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1. 发明申请

US20130053547A1 AGONIST ANTIBODY TO HUMAN THROMBOPOIETIN RECEPTOR 审中-公开
标题翻译：人类抗抑郁药受体的激素抗体
公开(公告)号：US20130053547A1
公开(公告)日：2013-02-28
申请号：US13543183
申请日：2012-07-06
申请人： Masayuki KAI , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
发明人： Masayuki KAI , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
IPC分类号： C07K16/00
CPC分类号： C07K16/2866 , A61K2039/505 , C07K14/524 , C07K14/715 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/72 , C07K2317/74 , Y10S424/801 , Y10S424/809
摘要： This invention provides an agonist antibody to a human thrombopoietin receptor (human c-Mpl), and pharmaceutical compositions comprising the same for use in treatment of thrombocytopenia. The disclosed agonist antibody comprises (1) antibody constant regions comprising heavy and light chain constant regions, each of which may optionally contain domain substitutions, or may contain deletions, substitutions, additions, or insertions of amino acid residues, and (2) antibody variable regions capable of binding to and activating a human thrombopoietin receptor. The-agonist antibody further induces colony formation at a concentration of 10,000 ng/ml or lower, and has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less.
摘要翻译：本发明提供了对人类血小板生成素受体（人c-Mpl）的激动剂抗体，以及包含其用于治疗血小板减少症的药物组合物。所公开的激动剂抗体包含（1）包含重链和轻链恒定区的抗体恒定区，每个区可任选地含有结构域取代，或可含有氨基酸残基的缺失，替换，添加或插入，和（2）抗体可变能够结合并激活人血小板生成素受体的区域。激动剂抗体进一步诱导浓度为10,000ng / ml或更低的集落形成，并且具有比PEG-rHuMGDF高至少50％的最大活性和100nM或更低的50％有效浓度（EC 50）。

2. 发明申请

US20100004429A1 AGONIST ANTIBODY TO HUMAN THROMBOPOIETIN RECEPTOR 失效
标题翻译：人类抗抑郁药受体的激素抗体
公开(公告)号：US20100004429A1
公开(公告)日：2010-01-07
申请号：US12294171
申请日：2007-03-20
申请人： Masayuki Kai , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
发明人： Masayuki Kai , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
IPC分类号： C07K16/28 , C12P21/04 , C07H21/04
CPC分类号： C07K16/2866 , A61K2039/505 , C07K14/524 , C07K14/715 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/72 , C07K2317/74 , Y10S424/801 , Y10S424/809
摘要： This invention provides an agonist antibody to a human thrombopoietin receptor (alias: human c-Mpl). More particularly, this invention provides an agonist antibody to a human thrombopoietin receptor, wherein the agonist antibody comprises: antibody constant regions comprising (1) amino acid sequences in a heavy chain constant region and a light chain constant region of a human antibody, (2) an amino acid sequence of a heavy chain constant region with a domain substituted between human antibody subclasses, and an amino acid sequence of a light chain constant region of a human antibody, or (3) amino acid sequences comprising a deletion(s), substitution(s), addition(s), or insertion(s) of one or several amino acid residues in the amino acid sequences of (1) or (2) above; and antibody variable regions capable of binding to and activating a human thrombopoietin receptor; and wherein the agonist antibody has the properties: (a) that the antibody induces colony formation at a concentration of 10,000 ng/ml or lower as determined by the CFU-MK colony formation assay using human umbilical-cord-blood-derived CD34+ cells; and (b) that the antibody has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less in the cell proliferation assay using UT7/TPO cell. Also provided is a pharmaceutical composition for treating thrombocytopenia comprising said antibody.
摘要翻译：本发明提供了对人血小板生成素受体（别名：人c-Mpl）的激动剂抗体。更具体地，本发明提供了对人血小板生成素受体的激动剂抗体，其中所述激动剂抗体包含：抗体恒定区，其包含（1）重链恒定区中的氨基酸序列和人抗体的轻链恒定区，（2 ）具有在人抗体亚类和人抗体轻链恒定区的氨基酸序列之间取代的重链恒定区的氨基酸序列，或（3）包含缺失的氨基酸序列，上述（1）或（2）的氨基酸序列中一个或几个氨基酸残基的取代，添加或插入; 和能够结合并激活人血小板生成素受体的抗体可变区; 并且其中所述激动剂抗体具有以下性质：（a）所述抗体通过使用人脐带血衍生的CD34 +细胞通过CFU-MK集落形成测定法测定，浓度为10,000ng / ml或更低的浓度形成; 和（b）在使用UT7 / TPO细胞的细胞增殖测定中，抗体具有比PEG-rHuMGDF高至少50％的最大活性和100nM或更低的50％有效浓度（EC 50）。还提供了用于治疗血小板减少症的药物组合物，其包含所述抗体。

