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1. 发明授权

US08187584B2 Human tumor necrosis factor-α mutants 有权
标题翻译：人肿瘤坏死因子-α突变体
公开(公告)号：US08187584B2
公开(公告)日：2012-05-29
申请号：US13205053
申请日：2011-08-08
申请人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Tsunetaka Ohta
发明人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Tsunetaka Ohta
IPC分类号： A61K38/19 , C07K14/525
CPC分类号： A61K38/191 , C07K14/525 , Y02A50/411
摘要： The present invention has an object to provide a tumor necrosis factor mutant protein, particularly, a tumor necrosis factor mutant protein specific to TNF-R1 or TNF-R2; tumor necrosis factor inhibitor; or tumor necrosis factor preparation containing it as an effective ingredient, and the object is solved by providing a tumor necrosis factor mutant protein where one or more amino acid residues selected from the group consisting of 29th, 31st, 32nd, 145th, 146th and 147th, or the group consisting of 84th to 89th from the N-terminal of the amino acid sequence of SEQ ID NO:1 is/are replaced with other amino acid residue(s); a tumor necrosis factor inhibitor; and a tumor necrosis factor preparation containing it as an effective ingredient.
摘要翻译：本发明的目的是提供肿瘤坏死因子突变蛋白，特别是TNF-R1或TNF-R2特异的肿瘤坏死因子突变体蛋白; 肿瘤坏死因子抑制剂; 或含有其作为有效成分的肿瘤坏死因子制剂，其目的是通过提供一种或多种选自第29,31,32,35,146和147位的氨基酸残基的肿瘤坏死因子突变蛋白来解决，或由SEQ ID NO：1的氨基酸序列的N末端第84位至第89位的基团被其它氨基酸残基取代; 肿瘤坏死因子抑制剂; 和含有它作为有效成分的肿瘤坏死因子制剂。

2. 发明授权

US07993636B2 Tumor necrosis factor-alpha mutants 有权
标题翻译：肿瘤坏死因子-α突变体
公开(公告)号：US07993636B2
公开(公告)日：2011-08-09
申请号：US10585296
申请日：2005-01-05
申请人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Tsunetaka Ohta
发明人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Tsunetaka Ohta
IPC分类号： C07K14/525
CPC分类号： A61K38/191 , C07K14/525 , Y02A50/411
摘要： The present invention has an object to provide a tumor necrosis factor mutant protein, particularly, a tumor necrosis factor mutant protein specific to TNF-R1 or TNF-R2; tumor necrosis factor inhibitor; or tumor necrosis factor preparation containing it as an effective ingredient, and the object is solved by providing a tumor necrosis factor mutant protein where one or more amino acid residues selected from the group consisting of 29th, 31st, 32nd, 145th, 146th and 147th, or the group consisting of 84th to 89th from the N-terminal of the amino acid sequence of SEQ ID NO:1 is/are replaced with other amino acid residue(s); a tumor necrosis factor inhibitor; and a tumor necrosis factor preparation containing it as an effective ingredient.
摘要翻译：本发明的目的是提供肿瘤坏死因子突变蛋白，特别是TNF-R1或TNF-R2特异的肿瘤坏死因子突变体蛋白; 肿瘤坏死因子抑制剂; 或含有其作为有效成分的肿瘤坏死因子制剂，其目的是通过提供一种或多种选自第29,31,32,35,146和147位的氨基酸残基的肿瘤坏死因子突变蛋白来解决，或由SEQ ID NO：1的氨基酸序列的N末端第84位至第89位的基团被其它氨基酸残基取代; 肿瘤坏死因子抑制剂; 和含有它作为有效成分的肿瘤坏死因子制剂。

