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    SELECTIVE TARGETING OF TUMOR VASCULATURE USING RADIOLABELLED ANTIBODY MOLECULES
    3.
    发明申请
    SELECTIVE TARGETING OF TUMOR VASCULATURE USING RADIOLABELLED ANTIBODY MOLECULES 审中-公开
    使用放射性抗体分子的肿瘤血管的选择性靶向

    公开(公告)号：US20090214423A1

    公开(公告)日：2009-08-27

    申请号：US12350346

    申请日：2009-01-08

    申请人： Laura Borsi ,  Enrica Balza ,  Barbara Carnemolla ,  Patrizia Castellani ,  Luciano Zardi ,  Matthias Friebe ,  Christoph-Stephan Hilger

    发明人： Laura Borsi ,  Enrica Balza ,  Barbara Carnemolla ,  Patrizia Castellani ,  Luciano Zardi ,  Matthias Friebe ,  Christoph-Stephan Hilger

    IPC分类号： A61K51/10 ,  A61P35/00

    CPC分类号： A61K51/1045

    摘要： A specific binding member that binds human ED-B, wherein the specific binding member is labelled with an isotope selected from the group consisting of 76Br, 77Br, 123I, 124I, 131I and 211At and comprises an antigen-binding site that comprises an antibody VH domain and an antibody VL domain, wherein the antibody VH domain is selected from the group consisting of the L19 VH domain, and a VH domain comprising a VH CDR1, a VH CDR2 and a VH CDR3, wherein the VH CDR3 is the L19 VH CDR3 of SEQ ID NO. 3, the VH CDR1 is optionally L19 VH CDR1 of SEQ ID NO. 1, and the VH CDR2 is optionally L19 VH CDR2 of SEQ ID NO. 2; and wherein the antibody VL domain is optionally selected from the group consisting of the L19 VL domain, and a VL domain comprising a VL CDR1, a VL CDR2 and a VL CDR3, wherein the VL CDR3 is the L19 VL CDR3 of SEQ ID NO. 6, the VL CDR1 is optionally L19 VL CDR1 of SEQ ID NO. 4, and the VL CDR2 is optionally L19 VL CDR2 of SEQ ID NO. 5; the L19 VH domain and L19 VL domain sequences being disclosed in Pini et al. (1998) J. Biol. Chem. 273: 21769-21776; wherein the specific binding member comprises a mini-immunoglobulin comprising said antibody VH domain and antibody VL domain fused to εS2-CH4 and dimerized or comprises a whole IgG1 antibody molecule; also methods and uses employing such a specific binding member.

    摘要翻译： 结合人ED-B的特异性结合成员，其中所述特异性结合成员用选自76Br，77Br，123I，124I，131I和211At的同位素标记，并且包含抗原结合位点，其包含抗体VH 结构域和抗体VL结构域，其中抗体VH结构域选自L19VV结构域和包含VH CDR1，VH CDR2和VH CDR3的VH结构域，其中VH CDR3是L19 VH CDR3 的SEQ ID NO： 3，VH CDR1任选是SEQ ID NO：1的L19VV CDR1。 1，VH CDR2任选是SEQ ID NO：1的L19VH CDR2。 2; 并且其中抗体VL结构域任选地选自L19VL结构域和包含VL CDR1，VL CDR2和VL CDR3的VL结构域，其中VL CDR3是SEQ ID NO：1的L19VL CDR3。 如图6所示，VL CDR1任选是SEQ ID NO：1的L19VL CDR1。 4，VL CDR2任选是SEQ ID NO：1的L19VL CDR2。 5; Pini等人公开了L19VV结构域和L19VL结构域序列 （1998）J.Biol.Chem。 Chem。 273：21769-21776; 其中所述特异性结合成员包含包含所述抗体VH结构域的微型免疫球蛋白和与ε2-CH4融合并且二聚化或包含整个IgG1抗体分子的抗体VL结构域; 也是采用这种特异性结合成员的方法和用途。

    Selective targeting of tumor vasculature using radiolabelled antibody molecules
    4.
    发明申请
    Selective targeting of tumor vasculature using radiolabelled antibody molecules 审中-公开
    使用放射性标记的抗体分子选择性靶向肿瘤脉管系统

    公开(公告)号：US20050074401A1

    公开(公告)日：2005-04-07

    申请号：US10937882

    申请日：2004-09-10

    申请人： Laura Borsi ,  Enrica Balza ,  Barbara Carnemolla ,  Patrizia Castellani ,  Luciano Zardi ,  Matthias Friebe ,  Christoph-Stephan Hilger

    发明人： Laura Borsi ,  Enrica Balza ,  Barbara Carnemolla ,  Patrizia Castellani ,  Luciano Zardi ,  Matthias Friebe ,  Christoph-Stephan Hilger

