公开(公告)号：US08058232B2

公开(公告)日：2011-11-15

申请号：US12614805

申请日：2009-11-09

申请人： Silvano Fumero ,  Luisa Bertarione Rava Rossa ,  Domenico G. Barone ,  Lila Drittanti ,  Thierry Guyon ,  Gilles Borrelly ,  Barbara Canepa ,  Chiara Lorenzetto

发明人： Silvano Fumero ,  Luisa Bertarione Rava Rossa ,  Domenico G. Barone ,  Lila Drittanti ,  Thierry Guyon ,  Gilles Borrelly ,  Barbara Canepa ,  Chiara Lorenzetto

IPC分类号： A61K38/17 ,  C07K14/47 ,  C12N15/00 ,  C12P21/02

CPC分类号： C07K14/47

摘要： The present invention relates to polypeptide variants of the HMGB-1 high affinity binding domain Box-A (HMGB1 Box-A) or to a biologically active fragment of HMGB1 Box-A, which are obtained through systematic mutations of single amino acids of the wild-type HMGB1 Box-A protein and which show an increased resistance to proteases and which are therefore characterized by more favorable pharmacokinetic and pharmacodynamic profiles. Moreover, the present invention concerns the use of said polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and associated with RAGE.

摘要翻译： 本发明涉及HMGB-1高亲和力结合域Box-A（HMGB1 Box-A）或HMGB1 Box-A的生物活性片段的多肽变体，其通过野生型单个氨基酸的系统性突变获得 型HMGB1 Box-A蛋白，其表现出对蛋白酶的增加的抗性，因此其特征在于更有利的药代动力学和药效学特征。 此外，本发明涉及HMGB1 Box-A的所述多肽分子用于诊断，预防，缓解和/或治疗与细胞外HMGB1相关并与RAGE相关的病理学的用途。

公开(公告)号：US20110052493A1

公开(公告)日：2011-03-03

申请号：US12614805

申请日：2009-11-09

申请人： Silvano FUMERO ,  Luisa Bertarione Rava Rossa ,  Domenico G. Barone ,  Lila Drittanti ,  Thierry Guyon ,  Gilles Borrelly ,  Barbara Canepa ,  Chiara Lorenzetto

发明人： Silvano FUMERO ,  Luisa Bertarione Rava Rossa ,  Domenico G. Barone ,  Lila Drittanti ,  Thierry Guyon ,  Gilles Borrelly ,  Barbara Canepa ,  Chiara Lorenzetto

IPC分类号： A61K49/00 ,  C07K14/00 ,  C07H21/04 ,  C12N15/63 ,  C12P21/02 ,  A61K38/16 ,  A61K9/00 ,  A61K39/395 ,  A61P35/00 ,  A61P37/00 ,  A61P25/00

CPC分类号： C07K14/47

摘要： The present invention relates to polypeptide variants of the HMGB-1 high affinity binding domain Box-A (HMGB1 Box-A) or to a biologically active fragment of HMGB1 Box-A, which are obtained through systematic mutations of single amino acids of the wild-type HMGB1 Box-A protein and which show an increased resistance to proteases and which are therefore characterized by more favourable pharmacokinetic and pharmacodynamic profiles. Moreover, the present invention concerns the use of said polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and associated with RAGE.

摘要翻译： 本发明涉及HMGB-1高亲和力结合域Box-A（HMGB1 Box-A）或HMGB1 Box-A的生物活性片段的多肽变体，其通过野生型单个氨基酸的系统性突变获得 型HMGB1 Box-A蛋白，其表现出对蛋白酶的增加的抗性，因此其特征在于更有利的药代动力学和药效学特征。 此外，本发明涉及HMGB1 Box-A的所述多肽分子用于诊断，预防，缓解和/或治疗与细胞外HMGB1相关并与RAGE相关的病理学的用途。

公开(公告)号：US07635679B2

公开(公告)日：2009-12-22

申请号：US11713789

申请日：2007-03-05

申请人： Silvano Fumero ,  Luisa Bertarione Rava Rossa ,  Domenico G. Barone ,  Lila Drittanti ,  Thierry Guyon ,  Gilles Borrelly ,  Barbara Canepa ,  Chiara Lorenzetto

发明人： Silvano Fumero ,  Luisa Bertarione Rava Rossa ,  Domenico G. Barone ,  Lila Drittanti ,  Thierry Guyon ,  Gilles Borrelly ,  Barbara Canepa ,  Chiara Lorenzetto

IPC分类号： A61K38/17 ,  C07K14/47 ,  C12N15/00 ,  C12P21/02

CPC分类号： C07K14/47

摘要： The present invention relates to polypeptide variants of the HMGB-1 high affinity binding domain Box-A (HMGB1 Box-A) or to a biologically active fragment of HMGB1 Box-A, which are obtained through systematic mutations of single amino acids of the wild-type HMGB1 Box-A protein and which show an increased resistance to proteases and which are therefore characterized by more favorable pharmacokinetic and pharmacodynamic profiles. Moreover, the present invention concerns the use of said polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and associated with RAGE.

