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1. 发明申请

US20090233336A1 PROCESS FOR PRODUCING CHONDROITIN 审中-公开
标题翻译：生产氯苯醌的方法
公开(公告)号：US20090233336A1
公开(公告)日：2009-09-17
申请号：US12094208
申请日：2006-11-16
申请人： Nobuo Sugiura , Satoshi Shimokata , Koji Kimata
发明人： Nobuo Sugiura , Satoshi Shimokata , Koji Kimata
IPC分类号： C12P19/04
CPC分类号： C12P19/26
摘要： A method for producing a chondroitin (CH) with a desired sugar chain length; a method for producing a fraction containing a CH with a substantially single sugar chain length; etc. There is provided a method for producing a CH with desired sugar chain length, comprising alternately performing the steps (a) allowing a receptor substrate having a glucuronic acid residue at its non-reducing end (when this step is performed after the step (b), sugar chain obtained by the step (b)), an N-acetylgalactosamine donor and an N-acetylgalactosamine transferase to coexist in a reaction system and (b) allowing a receptor substrate having an N-acetylgalactosamine residue at its non-reducing end (when this step is performed after the step (a), sugar chain obtained by the step (a)), a glucuronic acid donor and a glucuronic acid transferase to coexist in a reaction system.
摘要翻译：一种制备具有所需糖链长度的软骨素（CH）的方法; 一种生产含有基本上单一糖链长度的CH的级分的方法; 提供了一种制备具有期望的糖链长度的CH的方法，其包括交替地执行以下步骤：（a）允许在其非还原末端具有葡萄糖醛酸残基的受体底物（步骤后步骤 b），通过步骤（b）获得的糖链），N-乙酰半乳糖胺供体和N-乙酰半乳糖胺转移酶共存于反应体系中，和（b）在其不还原条件下使具有N-乙酰半乳糖胺残基的受体底物（步骤（a）后的步骤，通过步骤（a）获得的糖链），葡萄糖醛酸供体和葡糖醛酸转移酶共存于反应体系中。

2. 发明授权

US5733892A Metastasis inhibitor composition comprising a phospholipid-linked glycosaminoglycan and method for inhibiting metastasis employing the same 失效
标题翻译：包含磷脂连接的糖胺聚糖的转移抑制剂组合物和使用其的抑制转移的方法
公开(公告)号：US5733892A
公开(公告)日：1998-03-31
申请号：US469930
申请日：1995-06-06
申请人： Katsukiyo Sakurai , Nobuo Sugiura , Koji Kimata , Sakaru Suzuki
发明人： Katsukiyo Sakurai , Nobuo Sugiura , Koji Kimata , Sakaru Suzuki
IPC分类号： C08B37/00 , A61K31/715 , C07H1/00
CPC分类号： A61K47/48053 , C08B37/0063
摘要： This invention relates to compounds prepared by linking glycosaminoglycan to phospholipid or lipid, which are expected to exert a pharmacological effect for inhibiting metastasis because of their excellent function to inhibit adhesion of cancer cells to blood vessel endothelial cells and extracellular matrix. This phospholipid- or lipid-linked glycosaminoglycan can be produced for example by: cleaving and oxidizing reducing terminal group of glycosaminoglycan, and allowing an aldehyde group or a lactone compound of the thus-formed derivative or a carboxyl group in the glycosaminoglycan chain to react with a primary amino group of a phospholipid; or linking a glycosaminoglycan derivative to a phospholipid or a lipid by allowing a primary amino group of the derivative to react with a carboxyl group of the phospholipid or lipid. This phospholipid- or lipid-linked glycosaminoglycan is useful as a metastasis inhibitor because it has no toxicity.
摘要翻译：本发明涉及通过将糖胺聚糖与磷脂或脂质连接而制备的化合物，由于其具有抑制癌细胞对血管内皮细胞和细胞外基质的粘附的优异功能，预期其具有抑制转移的药理作用。这种磷脂或脂质连接的糖胺聚糖可以例如通过以下方式制备：将糖胺聚糖的还原端基进行切割和氧化，并使得糖胺聚糖链中由此形成的衍生物或羧基的醛基或内酯化合物与磷脂的伯氨基; 或通过使该衍生物的伯氨基与磷脂或脂质的羧基反应来将糖胺聚糖衍生物与磷脂或脂质连接。这种磷脂或脂质连接的糖胺聚糖可用作转移抑制因子，因为它没有毒性。

