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1. 发明申请

US20130274446A1 FRAGMENT OF HUMANIZED ANTI-EGFR ANTIBODY SUBSTITUTED-LYSINE VARIABLE FRAGMENT AND USE THEREOF 有权
公开(公告)号：US20130274446A1
公开(公告)日：2013-10-17
申请号：US13816420
申请日：2011-07-16
申请人： Izumi Kumagai , Takeshi Nakanishi , Hideaki Sanada , Ryutaro Asano , Mitsuo Umetsu
发明人： Izumi Kumagai , Takeshi Nakanishi , Hideaki Sanada , Ryutaro Asano , Mitsuo Umetsu
IPC分类号： C07K16/28
CPC分类号： C07K16/2863 , C07K2317/24 , C07K2317/56 , C07K2317/622 , C07K2317/626
摘要： The purpose of the present invention is to provide fragments of humanized anti-EGFR antibody substituted-lysine light-chain or heavy-chain variable regions, and single-chain antibodies, etc, comprising the same, having sufficient binding activity (affinity) with target cells, and having the ability to undergo various site-specific and uniform chemical modifications. The present invention pertains to a humanized variable region on the light-chain or heavy-chain of antibody 528 against human epidermal cell growth factor receptor 1 (Her-1), said variable region comprising the amino acid sequence represented by SEQ ID NO: 2 or SEQ ID NO: 4, wherein fragments of humanized anti-EGFR antibody lysine-substituted light-chain variable regions are formed by substituting a different amino acid for all of the lysine residues, or all of the lysine residues except for the lysine residue(s) of one specified moiety.

2. 发明申请

US20100173360A1 ZINC OXIDE-BINDING ANTIBODY AND USE THEREOF 审中-公开
标题翻译： ZINC氧化物结合抗体及其用途
公开(公告)号：US20100173360A1
公开(公告)日：2010-07-08
申请号：US12527129
申请日：2008-02-14
申请人： Mitsuo Umetsu , Izumi Kumagai , Ryutaro Asano , Takeshi Nakanishi
发明人： Mitsuo Umetsu , Izumi Kumagai , Ryutaro Asano , Takeshi Nakanishi
IPC分类号： C12P21/02 , C07K16/00 , C12N15/00 , B01J19/00
CPC分类号： C07K16/44 , C07K2317/22 , C07K2318/10 , G01N33/54366
摘要： The present invention relates to a zinc oxide-binding antibody having high stability and binding activity, and high-throughput sensing technology using the antibody, such as biosensors. Specifically, the present invention relates to a peptide-grafted antibody that contains a zinc oxide-recognizing peptide in the CDR H-1 region of a camel antibody, and a solid support (e.g., a biosensor and a protein chip) containing a zinc oxide layer on which the antibody has been immobilized.
摘要翻译：本发明涉及具有高稳定性和结合活性的氧化锌结合抗体以及使用该抗体如生物传感器的高通量感测技术。具体地，本发明涉及在骆驼抗体的CDR H-1区域含有氧化锌识别肽的固体支持物（例如，生物传感器和蛋白质芯片），其含有氧化锌已经固定有抗体的层。

3. 发明授权

US08921525B2 Highly-functional mutant of humanized anti-EGFR antibody variable region 有权
标题翻译：人源化抗EGFR抗体可变区的高功能突变体
公开(公告)号：US08921525B2
公开(公告)日：2014-12-30
申请号：US13510516
申请日：2010-11-11
申请人： Izumi Kumagai , Takeshi Nakanishi , Ryutaro Asano , Mitsuo Umetsu
发明人： Izumi Kumagai , Takeshi Nakanishi , Ryutaro Asano , Mitsuo Umetsu
IPC分类号： C07K16/22 , C07K16/30 , C07K16/28
CPC分类号： C07K16/22 , C07K16/2809 , C07K16/2863 , C07K2317/24 , C07K2317/31 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2317/626 , C07K2317/73 , C07K2317/92
摘要： [Problem]Disclosed is an antibody that exhibits excellent cytotoxicity and cell growth inhibition and that is based on an anti-human epithelial cell growth factor receptor (1) (Her1) antibody (528). Further disclosed is a method for producing same, and the like.[Solution]The mutant of an H chain humanized variable region (5H) or an L chain humanized variable region (5L) of the anti-human epithelial cell growth factor receptor (1) (Her1) antibody (528) is the aforementioned antibody characterized by having one to a plurality (for example: 1 to 5, or 1 to 3) of amino acid mutations within CDR2. Further disclosed are antibody molecules containing said region, a nucleic acid molecule coding for these polypeptides, a method for producing said antibody molecules, and the like.
摘要翻译： [问题]公开了一种表现出优异的细胞毒性和细胞生长抑制的抗体，其基于抗人上皮细胞生长因子受体（1）（Her1）抗体（528）。进一步公开了其制造方法等。 [解决方案]抗人上皮细胞生长因子受体（1）（Her1）抗体（528）的H链人源化可变区（5H）或L链人源化可变区（5L）的突变体是上述抗体通过在CDR2内具有1至多个（例如：1至5个，或1至3个）氨基酸突变。进一步公开的是含有所述区域的抗体分子，编码这些多肽的核酸分子，产生所述抗体分子的方法等。

