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1. 发明授权

US10352927B2 Glycoform detection method and glycoform detection device 有权
公开(公告)号：US10352927B2
公开(公告)日：2019-07-16
申请号：US14419804
申请日：2013-08-09
申请人： NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY
发明人： Hisashi Narimatsu , Atsushi Kuno , Yuzuru Ikehara , Yasuhiro Hashimoto , Keiro Shirotani , Kiyomitsu Nara , Yoshinobu Kariya , Hiromi Ito , Kyoka Hoshi
IPC分类号： G01N33/543 , G01N33/536 , G01N33/53 , G01N33/68
摘要： It is intended to develop and provide a method for detecting a particular glycan-isoform rapidly and specifically by a small number of steps. The present invention provides a glycan-isoform detection method comprising quantifying an immune complex formed by the mixing of a test sample with a sugar chain non-reducing terminal residue-binding lectin and an antibody specifically binding to the protein moiety of the glycan-isoform, etc., comparing the obtained amount of the immune complex with the amount of a control immune complex obtained when a control sample is not mixed with the sugar chain non-reducing terminal residue-binding lectin or is mixed with a control protein, and determining the presence or absence of the glycan-isoform of interest in the test sample on the basis of the difference between these amounts.

2. 发明申请

US20180106814A1 METHOD FOR MEASURING GLYCOPROTEIN, METHOD FOR EXAMINING LIVER DISEASE, REAGENT FOR QUANTITATIVE DETERMINATION OF GLYCOPROTEIN, AND GLYCAN-MARKER GLYCOPROTEIN AS AN INDEX FOR CLINICAL CONDITIONS OF LIVER DISEASE 审中-公开
公开(公告)号：US20180106814A1
公开(公告)日：2018-04-19
申请号：US15809160
申请日：2017-11-10
申请人： SYSMEX CORPORATION , NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY , NAGOYA CITY UNIVERSITY , NATIONAL CENTER FOR GLOBAL HEALTH AND MEDICINE
发明人： Hisashi Narimatsu , Yuzuru Ikehara , Atsushi Kuno , Maki Sogabe , Yasuhito Tanaka , Masashi Mizokami , Kiyoaki Ito , Shunsuke Matsubara , Chikayuki Tsuruno , Youichi Takahama , Takashi Kagawa , Shinya Nagai
IPC分类号： G01N33/68 , G01N33/574 , C07K14/47
CPC分类号： G01N33/68 , C07K14/4726 , C07K14/473 , G01N33/5308 , G01N33/57438 , G01N33/6893 , G01N2333/4724 , G01N2333/4728 , G01N2400/00 , G01N2400/02 , G01N2800/085 , Y10T436/143333
摘要： An object of the present invention is to provide a method for measuring a glycan-marker glycoprotein, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Also, an object of the present invention is to provide a method for examining liver disease, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Also, an object of the present invention is to provide a reagent for quantitative determination of a glycoprotein, which is used for the above measurement methods. Furthermore, an object of the present invention is to provide a glycan-marker glycoprotein as an index for clinical conditions of liver disease, which is capable of identifying the clinical conditions of liver disease depending on the progress of liver disease. The method for measuring a glycoprotein is characterized in that: the glycoprotein is at least one glycoprotein selected from alpha-1-acid glycoprotein (AGP) and Mac-2-binding protein (M2BP) contained in a sample collected from a subject; when the glycoprotein is AGP, AGP binding to a first lectin selected from AOL and MAL is measured; and when the glycoprotein is M2BP, M2BP binding to a second lectin selected from WFA, BPL, AAL, RCA120, and TJAII is measured.

3. 发明申请

US20170283506A1 LUNG CANCER DIFFERENTIAL MARKER 审中-公开
公开(公告)号：US20170283506A1
公开(公告)日：2017-10-05
申请号：US15620214
申请日：2017-06-12
申请人： National Institute of Advanced Industrial Science and Technology , Tokyo Medical University
发明人： Hisashi Narimatsu , Akira Togayachi , Yuzuru Ikehara , Hiroyuki Kaji , Atsushi Kuno , Takashi Ohkura , Hideki Matsuzaki , Yoshitoshi Hirao , Jun Iwaki , Minako Abe , Masaharu Nomura , Masayuki Noguchi
IPC分类号： C07K16/30 , C07K14/47
摘要： An object of the present invention is to develop and provide a lung cancer differential marker with which lung cancer can be diagnosed conveniently and highly sensitively without depending only on increase or decrease in protein expression level between cancer patients and healthy persons. Another object of the present invention is to develop and provide a glycan marker capable of distinguishing histological types of lung cancer. Of serum glycoproteins, glycopeptide and glycoprotein groups whose glycan structures were altered specifically in lung cancer cell culture supernatants were identified, and they are provided as lung cancer differential markers.

