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1. 发明授权

US08546537B2 Streptavidin having low immunogenicity and use thereof 有权
标题翻译：具有低免疫原性的链霉亲和素及其用途
公开(公告)号：US08546537B2
公开(公告)日：2013-10-01
申请号：US13202102
申请日：2010-02-19
申请人： Tatsuhiko Kodama , Takao Hamakubo , Hirofumi Doi , Akira Sugiyama , Kouhei Tsumoto
发明人： Tatsuhiko Kodama , Takao Hamakubo , Hirofumi Doi , Akira Sugiyama , Kouhei Tsumoto
IPC分类号： C07K14/00 , C07H21/02
CPC分类号： B82Y5/00 , A61K47/6898 , C07K14/36 , C07K16/14 , C07K2317/56 , C07K2317/622 , C07K2317/92
摘要： It is an object of the present invention to provide a mutant streptavidin wherein the immunogenicity (antigenicity) in mammals of a streptavidin is reduced. The present invention provides a mutant streptavidin, which comprises an amino acid sequence in which (a) the arginine residue at position 72 is substituted with another amino acid residue, and (b) any one or more of the tyrosine residue at position 10, the tyrosine residue at position 71, the glutamic acid residue at position 89, the arginine residue at position 91, and the glutamic acid residue at position 104 are substituted with other amino acid residues, with respect to the amino acid sequence of a core streptavidin as shown in SEQ ID NO: 2, and which has decreased immunogenicity as compared with that of a wild-type streptavidin.
摘要翻译：本发明的目的是提供一种突变型链霉抗生物素蛋白，其中链霉亲和素的哺乳动物中的免疫原性（抗原性）降低。本发明提供一种突变链霉抗生物素蛋白，其包含其中（a）第72位的精氨酸残基被另一个氨基酸残基取代的氨基酸序列，和（b）第10位的任何一个或多个酪氨酸残基，相对于核心链霉亲和素的氨基酸序列，如图所示，位置71的酪氨酸残基，89位的谷氨酸残基，91位的精氨酸残基和104位的谷氨酸残基被其它氨基酸残基取代与野生型链霉抗生物素蛋白相比具有降低的免疫原性。

2. 发明申请

US20120039879A1 STREPTAVIDIN HAVING LOW IMMUNOGENICITY AND USE THEREOF 有权
标题翻译：具有低免疫原性的STREPTAVIDIN及其使用
公开(公告)号：US20120039879A1
公开(公告)日：2012-02-16
申请号：US13202102
申请日：2010-02-19
申请人： Tatsuhiko Kodama , Takao Hamakubo , Hirofumi Doi , Akira Sugiyama , Kouhei Tsumoto
发明人： Tatsuhiko Kodama , Takao Hamakubo , Hirofumi Doi , Akira Sugiyama , Kouhei Tsumoto
IPC分类号： A61K39/395 , G01N33/82 , C07K19/00 , C07K14/36 , C12N15/31
CPC分类号： B82Y5/00 , A61K47/6898 , C07K14/36 , C07K16/14 , C07K2317/56 , C07K2317/622 , C07K2317/92
摘要： It is an object of the present invention to provide a mutant streptavidin wherein the immunogenicity (antigenicity) in mammals of a streptavidin is reduced. The present invention provides a mutant streptavidin, which comprises an amino acid sequence in which (a) the arginine residue at position 72 is substituted with another amino acid residue, and (b) any one or more of the tyrosine residue at position 10, the tyrosine residue at position 71, the glutamic acid residue at position 89, the arginine residue at position 91, and the glutamic acid residue at position 104 are substituted with other amino acid residues, with respect to the amino acid sequence of a core streptavidin as shown in SEQ ID NO: 2, and which has decreased immunogenicity as compared with that of a wild-type streptavidin.
摘要翻译：本发明的目的是提供一种突变型链霉抗生物素蛋白，其中链霉亲和素的哺乳动物中的免疫原性（抗原性）降低。本发明提供一种突变链霉抗生物素蛋白，其包含其中（a）第72位的精氨酸残基被另一个氨基酸残基取代的氨基酸序列，和（b）第10位的任何一个或多个酪氨酸残基，相对于核心链霉亲和素的氨基酸序列，如图所示，位置71的酪氨酸残基，89位的谷氨酸残基，91位的精氨酸残基和104位的谷氨酸残基被其它氨基酸残基取代与野生型链霉抗生物素蛋白相比具有降低的免疫原性。

