitable as a drug.

摘要翻译： 本发明人成功地制备了包含抗体可变区的抗原结合分子，所述抗体可变区对T细胞表面表达的分子和任何其他免疫细胞表面上表达的分子具有结合活性，但不与这些分子结合 与此同时。 本发明允许制备能够避免可能由T细胞与其他免疫细胞的交联引起的不良反应的抗原结合分子，并提供适合作为药物的抗原结合分子。

公开(公告)号：EP2862875A4

公开(公告)日：2016-01-13

申请号：EP13803763

申请日：2013-06-14

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： IGAWA TOMOYUKI ,  HIRONIWA NAOKA ,  KADONO SHOJIRO ,  MATSUO ATSUSHI ,  KURAMOCHI TAICHI ,  MIMOTO FUTA

IPC分类号： C07K16/00 ,  A61K39/395 ,  C07K19/00 ,  C12N15/09 ,  C12P21/02

CPC分类号： C07K16/00 ,  C07K16/22 ,  C07K16/2848 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/94 ,  C07K2319/30

公开(公告)号：EP2728002A4

公开(公告)日：2015-03-25

申请号：EP12804446

申请日：2012-06-29

申请人： CHUGAI PHARMACEUTICAL CO LTD

发明人： MIMOTO FUTA ,  KURAMOCHI TAICHI ,  IGAWA TOMOYUKI ,  KAWAZOE MEIRI ,  KATADA HITOSHI ,  SHIRAIWA HIROTAKE ,  KADONO SHOJIRO

IPC分类号： C07K16/28 ,  A61K39/395 ,  C07K16/00 ,  C07K16/18 ,  C07K16/30 ,  C07K16/36 ,  C07K16/46 ,  C12N15/09

CPC分类号： C07K16/46 ,  C07K1/1075 ,  C07K16/00 ,  C07K16/18 ,  C07K16/22 ,  C07K16/2866 ,  C07K16/30 ,  C07K16/303 ,  C07K16/36 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/92 ,  C07K2317/94 ,  G01N33/566

摘要： The present inventors produced a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved Fc region function compared to that of a homodimer in which the Fc region is composed of only the first polypeptide or only the second polypeptide by conventional technology.