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1. 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）。

2. 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）。

3. 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）。

4. 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）。

5. 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。

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. 发明申请

US20050249729A1 Anti-TRAIL-R antibody 审中-公开
标题翻译：抗TRAIL-R抗体
公开(公告)号：US20050249729A1
公开(公告)日：2005-11-10
申请号：US10721763
申请日：2003-11-26
申请人： Eiji Mori , Kazuhiro Motoki , Shiro Kataoka
发明人： Eiji Mori , Kazuhiro Motoki , Shiro Kataoka
IPC分类号： C07K16/28 , C12N1/19 , C12N1/21 , C12N15/13 , C12P21/08 , A61K39/395 , C07K16/30 , C12N5/06
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/73
摘要： Anti-TRAIL-R1 and R2 antibodies or functional fragments thereof, having at least one property selected from the following (a) to (c) of: (a) having activity to induce apoptosis in carcinoma cells expressing TRAIL-R1 and/or TRAIL-R2; (b) not having effect on normal human cells expressing TRAIL-R1 and/or TRAIL-R2; and (c) not inducing human hepatocyte toxicity, and an anti-TRAIL-R1 and R2 antibodies or functional fragments thereof, having the following properties: having activity to induce apoptosis in carcinoma cells independently of exogenous factors and as a monomer of an antibody.
摘要翻译：具有选自以下（a）至（c）中的至少一种性质的抗TRAIL-R1和R2抗体或其功能片段：（a）具有诱导表达TRAIL-R1和/或TRAIL的癌细胞凋亡的活性 -R2; （b）对表达TRAIL-R1和/或TRAIL-R2的正常人细胞无作用; 和（c）不诱导人肝细胞毒性，以及具有以下性质的抗TRAIL-R1和R2抗体或其功能片段：具有独立于外源因子诱导癌细胞凋亡的活性和作为抗体单体的活性。

8. 发明授权

US08486402B2 Anti-CD98 antibody 有权
标题翻译：抗CD98抗体
公开(公告)号：US08486402B2
公开(公告)日：2013-07-16
申请号：US13106280
申请日：2011-05-12
申请人： Tomoyuki Tahara , Yoshikatsu Kanai , Hitoshi Endou , Shiro Kataoka , Kazumasa Hasegawa , Tetsuya Yoshino
发明人： Tomoyuki Tahara , Yoshikatsu Kanai , Hitoshi Endou , Shiro Kataoka , Kazumasa Hasegawa , Tetsuya Yoshino
IPC分类号： A61K38/00
CPC分类号： C07K16/2896 , A61K2039/505 , C07K2317/21 , C07K2317/30 , C07K2317/33 , C07K2317/34 , C07K2317/565 , C07K2317/73 , C07K2317/76
摘要： A human antibody or a functional fragment thereof having specific binding ability to CD98 which is derived from the cell membrane of cancer cells and is in the form of a complex with a protein having an amino acid transporter activity (for example, LAT1) is disclosed. This antibody binds to CD98 in the form of a dimer with LAT1 on the surface of cancer cells, specifically attacks cancer cells expressing CD98 via the immune system by ADCC or CDC, and further inhibits amino acid uptake of the cancer cells via LAT1, to suppress growth of the cancer cells. Accordingly, a preventive and therapeutic agent for cancer comprising this antibody or a fragment thereof, which acts on various cancers, is specific to cancer, and causes no side effect, is provided.
摘要翻译：公开了具有来自癌细胞的细胞膜的与CD98特异性结合能力并与具有氨基酸转运蛋白活性的蛋白质（例如LAT1）形成复合物的形式的人抗体或其功能片段。该抗体以癌细胞表面的LAT1二聚体形式结合CD98，特异性地通过ADCC或CDC通过免疫系统侵袭表达CD98的癌细胞，并进一步通过LAT1抑制癌细胞的氨基酸摄取，抑制癌细胞的生长。因此，提供了作用于各种癌症的该抗体或其片段的癌症的预防和治疗剂，其对癌症是特异性的，并且不产生副作用。

