公开(公告)号：US20070081984A1

公开(公告)日：2007-04-12

申请号：US11484870

申请日：2006-07-11

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

IPC分类号： A61K48/00 ,  A61K38/46

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。

公开(公告)号：US20190224283A1

公开(公告)日：2019-07-25

申请号：US15876892

申请日：2018-01-22

申请人： Adriana M. Montaño-Suarez ,  Angela Catalina Sosa-Molano ,  Alan Knutsen ,  Clifford Bellone ,  Shunji Tomatsu ,  Luis Barrera

发明人： Adriana M. Montaño-Suarez ,  Angela Catalina Sosa-Molano ,  Alan Knutsen ,  Clifford Bellone ,  Shunji Tomatsu ,  Luis Barrera

IPC分类号： A61K38/46 ,  A61K9/00

摘要： Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS.

公开(公告)号：US20110250187A1

公开(公告)日：2011-10-13

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

IPC分类号： A61K35/54 ,  A61P3/00 ,  A61K48/00 ,  C12N9/16 ,  A61K38/46

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。

公开(公告)号：US07943126B2

公开(公告)日：2011-05-17

申请号：US12405920

申请日：2009-03-17

申请人： Shunji Tomatsu ,  William S Sly ,  Jeffrey H Grubb ,  Tatsuo Nishioka ,  Ken-ichi Miyamoto ,  Seiji Yamaguchi

发明人： Shunji Tomatsu ,  William S Sly ,  Jeffrey H Grubb ,  Tatsuo Nishioka ,  Ken-ichi Miyamoto ,  Seiji Yamaguchi

IPC分类号： A61K38/43 ,  A61P19/08 ,  C12N9/00 ,  C12P21/02

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。

公开(公告)号：US07863238B2

公开(公告)日：2011-01-04

申请号：US10864758

申请日：2004-06-10

申请人： Shunji Tomatsu ,  Ken'ichi Miyamoto ,  Masamichi Yamada ,  Yasuhiro Tosaka ,  Mana Yamada

发明人： Shunji Tomatsu ,  Ken'ichi Miyamoto ,  Masamichi Yamada ,  Yasuhiro Tosaka ,  Mana Yamada

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。

公开(公告)号：US20100158889A1

公开(公告)日：2010-06-24

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

发明人： Shunji Tomatsu ,  Adriana Montano ,  Tatsuo Nishioka ,  Jeffrey H. Grubb ,  William S. Sly ,  Monica A. Gutierrez ,  Amelia Ortigoza Rodriguez

IPC分类号： A61K38/47 ,  A61K38/07 ,  A61K38/08 ,  A61K38/10 ,  A61K38/43 ,  A61P25/00

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。