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公开(公告)号：US20050276796A1
公开(公告)日：2005-12-15
申请号：US10864758
申请日：2004-06-10
CPC分类号： C12N15/625 , C07K2319/02 , C12N9/16
摘要： Disclosed are a fusion protein comprising enzyme N-acetylgalactosamine-6-sulfate sulfatase and a short peptide consisting of 4-15 acidic amino acids attached to the enzyme on its N-terminal side, a pharmaceutical composition containing the fusion protein, and a method for treatment of type A Morquio disease using the fusion protein. Compared with the native enzyme protein, the fusion protein exhibits higher transferability to bone tissues and improved, higher stability in the blood.
摘要翻译： 公开了包含N-乙酰半乳糖胺-6-硫酸酯硫酸酯酶的融合蛋白质和由其N-末端侧连接到酶上的4-15个酸性氨基酸组成的短肽，含有融合蛋白的药物组合物， 使用融合蛋白治疗A型Morquio病。 与天然酶蛋白相比，融合蛋白对骨组织的转移能力较高，血液中稳定性提高。
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公开(公告)号：US07863238B2
公开(公告)日：2011-01-04
申请号：US10864758
申请日：2004-06-10
IPC分类号： A61K38/00
CPC分类号： C12N15/625 , C07K2319/02 , C12N9/16
摘要： Disclosed are a fusion protein comprising enzyme N-acetylgalactosamine-6-sulfate sulfatase and a short peptide consisting of 4-15 acidic amino acids attached to the enzyme on its N-terminal side, a pharmaceutical composition containing the fusion protein, and a method for treatment of type A Morquio disease using the fusion protein. Compared with the native enzyme protein, the fusion protein exhibits higher transferability to bone tissues and improved, higher stability in the blood.
摘要翻译： 公开了包含N-乙酰半乳糖胺-6-硫酸酯硫酸酯酶的融合蛋白质和由其N-末端侧连接到酶上的4-15个酸性氨基酸组成的短肽，含有融合蛋白的药物组合物， 使用融合蛋白治疗A型Morquio病。 与天然酶蛋白相比，融合蛋白对骨组织的转移能力较高，血液中稳定性提高。
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公开(公告)号：US08299018B2
公开(公告)日：2012-10-30
申请号：US12333499
申请日：2008-12-12
IPC分类号： A61K38/00
CPC分类号： C12N15/625 , C07K2319/02 , C12N9/16
摘要： Disclosed are a fusion protein comprising enzyme N-acetylgalactosamine-6-sulfate sulfatase and a short peptide consisting of 4-15 acidic amino acids attached to the enzyme on its N-terminal side, a pharmaceutical composition containing the fusion protein, and a method for treatment of type A Morquio disease using the fusion protein. Compared with the native enzyme protein, the fusion protein exhibits higher transferability to bone tissues and improved, higher stability in the blood.
摘要翻译： 公开了包含N-乙酰半乳糖胺-6-硫酸酯硫酸酯酶的融合蛋白质和由其N-末端侧连接到酶上的4-15个酸性氨基酸组成的短肽，含有融合蛋白的药物组合物， 使用融合蛋白治疗A型Morquio病。 与天然酶蛋白相比，融合蛋白对骨组织的转移能力较高，血液中稳定性提高。
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公开(公告)号：US20090175839A1
公开(公告)日：2009-07-09
申请号：US12333499
申请日：2008-12-12
IPC分类号： A61K38/46
CPC分类号： C12N15/625 , C07K2319/02 , C12N9/16
摘要： Disclosed are a fusion protein comprising enzyme N-acetylgalactosamine-6-sulfate sulfatase and a short peptide consisting of 4-15 acidic amino acids attached to the enzyme on its N-terminal side, a pharmaceutical composition containing the fusion protein, and a method for treatment of type A Morquio disease using the fusion protein. Compared with the native enzyme protein, the fusion protein exhibits higher transferability to bone tissues and improved, higher stability in the blood.
