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11. 发明授权

US08226958B2 Modified SEB and prophylactics/remedies for immunopathy containing the same 失效
标题翻译：修饰的SEB和预防药物/含有其的免疫疾病的补救措施
公开(公告)号：US08226958B2
公开(公告)日：2012-07-24
申请号：US10551263
申请日：2004-03-25
申请人： Toshihiro Nakashima , Takumi Sasaki , Kazuhiko Kimachi , Shigeki Kuwata , Tsukasa Nishihara , Atsuko Sakata , Masao Ohkuchi , Tomoyuki Koshi , Toshiyuki Edano
发明人： Toshihiro Nakashima , Takumi Sasaki , Kazuhiko Kimachi , Shigeki Kuwata , Tsukasa Nishihara , Atsuko Sakata , Masao Ohkuchi , Tomoyuki Koshi , Toshiyuki Edano
IPC分类号： A61K39/00 , A61K39/02 , A61K39/085 , C07K1/00 , C07K14/00 , C07K17/00
CPC分类号： A61K38/164 , C07K14/31 , C07K16/1271
摘要： A novel prophylactic/remedy for immunopathy is provided which is not neutralized by a neutralizing antibody to Staphylococcal enterotoxin B (SEB), known as one of superantigens, and may effectively act as a superantigen. A modified SEB having a reduced reactivity with a neutralizing antibody to SEB (anti-SEB antibody) and a prophylactic/remedy for immunopathy comprising as an active ingredient said modified SEB. The modified SEB of the present invention may be prepared with the evolutionary molecular engineering technique by introducing amino acid substitution in the amino acid sequence of SEB, especially at an epitope recognition site of the anti-SEB antibody in the amino acid sequence of SEB.
摘要翻译：提供一种免疫病的新型预防/治疗方法，其不被被称为超抗原之一的葡萄球菌肠毒素B（SEB）的中和抗体中和，并且可以有效地作为超抗原。与SEB中和抗体（抗SEB抗体）具有降低的反应性的修饰SEB和用于免疫病的预防/治疗方法，其包含所述经修饰的SEB作为活性成分。本发明的经修饰的SEB可以通过在SEB的氨基酸序列中引入氨基酸取代，特别是在SEB的氨基酸序列中的抗SEB抗体的表位识别位点处进行进化分子工程技术来制备。

12. 发明申请

US20050065155A1 Novel pyridazine derivatives and medicines containing the same as effective ingredients 审中-公开
标题翻译：新颖的哒嗪衍生物和含有与有效成分相同的药物
公开(公告)号：US20050065155A1
公开(公告)日：2005-03-24
申请号：US10986350
申请日：2004-11-12
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
IPC分类号： A61K31/50 , A61K31/501 , A61P19/02 , A61P19/10 , A61P29/00 , A61P37/00 , C07D213/00 , C07D237/00 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/04 , C07D401/06 , C07D43/02
CPC分类号： C07D401/04 , C07D237/02 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/06 , C07D401/14 , C07D413/04
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4-位被低级烷氧基或低级烷硫基取代的苯基 R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代的）含氮杂环残基，（取代的））氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5位之间的碳 - 碳键 - 位是单键或双键，或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