3. 发明申请

US20110293555A1 TUMOR NECROSIS FACTOR-ALPHA MUTANTS 有权
标题翻译：肿瘤坏死因子-ALPHA突变体
公开(公告)号：US20110293555A1
公开(公告)日：2011-12-01
申请号：US13205053
申请日：2011-08-08
申请人： TADANORI MAYUMI , YASUO TSUTSUMI , SHINSAKU NAKAGAWA , TSUNETAKA OHTA
发明人： TADANORI MAYUMI , YASUO TSUTSUMI , SHINSAKU NAKAGAWA , TSUNETAKA OHTA
IPC分类号： A61K38/19 , A61P31/00 , C07K14/525
CPC分类号： A61K38/191 , C07K14/525 , Y02A50/411
摘要： The present invention has an object to provide a tumor necrosis factor mutant protein, particularly, a tumor necrosis factor mutant protein specific to TNF-R1 or TNF-R2; tumor necrosis factor inhibitor; or tumor necrosis factor preparation containing it as an effective ingredient, and the object is solved by providing a tumor necrosis factor mutant protein where one or more amino acid residues selected from the group consisting of 29th, 31st, 32nd, 145th, 146th and 147th, or the group consisting of 84th to 89th from the N-terminal of the amino acid sequence of SEQ ID NO:1 is/are replaced with other amino acid residue(s); a tumor necrosis factor inhibitor; and a tumor necrosis factor preparation containing it as an effective ingredient.
摘要翻译：本发明的目的是提供肿瘤坏死因子突变蛋白，特别是TNF-R1或TNF-R2特异的肿瘤坏死因子突变体蛋白; 肿瘤坏死因子抑制剂; 或含有其作为有效成分的肿瘤坏死因子制剂，其目的是通过提供一种或多种选自第29,31,32,35,146和147位的氨基酸残基的肿瘤坏死因子突变蛋白来解决，或由SEQ ID NO：1的氨基酸序列的N末端第84位至第89位的基团被其它氨基酸残基取代; 肿瘤坏死因子抑制剂; 和含有它作为有效成分的肿瘤坏死因子制剂。

4. 发明授权

US07189824B2 Tumor vessel endothelial cell-binding monoclonal antibodies 失效
标题翻译：肿瘤血管内皮细胞结合单克隆抗体
公开(公告)号：US07189824B2
公开(公告)日：2007-03-13
申请号：US10012271
申请日：2001-11-08
申请人： Tadanori Mayumi , Shinsaku Nakagawa , Yasuo Tsutsumi , Iwao Ohizumi
发明人： Tadanori Mayumi , Shinsaku Nakagawa , Yasuo Tsutsumi , Iwao Ohizumi
IPC分类号： C07K16/00 , C12P21/08 , A61K39/395 , G01N33/574 , C12P21/04
CPC分类号： C07K16/30 , A61K38/00 , C07K2317/73
摘要： A monoclonal antibody which recognizes an antigen of a molecular weight of 40 kD or 80 kD on the surface of tumor vessel endothelial cells, hybridomas producing the monoclonal antibody, pharmaceutical agents comprising the monoclonal antibody, as well as pharmaceutical or diagnostic agents comprising a conjugate of the monoclonal antibody and another conjugating molecule.
摘要翻译：识别肿瘤血管内皮细胞表面上分子量为40kD或80kD的抗原的单克隆抗体，产生单克隆抗体的杂交瘤，包含单克隆抗体的药物，以及含有该单克隆抗体的药物或诊断剂，单克隆抗体和另一种共轭分子。

5. 发明申请

US20050013795A1 Physiologically active complex 失效
标题翻译：生理活性复合物
公开(公告)号：US20050013795A1
公开(公告)日：2005-01-20
申请号：US10668178
申请日：2003-09-24
申请人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Hakuo Ikegami
发明人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Hakuo Ikegami
IPC分类号： A61K47/48 , C07K14/525 , A61K38/19 , C07K14/52
CPC分类号： C07K14/525 , A61K47/60
摘要： Disclosed is a physiologically active complex which comprises a proteinaceous part with TNF activity and a high molecular part bound artificially to the N-terminus of the proteinaceous part. The proteinaceous part in the complex has the amino acid sequence of SEQ ID NO:2 where Xaa is a member selected from the group consisting of asparagine, alanine, arginine, serine, threonine, proline, methionine, and leucine; while the high molecular part in the complex is a homopolymer of polyethylene glycol, copolymer of polyethylene glycol, or a derivative thereof.
摘要翻译：公开了一种生理活性配合物，其包含具有TNF活性的蛋白质部分和与蛋白质部分的N末端人工结合的高分子部分。复合物中的蛋白质部分具有SEQ ID NO：2的氨基酸序列，其中Xaa是选自天冬酰胺，丙氨酸，精氨酸，丝氨酸，苏氨酸，脯氨酸，甲硫氨酸和亮氨酸的成员; 而络合物中的高分子部分是聚乙二醇的均聚物，聚乙二醇或其衍生物的共聚物。

