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公开(公告)号：US08765669B2
公开(公告)日：2014-07-01
申请号：US12999654
申请日：2009-06-15
申请人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Naohiro Hayashi , Kazuyuki Ishii , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
发明人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Naohiro Hayashi , Kazuyuki Ishii , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
CPC分类号： C07K14/605 , A61K38/00
摘要： Oligosaccharide chain added GLP-1 peptides are more stable in blood and more active in controlling blood-sugar levels than GLP-1 peptides without added oligosaccharides. Oligosaccharide chain added GLP-1 peptides having GLP-1 activity include at least one or at least two amino acids each substituted with an oligosaccharide chain added amino acid in GLP-1; a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or a GLP-1 analog. Oligosaccharide chain added GLP-1 peptides with at least one amino acid substituted with an oligosaccharide chain added amino acid include an oligosaccharide chain with oligo hyaluronic acid. Oligosaccharide chain added amino acids include oligosaccharide chains attached to amino acids via linkers.
摘要翻译： 添加糖链的GLP-1肽在血液中更稳定，并且在没有添加低聚糖的情况下比GLP-1肽更有效地控制血糖水平。 具有GLP-1活性的添加糖链的GLP-1肽包括GLP-1中由糖链连接的氨基酸取代的至少一个或至少两个氨基酸; 具有GLP-1的氨基酸序列的肽，其具有缺失，取代或添加一个或几个氨基酸; 或GLP-1类似物。 具有至少一个被寡糖链添加的氨基酸取代的氨基酸的添加糖链的GLP-1肽包括具有寡聚透明质酸的寡糖链。 寡糖链添加的氨基酸包括通过接头连接到氨基酸的寡糖链。
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公开(公告)号：US08507429B2
公开(公告)日：2013-08-13
申请号：US13152082
申请日：2011-06-02
申请人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
发明人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
CPC分类号： C07K14/605 , A61K38/00
摘要： The present invention relates to an oligosaccharide chain added GLP-1 peptide that has higher stability in blood than that of GLP-1 and, preferably, exhibits higher activity of controlling blood-sugar levels than that of GLP-1. The present invention relates to an oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least one amino acid is substituted with an oligosaccharide chain added amino acid, in: (a) GLP-1; (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or (c) a GLP-1 analog.
摘要翻译： 本发明涉及一种与GLP-1相比血液中稳定性更高的糖链附加GLP-1肽，优选表现出比GLP-1更高的控制血糖水平的活性。 本发明涉及：（a）GLP-1;具有GLP-1活性的附加了糖链的GLP-1肽，其中至少一个氨基酸被添加了糖链的氨基酸取代。 （b）具有缺失，取代或添加一个或几个氨基酸的具有GLP-1氨基酸序列的肽; 或（c）GLP-1类似物。
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公开(公告)号：US07985731B2
公开(公告)日：2011-07-26
申请号：US12140866
申请日：2008-06-17
申请人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
发明人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
CPC分类号： C07K14/605 , A61K38/00
摘要： The present invention relates to an oligosaccharide chain added GLP-1 peptide that has higher stability in blood than that of GLP-1 and, preferably, exhibits higher activity of controlling blood-sugar levels than that of GLP-1. The present invention relates to an oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least one amino acid is substituted with an oligosaccharide chain added amino acid, in: (a) GLP-1; (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or (c) a GLP-1 analog.
摘要翻译： 本发明涉及一种与GLP-1相比血液中稳定性更高的糖链附加GLP-1肽，优选表现出比GLP-1更高的控制血糖水平的活性。 本发明涉及：（a）GLP-1;具有GLP-1活性的附加了糖链的GLP-1肽，其中至少一个氨基酸被添加了糖链的氨基酸取代。 （b）具有缺失，取代或添加一个或几个氨基酸的具有GLP-1氨基酸序列的肽; 或（c）GLP-1类似物。
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公开(公告)号：US20090111739A1
公开(公告)日：2009-04-30
申请号：US12140866
申请日：2008-06-17
申请人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
发明人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
CPC分类号： C07K14/605 , A61K38/00
摘要： The present invention relates to an oligosaccharide chain added GLP-1 peptide that has higher stability in blood than that of GLP-1 and, preferably, exhibits higher activity of controlling blood-sugar levels than that of GLP-1. The present invention relates to an oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least one amino acid is substituted with an oligosaccharide chain added amino acid, in: (a) GLP-1; (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or (c) a GLP-1 analog.