3. 发明授权

US08067204B2 Long-chain chondroitin sugar chain and method for producing the same and method for promoting synthesis of chondroitin 有权
标题翻译：长链软骨素糖链及其生产方法及促进软骨素合成的方法
公开(公告)号：US08067204B2
公开(公告)日：2011-11-29
申请号：US12097725
申请日：2006-12-14
申请人： Nobuo Sugiura , Satoshi Shimokata , Koji Kimata
发明人： Nobuo Sugiura , Satoshi Shimokata , Koji Kimata
IPC分类号： C12P19/00
CPC分类号： C12P19/26 , C08B37/0069
摘要： A method for producing a chondroitin sugar chain comprises reacting a glucuronic acid donor, an N-acetyl galactosamine donor, a sugar receptor and a bacterial cell enzyme which synthesizes chondroitin in the presence of a surfactant. The surfactant is selected from polyoxyethylene octadecyl amine, n-decanoyl-N-methylglucamide, sodium cholate, n-octyl-β-D-thioglucopyranoside, n-nonyl-β-D-thiomaltopyranoside, sucrose monocholate, sucrose monocaprate, and sucrose monolaurate. The chondroitin sugar chain has all the following properties: a weight average molecular weight: 50,000 or more when measured by gel filtration chromatography; it is completely degraded to disaccharides with chondroitinase ABC; and when the sugar chain is decomposed with chondroitinase ABC and the decomposed products are subjected to a disaccharide analysis, substantially all of them correspond to an unsaturated disaccharide unit of chondroitin.
摘要翻译：生产软骨素糖链的方法包括使葡糖醛酸供体，N-乙酰半乳糖胺供体，糖受体和在表面活性剂存在下合成软骨素的细菌细胞酶的反应。表面活性剂选自聚氧乙烯十八烷基胺，正癸酰基-N-甲基葡萄糖酰胺，胆酸钠，正辛基-β-硫代吡喃葡萄糖苷，正壬基-β-硫代木糖淀粉，蔗糖单胆酸酯，蔗糖单癸酸酯和蔗糖单月桂酸酯。软骨素糖链具有以下性质：通过凝胶过滤色谱法测定的重均分子量为50,000以上; 软骨素酶ABC完全降解成二糖; 并且当糖链用软骨素酶ABC分解并且分解产物进行二糖分析时，其基本上都对应于软骨素的不饱和二糖单元。

4. 发明授权

US07723092B2 Chondroitin polymerase and DNA encoding the same 有权
标题翻译：软骨素聚合酶和DNA编码相同
公开(公告)号：US07723092B2
公开(公告)日：2010-05-25
申请号：US11484752
申请日：2006-07-12
申请人： Toshio Ninomiya , Nobuo Sugiura , Koji Kimata
发明人： Toshio Ninomiya , Nobuo Sugiura , Koji Kimata
IPC分类号： C12N9/24 , C12N9/04 , C07K14/00
CPC分类号： C12N9/1051 , C12P19/18
摘要： A chondroitin polymerase having such properties that it transfers GlcUA and GalNAc alternately to a non-reduced terminal of a sugar chain from a GlcUA donor and a GalNAc donor, respectively, and the like; and a process for producing the chondroitin polymerase.
摘要翻译：具有这样性质的软骨素聚合酶分别将GlcUA和GalNAc交替地转移到来自GlcUA供体和GalNAc供体的糖链的非还原末端等; 以及生产软骨素聚合酶的方法。

5. 发明申请

US20100068759A1 MODIFIED CHONDROITIN SYNTHASE POLYPEPTIDE AND CRYSTAL THEREOF 有权
标题翻译：改性的合成酶聚合酶及其结晶
公开(公告)号：US20100068759A1
公开(公告)日：2010-03-18
申请号：US12304487
申请日：2007-06-12
申请人： Yoshimitsu Kakuta , Takuo Osawa , Nobuo Sugiura , Koji Kimata
发明人： Yoshimitsu Kakuta , Takuo Osawa , Nobuo Sugiura , Koji Kimata
IPC分类号： C12P21/06 , C12P19/04 , C12N9/10 , C07H21/04
CPC分类号： C12Y204/01175 , C12N9/1051 , C12P19/26
摘要： Disclosed are: (A) a polypeptide consisting of the amino acid sequence of SEQ ID NO:2, or (B) a polypeptide comprising an amino acid sequence of SEQ ID NO:2 including deletion, substitution or addition of one or several amino acid residues and having chondroitin synthase activity; a nucleic acid encoding the polypeptide; a method for producing the polypeptide, comprising at least the steps of: (1) expressing the nucleic acid to produce the polypeptide; and (2) collecting the polypeptide produced in the step (1); and a crystal of the polypeptide. The crystal may be a monoclinic or tetragonal crystal.
摘要翻译：公开了：（A）由SEQ ID NO：2的氨基酸序列组成的多肽，或（B）包含SEQ ID NO：2的氨基酸序列的多肽，包括缺失，取代或添加一个或几个氨基酸残留并具有软骨素合成酶活性; 编码该多肽的核酸; 一种生产多肽的方法，至少包括以下步骤：（1）表达所述核酸以产生所述多肽; 和（2）收集步骤（1）中产生的多肽; 和多肽的晶体。该晶体可以是单斜晶体或四方晶体。

