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1. 发明申请

WO2011098433A1 ZYKLISCHE KETOENOLE ZUR THERAPIE 审中-公开
标题翻译：骑行酮烯醇疗法
公开(公告)号：WO2011098433A1
公开(公告)日：2011-08-18
申请号：PCT/EP2011/051771
申请日：2011-02-08
申请人： BAYER SCHERING PHARMA AKTIENGESELLSCHAFT , LIU, Ningshu , THEDE, Kai , LIENAU, Philip , SCHOLZ, Arne , HILGER, Christoph-Stephan , BÖMER, Ulf , NAJJAR, Maher , EIS, Knut , FISCHER, Reiner , MORADI, Wahed, Ahmed
发明人： LIU, Ningshu , THEDE, Kai , LIENAU, Philip , SCHOLZ, Arne , HILGER, Christoph-Stephan , BÖMER, Ulf , NAJJAR, Maher , EIS, Knut , FISCHER, Reiner , MORADI, Wahed, Ahmed
IPC分类号： C07D207/38 , A61K31/4015 , A61P35/00
CPC分类号： C07D493/10 , C07D207/38 , C07D209/54 , C07D513/04
摘要： Die Erfindung betrifft 5' -Biphenyl - substituierte zyklische Ketoenole der Formel (I) zu therapeutischen Zwecken, Pharmazeutische Mittel und deren Verwendung in der Therapie, insbesondere zur Prophylaxe und Therapie von Tumorerkrankungen.
摘要翻译：本发明涉及5“ - 联苯 - 的式（I）用于治疗目的，药物制剂和它们在治疗肿瘤性疾病的预防和治疗中的用途，特别是取代的环酮 - 烯醇。

2. 发明申请

WO2012104428A1 (5S,8S)-3-(4'-CHLOR-3'-FLUOR-4-METHYLBIPHENYL-3-YL)-4-HYDROXY-8-METHOXY-1-AZASPIRO[4.5]DEC-3-EN-2-ON (VERBINDUNG A) ZUR THERAPIE 审中-公开
标题翻译：（5S，8S）-3-（4'-氯-3'-氟-4-甲基联苯-3-基）-4-羟基-8-甲氧基-1-氮杂螺[4.5]癸-3-烯-2- 酮（化合物A）治疗
公开(公告)号：WO2012104428A1
公开(公告)日：2012-08-09
申请号：PCT/EP2012/051895
申请日：2012-02-03
申请人： BAYER PHARMA AKTIENGESELLSCHAFT , LIU, Ningshu , THEDE, Kai , LIENAU, Philip , SCHOLZ, Arne , HILGER, Christoph-Stephan , BÖMER, Ulf , NAJJAR, Maher , EIS, Knut , FISCHER, Reiner , MORADI, Wahed, Ahmed
发明人： LIU, Ningshu , THEDE, Kai , LIENAU, Philip , SCHOLZ, Arne , HILGER, Christoph-Stephan , BÖMER, Ulf , NAJJAR, Maher , EIS, Knut , FISCHER, Reiner , MORADI, Wahed, Ahmed
IPC分类号： A61K31/4015 , A61K45/06
CPC分类号： C07D209/54 , A61K31/4015 , A61K45/06
摘要： Die Erfindung betrifft (5s,8s)-3-(4'-Chlor-3'-fluor-4-methylbiphenyl-3-yl)-4-hydroxy-8-methoxy-1-azaspiro[4.5]dec-3-en-2-on zu therapeutischen Zwecken, Pharmazeutische Mittel und deren Verwendung in der Therapie, insbesondere zur Prophylaxe und Therapie von Tumorerkrankungen.
摘要翻译：本发明涉及（5S，8S）-3-（4'-氯-3'-氟-4-甲基联苯-3-基）-4-羟基-8-甲氧基-1-氮杂螺[4.5]癸-3-烯 -2-酮用于治疗目的，药物制剂和它们在治疗肿瘤性疾病的预防和治疗中的用途，尤其如此。