摘要翻译： 本发明涉及HMGB-1高亲和力结合域Box-A（HMGB1 Box-A）或HMGB1 Box-A的生物活性片段的多肽变体，其通过野生型单个氨基酸的系统性突变获得 型HMGB1 Box-A蛋白，其表现出对蛋白酶的增加的抗性，因此其特征在于更有利的药代动力学和药效学特征。 此外，本发明涉及HMGB1 Box-A的所述多肽分子用于诊断，预防，缓解和/或治疗与细胞外HMGB1相关并与RAGE相关的病理学的用途。

公开(公告)号：US20080038309A1

公开(公告)日：2008-02-14

申请号：US11713789

申请日：2007-03-05

申请人： Silvano Fumero ,  Luisa Bertarione Rava Rossa ,  Domenico Barone ,  Lila Drittanti ,  Thierry Guyon ,  Gilles Borrelly ,  Barbara Canepa ,  Chiara Lorenzetto

发明人： Silvano Fumero ,  Luisa Bertarione Rava Rossa ,  Domenico Barone ,  Lila Drittanti ,  Thierry Guyon ,  Gilles Borrelly ,  Barbara Canepa ,  Chiara Lorenzetto

IPC分类号： A61F2/02 ,  A61K31/7052 ,  A61K38/16 ,  A61K39/395 ,  A61K9/00 ,  A61P17/00 ,  A61P25/00 ,  A61P29/00 ,  A61P3/00 ,  A61P31/00 ,  A61P35/00 ,  C07H21/00 ,  C07K14/00 ,  C07K2/00 ,  C12N15/63

CPC分类号： C07K14/47

摘要： The present invention relates to polypeptide variants of the HMGB-1 high affinity binding domain Box-A (HMGB1 Box-A) or to a biologically active fragment of HMGB1 Box-A, which are obtained through systematic mutations of single amino acids of the wild-type HMGB1 Box-A protein and which show an increased resistance to proteases and which are therefore characterized by more favourable pharmacokinetic and pharmacodynamic profiles. Moreover, the present invention concerns the use of said polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and associated with RAGE.

摘要翻译： 本发明涉及HMGB-1高亲和力结合域Box-A（HMGB1 Box-A）或HMGB1 Box-A的生物活性片段的多肽变体，其通过野生型单个氨基酸的系统性突变获得 型HMGB1 Box-A蛋白，其表现出对蛋白酶的增加的抗性，因此其特征在于更有利的药代动力学和药效学特征。 此外，本发明涉及HMGB1 Box-A的所述多肽分子用于诊断，预防，缓解和/或治疗与细胞外HMGB1相关并与RAGE相关的病理学的用途。

公开(公告)号：US08673347B2

公开(公告)日：2014-03-18

申请号：US12064461

申请日：2006-08-25

申请人： Silvio Traversa ,  Raffaella Bagnod ,  Domenico Barone ,  Luisa Bertarione Rava Rossa ,  Silvano Fumero ,  Valentina Mainero ,  Alessandra Marconi ,  Cecilia Oderda ,  Carlo Pincelli ,  Chiara Lorenzetto ,  Luca Beccaria

发明人： Silvio Traversa ,  Raffaella Bagnod ,  Domenico Barone ,  Luisa Bertarione Rava Rossa ,  Silvano Fumero ,  Valentina Mainero ,  Alessandra Marconi ,  Cecilia Oderda ,  Carlo Pincelli ,  Chiara Lorenzetto ,  Luca Beccaria

IPC分类号： A61K31/787 ,  C08G73/06 ,  A61K9/127 ,  A61P35/00

CPC分类号： C08G73/0672 ,  A61K47/60 ,  C08G61/124

摘要： The present invention relates to novel polymer conjugates of K-252a and derivatives thereof and to their use for the preparation of a pharmaceutical composition useful for the prevention, alleviation and treatment of kinase-associated pathologies. In particular, the present invention relates to the prevention, alleviation and treatment of HMGB1-associated pathologies. The invention relates to the use of the novel polymer conjugates of K-252a and derivatives thereof in the preparation of a pharmaceutical composition useful for the prevention, alleviation and treatment of a) neurological disorders, neuropathies and neurodegenerative disorders of the central and peripheral nervous system; b) dermal pathologies, in particular dermal pathologies associated with an excessive keratinocyte proliferation, in particular psoriasis; and c) NGF-related pain. More specifically, the present invention relates to a polymer conjugate of K-252a and derivatives thereof, wherein the polymer is polyethylene glycol or methoxy-polyethylene glycol formula (I).