6. 发明授权

US06440733B1 Monoclonal antibodies recognizing antigens on the surface of endothelial cells of tumor vessel 失效
标题翻译：识别肿瘤血管内皮细胞表面的抗原的单克隆抗体
公开(公告)号：US06440733B1
公开(公告)日：2002-08-27
申请号：US09125162
申请日：1998-08-17
申请人： Tadanori Mayumi , Shinsaku Nakagawa , Yasuo Tsutsumi , Iwao Ohizumi
发明人： Tadanori Mayumi , Shinsaku Nakagawa , Yasuo Tsutsumi , Iwao Ohizumi
IPC分类号： C12N506
CPC分类号： C07K16/30 , A61K38/00 , C07K2317/73
摘要： A monoclonal antibody which recognizes an antigen of a molecular weight of 40 kD or 80 kD on the surface of tumor vessel endothelial cells, hybridomas producing said monoclonal antibody, pharmaceutical agents comprising said monoclonal antibody, as well as pharmaceutical or diagnostic agents comprising a conjugate of said monoclonal antibody and another conjugating molecule.
摘要翻译：识别肿瘤血管内皮细胞表面上分子量为40kD或80kD的抗原的单克隆抗体，产生所述单克隆抗体的杂交瘤，包含所述单克隆抗体的药物，以及含有所述单克隆抗体的药物或诊断剂，所述单克隆抗体和另一种缀合分子。

7. 发明授权

US07666403B2 Mutant interferon α protein and use thereof 失效
标题翻译：突变型干扰素α蛋白及其用途
公开(公告)号：US07666403B2
公开(公告)日：2010-02-23
申请号：US11719283
申请日：2005-11-09
申请人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Madoka Taniai , Kakuji Torigoe , Masashi Kurimoto
发明人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Madoka Taniai , Kakuji Torigoe , Masashi Kurimoto
IPC分类号： C07K14/52 , C12N15/21 , A61K38/21
CPC分类号： C07K14/56 , A61K38/00
摘要： The present invention has objects to provide a mutant interferon-α protein having a higher anti-viral and anti-tumor activity and to provide an agent for susceptive diseases, which contains the mutant interferon-α protein as an effective ingredient; and solves the above objects by providing a mutant protein which has an amino acid sequence of human interferon-α subtype α8 represented by any one of SEQ ID NOs:1 to 3, where the arginine residue at the 145th has been replaced with leucine, isoleucine, or valine residue; the alanine residue at the 146th has been replaced with asparagine or serine residue; and the methionine residue at the 149th has been replaced with tyrosine residue; and an agent for susceptive diseases, containing the mutant protein.
摘要翻译：本发明的目的是提供具有较高抗病毒和抗肿瘤活性的突变型干扰素-α蛋白质，并提供含有突变型干扰素-α蛋白作为有效成分的感染性疾病药物; 通过提供具有SEQ ID NO：1〜3中任一项所示的人干扰素-α亚型α8的氨基酸序列的突变蛋白来解决上述目的，其中第145位的精氨酸残基被亮氨酸替代，异亮氨酸，或缬氨酸残基; 第146位的丙氨酸残基被天冬酰胺或丝氨酸残基取代; 第149位的甲硫氨酸残基被酪氨酸残基取代; 和含有突变蛋白的感染性疾病的药剂。