摘要翻译： 本发明涉及一种与GLP-1相比血液中稳定性更高的糖链附加GLP-1肽，优选表现出比GLP-1更高的控制血糖水平的活性。 本发明涉及：（a）GLP-1;具有GLP-1活性的附加了糖链的GLP-1肽，其中至少一个氨基酸被添加了糖链的氨基酸取代。 （b）具有缺失，取代或添加一个或几个氨基酸的具有GLP-1氨基酸序列的肽; 或（c）GLP-1类似物。
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公开(公告)号：US20110195897A1
公开(公告)日：2011-08-11
申请号：US12999654
申请日：2009-06-15
申请人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Naohiro Hayashi , Kazuyuki Ishii , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
发明人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Naohiro Hayashi , Kazuyuki Ishii , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
IPC分类号： A61K38/26 , C07K14/605 , A61P3/10
CPC分类号： C07K14/605 , A61K38/00
摘要： Oligosaccharide chain added GLP-1 peptides are more stable in blood and more active in controlling blood-sugar levels than GLP-1 peptides without added oligosaccharides. Oligosaccharide chain added GLP-1 peptides having GLP-1 activity include at least one or at least two amino acids each substituted with an oligosaccharide chain added amino acid in GLP-1; a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or a GLP-1 analog. Oligosaccharide chain added GLP-1 peptides with at least one amino acid substituted with an oligosaccharide chain added amino acid include an oligosaccharide chain with oligo hyaluronic acid. Oligosaccharide chain added amino acids include oligosaccharide chains attached to amino acids via linkers.
摘要翻译： 添加糖链的GLP-1肽在血液中更稳定，并且在没有添加低聚糖的情况下比GLP-1肽更有效地控制血糖水平。 具有GLP-1活性的添加糖链的GLP-1肽包括GLP-1中由糖链连接的氨基酸取代的至少一个或至少两个氨基酸; 具有GLP-1的氨基酸序列的肽，其具有缺失，取代或添加一个或几个氨基酸; 或GLP-1类似物。 具有至少一个被寡糖链添加的氨基酸取代的氨基酸的添加糖链的GLP-1肽包括具有寡聚透明质酸的寡糖链。 寡糖链添加的氨基酸包括通过接头连接到氨基酸的寡糖链。
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公开(公告)号：US08809258B2
公开(公告)日：2014-08-19
申请号：US12671238
申请日：2008-07-30
申请人： Yasuhiro Kajihara , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai
发明人： Yasuhiro Kajihara , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai
CPC分类号： C07K1/1133 , C07K1/04 , C07K1/1077 , C07K5/1008 , C07K7/06 , C07K9/00 , C07K14/001 , C07K14/4727
摘要： The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an -SMe group; (b) allowing the -SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).
摘要翻译： 本发明提供一种生产肽的方法，其特征在于包括将包含具有-SH基团的氨基酸残基的肽的-SH基转化为-OH基团，其中所述方法包括以下步骤（a） 至（c）：（a）使肽中的-SH基团与甲基化剂反应以将-SH基团转化为-SMe基团; （b）使步骤（a）中得到的-SMe基与氰化剂反应生成反应中间体; 和（c）将步骤（b）中获得的反应中间体转化为比在步骤（b）中的条件更碱性的条件下包含具有-OH基团的氨基酸残基的肽。
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公开(公告)号：US20110172392A1
公开(公告)日：2011-07-14
申请号：US12671238
申请日：2008-07-30
申请人： Yasuhiro Kajihara , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai
发明人： Yasuhiro Kajihara , Izumi Sakamoto , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai
IPC分类号： C07K1/113
CPC分类号： C07K1/1133 , C07K1/04 , C07K1/1077 , C07K5/1008 , C07K7/06 , C07K9/00 , C07K14/001 , C07K14/4727
摘要： The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an —SMe group; (b) allowing the —SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).