摘要翻译： 本发明涉及K-252a及其衍生物的新型聚合物缀合物及其用于制备可用于预防，缓解和治疗激酶相关病理学的药物组合物的用途。 特别地，本发明涉及HMGB1相关病理学的预防，缓解和治疗。 本发明涉及K-252a及其衍生物的新型聚合物缀合物在制备用于预防，缓解和治疗a）中枢和周围神经系统的神经障碍，神经病变和神经变性疾病的药物组合物中的用途 ; b）皮肤病理学，特别是与过度角质形成细胞增殖相关的皮肤病理学，特别是牛皮癣; 和c）NGF相关的疼痛。 更具体地说，本发明涉及K-252a及其衍生物的聚合物缀合物，其中聚合物是聚乙二醇或甲氧基 - 聚乙二醇配方（I）。

公开(公告)号：US20080193517A1

公开(公告)日：2008-08-14

申请号：US12064461

申请日：2006-08-25

申请人： Silvio Traversa ,  Raffaella Bagnod ,  Domenico Barone ,  Luisa Bertarione Rava Rossa ,  Silvano Fumero ,  Valentina Mainero ,  Alessandra Marconi ,  Cecilia Oderda ,  Carlo Pincelli ,  Chiara Lorenzetto ,  Luca Beccaria

发明人： Silvio Traversa ,  Raffaella Bagnod ,  Domenico Barone ,  Luisa Bertarione Rava Rossa ,  Silvano Fumero ,  Valentina Mainero ,  Alessandra Marconi ,  Cecilia Oderda ,  Carlo Pincelli ,  Chiara Lorenzetto ,  Luca Beccaria

IPC分类号： A61K31/787 ,  C08G73/06 ,  A61K9/127 ,  A61P35/00 ,  A61P17/00 ,  A61P19/00 ,  A61P25/00

CPC分类号： C08G73/0672 ,  A61K47/60 ,  C08G61/124

摘要： The present invention relates to novel polymer conjugates of K-252a and derivatives thereof and to their use for the preparation of a pharmaceutical composition useful for the prevention, alleviation and treatment of kinase-associated pathologies. In particular, the present invention relates to the prevention, alleviation and treatment of HMGB1-associated pathologies. In a particular aspect, the invention relates to the use of the novel polymer conjugates of K-252a and derivatives thereof in the preparation of a pharmaceutical composition useful for the prevention, alleviation and treatment of neurological disorders, neuropathies and neurodegenerative disorders of the central and peripheral nervous system. In a further preferred aspect, the invention relates to the use of the polymer conjugates in the preparation of a pharmaceutical composition useful for the prevention, alleviation and treatment of dermal pathologies, in particular dermal pathologies associated with an excessive keratinocyte proliferation, in particular psoriasis. In a still further aspect, the invention relates to the use of the polymer conjugates in the prevention, alleviation and treatment of NGF-related pain. More specifically, the present invention relates to a polymer conjugate of K-252a and derivatives thereof, wherein the polymer is polyethylene glycol or methoxy-polyethylene glycol formula (I).

摘要翻译： 本发明涉及K-252a及其衍生物的新型聚合物缀合物及其用于制备可用于预防，缓解和治疗激酶相关病理学的药物组合物的用途。 特别地，本发明涉及HMGB1相关病变的预防，缓解和治疗。 在一个特定方面，本发明涉及K-252a及其衍生物的新型聚合物缀合物在制备药物组合物中的用途，所述药物组合物可用于预防，缓解和治疗中枢神经系统疾病，神经病和神经变性疾病 外周神经系统。 在另一优选方面，本发明涉及聚合物缀合物在制备用于预防，减轻和治疗真皮病理学，特别是与过度角质形成细胞增殖相关的皮肤病理学，特别是牛皮癣的药物组合物中的用途。 在另一方面，本发明涉及聚合物缀合物在预防，减轻和治疗NGF相关疼痛中的用途。 更具体地说，本发明涉及K-252a及其衍生物的聚合物缀合物，其中聚合物是聚乙二醇或甲氧基 - 聚乙二醇配方（I）。