3. 发明申请

WO2013017600A1 SUBSTITUIERTE 3-(BIPHENYL-3-YL)-4-HYDROXY-8-METHOXY-1-AZASPIRO[4.5]DEC-3-EN-2-ONE 审中-公开
标题翻译：取代的3-（联苯-3-基）-4-羟基-8-甲氧基-1-氮杂螺[4.5]癸-3-烯-2-酮
公开(公告)号：WO2013017600A1
公开(公告)日：2013-02-07
申请号：PCT/EP2012/064974
申请日：2012-07-31
申请人： BAYER INTELLECTUAL PROPERTY GMBH , LIU, Ningshu , THEDE, Kai , MÖNNING, Ursula , SCHOLZ, Arne , HILGER, Christoph-Stephan , BÖMER, Ulf , FISCHER, Reiner
发明人： LIU, Ningshu , THEDE, Kai , MÖNNING, Ursula , SCHOLZ, Arne , HILGER, Christoph-Stephan , BÖMER, Ulf , FISCHER, Reiner
IPC分类号： C07D209/54 , A61K31/403 , A61P35/00
CPC分类号： C07D209/54 , A61K31/403
摘要： Die Erfindung betrifft substituierte 3-(Biphenyl-3-yl)-4-hydroxy-8-methoxy-1-azaspiro[4.5]dec-3- en-2-one, insbesondere zu therapeutischen Zwecken, pharmazeutische Mittel und deren Verwendung in der Therapie, insbesondere zur Prophylaxe und Therapie von Tumorerkrankungen.
摘要翻译：本发明涉及取代的3-（联苯-3-基）-4-羟基-8-甲氧基-1-氮杂螺[4.5]癸-3-烯-2-酮，特别是用于治疗目的，药物组合物和它们在使用治疗，特别是对于肿瘤疾病的预防和治疗。

4. 发明申请

WO2012110518A1 SUBSTITUIERTE 3-(BIPHENYL-3-YL)-8,8-DIFLUOR-4-HYDROXY-1-AZASPIRO[4.5]DEC-3-EN-2-ONE ZUR THERAPIE 审中-公开
标题翻译：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-酮用于治疗
公开(公告)号：WO2012110518A1
公开(公告)日：2012-08-23
申请号：PCT/EP2012/052520
申请日：2012-02-14
申请人： Bayer Pharma Aktiengesellschaft , Bayer CropScience AG , LIU, Ningshu , THEDE, Kai , MÖNNING, Ursula , SCHOLZ, Arne , HILGER, Christoph-Stephan , BÖMER, Ulf , FISCHER, Reiner
发明人： LIU, Ningshu , THEDE, Kai , MÖNNING, Ursula , SCHOLZ, Arne , HILGER, Christoph-Stephan , BÖMER, Ulf , FISCHER, Reiner
IPC分类号： C07D209/54 , A61K31/403 , A61P35/00
CPC分类号： A01N43/38 , A01N43/12 , A61K31/403 , A61K45/06 , C07D209/54
摘要： Die Erfindung betrifft substituierte 3-(Biphenyl-3-yl)-8,8-difluor-4-hydroxy-l-azaspiro[4.5]dec-3- en-2-one der Formel (la) zu therapeutischen Zwecken, pharmazeutische Mittel und deren Verwendung in der Therapie, insbesondere zur Prophylaxe und Therapie von Tumorerkrankungen. Die Erfindung betrifft außerdem neue Verbindungen der Formel (I), in welcher W, X, Y, Z, A, B, D und G die oben angegebenen Bedeutungen haben, mehrere Verfahren und Zwischenprodukte zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel und/oder Herbizide und/oder Fungizide. Außerdem betrifft die Erfindung selektiv herbizide Mittel, die halogensubstituierte spirocyclische Ketoenole einerseits und eine die Kulturpflanzenverträglichkeit verbessernde Verbindung andererseits enthalten. Die vorliegende Erfindung betrifft weiterhin die Steigerung der Wirkung von Pflanzenschutzmitteln enthaltend insbesondere halogensubstituierte spirocyclische Ketoenole, durch die Zugabe von Ammonium- oder Phosphoniumsalzen und gegebenenfalls Penetrationsförderern, die entsprechenden Mittel, Verfahren zur ihrer Herstellung und ihre Anwendung im Pflanzenschutz als Schädlingsbekämpfungsmittel und/oder Fungizide und/oder zur Verhinderung von unerwünschtem Pflanzen wuchs.
摘要翻译：本发明涉及取代的3-（联苯-3-基）-8,8-二氟-4-羟基-1-氮杂螺[4.5]癸-3-烯-2-酮的式（Ia），用于治疗目的的，药剂的和它们在治疗中的用途，特别是用于肿瘤疾病的预防和治疗。本发明还涉及式（I），其中W，X，Y，Z，A，B，D和G具有上文给出的含义，多个用于其制备方法及其作为杀虫剂和/或使用的方法和中间体的新化合物除草剂和/或杀真菌剂。本发明还选择性除草组合物中，卤素取代的螺环酮烯醇一方面，作物植物相容性改善化合物涉及包括上另一方面。本发明还涉及提高包含在特别是卤素取代的螺环酮 - 烯醇的作物保护组合物的活性，通过加入铵盐或鏻盐和任选的渗透促进剂，相应的组合物，其制备方法及其在植物保护作为杀虫剂和/或杀真菌剂和/应用的或增长，以防止不希望的植物。