6. 发明授权

US07598068B2 Chondroitin polymerase and DNA encoding the same 有权
标题翻译：软骨素聚合酶和DNA编码相同
公开(公告)号：US07598068B2
公开(公告)日：2009-10-06
申请号：US10216289
申请日：2002-08-12
申请人： Toshio Ninomiya , Nobuo Sugiura , Koji Kimata
发明人： Toshio Ninomiya , Nobuo Sugiura , Koji Kimata
IPC分类号： C12N9/24 , C12N9/04 , C07K14/00
CPC分类号： C12N9/1051 , C12P19/18
摘要： A chondroitin polymerase having such properties that it transfers GlcUA and GalNAc alternately to a non-reduced terminal of a sugar chain from a GlcUA donor and a GalNAc donor, respectively, and the like; and a process for producing the chondroitin polymerase.
摘要翻译：具有这样性质的软骨素聚合酶分别将GlcUA和GalNAc交替地转移到来自GlcUA供体和GalNAc供体的糖链的非还原末端等; 以及生产软骨素聚合酶的方法。

7. 发明申请

US20070015249A1 Chondroitin polymerase and DNA encoding the same 有权
标题翻译：软骨素聚合酶和DNA编码相同
公开(公告)号：US20070015249A1
公开(公告)日：2007-01-18
申请号：US11484752
申请日：2006-07-12
申请人： Toshio Ninomiya , Nobuo Sugiura , Koji Kimata
发明人： Toshio Ninomiya , Nobuo Sugiura , Koji Kimata
IPC分类号： C12P21/06 , C07H21/04 , C08B37/00 , C12N9/24 , C12N1/21 , C12N15/74
CPC分类号： C12N9/1051 , C12P19/18
摘要： A chondroitin polymerase having such properties that it transfers GlcUA and GalNAc alternately to a non-reduced terminal of a sugar chain from a GlcUA donor and a GalNAc donor, respectively, and the like; and a process for producing the chondroitin polymerase.
摘要翻译：具有这样性质的软骨素聚合酶分别将GlcUA和GalNAc交替地转移到来自GlcUA供体和GalNAc供体的糖链的非还原末端等; 以及生产软骨素聚合酶的方法。

8. 发明授权

US5464942A Phospholipid- or lipid-linked glycosaminoglycan and process for producing the same 失效
标题翻译：磷脂或脂质连接的糖胺聚糖及其制备方法
公开(公告)号：US5464942A
公开(公告)日：1995-11-07
申请号：US847065
申请日：1991-03-24
申请人： Katsukiyo Sakurai , Nobuo Sugiura , Koji Kimata , Sakaru Suzuki
发明人： Katsukiyo Sakurai , Nobuo Sugiura , Koji Kimata , Sakaru Suzuki
IPC分类号： C08B37/00 , A61K31/725 , C08B37/10
CPC分类号： A61K47/48053 , C08B37/0063
摘要： This invention relates to compounds prepared by linking glycosaminoglycan to phospholipid or lipid, which are expected to exert a pharmacological effect for inhibiting metastasis because of their excellent function to inhibit adhesion of cancer cells to blood vessel endothelial cells and extracellular matrix. This phospholipid- or lipid-linked glycosaminoglycan can be produced for example by: cleaving and oxidizing reducing terminal group of glycosaminoglycan, and allowing an aldehyde group or a lactone compound of the thus-formed derivative or a carboxyl group in the glycosaminoglycan chain to react with a primary amino group of a phospholipid; or linking a glycosaminoglycan derivative to a phospholipid or a lipid by allowing a primary amino group of the derivative to react with a carboxyl group of the phospholipid or lipid. This phospholipid- or lipid-linked glycosaminoglycan is useful as a metastasis inhibitor because it has no toxicity.
摘要翻译： PCT No.PCT / JP91 / 00995 Sec。 371日期：1992年3月24日 102（e）1992年3月24日PCT PCT 1991年7月24日PCT公布。出版物WO92 / 01720 本发明涉及通过将糖胺聚糖与磷脂或脂质连接而制备的化合物，其预期具有抑制转移的药理作用，因为其具有抑制癌细胞对血管内皮细胞和细胞外的粘附的优异功能矩阵。这种磷脂或脂质连接的糖胺聚糖可以例如通过以下方式制备：将糖胺聚糖的还原端基进行切割和氧化，并使得糖胺聚糖链中由此形成的衍生物或羧基的醛基或内酯化合物与磷脂的伯氨基; 或通过使该衍生物的伯氨基与磷脂或脂质的羧基反应来将糖胺聚糖衍生物与磷脂或脂质连接。这种磷脂或脂质连接的糖胺聚糖可用作转移抑制因子，因为它没有毒性。