3. 发明授权

US08999329B2 Agonist antibody to human thrombopoietin receptor 有权
标题翻译：抗人血小板生成素受体的激动剂抗体
公开(公告)号：US08999329B2
公开(公告)日：2015-04-07
申请号：US13543183
申请日：2012-07-06
申请人： Masayuki Kai , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
发明人： Masayuki Kai , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
IPC分类号： A61K39/395 , C07K16/28 , C07K14/52 , C07K14/715 , A61K39/00
CPC分类号： C07K16/2866 , A61K2039/505 , C07K14/524 , C07K14/715 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/72 , C07K2317/74 , Y10S424/801 , Y10S424/809
摘要： This invention provides an agonist antibody to a human thrombopoietin receptor (human c-Mpl), and pharmaceutical compositions comprising the same for use in treatment of thrombocytopenia. The disclosed agonist antibody comprises (1) antibody constant regions comprising heavy and light chain constant regions, each of which may optionally contain domain substitutions, or may contain deletions, substitutions, additions, or insertions of amino acid residues, and (2) antibody variable regions capable of binding to and activating a human thrombopoietin receptor. The-agonist antibody further induces colony formation at a concentration of 10,000 ng/ml or lower, and has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less.
摘要翻译：本发明提供了对人类血小板生成素受体（人c-Mpl）的激动剂抗体，以及包含其用于治疗血小板减少症的药物组合物。所公开的激动剂抗体包含（1）包含重链和轻链恒定区的抗体恒定区，每个区可任选地含有结构域取代，或可含有氨基酸残基的缺失，替换，添加或插入，和（2）抗体可变能够结合并激活人血小板生成素受体的区域。激动剂抗体进一步诱导浓度为10,000ng / ml或更低的集落形成，并且具有比PEG-rHuMGDF高至少50％的最大活性和100nM或更低的50％有效浓度（EC 50）。

4. 发明授权

US08236314B2 Agonist antibody to human thrombopoietin receptor 失效
标题翻译：抗人血小板生成素受体的激动剂抗体
公开(公告)号：US08236314B2
公开(公告)日：2012-08-07
申请号：US13232277
申请日：2011-09-14
申请人： Masayuki Kai , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
发明人： Masayuki Kai , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
IPC分类号： A61K39/395
CPC分类号： C07K16/2866 , A61K2039/505 , C07K14/524 , C07K14/715 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/72 , C07K2317/74 , Y10S424/801 , Y10S424/809
摘要： This invention provides an agonist antibody to a human thrombopoietin receptor (human c-Mpl), and pharmaceutical compositions comprising the same for use in treatment of thrombocytopenia. The disclosed agonist antibody comprises (1) antibody constant regions comprising heavy and light chain constant regions, each of which may optionally contain domain substitutions, or may contain deletions, substitutions, additions, or insertions of amino acid residues, and (2) antibody variable regions capable of binding to and activating a human thrombopoietin receptor. The-agonist antibody further induces colony formation at a concentration of 10,000 ng/ml or lower, and has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less.
摘要翻译：本发明提供了对人类血小板生成素受体（人c-Mpl）的激动剂抗体，以及包含其用于治疗血小板减少症的药物组合物。所公开的激动剂抗体包含（1）包含重链和轻链恒定区的抗体恒定区，每个区可任选地含有结构域取代，或可含有氨基酸残基的缺失，替换，添加或插入，和（2）抗体可变能够结合并激活人血小板生成素受体的区域。激动剂抗体进一步诱导浓度为10,000ng / ml或更低的集落形成，并且具有比PEG-rHuMGDF高至少50％的最大活性和100nM或更低的50％有效浓度（EC 50）。