4. 发明申请

US20150329602A1 MODIFIED LECTIN DERIVED FROM WISTERIA FLORIBUNDA 有权
标题翻译：来自WISTERIA FLORIBUNDA的改良的LECTIN
公开(公告)号：US20150329602A1
公开(公告)日：2015-11-19
申请号：US14654223
申请日：2013-12-18
申请人： NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY
发明人： Takashi Sato , Yasunori Chiba , Hiroaki Tateno , Hiroyuki Kaji , Masanori Goto , Hisashi Narimatsu
IPC分类号： C07K14/42 , G01N33/53
CPC分类号： C07K14/42 , G01N33/5308 , G01N2333/42 , G01N2400/00
摘要： [Problem] The purpose of the present invention is to stably supply high-quality and highly uniform Wisteria floribunda agglutinin (WFA) that recognizes biologically important sugar-chain markers, to elucidate the sugar-chain recognition activity in detail, and to furthermore increase the specificity of the sugar-chain recognition activity. [Solution] The present invention involves the development of a technique for cloning genes for coding Wisteria floribunda agglutinin (WFA) and producing recombinant WFA having the same sugar-chain recognition activity as natural WFA from transformed bacteria. Natural WFA is reduced to thereby manufacture a reduced WFA monomer for specifically recognizing terminal GalNAc residue. A recombinant monomer WFA for recognizing LDN (GalNAcβ1, 4GlcNAc) sugar chain, which is important as a diagnostic marker among sugar chains having a terminal GalNAc residue, is manufactured by introducing cysteine mutation to recombinant WFA or by C-terminal-side amino acid deletion.
摘要翻译： [问题]本发明的目的是稳定地提供识别生物重要的糖链标记物的高品质和高度均匀的紫藤凝集素（WFA），以详细阐明糖链识别活性，并进一步增加糖链识别活性的特异性。 [解决方案]本发明涉及开发克隆用于编码Wisteria floribunda凝集素（WFA）的基因的克隆技术，并且生产与来自转化细菌的天然WFA具有相同糖链识别活性的重组WFA。减少天然WFA，从而制造用于特异性识别末端GalNAc残基的还原的WFA单体。通过将半胱氨酸突变引入重组WFA或C末端侧氨基酸来制备重要单体WFA，其用于识别LDN（GalNAc＆bgr; 1,4GlcNAc）糖链，其作为具有末端GalNAc残基的糖链中的诊断标记是重要的酸缺失。

5. 发明授权

US11571473B2 Method for efficiently inducing antibody, antibody and detection system for hepatitis virus 有权
公开(公告)号：US11571473B2
公开(公告)日：2023-02-07
申请号：US16972367
申请日：2019-06-06
申请人： NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY , UNIVERSITY OF TOYAMA
发明人： Hisashi Narimatsu , Kiyohiko Angata , Hiroyuki Kaji , Atsushi Kuno , Takashi Sato , Yasunori Chiba , Akira Togayachi , Hiroki Shimizu , Maki Sogabe , Takanori Wagatsuma , Masashi Mizokami , Masaaki Korenaga , Kazuto Tajiri , Tatsuhiko Ozawa
IPC分类号： A61K39/29 , C07K14/005 , A61P31/20 , C07K16/08 , G01N33/576 , A61K39/00
摘要： An examination system that recognizes a glycosylated antigen in Dane particles of hepatitis B virus (HBV) and a neutralizing antibody that recognizes the glycosylated antigen and that exhibits an infection-inhibiting activity. It was elucidated that Dane particles are associated with specific glycan structures, and this enabled the construction of a new detection system for infectious, i.e., nucleic acid-containing, hepatitis B virus particles and the provision of a neutralizing antibody that recognizes a glycosylated antigen and that exhibits an infection-inhibiting activity.

6. 发明授权

US10358466B2 Modified lectin derived from Wisteria floribunda 有权
公开(公告)号：US10358466B2
公开(公告)日：2019-07-23
申请号：US15706144
申请日：2017-09-15
申请人： NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY
发明人： Takashi Sato , Yasunori Chiba , Hiroaki Tateno , Hiroyuki Kaji , Masanori Goto , Hisashi Narimatsu
IPC分类号： C07K14/42 , G01N33/53
摘要： A Wisteria floribunda monomeric lectin polypeptide is provided. The Wisteria floribunda monomeric lectin polypeptide includes any one of the amino acid sequences selected from the group consisting of: (1) the amino acid sequence represented by SEQ ID NO: 2; (2) the amino acid sequence defined in (1) above, except that one to 20 amino acids at positions other than Cys272 position is/are deleted, substituted, inserted, or added; and (3) the amino acid sequence defined in (1) or (2) above, further having an N-terminus deletion of one to 30 amino acids, in which Cys272 is alkylated, and the polypeptide is capable of specifically binding to a GalNAc terminal sugar chain.