9. 发明授权

US08129148B2 Process for preparation of chondroitin fraction 有权
$Process for preparation of chondroitin fraction$
标题翻译：软骨素部分的制备方法
公开(公告)号：US08129148B2
公开(公告)日：2012-03-06
申请号：US12064810
申请日：2006-08-23
申请人： Nobuo Sugiura , Koji Kimata
发明人： Nobuo Sugiura , Koji Kimata
IPC分类号： C12P19/28
CPC分类号： C12P19/26
摘要： Provided are a method for producing a fraction containing more than 50% of CH represented by the general formula (1), which comprises at least the step of allowing a glucuronic acid donor, an N-acetylgalactosamine donor, a saccharide receptor, a chondroitin polymerase derived from the Escherichia coli K4 strain, and Mn2+ at a final concentration of 0.02 to 100 mM to coexist, and performing a reaction thereof under conditions of 20 to 40° C. and pH 6 to 8 for 0.5 minutes to 4 hours, and a method for producing a fraction containing more than 50% of CH represented by the general formula (2), which comprises at least the step of performing the reaction under same conditions for 10 hours or longer, which enable industrial scale production of a CH fraction of a controlled even number saccharide and odd number saccharide content ratio by a simple procedure at a low cost. (GlcA-GalNAc)n (1) GalNAc-(GlcA-GalNAc)n (2) (In the formula, GlcA represents a glucuronic acid residue, GalNCAc represents a N-acetylgalactosamine residue, - represents a glycosidic bond, and n represents an arbitrary integer.)
摘要翻译：本发明提供了一种生产含有通式（1）所示的超过50％的CH的级分的方法，该方法至少包括使葡糖醛酸供体，N-乙酰半乳糖胺供体，糖受体，软骨素聚合酶来源于大肠杆菌K4菌株，最终浓度为0.02〜100mM的Mn2 +共存，在20〜40℃，pH6〜8的条件下进行0.5分钟〜4小时的反应，制备含有超过50％由通式（2）表示的CH的级分的方法，该方法至少包括在相同条件下进行反应10小时或更长时间的步骤，这使得工业规模生产CH部分通过简单的程序以低成本控制偶数糖和奇数糖含量比。（GlcA-GalNAc）n（1）GalNAc-（GlcA-GalNAc）n（2）（式中，GlcA表示葡萄糖醛酸残基，GaINCAc表示N-乙酰半乳糖胺残基， - 表示糖苷键，n表示任意整数）

10. 发明申请

US20110195476A1 MODIFIED CHONDROITIN SYNTHASE POLYPEPTIDE AND CRYSTAL THEREOF 有权
标题翻译：改性的合成酶聚合酶及其结晶
公开(公告)号：US20110195476A1
公开(公告)日：2011-08-11
申请号：US13046172
申请日：2011-03-11
申请人： Yoshimitsu KAKUTA , Takuo Osawa , Nobuo Sugiura , Koji Kimata
发明人： Yoshimitsu KAKUTA , Takuo Osawa , Nobuo Sugiura , Koji Kimata
IPC分类号： C12N9/00 , C12N1/00 , C12N15/63 , C07H21/04
CPC分类号： C12Y204/01175 , C12N9/1051 , C12P19/26
摘要： Disclosed are: (A) a polypeptide consisting of the amino acid sequence of SEQ ID NO:2, or (B) a polypeptide comprising an amino acid sequence of SEQ ID NO:2 including deletion, substitution or addition of one or several amino acid residues and having chondroitin synthase activity; a nucleic acid encoding the polypeptide; a method for producing the polypeptide, comprising at least the steps of: (1) expressing the nucleic acid to produce the polypeptide; and (2) collecting the polypeptide produced in the step (1); and a crystal of the polypeptide. The crystal may be a monoclinic or tetragonal crystal.
摘要翻译：公开了：（A）由SEQ ID NO：2的氨基酸序列组成的多肽，或（B）包含SEQ ID NO：2的氨基酸序列的多肽，包括缺失，取代或添加一个或几个氨基酸残留并具有软骨素合成酶活性; 编码该多肽的核酸; 一种生产多肽的方法，至少包括以下步骤：（1）表达所述核酸以产生所述多肽; 和（2）收集步骤（1）中产生的多肽; 和多肽的晶体。该晶体可以是单斜晶体或四方晶体。

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