5. 发明申请

WO2005023318A1 TARGETING OF TUMOR VASCULATURE USING RADIOLABELLED ANTIBODY L19 AGAINST FIBRONECTIN ED-B 审中-公开
标题翻译：使用放射性抗体L19对FIBRONECTIN ED-B进行肿瘤血管造影
公开(公告)号：WO2005023318A1
公开(公告)日：2005-03-17
申请号：PCT/EP2004/009733
申请日：2004-09-01
申请人： PHILOGEN S.P.A , SCHERING AG , BORSI, Laura , CARNEMOLLA, Barbara , BALZA, Enrica , CASTELLANI, Patrizia , ZARDI, Luciano , FRIEBE, Matthias , HILGER, Christoph-Stephan
发明人： BORSI, Laura , CARNEMOLLA, Barbara , BALZA, Enrica , CASTELLANI, Patrizia , ZARDI, Luciano , FRIEBE, Matthias , HILGER, Christoph-Stephan
IPC分类号： A61K51/10
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 eS2-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：如图3所示，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。化学。 273：21769-21776; 其特征在于，所述特异性结合成员包含包含与eS2-CH4融合的所述抗体VH结构域和抗体VL结构域的微型免疫球蛋白，其二聚化或包含整个IgG1抗体分子; 也是采用这种特异性结合成员的方法和用途。

6. 发明申请

WO2003076469A3 ANTIBODIES DERIVED ROM ANTI ED-B L19 AND TARGETING TUMOR VASCULATURE 审中-公开
公开(公告)号：WO2003076469A3
公开(公告)日：2003-09-18
申请号：PCT/IB2003/001458
申请日：2003-03-11
申请人： PHILOGEN S R L , SCHERING AG , BORSI, Laura , CARNEMOLLA, Barbara , BALZA, Enrica , CASTELLANI, Patrizia , ZARDI, Luciano , FRIEBE, Matthias , HILGER, Christoph-Stephan
发明人： BORSI, Laura , CARNEMOLLA, Barbara , BALZA, Enrica , CASTELLANI, Patrizia , ZARDI, Luciano , FRIEBE, Matthias , HILGER, Christoph-Stephan
IPC分类号： C07K16/46
摘要： The present invention relates to selectively targeting tumoral vasculature in vivo using a human recombinant scFv, L19, to the angiogenesis marker ED-B domain of fibronectin. In preferred embodiments, a complete human IgG1 is employed having the variable regions of L19. In other embodiments is employed a mini-immunoglobulin generated by fusing the scFv L19 to the constant CH4 domain of a secretory IgE isoform that naturally contains a cysteine in its COOH terminal and which forms a covalently linked dimer. Different in vivo behaviour of the antibody formats is exploitable for different diagnostic and/or therapeutic purposes, depending on clinical needs and disease. The antibody molecules may be labelled as described.

