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1. 发明申请

WO2010131733A9 ANTI-AXL ANTIBODY 审中-公开
标题翻译：抗轴抗体
公开(公告)号：WO2010131733A9
公开(公告)日：2012-01-19
申请号：PCT/JP2010058166
申请日：2010-05-14
申请人： CHUGAI PHARMACEUTICAL CO LTD , MAEDA ATSUHIKO , MIYAMOTO HAJIME , KURAMOCHI TAICHI , MATSUO ATSUSHI , IGAWA TOMOYUKI , SHIRAIWA HIROTAKE , TSUNODA HIROYUKI , TACHIBANA TATSUHIKO
发明人： MAEDA ATSUHIKO , MIYAMOTO HAJIME , KURAMOCHI TAICHI , MATSUO ATSUSHI , IGAWA TOMOYUKI , SHIRAIWA HIROTAKE , TSUNODA HIROYUKI , TACHIBANA TATSUHIKO
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , C07K16/46
CPC分类号： C07K16/2863 , A61K2039/505 , C07K16/303 , C07K2317/24 , C07K2317/30 , C07K2317/76 , C07K2317/92
摘要： By humanizing an anti-AXL antibody originating from mouse, the immunogenicity thereof in humans can be reduced. Provided are an antibody capable of binding to a specific region in Anexelekto (AXL); and a humanized antibody constructed on the basis of this antibody. The aforesaid anti-AXL antibody has a high antitumor activity and, therefore, is useful as an agent for reducing the expression amount of AXL, an anticancer drug and a cancer diagnostic.
摘要翻译：通过将源自小鼠的抗AXL抗体人源化，可以降低人的免疫原性。提供能够结合Anexelekto（AXL）中的特定区域的抗体; 和基于该抗体构建的人源化抗体。上述抗AXL抗体具有高抗肿瘤活性，因此可用作降低AXL，抗癌药物和癌症诊断的表达量的药剂。

2. 发明申请

WO2010106812A1 PHARMACEUTICAL FORMULATION CONTAINING IMPROVED ANTIBODY MOLECULES 审中-公开
标题翻译：包含改进的抗体分子的药物制剂
公开(公告)号：WO2010106812A1
公开(公告)日：2010-09-23
申请号：PCT/JP2010/001977
申请日：2010-03-19
申请人： CHUGAI SEIYAKU KABUSHIKI KAISHA , IGAWA, Tomoyuki , ISHII, Shinya , MAEDA, Atsuhiko , SAKURAI, Mika , KOJIMA, Tetsuo , TACHIBANA, Tatsuhiko , SHIRAIWA, Hirotake , TSUNODA, Hiroyuki , HIGUCHI, Yoshinobu , MORIYAMA, Chifumi , HAYASAKA, Akira
发明人： IGAWA, Tomoyuki , ISHII, Shinya , MAEDA, Atsuhiko , SAKURAI, Mika , KOJIMA, Tetsuo , TACHIBANA, Tatsuhiko , SHIRAIWA, Hirotake , TSUNODA, Hiroyuki , HIGUCHI, Yoshinobu , MORIYAMA, Chifumi , HAYASAKA, Akira
IPC分类号： A61K38/00 , A61K39/395 , A61K47/18 , A61P17/00 , A61P19/02 , A61P29/00 , A61P35/00 , A61P37/06
CPC分类号： A61K38/16 , A61K9/08 , A61K9/19 , A61K47/18 , A61K2039/505 , C07K16/2866 , C07K2317/24 , C07K2317/52 , C07K2317/53 , C07K2317/54 , C07K2317/55 , C07K2317/565 , C07K2317/567 , C07K2317/72 , C07K2317/76 , C07K2317/92
摘要： An objective of the present invention is to provide pharmaceutical formulations containing improved antibody molecules. The present invention provides pharmaceutical formulations comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. Present formulations contain preferably arginine as stabilizer and are provided in liquid or solid form.
摘要翻译：本发明的目的是提供含有改进的抗体分子的药物制剂。本发明通过改变作为人源化抗IL-6受体IgG1抗体的TOCILIZUMAB的可变区和恒定区的氨基酸序列来提供优于TOCILIZUMAB的第二代分子的药物制剂，以增强抗原 - 中和能力增强，药代动力学改善，治疗效果较差，免疫原性，安全性和物理化学性质（稳定性和均一性）均有改善。本发明的制剂优选含有精氨酸作为稳定剂，并以液体或固体形式提供。