3. 发明授权

US06482596B1 Method for measuring antigen concentration 有权
标题翻译：抗原浓度测定方法
公开(公告)号：US06482596B1
公开(公告)日：2002-11-19
申请号：US09313350
申请日：1999-05-18
申请人： Hiroshi Ueda , Teruyuki Nagamune , Hajime Nishimura , Izumi Kumagai , Kouhei Tsumoto , Walter C. Mahoney , Greg Winter , Paula A. Schueler
发明人： Hiroshi Ueda , Teruyuki Nagamune , Hajime Nishimura , Izumi Kumagai , Kouhei Tsumoto , Walter C. Mahoney , Greg Winter , Paula A. Schueler
IPC分类号： G01N3353
CPC分类号： G01N33/6845 , C07K16/18 , G01N33/68 , G01N33/6857
摘要： This invention provides a method for measuring an antigen concentration in a sample, which comprises: preparing VH-domain polypeptide and VL-domain polypeptide of an antibody specific to the antigen; labeling one of the polypeptides with a reporter molecule to form labeled polypeptides, and immobilizing the other polypeptide onto solid-phase to form immobilized polypeptides; contacting the antigen-containing sample and the labeled polypeptides with the solid-phase; and measuring the reporter molecule of the labeled polypeptides bound to the immobilized polypeptides. The present invention permits simpler and quicker sandwich ELISA for measurements of an antigen concentration in high sensitivity.
摘要翻译：本发明提供了一种测定样品中抗原浓度的方法，包括：制备抗原特异性抗体的VH结构域多肽和VL结构域多肽; 用报告分子标记多肽之一以形成标记的多肽，并将另一多肽固定在固相上以形成固定的多肽; 使含抗原的样品和标记的多肽与固相接触; 并测量与固定化多肽结合的标记多肽的报道分子。本发明允许更快和更快速的夹心ELISA来测量高灵敏度的抗原浓度。

4. 发明授权

US07635475B2 Diabody-type bispecific antibody 失效
标题翻译：双抗体型双特异性抗体
公开(公告)号：US07635475B2
公开(公告)日：2009-12-22
申请号：US10642284
申请日：2003-08-18
申请人： Izumi Kumagai , Toshio Kudo , Kouhei Tsumoto , Ryutaro Asano
发明人： Izumi Kumagai , Toshio Kudo , Kouhei Tsumoto , Ryutaro Asano
IPC分类号： A61K39/395 , C12P21/08
CPC分类号： C07K16/2863 , A61K2039/505 , C07K16/2809 , C07K2317/24 , C07K2317/56 , C07K2317/626
摘要： The purpose of the present invention is to provide a diabody-type bispecific antibody, which is characterized by having low immunogenicity and high infiltrating activity into tumor tissues, and by being easily mass-produced at a low cost with use of microorganisms, and by being easily altered in function by means of genetic engineering. The diabody-type bispecific antibody shows a more remarkable effect than the conventional diabody-type bispecific antibodies and chemically synthesized bispecific antibodies even in a very low concentration and in the absence of the super antigen. The present invention is related to a diabody-type bispecific antibody, having a first specificity to a human epidermal growth factor (EGF) receptor and a second specificity to a surface antigen expressed by a cell having phagocytosis or cytotoxic activity, a single-chain polypeptide constituting the antibody or each region contained therein, a nucleic acid encoding the polypeptide, a replicable cloning vector or expression vector comprising the nucleic acid, a host cell transformed with the vector, and a pharmaceutical preparation comprising thereof.
摘要翻译：本发明的目的是提供一种双抗体型双特异性抗体，其特征在于对肿瘤组织具有低的免疫原性和高的渗透活性，并且通过使用微生物容易地以低成本批量生产，并且通过通过遗传工程容易地改变功能。双抗体双特异性抗体比常规的双抗体型双特异性抗体和化学合成的双特异性抗体甚至在非常低的浓度和不存在超抗原的情况下显示出更显着的效果。本发明涉及对人表皮生长因子（EGF）受体具有第一特异性的双抗体型双特异性抗体和由具有吞噬作用或细胞毒活性的细胞表达的表面抗原的第二特异性，单链多肽构成抗体或其中包含的每个区域，编码多肽的核酸，可复制的克隆载体或包含该核酸的表达载体，用该载体转化的宿主细胞及其包含的药物制剂。

