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1. 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。

2. 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）。

3. 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。

4. 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）。

5. 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）。

6. 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）。

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