9. 发明申请

US20070141054A1 Anti-a33 antibody 失效
标题翻译：抗-33抗体
公开(公告)号：US20070141054A1
公开(公告)日：2007-06-21
申请号：US11629779
申请日：2005-09-02
申请人： Shiro Kataoka , Takafumi Tomura , Noriko Otani
发明人： Shiro Kataoka , Takafumi Tomura , Noriko Otani
IPC分类号： A61K39/395 , C12N5/06
CPC分类号： C07K16/30 , A61K2039/505 , C07K16/2803 , C07K2317/21 , C07K2317/24 , C07K2317/56 , C07K2317/732 , C07K2317/734 , C07K2317/76
摘要： The present invention provides: an antibody or a antibody fragment thereof, which can bind to A33, which specifically attacks A33-expressing tumor cells with the use of ADCC and CDC based on the immune system, and for which no HAHA is produced; and a preventive or therapeutic agent for various malignant tumors including solid tumors that are currently treated with difficulty, which contains the antibody or an antibody fragment thereof. Specifically, the antibody or a functional fragment thereof is capable of binding to A33 and is produced by a hybridoma M10 (accession No. FERM BP-10107), M96 (accession No. FERM BP-10108), M165 (accession No. FERM BP-10106), N26 (accession No. FERM BP-10109), Q47 (accession No. FERM BP-10104), Q54 (accession No. FERM BP-10105), or R5 (accession No. FERM BP-10107). The preventive or therapeutic agent for tumors contains the antibody or a functional fragment thereof.
摘要翻译：本发明提供：可以结合A33的抗体或其抗体片段，其特异性地使用基于免疫系统的ADCC和CDC，并且不产生HAHA特异性攻击表达A33的肿瘤细胞; 以及包含抗体或其抗体片段的目前难以治疗的各种恶性肿瘤（包括实体瘤）的预防或治疗剂。具体地，抗体或其功能片段能够结合A33，并且由杂交瘤M10（登录号FERM BP-10107），M96（登录号FERM BP-10108），M165（登录号FERM BP -10106），N26（登录号FERM BP-10109），Q47（登录号FERM BP-10104），Q54（登录号FERM BP-10105）或R5（登录号FERM BP-10107）。肿瘤的预防或治疗剂含有抗体或其功能片段。

10. 发明授权

US07943745B2 Anti-CD98 antibody 有权
标题翻译：抗CD98抗体
公开(公告)号：US07943745B2
公开(公告)日：2011-05-17
申请号：US12295991
申请日：2007-04-05
申请人： Tomoyuki Tahara , Yoshikatsu Kanai , Hitoshi Endou , Shiro Kataoka , Kazumasa Hasegawa , Tetsuya Yoshino
发明人： Tomoyuki Tahara , Yoshikatsu Kanai , Hitoshi Endou , Shiro Kataoka , Kazumasa Hasegawa , Tetsuya Yoshino
IPC分类号： C12P21/08 , C12P21/04 , C07K16/00 , C07K17/00 , C07K17/14 , A61K39/395 , A61K39/00
CPC分类号： C07K16/2896 , A61K2039/505 , C07K2317/21 , C07K2317/30 , C07K2317/33 , C07K2317/34 , C07K2317/565 , C07K2317/73 , C07K2317/76
摘要： A human antibody or a functional fragment thereof having specific binding ability to CD98 which is derived from the cell membrane of cancer cells and is in the form of a complex with a protein having an amino acid transporter activity (for example, LAT1) is disclosed. This antibody binds to CD98 in the form of a dimer with LAT1 on the surface of cancer cells, specifically attacks cancer cells expressing CD98 via the immune system by ADCC or CDC, and further inhibits amino acid uptake of the cancer cells via LAT1, to suppress growth of the cancer cells. Accordingly, a preventive and therapeutic agent for cancer comprising this antibody or a fragment thereof, which acts on various cancers, is specific to cancer, and causes no side effect, is provided.
摘要翻译：公开了具有来自癌细胞的细胞膜的与CD98特异性结合能力并与具有氨基酸转运蛋白活性的蛋白质（例如LAT1）形成复合物的形式的人抗体或其功能片段。该抗体以癌细胞表面的LAT1二聚体形式结合CD98，特异性地通过ADCC或CDC通过免疫系统侵袭表达CD98的癌细胞，并进一步通过LAT1抑制癌细胞的氨基酸摄取，抑制癌细胞的生长。因此，提供了作用于各种癌症的该抗体或其片段的癌症的预防和治疗剂，其对癌症是特异性的，并且不产生副作用。

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