摘要翻译： 本发明提供一种生产肽的方法，其特征在于包括将包含具有-SH基团的氨基酸残基的肽的-SH基转化为-OH基团，其中所述方法包括以下步骤（a） 至（c）：（a）使肽中的-SH基团与甲基化剂反应以将-SH基团转化为-SMe基团; （b）使步骤（a）中得到的-SMe基与氰化剂反应生成反应中间体; 和（c）将步骤（b）中获得的反应中间体转化为比在步骤（b）中的条件更碱性的条件下包含具有-OH基团的氨基酸残基的肽。
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公开(公告)号：US20120047586A9
公开(公告)日：2012-02-23
申请号：US12739480
申请日：2008-10-23
申请人： Takashi Tsuji , Yasuhiro Kajihara , Katsunari Tezuka , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai
发明人： Takashi Tsuji , Yasuhiro Kajihara , Katsunari Tezuka , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai
CPC分类号： C07K16/00 , A61K38/00 , C07K16/2887 , C07K2317/72 , C07K2317/732 , C07K2319/30 , C07K2319/33
摘要： Disclosed is a polypeptide having an enhanced effector function. Specifically disclosed are: a polypeptide having a modified Fc region; a nucleic acid encoding the polypeptide; a vector carrying the nucleic acid; a host cell or a host organism harboring the vector; a pharmaceutical composition comprising the polypeptide; a method for producing the polypeptide; a method for enhancing the effector function of an antibody; and a method for producing a cell capable of producing an antibody having a high effector function.
摘要翻译： 公开了具有增强的效应子功能的多肽。 具体公开的是：具有修饰的Fc区的多肽; 编码该多肽的核酸; 携带核酸的载体; 携带载体的宿主细胞或宿主生物体; 包含该多肽的药物组合物; 一种生产该多肽的方法; 用于增强抗体的效应子功能的方法; 以及能够产生具有高效应功能的抗体的细胞的制备方法。
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公开(公告)号：US20100080794A1
公开(公告)日：2010-04-01
申请号：US12296901
申请日：2007-04-12
申请人： Takashi Tsuji , Yasuhiro Kajihara , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai , Akihiro Murakami
发明人： Takashi Tsuji , Yasuhiro Kajihara , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai , Akihiro Murakami
CPC分类号： C07K14/47 , C07K16/2887 , C07K2317/41 , C07K2317/72 , C07K2317/732
摘要： Mutant polypeptides of the present invention contain an Fc region in which a cysteine residue is substituted for the second amino acid from the glycosylation site to the N terminal side in the Fc region. The Fc region is preferably a human IgG Fc region. The mutant polypeptides of the present invention may also contain an N-linked sugar chain at the glycosylation site in Fc region. Furthermore, a polypeptide domain other than the Fc region of the mutant polypeptides of the present invention may be a polypeptide molecule that recognizes a human cell surface molecule.
摘要翻译： 本发明的突变体多肽含有Fc区，其中半胱氨酸残基取代Fc区中糖基化位点至N末端侧的第二个氨基酸。 Fc区优选为人IgG Fc区。 本发明的突变体多肽还可以在Fc区的糖基化位点含有N-连接的糖链。 此外，本发明的突变多肽的Fc区以外的多肽结构域可以是识别人细胞表面分子的多肽分子。
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公开(公告)号：US08058394B2
公开(公告)日：2011-11-15
申请号：US12295113
申请日：2007-03-28
申请人： Yasuhiro Kajihara , Naoki Yamamoto , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai
发明人： Yasuhiro Kajihara , Naoki Yamamoto , Yuri Nambu , Kazuhiro Fukae , Hiroaki Asai
CPC分类号： C07K14/001 , C07K1/04 , C07K1/042 , C07K9/00
摘要： The present invention provides a process for producing a peptide thioester compound. The process involves: (A) forming a peptide by a solid-phase synthesis method using a resin modified with a linker represented by the formula (1) as a solid phase: wherein R1 represents C1-4 alkyl group, R2 represents hydrogen atom or C1-4 alkoxy group, and n represents an integer of 1 to 4; (B) cleaving a bond between the solid phase and the peptide with at least one acid selected from dilute hydrochloric acid, dilute sulfuric acid, formic acid, and acetic acid to produce a peptide having a carboxyl group at the C-terminus; and (C) reacting a thiol compound with the peptide at −100 to 0° C. in the presence of a condensing agent in a solvent.
摘要翻译： 本发明提供了制备肽硫酯化合物的方法。 该方法包括：（A）使用由式（1）表示的接头改性的树脂作为固相，通过固相合成法形成肽：其中R1表示C1-4烷基，R2表示氢原子或 C 1-4烷氧基，n表示1〜4的整数。 （B）用至少一种选自稀盐酸，稀硫酸，甲酸和乙酸的酸，在固相和肽之间切断键，以产生C-末端具有羧基的肽; 和（C）在-100至0℃下在缩合剂存在下在溶剂中使硫醇化合物与肽反应。
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