5. 发明授权

US5981199A Method for measuring antigen concentration 失效
标题翻译：抗原浓度测定方法
公开(公告)号：US5981199A
公开(公告)日：1999-11-09
申请号：US663922
申请日：1996-06-14
申请人： Hiroshi Ueda , Teruyuki Nagamune , Hajime Nishimura , Izumi Kumagai , Kouhei Tsumoto , Walter C. Mahoney , Greg Winter , Paula A. Schueler
发明人： Hiroshi Ueda , Teruyuki Nagamune , Hajime Nishimura , Izumi Kumagai , Kouhei Tsumoto , Walter C. Mahoney , Greg Winter , Paula A. Schueler
IPC分类号： C07K16/18 , G01N33/68 , G01N33/573 , G01N33/53 , G01N33/543
CPC分类号： G01N33/6845 , C07K16/18 , G01N33/68 , G01N33/6857
摘要： This invention provides a method for measuring an antigen concentration in a sample, which comprises: preparing VH-domain polypeptide and VL-domain polypeptide of an antibody specific to the antigen; labeling one of the polypeptides with a reporter molecule to form labeled polypeptides, and immobilizing the other polypeptides onto solid-phase to form immobilized polypeptides; contacting the antigen-containing sample and the labeled polypeptides with the solid-phase; and measuring the reporter molecule of the labeled polypeptides bound to the immobilized polypeptides. The present invention permits simpler and quicker sandwich ELISA for measurements of an antigen concentration in high sensitivity.
摘要翻译：本发明提供了一种测定样品中抗原浓度的方法，其包括：制备抗原特异性抗体的VH结构域多肽和VL结构域多肽; 用报告分子标记多肽之一以形成标记的多肽，并将其它多肽固定在固相上以形成固定的多肽; 使含抗原的样品和标记的多肽与固相接触; 并测量与固定化多肽结合的标记多肽的报道分子。本发明允许更快和更快速的夹心ELISA来测量高灵敏度的抗原浓度。

6. 发明申请

US20060210564A1 Novel diabody-type bispecific antibody 失效
标题翻译：新型双抗体型双特异性抗体
公开(公告)号：US20060210564A1
公开(公告)日：2006-09-21
申请号：US10642284
申请日：2003-08-18
申请人： Izumi Kumagai , Toshio Kudo , Kouhei Tsumoto , Ryutaro Asano
发明人： Izumi Kumagai , Toshio Kudo , Kouhei Tsumoto , Ryutaro Asano
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C12N15/74 , C12N1/21 , C07K16/24
CPC分类号： C07K16/2863 , A61K2039/505 , C07K16/2809 , C07K2317/24 , C07K2317/56 , C07K2317/626
摘要： The purpose of the present invention is to provide a diabody-type bispecific antibody, which is characterized by having low immunogenicity and high infiltrating activity into tumor tissues, and by being easily mass-produced at a low cost with use of microorganisms, and by being easily altered in function by means of genetic engineering. The diabody-type bispecific antibody shows a more remarkable effect than the conventional diabody-type bispecific antibodies and chemically synthesized bispecific antibodies even in a very low concentration and in the absence of the super antigen. The present invention is related to a diabody-type bispecific antibody, having a first specificity to a human epidermal growth factor (EGF) receptor and a second specificity to a surface antigen expressed by a cell having phagocytosis or cytotoxic activity, a single-chain polypeptide constituting the antibody or each region contained therein, a nucleic acid encoding the polypeptide, a replicable cloning vector or expression vector comprising the nucleic acid, a host cell transformed with the vector, and a pharmaceutical preparation comprising thereof.
摘要翻译：本发明的目的是提供一种双抗体型双特异性抗体，其特征在于对肿瘤组织具有低的免疫原性和高的渗透活性，并且通过使用微生物容易地以低成本批量生产，并且通过通过遗传工程容易地改变功能。双抗体双特异性抗体比常规的双抗体型双特异性抗体和化学合成的双特异性抗体甚至在非常低的浓度和不存在超抗原的情况下显示出更显着的效果。本发明涉及对人表皮生长因子（EGF）受体具有第一特异性的双抗体型双特异性抗体和由具有吞噬作用或细胞毒活性的细胞表达的表面抗原的第二特异性，单链多肽构成抗体或其中包含的每个区域，编码多肽的核酸，可复制的克隆载体或包含该核酸的表达载体，用该载体转化的宿主细胞及其包含的药物制剂。

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