7. 发明申请

US20170336413A1 RHEUMATOID ARTHRITIS MARKER 审中-公开
公开(公告)号：US20170336413A1
公开(公告)日：2017-11-23
申请号：US15522152
申请日：2015-10-29
申请人： NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY , KEIO UNIVERSITY , GLYCOBIOMARKER LEADING INNOVATION CO. LTD.
发明人： Atsushi Kuno , Atsushi Matsuda , Hisashi Narimatsu , Tsutomu Takeuchi , Katsuya Suzuki , Masaru Taskeshita
IPC分类号： G01N33/573 , C07K16/40 , C07K14/42 , G01N33/564
CPC分类号： G01N33/573 , C07K14/42 , C07K16/40 , C12N9/64 , C12Y304/24017 , G01N33/53 , G01N33/564 , G01N2333/96494 , G01N2800/102
摘要： A method of evaluating disease activity of rheumatoid arthritis with good sensitivity by a simple method, and a kit for use in the method. It provides a Jacalin-binding O-linked oligosaccharide epitope as a negative marker for diagnosing rheumatoid arthritis, and enables more accurate assessment of disease condition by more objectively determining disease activity of rheumatoid arthritis using the amount of variation of a value obtained by multiplying the amount of MMP-3 in the blood or the amount of bound MMP-3 and ABA, ACA, or ACG in the blood by the reciprocal of the amount of bound MMP-3 and Jacalin in the blood. Through the discovery that an LEL or STL-reactive sugar chain on MMP-3 in the blood is a sugar chain marker for diagnosing polymyalgia rheumatica and relapsing polychondritis, the present invention also provides a method for accurate diagnosis of polymyalgia rheumatica and relapsing polychondritis.

8. 发明授权

US09371519B2 Complex type sugar chain hydrolase 有权
标题翻译：复合型糖链水解酶
公开(公告)号：US09371519B2
公开(公告)日：2016-06-21
申请号：US14349569
申请日：2012-10-03
申请人： National Institute of Advanced Industrial Science and Technology
发明人： Yasunori Chiba , Satoshi Murakami , Hisashi Narimatsu
IPC分类号： C12N9/24 , C12N9/42 , C12P21/00
CPC分类号： C12N9/2434 , C12N9/2402 , C12P21/005 , C12Y302/01052 , C12Y302/01096 , Y02P20/52
摘要： The present invention provides a novel endo-β-N-acetylglucosaminidase (Endo-Om) using a transformant produced by cloning an endo-β-N-acetylglucosaminidase (Endo-Om) gene originated from a methylotrophic yeast Ogataea minuta IFO10746 strain. The Endo-Om according to the present invention has a specific activity 13-fold higher than that of known Endo-M and a Vmax value 55-fold higher than that of the known Endo-M, and is useful for the analysis of the structures of sugar chains, including complex type sugar chains, in glycoproteins and the modification of the sugar chains. Also provided are an endo-β-N-acetylglucosaminidase (Endo-Cp), an endo-β-N-acetylglucosaminidase (Endo-Pa) and an endo-β-N-acetylglucosamimidase (Endo Zr) which are produced from Candida parapolymorpha DL-1 ATCC26012 strain, Pichia anomala ATCC36904 strain and Zygosaccharomyces rouxii ATCC2623 strain, respectively, on the basis of an Endo-Om gene sequence, and each of which has a similar level of complex type sugar chain cleavage activity and a similar level of complex type sugar chain transfer activity to those of Endo-Om.
摘要翻译：本发明提供了一种利用克隆衍生于甲基营养酵母Ogataea minuta IFO10746菌株的内切-G-乙酰氨基葡萄糖苷酶（Endo-Om）基因产生的转化体的新型内切-N-乙酰氨基葡糖苷酶（Endo-Om）。根据本发明的内消旋体具有比已知Endo-M高13倍的比活性，和比已知Endo-M高55倍的Vmax值，并且可用于分析结构的糖链，包括复合型糖链，糖蛋白和糖链的修饰。还提供了内源性N-乙酰氨基葡萄糖苷酶（Endo-Cp），内含量 - 乙酰氨基葡糖苷酶（Endo-Pa）和内含量 - 乙酰葡糖苷酶（Endo Zr），其由基于Endo-Om基因序列，分别具有类似水平的复合型糖链切割活性和类似水平的Paradolymorpha DL-1 ATCC26012菌株，异
毕赤酵母ATCC36904菌株和接合酵母属（Lygosaccharomyces rouxii）ATCC2623菌株的复合型糖链转移活性与Endo-Om的活性。