摘要翻译： 公开了包含N-乙酰半乳糖胺-6-硫酸酯硫酸酯酶的融合蛋白质和由其N-末端侧连接到酶上的4-15个酸性氨基酸组成的短肽，含有融合蛋白的药物组合物， 使用融合蛋白治疗A型Morquio病。 与天然酶蛋白相比，融合蛋白对骨组织的转移能力较高，血液中稳定性提高。
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5.发明申请公开(公告)号：US20070081986A1
公开(公告)日：2007-04-12
申请号：US11245424
申请日：2005-10-07
申请人： Shunji Tomatsu , Ken'jchi Miyamoto , Masamichi Yamada , Yasuhiro Tosaka , Mana Yamada , Jeffrey Grubb
发明人： Shunji Tomatsu , Ken'jchi Miyamoto , Masamichi Yamada , Yasuhiro Tosaka , Mana Yamada , Jeffrey Grubb
CPC分类号： C12Y302/01031 , A61K38/00 , C07K2319/31 , C12N9/2402 , C12N9/96
摘要： Disclosed are a fusion protein comprising enzyme β-glucuronidase and short peptide consisting 4-15 acidic amino acids attached to the enzyme on its N-terminal side, pharmaceutical composition containing the fusion protein, and a method for treatment of type VII mucopolysaccharidosis using the fusion protein. Compared with the native enzyme, the fusion protein exhibits higher stability in the blood.
摘要翻译： 公开了包含酶β-葡糖醛酸糖苷酶和短肽的融合蛋白，所述短肽与其N-末端侧的酶连接4-15个酸性氨基酸，含有融合蛋白的药物组合物和使用该融合物治疗VII型粘多糖贮积病的方法 蛋白。 与天然酶相比，融合蛋白在血液中表现出更高的稳定性。
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公开(公告)号：US08691208B2
公开(公告)日：2014-04-08
申请号：US13071445
申请日：2011-03-24
申请人： Shunji Tomatsu , William Sly , Jeffrey Grubb , Tatsuo Nishioka , Ken-ichi Miyamoto , Seiji Yamaguchi
发明人： Shunji Tomatsu , William Sly , Jeffrey Grubb , Tatsuo Nishioka , Ken-ichi Miyamoto , Seiji Yamaguchi
CPC分类号： A61K38/465 , C12Y301/03001
摘要： The present invention provides compositions and methods for use in enzyme replacement therapy. The inventors disclose a method of producing membrane bound enzymes in an active soluble form by eliminating the glycosylphosphatidylinositol (GPI) membrane anchor. In particular the inventors disclose a soluble active form of the membrane bound enzyme TNSALP which they produced by deleting the GPI anchor single peptide sequence. They have further shown that this composition is useful for treatment of hypophosphatasia. The inventors also disclose oligo acid amino acid variants thereof which specifically target bone tissue.
摘要翻译： 本发明提供了用于酶替代疗法的组合物和方法。 本发明人公开了通过消除糖基磷脂酰肌醇（GPI）膜锚定点来生产活性可溶形式的膜结合酶的方法。 特别地，本发明人公开了通过缺失GPI锚单肽序列产生的膜结合酶TNSALP的可溶性活性形式。 他们进一步表明，该组合物可用于治疗下尿失禁。 本发明人还公开了特异性靶向骨组织的寡糖氨基酸变体。
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7.发明授权公开(公告)号：US08226940B2
公开(公告)日：2012-07-24
申请号：US12714534
申请日：2010-02-28
申请人： Shunji Tomatsu , Adriana Montano , Tatsuo Nishioka , Jeffrey H. Grubb , William S. Sly , Monica A. Gutierrez , Amelia Ortigoza Rodriguez, legal representative
发明人： Shunji Tomatsu , Adriana Montano , Tatsuo Nishioka , Jeffrey H. Grubb , William S. Sly , Monica A. Gutierrez
CPC分类号： C12N15/625 , A61K38/00 , C07K2319/02 , C07K2319/31 , C12N9/2402 , C12N9/96 , C12Y302/01031
摘要： The present invention provides a polypeptide therapeutic agent, useful in enzyme replacement therapy, with increased therapeutic benefits for the central nervous system. The invention provides a method of enhancing the effect of a polypeptide or protein on the central nervous system by the attachment of a short acidic amino acid sequence. Specifically the inventors disclose the attachment of a 4-15 acidic amino acid sequence to human β-glucuronidase by construction of a fusion protein. This molecule is useful in the treatment of type VII mucopolysaccharidosis when administered to a patient.