公开(公告)号：US08926955B2

公开(公告)日：2015-01-06

申请号：US13141354

申请日：2009-12-22

申请人： Raffaella Bagnod ,  Luca Beccaria ,  Luisa Bertarione Rava Rossa ,  Domenico Criscuolo ,  Chiara Lorenzetto ,  Valentina Mainero ,  Alessandra Marconi ,  Carlo Pincelli ,  Silvio Traversa

发明人： Raffaella Bagnod ,  Luca Beccaria ,  Luisa Bertarione Rava Rossa ,  Domenico Criscuolo ,  Chiara Lorenzetto ,  Valentina Mainero ,  Alessandra Marconi ,  Carlo Pincelli ,  Silvio Traversa

IPC分类号： A61K47/48

CPC分类号： A61K47/48215 ,  A61K47/60

摘要： The present invention relates to a process for the preparation of polymer conjugates of indolocarbaxole compounds, in particular of polymer conjugates of K-252a and derivatives thereof, by a synthetic route which results in a highly pure product, with a high product yield. In a further aspect the present invention relates to novel polymer conjugates of K-252a and derivatives thereof, wherein the chemical group linking the polymer unity to the K-252a or to the K-252a derivative compound is characterized by a 5-member oxazolidindionic cyclic structure. These novel polymer conjugates are obtained through the novel synthetic route with high purity and high yields.

摘要翻译： 本发明涉及通过合成途径制备吲哚并噻唑化合物，特别是K-252a及其衍生物的聚合物共轭物的聚合物共轭物的方法，该合成途径产生高产率的高纯度产物。 另一方面，本发明涉及K-252a及其衍生物的新型聚合物共轭物，其中连接聚合物单元与K-252a或K-252a衍生物化合物的化学基团的特征在于5-构恶唑烷基吲哚环 结构体。 这些新型聚合物共轭物通过高纯度和高产率的新型合成路线得到。

公开(公告)号：US20110311451A1

公开(公告)日：2011-12-22

申请号：US13141354

申请日：2009-12-22

申请人： Raffaella Bagnod ,  Luca Beccaria ,  Luisa Bertarione Rava Rossa ,  Domenico Criscuolo ,  Chiara Lorenzetto ,  Valentina Mainero ,  Alessandra Marconi ,  Carlo Pincelli ,  Silvio Traversa

发明人： Raffaella Bagnod ,  Luca Beccaria ,  Luisa Bertarione Rava Rossa ,  Domenico Criscuolo ,  Chiara Lorenzetto ,  Valentina Mainero ,  Alessandra Marconi ,  Carlo Pincelli ,  Silvio Traversa

IPC分类号： A61K49/00 ,  A61K31/553 ,  A61K9/127 ,  A61P29/00 ,  A61P9/00 ,  A61P9/10 ,  A61P37/06 ,  A61P31/00 ,  A61P35/00 ,  A61P25/28 ,  A61P25/00 ,  A61P17/00 ,  A61P17/06 ,  A61P17/10 ,  A61P37/08 ,  A61P13/12 ,  A61P3/00 ,  A61P27/02 ,  A61P15/00 ,  C07D513/22

CPC分类号： A61K47/48215 ,  A61K47/60

摘要： The present invention relates to a process for the preparation of polymer conjugates of iπdolocarbazole compounds, in particular of polymer conjugates of K-252a and derivatives thereof, by a synthetic route which results in a highly pure product, with a high product yield. In a further aspect the present invention relates to novel polymer conjugates of K-252a and derivatives thereof, wherein the chemical group linking the polymer unity to the K-252a or to the K-252a derivative compound is characterised by a 5-member oxazolidindionic cyclic structure. These novel polymer conjugates are obtained through the novel synthetic route with high purity and high yields,

摘要翻译： 本发明涉及一种通过合成途径制备I＆amp;多沙唑化合物，特别是K-252a及其衍生物的聚合物共轭物的聚合物共轭物的方法，该合成途径产生高产物的高纯度产物。 另一方面，本发明涉及K-252a及其衍生物的新型聚合物共轭物，其中连接聚合物单元与K-252a或K-252a衍生物化合物的化学基团的特征在于5-构恶唑烷基吲哚环 结构体。 这些新型聚合物共轭物通过高纯度和高收率的新型合成路线获得，