13. 发明申请

US20090143430A1 ERYTHROPOIETIN PRODUCTION ACCELERATOR 审中-公开
标题翻译：生产加速器
公开(公告)号：US20090143430A1
公开(公告)日：2009-06-04
申请号：US12326204
申请日：2008-12-02
申请人： Shigehiko IMAGAWA , Takeshi Doi , Masahiro Tamura , Masao Ohkuchi
发明人： Shigehiko IMAGAWA , Takeshi Doi , Masahiro Tamura , Masao Ohkuchi
IPC分类号： A61K31/4545
CPC分类号： A61K31/444 , A61K31/4468 , A61K31/4545 , C07D211/58 , C07D213/38 , C07D401/06 , C07D401/12 , C07D401/14
摘要： The present invention relates to a preventive or therapeutic agent for pathological conditions caused by reduced production of erythropoietin, or for anemia, or for chronic anemia, renal anemia, aplastic anemia, or pure red cell aplasia, the agent comprising, as an active ingredient, a cyclic amine compound represented by the following formula (1): wherein, R1, R2 and R3 each independently represent a hydrogen atom, a halogen atom, or hydroxy, alkyl, halogen-substituted alkyl, alkoxy, alkylthio, carboxyl, alkoxycarbonyl or alkanoyl group; W1 and W2 each independently represent N or CH; X represents O, NR4, CONR4 or NR4CO; R4 each represents a hydrogen atom, or an alkyl, alkenyl, alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, or substituted or unsubstituted heteroaralkyl group; and l, m and n each represents a number of 0 or 1, or a salt thereof or a solvate thereof.
摘要翻译：本发明涉及由促红细胞生成素或贫血，贫血，慢性贫血，肾性贫血，再生障碍性贫血或纯红细胞发育不全引起的病理状况的预防或治疗剂，所述药物包含作为活性成分的，由下式（1）表示的环胺化合物：其中，R 1，R 2和R 3各自独立地表示氢原子，卤素原子或羟基，烷基，卤素取代的烷基，烷氧基，烷硫基，羧基，烷氧基羰基或烷酰基组; W1和W2各自独立地表示N或CH; X表示O，NR4，CONR4或NR4CO; R 4各自表示氢原子，或烷基，烯基，炔基，取代或未取代的芳基，取代或未取代的杂芳基，取代或未取代的芳烷基或取代或未取代的杂芳烷基; l，m和n各自表示0或1的数，或其盐或其溶剂合物。

14. 发明申请

US20070166331A1 Modified seb and prophylactics/remedies for immunopathy containing the same 失效
标题翻译：用于含有其的免疫疾病的修饰型和预防药物/补救剂
公开(公告)号：US20070166331A1
公开(公告)日：2007-07-19
申请号：US10551263
申请日：2003-03-28
申请人： Toshihiro Nakashima , Takumi Sasaki , Kazuhiko Kimachi , Shigeki Kuwata , Tsukasa Nishihara , Atsuko Sakata , Masao Ohkuchi , Tomoyuki Koshi , Toshiyuki Edano
发明人： Toshihiro Nakashima , Takumi Sasaki , Kazuhiko Kimachi , Shigeki Kuwata , Tsukasa Nishihara , Atsuko Sakata , Masao Ohkuchi , Tomoyuki Koshi , Toshiyuki Edano
IPC分类号： A61K39/09 , C07K14/31
CPC分类号： A61K38/164 , C07K14/31 , C07K16/1271
摘要： A novel prophylactic/remedy for immunopathy is provided which is not neutralized by a neutralizing antibody to Staphylococcal enterotoxin B (SEB), known as one of superantigens, and may effectively act as a superantigen. A modified SEB having a reduced reactivity with a neutralizing antibody to SEB (anti-SEB antibody) and a prophylactic/remedy for immunopathy comprising as an active ingredient said modified SEB. The modified SEB of the present invention may be prepared with the evolutionary molecular engineering technique by introducing amino acid substitution in the amino acid sequence of SEB, especially at an epitope recognition site of the anti-SEB antibody in the amino acid sequence of SEB.
摘要翻译：提供一种免疫病的新型预防/治疗方法，其不被被称为超抗原之一的葡萄球菌肠毒素B（SEB）的中和抗体中和，并且可以有效地作为超抗原。与SEB中和抗体（抗SEB抗体）具有降低的反应性的修饰SEB和用于免疫病的预防/治疗方法，其包含所述经修饰的SEB作为活性成分。本发明的经修饰的SEB可以通过在SEB的氨基酸序列中引入氨基酸取代，特别是在SEB的氨基酸序列中的抗SEB抗体的表位识别位点处进行进化分子工程技术来制备。