9. 发明申请

US20140057286A1 Method for Measuring Glycoprotein, Method for Examining Liver Desease, Reagent for Quantitative Determination of Glycoprotein and Glycan-Marker Glycoprotein as an Index for Clinical Conditions of Liver Disease 审中-公开
标题翻译：测定糖蛋白的方法，检测肝脏酶的方法，定量测定糖蛋白和糖标记糖蛋白作为肝脏疾病临床指标的试剂
公开(公告)号：US20140057286A1
公开(公告)日：2014-02-27
申请号：US14051729
申请日：2013-10-11
申请人： Sysmex Corporation , National Center for Global Health and Medicine , Nagoya City University , National Institute of Advanced Industrial Science and Technology
发明人： Hisashi Narimatsu , Yuzuru Ikehara , Atsushi Kuno , Maki Sogabe , Yasuhito Tanaka , Masashi Mizokami , Kiyoaki Ito , Shunsuke Matsubara , Chikayuki Tsuruno , Youichi Takahama , Takashi Kagawa , Shinya Nagai
IPC分类号： G01N33/68
CPC分类号： G01N33/68 , C07K14/4726 , C07K14/473 , G01N33/5308 , G01N33/57438 , G01N33/6893 , G01N2333/4724 , G01N2333/4728 , G01N2400/00 , G01N2400/02 , G01N2800/085 , Y10T436/143333
摘要： An object of the present invention is to provide a method for measuring a glycan-marker glycoprotein, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Also, an object of the present invention is to provide a method for examining liver disease, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Also, an object of the present invention is to provide a reagent for quantitative determination of a glycoprotein, which is used for the above measurement methods. Furthermore, an object of the present invention is to provide a glycan-marker glycoprotein as an index for clinical conditions of liver disease, which is capable of identifying the clinical conditions of liver disease depending on the progress of liver disease. The method for measuring a glycoprotein is characterized in that: the glycoprotein is at least one glycoprotein selected from alpha-1-acid glycoprotein (AGP) and Mac-2-binding protein (M2BP) contained in a sample collected from a subject; when the glycoprotein is AGP, AGP binding to a first lectin selected from AOL and MAL is measured; and when the glycoprotein is M2BP, M2BP binding to a second lectin selected from WFA, BPL, AAL, RCA120, and TJAII is measured.
摘要翻译：本发明的目的是提供一种测定聚糖标记糖蛋白的方法，通过该方法可以以比常规方法更高的精度检测肝脏疾病。另外，本发明的目的在于提供一种检查肝脏疾病的方法，通过该方法能够以比常规方法更高的精度检测肝脏疾病。另外，本发明的目的在于提供一种用于上述测定方法的糖蛋白定量试剂。此外，本发明的目的是提供聚糖标记糖蛋白作为肝病临床病症的指标，其能够根据肝病的进展来鉴定肝脏疾病的临床状况。测定糖蛋白的方法的特征在于：糖蛋白是从受试者收集的样品中含有的至少一种糖蛋白，其选自α-1-酸糖蛋白（AGP）和Mac-2结合蛋白（M2BP）当糖蛋白为AGP时，测量与选自AOL和MAL的第一凝集素结合的AGP; 并且当糖蛋白为M2BP时，测量与选自WFA，BPL，AAL，RCA120和TJAII的第二凝集素结合的M2BP。

10. 发明授权

US09796765B2 Modified lectin derived from Wisteria floribunda 有权
公开(公告)号：US09796765B2
公开(公告)日：2017-10-24
申请号：US14654223
申请日：2013-12-18
申请人： NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY
发明人： Takashi Sato , Yasunori Chiba , Hiroaki Tateno , Hiroyuki Kaji , Masanori Goto , Hisashi Narimatsu
IPC分类号： C07K14/42 , G01N33/53
CPC分类号： C07K14/42 , G01N33/5308 , G01N2333/42 , G01N2400/00
摘要： [Problem] The purpose of the present invention is to stably supply high-quality and highly uniform Wisteria floribunda agglutinin (WFA) that recognizes biologically important sugar-chain markers, to elucidate the sugar-chain recognition activity in detail, and to furthermore increase the specificity of the sugar-chain recognition activity.[Solution] The present invention involves the development of a technique for cloning genes for coding Wisteria floribunda agglutinin (WFA) and producing recombinant WFA having the same sugar-chain recognition activity as natural WFA from transformed bacteria. Natural WFA is reduced to thereby manufacture a reduced WFA monomer for specifically recognizing terminal GalNAc residue. A recombinant monomer WFA for recognizing LDN (GalNAcβ1, 4GlcNAc) sugar chain, which is important as a diagnostic marker among sugar chains having a terminal GalNAc residue, is manufactured by introducing cysteine mutation to recombinant WFA or by C-terminal-side amino acid deletion.

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