5. 发明申请

US20120053326A1 AGONIST ANTIBODY TO HUMAN THROMBOPOIETIN RECEPTOR 失效
标题翻译：人类抗抑郁药受体的激素抗体
公开(公告)号：US20120053326A1
公开(公告)日：2012-03-01
申请号：US13232277
申请日：2011-09-14
申请人： Masayuki KAI , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
发明人： Masayuki KAI , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
IPC分类号： C07K16/28
CPC分类号： C07K16/2866 , A61K2039/505 , C07K14/524 , C07K14/715 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/72 , C07K2317/74 , Y10S424/801 , Y10S424/809
摘要： This invention provides an agonist antibody to a human thrombopoietin receptor (human c-Mpl), and pharmaceutical compositions comprising the same for use in treatment of thrombocytopenia. The disclosed agonist antibody comprises (1) antibody constant regions comprising heavy and light chain constant regions, each of which may optionally contain domain substitutions, or may contain deletions, substitutions, additions, or insertions of amino acid residues, and (2) antibody variable regions capable of binding to and activating a human thrombopoietin receptor. The-agonist antibody further induces colony formation at a concentration of 10,000 ng/ml or lower, and has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less.
摘要翻译：本发明提供了对人类血小板生成素受体（人c-Mpl）的激动剂抗体，以及包含其用于治疗血小板减少症的药物组合物。所公开的激动剂抗体包含（1）包含重链和轻链恒定区的抗体恒定区，每个区可任选地含有结构域取代，或可含有氨基酸残基的缺失，替换，添加或插入，和（2）抗体可变能够结合并激活人血小板生成素受体的区域。激动剂抗体进一步诱导浓度为10,000ng / ml或更低的集落形成，并且具有比PEG-rHuMGDF高至少50％的最大活性和100nM或更低的50％有效浓度（EC 50）。

6. 发明授权

US08048421B2 Agonist antibody to human thrombopoietin receptor 失效
标题翻译：抗人血小板生成素受体的激动剂抗体
公开(公告)号：US08048421B2
公开(公告)日：2011-11-01
申请号：US12294171
申请日：2007-03-20
申请人： Masayuki Kai , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
发明人： Masayuki Kai , Kazuhiro Motoki , Shiro Kataoka , Hideaki Yoshida , Tetsuya Hagiwara
IPC分类号： A61K39/395
CPC分类号： C07K16/2866 , A61K2039/505 , C07K14/524 , C07K14/715 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/72 , C07K2317/74 , Y10S424/801 , Y10S424/809
摘要： This invention provides an agonist antibody to a human thrombopoietin receptor (alias: human c-Mpl). More particularly, this invention provides an agonist antibody to a human thrombopoietin receptor, wherein the agonist antibody comprises: antibody constant regions comprising (1) amino acid sequences in a heavy chain constant region and a light chain constant region of a human antibody, (2) an amino acid sequence of a heavy chain constant region with a domain substituted between human antibody subclasses, and an amino acid sequence of a light chain constant region of a human antibody, or (3) amino acid sequences comprising a deletion(s), substitution(s), addition(s), or insertion(s) of one or several amino acid residues in the amino acid sequences of (1) or (2) above; and antibody variable regions capable of binding to and activating a human thrombopoietin receptor; and wherein the agonist antibody has the properties: (a) that the antibody induces colony formation at a concentration of 10,000 ng/ml or lower as determined by the CFU-MK colony formation assay using human umbilical-cord-blood-derived CD34+ cells; and (b) that the antibody has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less in the cell proliferation assay using UT7/TPO cell. Also provided is a pharmaceutical composition for treating thrombocytopenia comprising said antibody.
摘要翻译：本发明提供了对人血小板生成素受体（别名：人c-Mpl）的激动剂抗体。更具体地，本发明提供了对人血小板生成素受体的激动剂抗体，其中所述激动剂抗体包含：抗体恒定区，其包含（1）重链恒定区中的氨基酸序列和人抗体的轻链恒定区，（2 ）具有在人抗体亚类和人抗体轻链恒定区的氨基酸序列之间取代的重链恒定区的氨基酸序列，或（3）包含缺失的氨基酸序列，上述（1）或（2）的氨基酸序列中一个或几个氨基酸残基的取代，添加或插入; 和能够结合并激活人血小板生成素受体的抗体可变区; 并且其中所述激动剂抗体具有以下性质：（a）所述抗体通过使用人脐带血衍生的CD34 +细胞通过CFU-MK集落形成测定法测定，浓度为10,000ng / ml或更低的浓度形成; 和（b）在使用UT7 / TPO细胞的细胞增殖测定中，抗体具有比PEG-rHuMGDF高至少50％的最大活性和100nM或更低的50％有效浓度（EC 50）。还提供了用于治疗血小板减少症的药物组合物，其包含所述抗体。