15. 发明申请

US20070049595A1 Novel pyridazine derivatives and medicines containing the same as effective ingredients 审中-公开
标题翻译：新颖的哒嗪衍生物和含有与有效成分相同的药物
公开(公告)号：US20070049595A1
公开(公告)日：2007-03-01
申请号：US11590811
申请日：2006-11-01
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
IPC分类号： A61K31/50 , C07D237/02
CPC分类号： C07D401/04 , C07D237/02 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/06 , C07D401/14 , C07D413/04
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4位被取代的苯基通过低级烷氧基或低级烷硫基，R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代）的含氮杂环残基，（取代）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5-位之间的碳 - 碳键是单键或双键，或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

16. 发明申请

US20060160804A1 Novel pyridazine derivatives and medicines containing the same as effective ingredients 审中-公开
标题翻译：新颖的哒嗪衍生物和含有与有效成分相同的药物
公开(公告)号：US20060160804A1
公开(公告)日：2006-07-20
申请号：US11385995
申请日：2006-03-22
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
IPC分类号： A61K31/5377 , A61K31/501 , C07D413/02 , C07D403/02
CPC分类号： C07D401/04 , C07D237/02 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/06 , C07D401/14 , C07D413/04
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4位被取代的苯基通过低级烷氧基或低级烷硫基，R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代）的含氮杂环残基，（取代）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5-位之间的碳 - 碳键是单键或双键，或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

17. 发明授权

US06680316B1 Pyridazin-3-one derivatives and medicines containing the same 失效
标题翻译：哒嗪-3-酮衍生物及含有其的药物
公开(公告)号：US06680316B1
公开(公告)日：2004-01-20
申请号：US09926040
申请日：2001-08-20
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Hideo Yoshizaki , Tomoyuki Koshi , Takahiro Kitamura , Takayuki Matsuda , Kyoko Yasuoka , Tomoko Furuyama
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Hideo Yoshizaki , Tomoyuki Koshi , Takahiro Kitamura , Takayuki Matsuda , Kyoko Yasuoka , Tomoko Furuyama
IPC分类号： C07D23724
CPC分类号： C07D237/24
摘要： Objects of the invention are to provide compounds having excellent activity against interleukin-1&bgr; production and also medicines comprising them as effective ingredients. Pyridazin-3-one derivatives represented by the following formula (1): wherein Ar1 represents a substituted or unsubstituted aromatic group, Ar2 represents a phenyl group having a substituent at least at the 4-position thereof, R1 represents a linear or branched alkyl group, an alkyl group having a cyclic structure, a substituted or unsubstituted phenyl group or a substituted or unsubstituted phenyl(lower alkyl) group, and R2 represents a cyano group, a carboxyl group, a (lower alkoxy)carbonyl group, a substituted or unsubstituted lower alkyl group or a substituted or unsubstituted carbamoyl group, or salts thereof; and medicines comprising them as effective ingredients.
摘要翻译：本发明的目的是提供对白细胞介素-1β生产具有优异活性的化合物以及包含它们作为有效成分的药物。由下式（1）表示的哒嗪-3-酮衍生物：其中Ar 1表示取代或未取代的芳基，Ar 2表示至少在其4位具有取代基的苯基，R 1表示直链或支链烷基，具有环状结构的烷基，取代或未取代的苯基或取代或未取代的苯基（低级烷基），R 2表示氰基，羧基，（低级烷氧基）羰基，取代或未取代的低级烷基或取代或未取代的氨基甲酰基，或盐的; 和包含它们作为有效成分的药物。