摘要翻译： 本发明提供了可用于酶替代疗法的多中心治疗剂，对中枢神经系统具有增加的治疗益处。 本发明提供了通过连接短酸性氨基酸序列增强多肽或蛋白质对中枢神经系统的作用的方法。 具体地，本发明人通过构建融合蛋白来公开了将4-15个酸性氨基酸序列与人类 - 葡萄糖醛酸苷酶的连接。 当给予患者时，该分子可用于治疗VII型粘多糖贮积病。
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8.发明申请公开(公告)号：US20070207139A1
公开(公告)日：2007-09-06
申请号：US11614970
申请日：2006-12-21
申请人： Shunji Tomatsu , Adriana Montano , Tatsuo Nishioka , Jeffrey Grubb , William Sly , Monica Gutierrez , Amelia Rodriguez
发明人： Shunji Tomatsu , Adriana Montano , Tatsuo Nishioka , Jeffrey Grubb , William Sly , Monica Gutierrez , Amelia Rodriguez
CPC分类号： C12N15/625 , A61K38/00 , C07K2319/02 , C07K2319/31 , C12N9/2402 , C12N9/96 , C12Y302/01031
摘要： The present invention provides a polypeptide therapeutic agent, useful in enzyme replacement therapy, with increased therapeutic benefits for the central nervous system. The invention provides a method of enhancing the effect of a polypeptide or protein on the central nervous system by the attachment of a short acidic amino acid sequence. Specifically the inventors disclose the attachment of a 4-15 acidic amino acid sequence to human β-glucuronidase by construction of a fusion protein. This molecule is useful in the treatment of type VII mucopolysaccharidosis when administered to a patient.
摘要翻译： 本发明提供了可用于酶替代疗法的多中心治疗剂，对中枢神经系统具有增加的治疗益处。 本发明提供了通过连接短酸性氨基酸序列增强多肽或蛋白质对中枢神经系统的作用的方法。 具体地，本发明人公开了通过构建融合蛋白将4-15个酸性氨基酸序列与人β-葡糖醛酸糖苷酶的连接。 当给予患者时，该分子可用于治疗VII型粘多糖贮积病。
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公开(公告)号：US20110311487A1
公开(公告)日：2011-12-22
申请号：US13112924
申请日：2011-05-20
CPC分类号： C12N9/96 , A61K38/00 , C07K2319/02 , C07K2319/31 , C12N9/16 , C12N9/2402 , C12N15/625 , C12Y301/03001 , C12Y301/06014 , C12Y302/01031
摘要： This invention relates to compositions and methods of delivering therapeutic agents to bone. More specifically, the invention relates to endowing a large molecule vectors i.e., adeno virus, retrovirus, liposomes, micelles, natural and synthetic polymers, or combinations thereof, with the ability to target bone tissue in vivo and with improved stability in the blood, by attaching multiple copies of acid amino acid peptides. One preferred embodiment of the invention relates to endowing an adeno-associated virus (AAV) vector with the ability to target bone-tissue in vivo and improve its stability, by the addition of multiple acidic amino acid peptides attached to the capsid of the viral vector.
摘要翻译： 本发明涉及将治疗剂递送至骨骼的组合物和方法。 更具体地，本发明涉及赋予大分子载体，即腺病毒，逆转录病毒，脂质体，胶束，天然和合成聚合物或其组合，具有在体内靶向骨组织并具有改善的血液稳定性的能力，通过 附加多份酸性氨基酸肽。 本发明的一个优选实施方案涉及赋予腺相关病毒（AAV）载体，该载体具有通过加入与病毒载体的衣壳连接的多个酸性氨基酸肽，能够在体内靶向骨组织并提高其稳定性 。
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公开(公告)号：US20050221407A1
公开(公告)日：2005-10-06
申请号：US10512839
申请日：2003-04-30
申请人： Kazuo Okamura , Shuichi Miyaura , Shunji Tomatsu
发明人： Kazuo Okamura , Shuichi Miyaura , Shunji Tomatsu
CPC分类号： G01N33/00 , G01N33/6893 , G01N2400/40 , G01N2800/042 , G01N2800/10 , Y10S436/811
摘要： A method for detecting lysosomal storage diseases including the steps of performing an assay for a single species of glycosaminoglycan contained in a specimen and correlating results of the assay with lysosomal storage diseases. A body fluid such as urine or blood can be employed as a specimen. The assay can be performed by use of a polypeptide that is capable of specifically binding to a glycosaminoglycan-containing molecule. The polypeptide may be an antibody, or a polypeptide having an antigen-binding site of an antibody.
摘要翻译： 一种检测溶酶体贮积病的方法，包括对样品中所含的单一种类的糖胺聚糖进行测定，并将测定结果与溶酶体贮积病相关联的步骤。 可以使用尿液或血液等体液作为标本。 该测定可以通过使用能够特异性结合含糖胺聚糖的分子的多肽进行。 多肽可以是抗体或具有抗体的抗原结合位点的多肽。
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