7. 发明授权

US08716451B2 Stabilized human IgG2 and IgG3 antibodies 有权
标题翻译：稳定的人IgG2和IgG3抗体
公开(公告)号：US08716451B2
公开(公告)日：2014-05-06
申请号：US11794950
申请日：2006-01-12
申请人： Nobuaki Takahashi , Hideaki Yoshida
发明人： Nobuaki Takahashi , Hideaki Yoshida
IPC分类号： C07K16/00 , C12N15/00
CPC分类号： C07K16/00 , C07K16/2878 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/94
摘要： It is intended to provide highly stable variants of human antibody IgG2 and IgG3 subclasses. The present invention provides an IgG heavy chain comprising the constant region of a human IgG2 heavy chain having at least a substitution of Y for F at the 300th position, L for V at the 309th position, or A for T at the 339th position designated by the EU index of Kabat et al. and an IgG heavy chain comprising the constant region of a human IgG3 heavy chain having at least a substitution of K for N at the 392nd position or V for M at the 397th position designated by the EU index of Kabat et al. The present invention also provides monoclonal antibodies comprising these heavy chains.
摘要翻译：旨在提供人抗体IgG2和IgG3亚类的高度稳定的变体。本发明提供一种IgG重链，其包含人IgG2重链的恒定区，其在第300位具有至少取代F的F，在第309位具有至少取代F的L，在第309位具有至少取代F的第三十九位，欧盟指数Kabat等和IgG重链，其包含人类IgG3重链的恒定区，在Kabat等人的EU指数指定的第397位具有至少在第392位具有K取代为N或V代表M。本发明还提供了包含这些重链的单克隆抗体。

8. 发明申请

US20120330169A1 BLOOD PRESSURE INFORMATION MEASUREMENT DEVICE CUFF AND BLOOD PRESSURE INFORMATION MEASUREMENT DEVICE PROVIDED THEREWITH 有权
标题翻译：血液压力信息测量装置和血液压力信息测量装置
公开(公告)号：US20120330169A1
公开(公告)日：2012-12-27
申请号：US13538371
申请日：2012-06-29
申请人： Yoshihiko Sano , Hideaki Yoshida , Minoru Taniguchi
发明人： Yoshihiko Sano , Hideaki Yoshida , Minoru Taniguchi
IPC分类号： A61B5/022
CPC分类号： A61B5/02233 , A61B5/02141
摘要： In a blood pressure information measurement device cuff, a first flexion point and a second flexion point at which a curvature radius changes are provided in a curler, and a straight line-shaped connection portion is provided between the first flexion point and the second flexion point so as to be located inside a curve formed by extending a first curved portion and a second curved portion that are located at the ends of the curler at the first flexion point and the second flexion point, according to the respective curvatures. Through this, it is possible to provide a blood pressure information measurement device cuff, and a blood pressure information measurement device provided with such a cuff, that can reduce error in a blood pressure measurement by reducing errors in changes in the volume of a fluid bladder.
摘要翻译：在血压信息测量装置袖带中，在卷曲器中设置曲率半径变化的第一屈曲点和第二屈曲点，并且在第一屈曲点和第二屈曲点之间设置直线状连接部以便位于通过根据各自的曲率在第一弯曲点和第二屈曲点处延伸位于卷曲器的端部处的第一弯曲部分和第二弯曲部分所形成的曲线内部。通过这种方式，可以提供一种血压信息测量装置袖带和具有这种袖带的血压信息测量装置，其可以通过减少流体囊体积的变化的误差来减少血压测量的误差。