    IPC分类号： A61K51/00 ,  A61K51/10 ,  A61P35/00 ,  C07K16/46

    CPC分类号： A61K51/1045

    摘要： A specific binding member that binds human ED-B, wherein the specific binding member is labelled with an isotope selected from the group consisting of 76Br, 77Br, 123I, 124I, 131I and 211At and comprises an antigen-binding site that comprises an antibody VH domain and an antibody VL domain, wherein the antibody VH domain is selected from the group consisting of the L19 VH domain, and a VH domain comprising a VH CDR1, a VH CDR2 and a VH CDR3, wherein the VH CDR3 is the L19 VH CDR3 of SEQ ID NO. 3, the VH CDR1 is optionally L19 VH CDR1 of SEQ ID NO. 1, and the VH CDR2 is optionally L19 VH CDR2 of SEQ ID NO. 2; and wherein the antibody VL domain is optionally selected from the group consisting of the L19 VL domain, and a VL domain comprising a VL CDR1, a VL CDR2 and a VL CDR3, wherein the VL CDR3 is the L19 VL CDR3 of SEQ ID NO. 6, the VL CDR1 is optionally L19 VL CDR1 of SEQ ID NO. 4, and the VL CDR2 is optionally L19 VL CDR2 of SEQ ID NO. 5; the L19 VH domain and L19 VL domain sequences being disclosed in Pini et al. (1998) J. Biol. Chem. 273: 21769-21776; wherein the specific binding member comprises a mini-immunoglobulin comprising said antibody VH domain and antibody VL domain fused to εS2-CH4 and dimerized or comprises a whole IgG1 antibody molecule; also methods and uses employing such a specific binding member.

    摘要翻译： 结合人ED-B的特异性结合成员，其中特异性结合成员用选自76 Br，77 Br，123 I，124 I，131 I的同位素标记。 I和211包含抗体结合位点，其包含抗体VH结构域和抗体VL结构域，其中抗体VH结构域选自L19VV结构域和包含VH CDR1的VH结构域 ，VH CDR2和VH CDR3，其中VH CDR3是SEQ ID NO.1的L19VV CDR3。 3，VH CDR1任选是SEQ ID NO：1的L19VV CDR1。 1，VH CDR2任选是SEQ ID NO：1的L19VH CDR2。 2; 并且其中抗体VL结构域任选地选自L19VL结构域和包含VL CDR1，VL CDR2和VL CDR3的VL结构域，其中VL CDR3是SEQ ID NO：1的L19VL CDR3。 如图6所示，VL CDR1任选是SEQ ID NO：1的L19VL CDR1。 4，VL CDR2任选是SEQ ID NO：1的L19VL CDR2。 5; Pini等人公开了L19VV结构域和L19VL结构域序列 （1998）J.Biol.Chem。 Chem。 273：21769-21776; 其中所述特异性结合成员包含包含所述抗体VH结构域的微型免疫球蛋白和与ε2-CH4融合并且二聚化或包含整个IgG1抗体分子的抗体VL结构域; 也是采用这种特异性结合成员的方法和用途。

    Substituted 3-(biphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-ones for therapy
    6.
    发明授权
    Substituted 3-(biphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-ones for therapy 有权
    取代3-（联苯-3-基）-8,8-二氟-4-羟基-1-氮杂螺[4.5]癸-3-烯-2-酮治疗

    公开(公告)号：US09000026B2

    公开(公告)日：2015-04-07

    申请号：US13985940

    申请日：2012-02-14

    申请人： Ningshu Liu ,  Kai Thede ,  Ursula Mönning ,  Arne Scholz ,  Christoph-Stephan Hilger ,  Ulf Bömer ,  Reiner Fischer

    发明人： Ningshu Liu ,  Kai Thede ,  Ursula Mönning ,  Arne Scholz ,  Christoph-Stephan Hilger ,  Ulf Bömer ,  Reiner Fischer

    IPC分类号： A61K31/4015 ,  C07D209/54 ,  A01N43/38 ,  A61K31/403 ,  A61K45/06 ,  A01N43/12

    CPC分类号： A01N43/38 ,  A01N43/12 ,  A61K31/403 ,  A61K45/06 ,  C07D209/54

    摘要： The invention relates to substituted 3-(biphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-ones of the formula (Ia) for therapeutic purposes, to pharmaceutical compositions and to their use in therapy, in particular for the prophylaxis and therapy of tumor disorders.The invention also relates to novel compounds of the formula (I) in which W, X, Y, Z, A, B, D and G have the meanings given above, to a plurality of processes and intermediates for their preparation, and to their use as pesticides and/or herbicides and/or fungicides. The invention also relates to selectively herbicidal compositions comprising, firstly, the halogen-substituted spirocyclic ketoenols and, secondly, a crop plant compatibility-improving compound.The present invention furthermore relates to the boosting of the action of crop protection compositions comprising, in particular, halogen-substituted spirocyclic ketoenols, through the addition of ammonium salts or phosphonium salts and optionally penetrants, to the corresponding compositions, to processes for producing them and to their application in crop protection as pesticides and/or fungicides and/or for preventing unwanted plant growth.