3. 发明申请

WO2011122011A2 ANTIGEN-BINDING MOLECULES THAT PROMOTE ANTIGEN CLEARANCE 审中-公开
标题翻译：促进抗原清除的抗原结合分子
公开(公告)号：WO2011122011A2
公开(公告)日：2011-10-06
申请号：PCT/JP2011/001888
申请日：2011-03-30
申请人： CHUGAI SEIYAKU KABUSHIKI KAISHA , IGAWA, Tomoyuki , ISHII, Shinya , MAEDA, Atsuhiko , NAKAI, Takashi
发明人： IGAWA, Tomoyuki , ISHII, Shinya , MAEDA, Atsuhiko , NAKAI, Takashi
IPC分类号： C07K16/00
CPC分类号： C07K16/18 , A61K2039/505 , A61K2039/545 , C07K14/70535 , C07K16/248 , C07K16/28 , C07K16/2866 , C07K16/4241 , C07K2317/24 , C07K2317/31 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94 , C07K2319/30
摘要： An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above. The present inventors discovered that antigen uptake into cells is facilitated by an antibody having human FcRn-binding activity at the plasma pH and a lower antigen-binding activity at the early endosomal pH than at the plasma pH; such antibodies can increase the number of antigens to which a single antibody molecule can bind; the reduction of antigen in plasma can be facilitated by administering such an antibody; and antibody pharmacokinetics can be improved by using such antibodies.
摘要翻译：本发明的目的是提供促进抗原结合分子介导的抗原向细胞摄取的方法，促进血浆中抗原浓度降低的方法，增加单一抗原结合分子可以抗原数目的方法结合，用于改善抗原结合分子的药代动力学的方法，改进用于促进抗原摄入细胞的抗原结合分子，能够促进血浆中抗原浓度降低的抗原结合分子，能够重复结合抗原的抗原结合分子，具有改善的药代动力学的抗原结合分子，包含这种抗原结合分子的药物组合物，以及用于制备上述那些的方法。本发明人发现，通过在血浆pH下具有人FcRn结合活性的抗体和在早期内体体内的pH低于等离子体pH下抗原结合活性较低的抗体促进了对细胞的吸收; 这样的抗体可以增加单个抗体分子可以结合的抗原的数量; 可以通过施用这样的抗体来促进血浆中抗原的降低; 可以通过使用这样的抗体来改善抗体药代动力学。

4. 发明申请

WO2011122011A3 ANTIBODIES WITH MODIFIED AFFINITY TO FCRN THAT PROMOTE ANTIGEN CLEARANCE 审中-公开
标题翻译：具有改良亲和力的抗体以促进抗原性清除
公开(公告)号：WO2011122011A3
公开(公告)日：2012-01-05
申请号：PCT/JP2011001888
申请日：2011-03-30
申请人： CHUGAI PHARMACEUTICAL CO LTD , IGAWA TOMOYUKI , ISHII SHINYA , MAEDA ATSUHIKO , NAKAI TAKASHI
发明人： IGAWA TOMOYUKI , ISHII SHINYA , MAEDA ATSUHIKO , NAKAI TAKASHI
IPC分类号： C07K16/00
CPC分类号： C07K16/18 , A61K2039/505 , A61K2039/545 , C07K14/70535 , C07K16/248 , C07K16/28 , C07K16/2866 , C07K16/4241 , C07K2317/24 , C07K2317/31 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94 , C07K2319/30
摘要： An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above. The present inventors discovered that antigen uptake into cells is facilitated by an antibody having human FcRn-binding activity at the plasma pH and a lower antigen-binding activity at the early endosomal pH than at the plasma pH; such antibodies can increase the number of antigens to which a single antibody molecule can bind; the reduction of antigen in plasma can be facilitated by administering such an antibody; and antibody pharmacokinetics can be improved by using such antibodies.
摘要翻译：本发明的目的是提供促进抗原结合分子介导的细胞吸收细胞的方法，促进血浆中抗原浓度降低的方法，增加单个抗原结合分子可以抗原数目的方法结合，用于改善抗原结合分子的药代动力学的方法，改善促进抗原摄入细胞的抗原结合分子，能够促进血浆中抗原浓度降低的抗原结合分子，能够重复结合抗原的抗原结合分子，具有改善的药物动力学的抗原结合分子，包含这种抗原结合分子的药物组合物，以及用于制备上述那些的方法。本发明人发现，通过在血浆pH下具有人FcRn结合活性的抗体和在早期内体内pH下比在血浆pH下具有较低的抗原结合活性来促进对细胞的吸收; 这样的抗体可以增加单个抗体分子可以结合的抗原的数量; 可以通过施用这样的抗体来促进血浆中抗原的降低; 并且可以通过使用这样的抗体来改善抗体药代动力学。

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