9. 发明申请

US20120302901A1 BLOOD PRESSURE INFORMATION MEASUREMENT DEVICE 有权
标题翻译：血压信息测量装置
公开(公告)号：US20120302901A1
公开(公告)日：2012-11-29
申请号：US13567525
申请日：2012-08-06
申请人： Tatsuya Kobayashi , Kenji Fujii , Hideaki Yoshida
发明人： Tatsuya Kobayashi , Kenji Fujii , Hideaki Yoshida
IPC分类号： A61B5/0235 , A61B5/025
CPC分类号： A61B5/02233 , A61B5/022 , A61B5/02225 , A61B5/0235 , A61B5/7203
摘要： A blood pressure information measurement device includes a main body, including an inflation pump and an exhaust valve, and a cuff, including an air bladder for pulse wave measurement and an air bladder for blood pressure value measurement. The air bladder for pulse wave measurement and the air bladder for blood pressure value measurement are wrapped around a proximal side and a distal side of the upper arm, respectively. A first piping portion connects the air bladder for blood pressure value measurement to the inflation pump and the exhaust valve. A second piping portion branching from the first piping portion connects the air bladder for pulse wave measurement to the first piping portion. The second piping portion includes a 2-port valve that switches between connecting and disconnecting the air bladder for pulse wave measurement and the first piping portion, and a pressure sensor for measuring a pulse wave.
摘要翻译：血压信息测量装置包括包括充气泵和排气阀的主体和包括用于脉搏波测量的气囊和用于血压值测量的气囊的袖带。用于脉搏波测量的气囊和用于血压值测量的气囊分别围绕上臂的近侧和远侧缠绕。第一管道部分将用于血压值测量的气囊连接到充气泵和排气阀。从第一管道部分分支的第二管道部分将用于脉搏波测量的气囊连接到第一管道部分。第二管道部分包括在连接和断开用于脉搏波测量的气囊和第一管道部分之间切换的2通阀，以及用于测量脉搏波的压力传感器。

10. 发明授权

US08226623B2 Spread out-type paper diaper 有权
标题翻译：散布纸尿布
公开(公告)号：US08226623B2
公开(公告)日：2012-07-24
申请号：US10594663
申请日：2005-03-30
申请人： Hideaki Yoshida
发明人： Hideaki Yoshida
IPC分类号： A61F13/15 , A61F13/20
CPC分类号： A61F13/495
摘要： A comfortably wearable development type paper diaper comprises a back sheet, a first absorbent, a second absorbent and a liquid-permeable top sheet in the recited order. The first absorbent extends, when worn, from the back side through the crotch to the abdomen side of the user. The second absorbent extends, when worn, from the back side to the crotch of the user. A leakage preventing sheet allowing no liquid permeation is interposed between the first absorbent and the second absorbent. The second absorbent leaves the first absorbent from the crotch to the back side thereby to form a pocket PO for holding the excrement between the first absorbent and the second absorbent. The leakage preventing sheet is arranged to contact in the pocket PO with the second absorbent. The top sheet is so conformed to the shape of the pocket PO as to cover the leakage preventing sheet.
摘要翻译：一种舒适可佩戴的显影型纸尿布包括按照顺序的背片，第一吸收剂，第二吸收剂和透液性顶片。第一种吸收剂在穿戴时从背侧延伸穿过裆部到使用者的腹部侧。第二吸收剂在穿戴时从使用者的背侧延伸到裆部。在第一吸收剂和第二吸收剂之间插入不能透液的防漏片。第二吸收剂将第一吸收剂从裆部离开到后侧，从而形成用于将排泄物保持在第一吸收剂和第二吸收剂之间的口袋PO。泄漏防止片被布置成在袋PO中与第二吸收剂接触。顶片符合口袋PO的形状，以覆盖防漏片。

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