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

US09315584B2 LH-type bispecific antibody 有权
标题翻译： LH型双特异性抗体
公开(公告)号：US09315584B2
公开(公告)日：2016-04-19
申请号：US13257614
申请日：2010-01-04
申请人： Izumi Kumagai , Ryutaro Asano , Mitsuo Umetsu
发明人： Izumi Kumagai , Ryutaro Asano , Mitsuo Umetsu
IPC分类号： A61K39/00 , C07K16/18 , C07K16/46 , C07K16/28
CPC分类号： C07K16/468 , C07K16/2809 , C07K16/2863 , C07K16/46 , C07K2317/14 , C07K2317/24 , C07K2317/31 , C07K2317/622 , C07K2317/626
摘要： Provided are a novel diabody type bispecific antibody, the function of which as a bispecific antibody is improved to provide a higher additional value, such as cost saving caused by a reduction in dose, to a drug; and a method for producing the same. A humanized diabody type bispecific antibody (LH-diabody type bispecific antibody) characterized in that an L-chain is located in the N-terminal side in each polypeptide (LH type); a humanized high-functional bispecific antibody which contains said LH diabody type bispecific antibody; a nucleic acid molecule encoding both of two kinds of single-stranded polypeptides constituting said bispecific antibody; and a method for producing said antibody which comprises culturing a host cell having been transformed by an expression vector containing said nucleic acid molecule.
摘要翻译：提供了一种新的双抗体型双特异性抗体，其作为双特异性抗体的功能被改进以提供更高的额外价值，例如药物降低引起的成本节省; 及其制造方法。一种人源化双抗体型双特异性抗体（LH-双抗体型双特异性抗体），其特征在于L链位于每个多肽（LH型）中的N末端侧; 含有所述LH双抗体型双特异性抗体的人源化高功能双特异性抗体; 编码构成所述双特异性抗体的两种单链多肽的核酸分子; 以及生产所述抗体的方法，包括培养已经通过含有所述核酸分子的表达载体转化的宿主细胞。

6. 发明申请

US20130131320A1 HIGHLY-FUNCTIONAL MUTANT OF HUMANIZED ANTI-EGFR ANTIBODY VARIABLE REGION 有权
标题翻译：人类抗EGFR抗体可变区域的高功能突变体
公开(公告)号：US20130131320A1
公开(公告)日：2013-05-23
申请号：US13510516
申请日：2010-11-11
申请人： Izumi Kumagai , Takeshi Nakanishi , Ryutaro Asano , Mitsuo Umetsu
发明人： Izumi Kumagai , Takeshi Nakanishi , Ryutaro Asano , Mitsuo Umetsu
IPC分类号： C07K16/22
CPC分类号： C07K16/22 , C07K16/2809 , C07K16/2863 , C07K2317/24 , C07K2317/31 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2317/626 , C07K2317/73 , C07K2317/92
摘要： [Problem]Disclosed is an antibody that exhibits excellent cytotoxicity and cell growth inhibition and that is based on an anti-human epithelial cell growth factor receptor (1) (Her1) antibody (528). Further disclosed is a method for producing same, and the like.[Solution]The mutant of an H chain humanized variable region (5H) or an L chain humanized variable region (5L) of the anti-human epithelial cell growth factor receptor (1) (Her1) antibody (528) is the aforementioned antibody characterized by having one to a plurality (for example: 1 to 5, or 1 to 3) of amino acid mutations within CDR2. Further disclosed are antibody molecules containing said region, a nucleic acid molecule coding for these polypeptides, a method for producing said antibody molecules, and the like.
摘要翻译： [问题]公开了一种表现出优异的细胞毒性和细胞生长抑制的抗体，其基于抗人上皮细胞生长因子受体（1）（Her1）抗体（528）。进一步公开了其制造方法等。 [解决方案]抗人上皮细胞生长因子受体（1）（Her1）抗体（528）的H链人源化可变区（5H）或L链人源化可变区（5L）的突变体是上述抗体通过在CDR2内具有1至多个（例如：1至5个，或1至3个）氨基酸突变。进一步公开的是含有所述区域的抗体分子，编码这些多肽的核酸分子，产生所述抗体分子的方法等。

