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1. 发明授权

US08491906B2 Selective targeting of tumor vasculature using antibody molecules 有权
标题翻译：使用抗体分子选择性靶向肿瘤脉管系统
公开(公告)号：US08491906B2
公开(公告)日：2013-07-23
申请号：US10507178
申请日：2003-03-11
申请人： Laura Borsi , Barbara Carnemolla , Enrica Balza , Patrizia Castellani , Luciano Zardi , Matthias Friebe , Christoph-Stephan Hilger
发明人： Laura Borsi , Barbara Carnemolla , Enrica Balza , Patrizia Castellani , Luciano Zardi , Matthias Friebe , Christoph-Stephan Hilger
IPC分类号： A61K39/395 , C07K16/30
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 preferred 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 behavior 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.
摘要翻译：本发明涉及使用人重组scFv L19向体内血管生成标记ED-B结构域选择性靶向肿瘤脉管系统。在优选的实施方案中，使用具有L19可变区的完整人IgG1。在其它优选实施方案中，使用通过将scFv L19融合到其COOH末端中天然含有半胱氨酸且形成共价连接的二聚体的分泌型IgE同种型的恒定CH4结构域产生的微型免疫球蛋白。根据临床需要和疾病，抗体形式的不同体内行为可用于不同的诊断和/或治疗目的。抗体分子可以如所述标记。

2. 发明申请

US20090214423A1 SELECTIVE TARGETING OF TUMOR VASCULATURE USING RADIOLABELLED ANTIBODY MOLECULES 审中-公开
标题翻译：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。

3. 发明申请

US20050074401A1 Selective targeting of tumor vasculature using radiolabelled antibody molecules 审中-公开
标题翻译：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。

4. 发明申请

US20060057146A1 Selective targeting of tumor vasculature using antibody molecules 有权
标题翻译：使用抗体分子选择性靶向肿瘤脉管系统
公开(公告)号：US20060057146A1
公开(公告)日：2006-03-16
申请号：US10507178
申请日：2003-03-11
申请人： Laura Borsi , Barbara Carnemolla , Enrica Balza , Patrizia Castellani , Luciano Zardi , Mathias Friebe , Christoph-Stephan Hilger
发明人： Laura Borsi , Barbara Carnemolla , Enrica Balza , Patrizia Castellani , Luciano Zardi , Mathias Friebe , Christoph-Stephan Hilger
IPC分类号： C07K16/30 , A61K39/395
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.
摘要翻译：本发明涉及使用人重组scFv L19向体内血管生成标记ED-B结构域选择性靶向肿瘤脉管系统。在优选的实施方案中，使用具有L19可变区的完整人IgG1。在其它实施方案中，使用通过将scFv L19融合到其COOH末端中天然含有半胱氨酸且形成共价连接的二聚体的分泌型IgE同种型的恒定CH4结构域产生的微型免疫球蛋白。根据临床需要和疾病，抗体形式的不同体内行为可用于不同的诊断和/或治疗目的。抗体分子可以如所述标记。

5. 发明授权

US09278925B2 Substituted 3-(biphenyl-3-yl)-4-hydroxy-8-methoxy-1-azaspiro[4.5]dec-3-en-2-one 有权
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：US09278925B2
公开(公告)日：2016-03-08
申请号：US14236279
申请日：2012-07-31
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： C07D207/18 , C07D209/54 , A61K31/403
CPC分类号： C07D209/54 , A61K31/403
摘要： The invention relates to substituted 3-(biphenyl-3-yl)-4-hydroxy-8-methoxy-1-azaspiro[4.5]dec-3-en-2-ones, in particular for therapeutic purposes, to pharmaceutical compositions and to their use in therapy, in particular for the prophylaxis and therapy of neoplastic disorders.
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，用于药物组合物，它们在治疗中的用途，特别是用于预防和治疗肿瘤性疾病。

6. 发明授权

US09000026B2 Substituted 3-(biphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-ones for therapy 有权
标题翻译：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。