7. 发明授权

EP1663320B1 TARGETING OF TUMOR VASCULATURE USING RADIOLABELLED ANTIBODY L19 AGAINST FIBRONECTIN ED-B 有权
标题翻译：肿瘤血管目标方向使用纤连蛋白的ED-B抗体放射标记的L19
公开(公告)号：EP1663320B1
公开(公告)日：2011-03-02
申请号：EP04764695.5
申请日：2004-09-01
申请人： Philogen S.p.A. , Bayer Schering Pharma Aktiengesellschaft
发明人： BORSI, Laura, Ist. Naz. per la Ricerca sul Cancro , CARNEMOLLA, B., Inst. Naz. per Ricerca sul Cancro , BALZA, Enrica, Ist. Naz. per la Ricerca sul Cancro , CASTELLANI, P. Ist. Naz. per la Ricerca sul Cancro , ZARDI, L., Ist. Naz. per la Ricerca sul Cancro , FRIEBE, Matthias , HILGER, Christoph-Stephan
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 eS2-CH4 and dimerized or comprises a whole IgG1 antibody molecule; also methods and uses employing such a specific binding member.

8. 发明授权

EP1461360B1 CONJUGATES COMPRISING AN ANTIBODY SPECIFIC FOR THE ED-B DOMAIN OF FIBRONECTIN AND THEIR USE FOR THE DETECTION AND TREATMENT OF TUMOURS 有权
标题翻译：有纤连蛋白特异性抗体的ED-B域及其用途的检测和治疗肿瘤的缀合物
公开(公告)号：EP1461360B1
公开(公告)日：2010-08-18
申请号：EP03726977.6
申请日：2003-01-02
申请人： Bayer Schering Pharma Aktiengesellschaft
发明人： HILGER, Christoph-Stephan , BERNDORFF, Dietmar , DINKELBORG, Ludger , MOOSMAYER, Dieter, Schering Aktiengesellschaft , NERI, Giovanni, Philogen S.r.l.
IPC分类号： C07K19/00 , A61K47/48 , A61K51/10 , A61P35/00
CPC分类号： A61K51/1018 , A61K9/0024 , A61K51/08 , A61K51/088 , A61K2039/505 , C07K16/18 , C07K2317/21 , C07K2317/622
摘要： The present invention relates to methods for diagnosis and treatment of tumours, using peptides for binding radionuclides. The peptides comprise an antigen- binding site for the extra domain B (ED-B) of fibronectin.

9. 发明授权

EP1483297B1 ANTIBODIES DERIVED FROM ANTI ED-B L19 AND TARGETING TUMOR VASCULATURE 有权
标题翻译：抗体抗ED-B L19针对肿瘤血管
公开(公告)号：EP1483297B1
公开(公告)日：2009-12-23
申请号：EP03715180.0
申请日：2003-03-11
申请人： Philogen S.p.A. , Bayer Schering Pharma Aktiengesellschaft
发明人： BORSI, Laura, Lab. of Cell Biology , CARNEMOLLA, Barbara, Lab of Cell Biology , BALZA, Enrica, Lab. of Cell Biology , CASTELLANI, Patrizia, Lab. of Cell Biology , ZARDI, Luciano, Lab. of Cell Biology , FRIEBE, Matthias , HILGER, Christoph-Stephan
IPC分类号： C07K16/46 , C07K16/18 , A61K51/10 , G01N33/68 , C12N1/21 , C12N15/13 , A61K39/395 , A61P9/00 , A61P35/00
CPC分类号： A61K51/1018 , C07K16/18 , C07K2317/21 , C07K2317/52 , C07K2317/565 , C07K2317/622 , C07K2319/00
摘要： The present invention relates to selectively targeting tumoral vasculature in vivo using a human recombinant scFv, L19, to the angiogenesis marker ED-B domain of fibronectin. In preferred embodiments, a complete human IgG1 is employed having the variable regions of L19. In other embodiments is employed a mini-immunoglobulin generated by fusing the scFv L19 to the constant CH4 domain of a secretory IgE isoform that naturally contains a cysteine in its COOH terminal and which forms a covalently linked dimer. Different in vivo behaviour of the antibody formats is exploitable for different diagnostic and/or therapeutic purposes, depending on clinical needs and disease. The antibody molecules may be labelled as described.

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