    摘要翻译： 为了治疗目的，本发明涉及式（Ia）的取代的3-（联苯-3-基）-8,8-二氟-4-羟基-1-氮杂螺[4.5]癸-3-烯-2-酮， 药物组合物及其在治疗中的用途，特别是用于预防和治疗肿瘤病症。 本发明还涉及其中W，X，Y，Z，A，B，D和G具有上述含义的式（I）的新化合物，涉及多种制备方法和中间体，以及它们 用作农药和/或除草剂和/或杀真菌剂。 本发明还涉及选择性除草组合物，其包含首先是卤素取代的螺环酮醇，其次是作物植物相容性改善化合物。 本发明还涉及通过将铵盐或鏻盐和任选的渗透剂加入到相应的组合物中来增强作物保护组合物的作用，包括特别是卤素取代的螺环酮醇，制备它们的方法和 在农作物保护中作为农药和/或杀真菌剂的应用和/或用于防止不期望的植物生长。

    SUBSTITUTED 3-(BIPHENYL-3-YL)-8,8-DIFLUORO-4-HYDROXY-1-AZASPIRO[4.5]DEC-3-EN-2-ONES FOR THERAPY
    8.
    发明申请
    SUBSTITUTED 3-(BIPHENYL-3-YL)-8,8-DIFLUORO-4-HYDROXY-1-AZASPIRO[4.5]DEC-3-EN-2-ONES FOR THERAPY 有权
    取代的3-（联苯-3-基）-8,8-二氟-4-羟基-1-氮杂[4.5] DEC-3-EN-2-ONES治疗

    公开(公告)号：US20140011853A1

    公开(公告)日：2014-01-09

    申请号：US13985940

    申请日：2012-02-14

    申请人： Ningshu Liu ,  Kai Thede ,  Ursula Mönning ,  Arne Scholz ,  Christoph-Stephan Hilger ,  Ulf Bömer ,  Reiner Fischer

    发明人： Ningshu Liu ,  Kai Thede ,  Ursula Mönning ,  Arne Scholz ,  Christoph-Stephan Hilger ,  Ulf Bömer ,  Reiner Fischer

    IPC分类号： A61K31/403 ,  A61K45/06 ,  C07D209/54

    CPC分类号： A01N43/38 ,  A01N43/12 ,  A61K31/403 ,  A61K45/06 ,  C07D209/54

    摘要： The invention relates to substituted 3-(biphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-ones of the formula (Ia) for therapeutic purposes, to pharmaceutical compositions and to their use in therapy, in particular for the prophylaxis and therapy of tumour disorders.The invention also relates to novel compounds of the formula (I) in which W, X, Y, Z, A, B, D and G have the meanings given above, to a plurality of processes and intermediates for their preparation, and to their use as pesticides and/or herbicides and/or fungicides. The invention also relates to selectively herbicidal compositions comprising, firstly, the halogen-substituted spirocyclic ketoenols and, secondly, a crop plant compatibility-improving compound.The present invention furthermore relates to the boosting of the action of crop protection compositions comprising, in particular, halogen-substituted spirocyclic ketoenols, through the addition of ammonium salts or phosphonium salts and optionally penetrants, to the corresponding compositions, to processes for producing them and to their application in crop protection as pesticides and/or fungicides and/or for preventing unwanted plant growth.

    摘要翻译： 为了治疗目的，本发明涉及式（Ia）的取代的3-（联苯-3-基）-8,8-二氟-4-羟基-1-氮杂螺[4.5]癸-3-烯-2-酮， 药物组合物及其在治疗中的用途，特别是用于预防和治疗肿瘤病症。 本发明还涉及其中W，X，Y，Z，A，B，D和G具有上述含义的式（I）的新化合物，涉及多种制备方法和中间体，以及它们 用作农药和/或除草剂和/或杀真菌剂。 本发明还涉及选择性除草组合物，其包含首先是卤素取代的螺环酮醇，其次是作物植物相容性改善化合物。 本发明还涉及通过将铵盐或鏻盐和任选的渗透剂加入到相应的组合物中来增强作物保护组合物的作用，包括特别是卤素取代的螺环酮醇，用于生产它们的方法和 在农作物保护中作为农药和/或杀真菌剂的应用和/或用于防止不期望的植物生长。