7. 发明授权

US07025949B2 In-vivo diagnostic method by means of near infrared radiation 有权
公开(公告)号：US07025949B2
公开(公告)日：2006-04-11
申请号：US09850660
申请日：2001-05-07
申请人： Kai Licha , Bjorn Riefke , Wolfhard Semmler , Ulrich Speck , Christoph-Stephan Hilger
发明人： Kai Licha , Bjorn Riefke , Wolfhard Semmler , Ulrich Speck , Christoph-Stephan Hilger
IPC分类号： A61B10/00 , A61B5/00 , A61B8/00
CPC分类号： A61K49/0032 , A61K49/0017 , A61K49/0021 , A61K49/005 , C09B23/086 , C09B69/105
摘要： This invention relates to an in-vivo diagnostic method based on near infrared radiation (NIR radiation) that uses water-soluble dyes and their biomolecule adducts, each having specific photophysical and pharmaco-chemical properties, as a contrast medium for fluorescence and transillumination diagnostics in the NIR range, to new dyes and pharmaceuticals containing such dyes.

8. 发明申请

US20140011853A1 SUBSTITUTED 3-(BIPHENYL-3-YL)-8,8-DIFLUORO-4-HYDROXY-1-AZASPIRO[4.5]DEC-3-EN-2-ONES FOR THERAPY 有权
标题翻译：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。

9. 发明授权

US07655217B2 Near infrared imaging agent 失效
标题翻译：近红外成像剂
公开(公告)号：US07655217B2
公开(公告)日：2010-02-02
申请号：US11387367
申请日：2006-03-22
申请人： Kai Licha , Björn Riefke , Wolfhard Semmler , Ulrich Speck , Christoph-Stephan Hilger
发明人： Kai Licha , Björn Riefke , Wolfhard Semmler , Ulrich Speck , Christoph-Stephan Hilger
IPC分类号： A61B10/00 , A61B5/00 , A61B8/00
CPC分类号： A61K49/0032 , A61K49/0017 , A61K49/0021 , A61K49/005 , C09B23/086 , C09B69/105
摘要： This invention relates to an in-vivo diagnostic method based on near infrared radiation (NIR radiation) that uses water-soluble dyes and their biomolecule adducts, each having specific photophysical and pharmaco-chemical properties, as a contrast medium for fluorescence and transillumination diagnostics in the NIR range, to new dyes and pharmaceuticals containing such dyes.
摘要翻译：本发明涉及一种基于近红外辐射（NIR辐射）的体内诊断方法，其使用水溶性染料及其生物分子加合物，其具有特定的光物理和药物化学性质，作为用于荧光和透照诊断的造影剂 NIR范围，新染料和含有这些染料的药物。

10. 发明授权

US06709693B1 Stents with a radioactive surface coating, processes for their production and their use for restenosis prophylaxis 失效
标题翻译：具有放射性表面涂层的支架，其生产过程及其用于再狭窄预防
公开(公告)号：US06709693B1
公开(公告)日：2004-03-23
申请号：US09627321
申请日：2000-07-27
申请人： Ludger Dinkelborg , Friedhelm Blume , Christoph-Stephan Hilger , Dieter Heldmann , Johannes Platzek , Ulrich Niedballa , Heribert Miklautz , Ulrich Speck , Stephan Duda , Gunnar Tepe , Bernhard Noll , Heidemarie Goerner
发明人： Ludger Dinkelborg , Friedhelm Blume , Christoph-Stephan Hilger , Dieter Heldmann , Johannes Platzek , Ulrich Niedballa , Heribert Miklautz , Ulrich Speck , Stephan Duda , Gunnar Tepe , Bernhard Noll , Heidemarie Goerner
IPC分类号： A61L2700
CPC分类号： A61K51/1282 , A61F2/82 , A61F2210/0095 , A61L31/082 , A61L31/14 , A61L31/16 , A61L31/18 , A61L2300/416 , A61L2300/44 , A61L2300/606 , A61N5/1002
摘要： The invention relates to radioactive stents, characterized in that the stent is coated on the surface with the radioactive isotope, as well as processes for their production.
摘要翻译：本发明涉及放射性支架，其特征在于，用放射性同位素将支架涂覆在表面上，以及其生产方法。

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