8. 发明授权

US07521054B2 Reduction of the nonspecific animal toxicity of immunotoxins by mutating the framework regions of the Fv to lower the isoelectric point 有权
标题翻译：通过突变Fv的框架区域来降低免疫毒素的非特异性动物毒性以降低等电点
公开(公告)号：US07521054B2
公开(公告)日：2009-04-21
申请号：US10416129
申请日：2001-11-16
申请人： Ira H. Pastan , Masanori Onda , Satoshi Nagata , Yasuo Tsutsumi , James J. Vincent , Robert J. Kreitman , George Vasmatzis , Byungkook Lee
发明人： Ira H. Pastan , Masanori Onda , Satoshi Nagata , Yasuo Tsutsumi , James J. Vincent , Robert J. Kreitman , George Vasmatzis , Byungkook Lee
IPC分类号： A61K47/48 , C07K16/18 , C07K16/28
CPC分类号： C07K16/28 , A61K47/6829 , A61K47/6849 , A61K47/6867 , A61K2039/505 , C07K14/21 , C07K16/00 , C07K16/18 , C07K16/2803 , C07K16/2866 , C07K16/2896 , C07K16/30 , C07K2317/56 , C07K2317/567 , C07K2317/624 , C07K2319/02
摘要： The invention provides recombinant immunotoxins that have been modified from a parental immunotoxin to lower liver toxicity. The immunotoxins are created by specifically mutating charged residues in the framework regions of the heavy chain, the light chain, or both, of the antibody portion or antigen-binding fragment thereof of the parental immunotoxin to reduce the pI of the antibody or fragment. In preferred forms, the antibody portion of the parental is an anti-Tac, anti-mesothelin, or anti-LewisY antigen antibody or antigen-binding fragment, and in particularly preferred forms the antibody portion is an M16 dsFv, a St6 dsFv or a Mt9 dsFv, or a sequence that has at least 90% sequence identity to one of these molecules but retain the particular mutations that lower pI without affecting antibody activity. The invention further provides nucleic acids encoding the recombinant immunotoxins of the invention, expression cassettes comprising the nucleic acids, and host cells comprising the expression cassettes. The invention also provides a method for killing a cell comprising an antigen on the surface of the cell, the method comprising contacting the cell with a recombinant immunotoxin of the invention that has an antibody or antigen-binding fragment thereof that binds specifically to the antigen on the surface of the cell, and uses of immunotoxins of the invention for the manufacture of medicaments.
摘要翻译：本发明提供已经从亲本免疫毒素修饰以降低肝毒性的重组免疫毒素。免疫毒素通过在亲本免疫毒素的抗体部分或其抗原结合片段的重链，轻链或两者的构架区中特异性突变带电残基而产生，以减少抗体或片段的pI。在优选形式中，亲本的抗体部分是抗Tac，抗间皮素或抗LewisY抗原抗体或抗原结合片段，并且在特别优选的形式中，抗体部分是M16 dsFv，St6 dsFv或 Mt9 dsFv或与这些分子之一具有至少90％序列同一性的序列，但保留降低pI而不影响抗体活性的特定突变。本发明还提供编码本发明的重组免疫毒素的核酸，包含核酸的表达盒和包含表达盒的宿主细胞。本发明还提供了一种用于杀死细胞表面上包含抗原的细胞的方法，所述方法包括使细胞与本发明的重组免疫毒素接触，所述重组免疫毒素具有抗体或其抗原结合片段，其特异性与抗原结合细胞的表面，以及本发明的免疫毒素用于制备药物的用途。

9. 发明授权

US07179891B2 Physiologically active complex 失效
标题翻译：生理活性复合物
公开(公告)号：US07179891B2
公开(公告)日：2007-02-20
申请号：US10668178
申请日：2003-09-24
申请人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Hakuo Ikegami
发明人： Tadanori Mayumi , Yasuo Tsutsumi , Shinsaku Nakagawa , Hakuo Ikegami
IPC分类号： C01K1/00 , A61K45/00
CPC分类号： C07K14/525 , A61K47/60
摘要： Disclosed is a physiologically active complex which comprises a proteinaceous part with TNF activity and a high molecular part bound artificially to the N-terminus of the proteinaceous part. The proteinaceous part in the complex has the amino acid sequence of SEQ ID NO:2 where Xaa is a member selected from the group consisting of asparagine, alanine, arginine, serine, threonine, proline, methionine, and leucine; while the high molecular part in the complex is a homopolymer of polyethylene glycol, copolymer of polyethylene glycol, or a derivative thereof.
摘要翻译：公开了一种生理活性配合物，其包含具有TNF活性的蛋白质部分和与蛋白质部分的N末端人工结合的高分子部分。复合物中的蛋白质部分具有SEQ ID NO：2的氨基酸序列，其中Xaa是选自天冬酰胺，丙氨酸，精氨酸，丝氨酸，苏氨酸，脯氨酸，甲硫氨酸和亮氨酸的成员; 而络合物中的高分子部分是聚乙二醇的均聚物，聚乙二醇或其衍生物的共聚物。

10. 发明申请

US20060258005A1 Novel virus vector 审中-公开
标题翻译：新型病毒载体
公开(公告)号：US20060258005A1
公开(公告)日：2006-11-16
申请号：US10544986
申请日：2004-02-17
申请人： Tadanori Mayumi , Shinsaku Nakagawa , Yasuo Tsutsumi , Koichi Kawasaki , Mitsuko Maeda , Takao Hayakawa , Hiroyuki Mizuguchi
发明人： Tadanori Mayumi , Shinsaku Nakagawa , Yasuo Tsutsumi , Koichi Kawasaki , Mitsuko Maeda , Takao Hayakawa , Hiroyuki Mizuguchi
IPC分类号： C12N15/86 , C12N7/00
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10343 , C12N2810/405
摘要： There is provided a virus vector characterized in that a water-soluble polymer is directly or indirectly linked to a surface of a virus particle and a heterogeneous peptide having an affinity for integrin present on a surface of a target cell is linked to the water-soluble polymer.
摘要翻译：提供了一种病毒载体，其特征在于水溶性聚合物直接或间接连接到病毒颗粒的表面，并且对目标细胞表面上存在的整联蛋白具有亲和力的异质肽与水溶性聚合物。

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