7. 发明申请

US20090202532A1 High Functional Bispecific Antibody 有权
标题翻译：高功能双特异性抗体
公开(公告)号：US20090202532A1
公开(公告)日：2009-08-13
申请号：US12225308
申请日：2006-10-16
申请人： Izumi Kumagai , Ryutaro Asano
发明人： Izumi Kumagai , Ryutaro Asano
IPC分类号： A61K39/395 , C07K16/28 , C07H21/04 , C12N15/63 , C12N5/00 , C12P21/06
CPC分类号： C07K16/2809 , A61K35/12 , A61K39/39558 , C07K16/2863 , C07K2317/24 , C07K2317/31 , C07K2317/622 , C07K2317/626 , C07K2317/64 , C07K2317/732
摘要： [Problem]The purpose of the present invention is to provide a bispecific antibody that is structurally stable, and can show alone a sufficient effect without the co-administration of activated lymphocyte (T-LAK). [Solution] The present invention is therefore related to a humanized highly functional bispecific antibody comprising humanized variable regions of the heavy chain (5H) and the light chain (5L) of an anti-human EGF receptor 1 antibody 528, and humanized variable regions of the heavy chain (OH) and the light chain (OL) of an anti-CD3 antibody OKT3; and having one of the following structures (i)-(vi) in Claim 1, wherein the 5H, 5L, OH and OL have an amino acid sequence represented by SEQ ID Nos 25, 26, 27 and 28, respectively.
摘要翻译：本发明的目的是提供结构稳定的双特异性抗体，并且可以在没有共同给予活化淋巴细胞（T-LAK）的情况下显示出足够的效果。因此，本发明涉及包含抗人EGF受体1抗体528的重链（5H）和轻链（5L）的人源化可变区的人源化高功能双特异性抗体，以及人源化可变区抗CD3抗体OKT3的重链（OH）和轻链（OL）; 并且具有如权利要求1所述的以下结构（i） - （vi）之一，其中所述5H，5L，OH和OL分别具有由SEQ ID No：25,26,27和28表示的氨基酸序列。

8. 发明授权

US09315578B2 High functional bispecific antibody 有权
标题翻译：高功能双特异性抗体
公开(公告)号：US09315578B2
公开(公告)日：2016-04-19
申请号：US12225308
申请日：2006-10-16
申请人： Izumi Kumagai , Ryutaro Asano
发明人： Izumi Kumagai , Ryutaro Asano
IPC分类号： A61K39/395 , C07K16/00 , C07K16/28
CPC分类号： C07K16/2809 , A61K35/12 , A61K39/39558 , C07K16/2863 , C07K2317/24 , C07K2317/31 , C07K2317/622 , C07K2317/626 , C07K2317/64 , C07K2317/732
摘要： [Problem]The purpose of the present invention is to provide a bispecific antibody that is structurally stable, and can show alone a sufficient effect without the co-administration of activated lymphocyte (T-LAK).[Solution]The present invention is therefore related to a humanized highly functional bispecific antibody comprising humanized variable regions of the heavy chain (5H) and the light chain (5L) of an anti-human EGF receptor 1 antibody 528, and humanized variable regions of the heavy chain (OH) and the light chain (OL) of an anti-CD3 antibody OKT3; and having one of the following structures (i)-(vi) in Claim 1, wherein the 5H, 5L, OH and OL have an amino acid sequence represented by SEQ ID Nos 25, 26, 27 and 28, respectively.
摘要翻译：本发明的目的是提供结构稳定的双特异性抗体，并且可以在没有共同给予活化淋巴细胞（T-LAK）的情况下显示出足够的效果。因此，本发明涉及包含抗人EGF受体1抗体528的重链（5H）和轻链（5L）的人源化可变区的人源化高功能双特异性抗体，以及人源化可变区抗CD3抗体OKT3的重链（OH）和轻链（OL）; 并且具有如权利要求1所述的以下结构（i） - （vi）之一，其中所述5H，5L，OH和OL分别具有由SEQ ID No：25,26,27和28表示的氨基酸序列。