18. 发明授权

US06403586B1 Pyridazine derivatives and drugs containing the same as the active ingredient 有权
标题翻译：哒嗪衍生物和含有与活性成分相同的药物
公开(公告)号：US06403586B1
公开(公告)日：2002-06-11
申请号：US09622897
申请日：2000-08-31
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Hideo Yoshizaki , Tomoyuki Koshi , Takahiro Kitamura , Takayuki Matsuda , Soichi Oda , Yuriko Habata , Kyoko Kotaki
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Hideo Yoshizaki , Tomoyuki Koshi , Takahiro Kitamura , Takayuki Matsuda , Soichi Oda , Yuriko Habata , Kyoko Kotaki
IPC分类号： A61K3150
CPC分类号： C07D401/06 , C07D237/02 , C07D237/04 , C07D237/22 , C07D237/24 , C07D401/12
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a lower alkoxyl group, a lower alkylthio group or a halogen atom; R2 represents H, a lower alkoxyl group, a lower alkylthio group or a halogen atom; R3 represents a lower alkyl or lower alkenyl group, which may be substituted by one or more OHs, CNs, lower cycloalkyl groups, (substituted) aromatic groups or (substituted) carbamoyl groups; R4 represents COOH, a lower alkoxycarbonyl group, a (substituted) carbamoyl group, a (substituted) amino group, or a (substituted) ureido group; and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1&bgr; production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R1表示低级烷氧基，低级烷硫基或卤素原子; R2表示H，低级烷氧基，低级烷硫基或卤素原子; R 3表示低级烷基或低级烯基，其可以被一个或多个OH，CN，低级环烷基，（取代的）芳族基团或（取代的）氨基甲酰基取代; R4表示COOH，低级烷氧基羰基，（取代）氨基甲酰基，（取代）氨基或（取代）脲基; 虚线表示4位和5位之间的碳 - 碳键为单键或双键，或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

19. 发明授权

US06348468B1 Pyridazine compounds and compositions containing the same 失效
标题翻译：哒嗪化合物及其组合物
公开(公告)号：US06348468B1
公开(公告)日：2002-02-19
申请号：US09530949
申请日：2000-05-15
申请人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
发明人： Masao Ohkuchi , Yoshinori Kyotani , Hiromichi Shigyo , Tomoyuki Koshi , Takahiro Kitamura , Tadaaki Ohgiya , Takayuki Matsuda , Yukiyoshi Yamazaki , Natsuyo Kumai , Kyoko Kotaki , Hideo Yoshizaki , Yuriko Habata
IPC分类号： A61K31501
CPC分类号： C07D401/04 , C07D237/02 , C07D237/04 , C07D237/14 , C07D237/18 , C07D401/06 , C07D401/14 , C07D413/04
摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1&bgr; production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.
摘要翻译：本发明涉及由式（1）表示的哒嗪衍生物：其中R1表示（取代的）芳基，R2表示通过低级烷氧基或低级烷硫基在4位被取代的苯基，R3表示低级烷氧基基团，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代的）含氮杂环残基，（取代的）氨基羰基或低级烷基羰基， A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5-位之间的碳 - 碳键为单键或双键键或其盐; 以及含有它们作为有效成分的药物。这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

20. 发明授权

US07947290B2 Protease-resistant modified SEB and vaccine containing the same 有权
标题翻译：蛋白酶抗性修饰SEB和含有相同的疫苗
公开(公告)号：US07947290B2
公开(公告)日：2011-05-24
申请号：US12644952
申请日：2009-12-22
申请人： Toshihiro Nakashima , Takumi Sasaki , Tsukasa Nishihara , Sumiyo Takemoto , Atsuko Sakata , Masao Ohkuchi , Tomoyuki Koshi , Toshiyuki Edano
发明人： Toshihiro Nakashima , Takumi Sasaki , Tsukasa Nishihara , Sumiyo Takemoto , Atsuko Sakata , Masao Ohkuchi , Tomoyuki Koshi , Toshiyuki Edano
IPC分类号： A61K39/085 , A61K39/09 , C07K1/00 , C07K14/00 , C07K17/00
CPC分类号： C07K14/31 , A61K39/00
摘要： A modified Staphylococcal enterotoxin B (SEB) having resistance to a protease and a reduced toxicity and a vaccine comprising said modified SEB are provided. A modified SEB which has an amino acid sequence as set forth in SEQ ID NO: 1 wherein each of the lysine at 97-position and the lysine at 98-position are substituted with any other amino acid, or a derivative thereof and a vaccine comprising said modified SEB or a derivative thereof.
摘要翻译：提供了具有对蛋白酶的抗性和毒性降低的改良的葡萄球菌肠毒素B（SEB）和包含所述修饰的SEB的疫苗。具有如SEQ ID NO：1所示的氨基酸序列的修饰的SEB，其中97位的赖氨酸和98位的赖氨酸都被任何其它氨基酸或其衍生物和包含所述修饰的SEB或其衍生物。

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