9. 发明授权

US09139650B2 Fragment of humanized anti-EGFR antibody substituted-lysine variable fragment and use thereof 有权
标题翻译：人源化抗EGFR抗体取代赖氨酸可变片段的片段及其用途
公开(公告)号：US09139650B2
公开(公告)日：2015-09-22
申请号：US13816420
申请日：2011-07-16
申请人： Izumi Kumagai , Takeshi Nakanishi , Hideaki Sanada , Ryutaro Asano , Mitsuo Umetsu
发明人： Izumi Kumagai , Takeshi Nakanishi , Hideaki Sanada , Ryutaro Asano , Mitsuo Umetsu
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2863 , C07K2317/24 , C07K2317/56 , C07K2317/622 , C07K2317/626
摘要： The purpose of the present invention is to provide fragments of humanized anti-EGFR antibody substituted-lysine light-chain or heavy-chain variable regions, and single-chain antibodies, etc, comprising the same, having sufficient binding activity (affinity) with target cells, and having the ability to undergo various site-specific and uniform chemical modifications. The present invention pertains to a humanized variable region on the light-chain or heavy-chain of antibody 528 against human epidermal cell growth factor receptor 1 (Her-1), said variable region comprising the amino acid sequence represented by SEQ ID NO: 2 or SEQ ID NO: 4, wherein fragments of humanized anti-EGFR antibody lysine-substituted light-chain variable regions are formed by substituting a different amino acid for all of the lysine residues, or all of the lysine residues except for the lysine residue(s) of one specified moiety.
摘要翻译：本发明的目的是提供人源化抗EGFR抗体取代的赖氨酸轻链或重链可变区的片段，以及包含该片段的具有足够的与靶标结合活性（亲和力）的单链抗体并且具有进行各种位点特异性和均匀化学修饰的能力。本发明涉及针对人表皮细胞生长因子受体1（Her-1）的抗体528的轻链或重链上的人源化可变区，所述可变区包含SEQ ID NO：2所示的氨基酸序列或SEQ ID NO：4，其中人源化抗EGFR抗体赖氨酸取代的轻链可变区的片段通过用不同的氨基酸取代所有赖氨酸残基或除赖氨酸残基之外的所有赖氨酸残基形成（ s）。

10. 发明申请

US20120095191A1 LH-TYPE BISPECIFIC ANTIBODY 有权
标题翻译： LH型双相抗体
公开(公告)号：US20120095191A1
公开(公告)日：2012-04-19
申请号：US13257614
申请日：2010-01-04
申请人： Izumi Kumagai , Ryutaro Asano , Mitsuo Umetsu
发明人： Izumi Kumagai , Ryutaro Asano , Mitsuo Umetsu
IPC分类号： C07K16/46 , C12P21/02 , C12N1/21 , C12N15/62 , C12N15/63
CPC分类号： C07K16/468 , C07K16/2809 , C07K16/2863 , C07K16/46 , C07K2317/14 , C07K2317/24 , C07K2317/31 , C07K2317/622 , C07K2317/626
摘要： Provided are a novel diabody type bispecific antibody, the function of which as a bispecific antibody is improved to provide a higher additional value, such as cost saving caused by a reduction in dose, to a drug; and a method for producing the same. A humanized diabody type bispecific antibody (LH-diabody type bispecific antibody) characterized in that an L-chain is located in the N-terminal side in each polypeptide (LH type); a humanized high-functional bispecific antibody which contains said LH diabody type bispecific antibody; a nucleic acid molecule encoding both of two kinds of single-stranded polypeptides constituting said bispecific antibody; and a method for producing said antibody which comprises culturing a host cell having been transformed by an expression vector containing said nucleic acid molecule.
摘要翻译：提供了一种新的双抗体型双特异性抗体，其作为双特异性抗体的功能被改进以提供更高的额外价值，例如药物降低引起的成本节省; 及其制造方法。一种人源化双抗体型双特异性抗体（LH-双抗体型双特异性抗体），其特征在于L链位于每个多肽（LH型）中的N末端侧; 含有所述LH双抗体型双特异性抗体的人源化高功能双特异性抗体; 编码构成所述双特异性抗体的两种单链多肽的核酸分子; 以及生产所述抗体的方法，包括培养已经通过含有所述核酸分子的表达载体转化的宿主细胞。

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