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1. 发明申请

WO03076469A9 ANTIBODIES DERIVED ROM ANTI ED-B L19 AND TARGETING TUMOR VASCULATURE 审中-公开
标题翻译：抗体衍生物抗体ED-B L19和靶向肿瘤血管
公开(公告)号：WO03076469A9
公开(公告)日：2005-09-29
申请号：PCT/IB0301458
申请日：2003-03-11
申请人： PHILOGEN SPA , 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： C12N15/09 , A61K38/00 , A61K39/395 , A61K51/10 , A61P9/00 , A61P35/00 , A61P43/00 , C07K16/18 , C07K16/44 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/13 , C12P21/00 , C07K16/46 , G01N33/68
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。

2. 发明专利

JP2012036216A Composition and method for treatment of angiogenesis in pathological lesion 审中-公开
标题翻译：用于治疗病理学中血管生成的组合物和方法
公开(公告)号：JP2012036216A
公开(公告)日：2012-02-23
申请号：JP2011236144
申请日：2011-10-27
申请人： Philogen Spa , フィロジェンソチエタペルアツィオニ
发明人： ZARDI LUCIANO , NERI DARIO , CARNEMOLLA BARBARA , NILSSON FREDRIK , TARLI LORENZO , BORSI LAURA , HALIN CORNELIA
IPC分类号： A61K38/00 , A61K39/395 , A61K47/48 , A61P9/00 , A61P27/02 , A61P29/00 , A61P35/00 , C07K14/475 , C07K14/525 , C07K14/54 , C07K14/55 , C07K14/57 , C07K14/705 , C07K16/18 , C07K16/24 , C12N15/09
CPC分类号： A61K47/48423 , A61K31/704 , A61K38/1709 , A61K38/191 , A61K38/2013 , A61K38/208 , A61K38/217 , A61K47/62 , A61K47/6803 , A61K47/6813 , A61K47/6851 , A61K2039/505 , C07K14/475 , C07K14/525 , C07K14/5434 , C07K14/55 , C07K14/57 , C07K14/70596 , C07K16/18 , C07K2317/622 , C07K2319/00
摘要： PROBLEM TO BE SOLVED: To provide treatment for lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration, and angiomas.SOLUTION: A conjugate is used comprising a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. The antibody can be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12(IL-12), Interferon-γ (IFN-γ), Tumor Necrosis Factorα (TNFα) or Tissue Factor protein (which can be truncated).
摘要翻译：要解决的问题：提供病理性血管生成病变，特别是肿瘤，类风湿性关节炎，糖尿病性视网膜病变，年龄相关性肌肉变性和血管瘤的治疗。解决方案：使用包含对损伤中的靶细胞具有杀生物或细胞毒性作用的分子的缀合物和针对存在于这种损伤中的细胞外基质成分的抗体。抗体可以针对纤连蛋白-2（IL-2），多柔比星，白细胞介素-12（IL-12），干扰素-γ（IFN-γ），肿瘤坏死因子α（TNFα）或组织因子蛋白（可被截短））。版权所有（C）2012，JPO＆INPIT

3. 发明专利

CA2478414C SELECTIVE TARGETING OF TUMOR VASCULATURE USING ANTIBODY MOLECULES 未知
公开(公告)号：CA2478414C
公开(公告)日：2012-11-13
申请号：CA2478414
申请日：2003-03-11
申请人： PHILOGEN SPA , SCHERING AG
发明人： BORSI LAURA , CARNEMOLLA BARBARA , BALZA ENRICA , CASTELLANI PATRIZIA , ZARDI LUCIANO , FRIEBE MATTHIAS , HILGER CHRISTOPH-STEPHAN
IPC分类号： C12N15/09 , C12N15/13 , A61K38/00 , A61K39/395 , A61K51/10 , A61P9/00 , A61P35/00 , A61P43/00 , C07K16/18 , C07K16/44 , C07K16/46 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12P21/00 , C12P21/02 , G01N33/53
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.

4. 发明专利

CA2536256A1 TARGETING OF TUMOR VASCULATURE USING RADIOLABELLED ANTIBODY L19 AGAINST FIBRONECTIN ED-B 未知
公开(公告)号：CA2536256A1
公开(公告)日：2005-03-17
申请号：CA2536256
申请日：2004-09-01
申请人： PHILOGEN SPA , SCHERING AG
发明人： HILGER CHRISTOPH-STEPHAN , FRIEBE MATTHIAS , CASTELLANI PATRIZIA , ZARDI LUCIANO , BALZA ENRICA , CARNEMOLLA BARBARA , BORSI LAURA
IPC分类号： A61K51/10 , A61K51/00 , A61P35/00 , C07K16/46
摘要： A specific binding member that binds human ED-B, wherein the specific bindin g member is labelled with an isotope selected from the group consisting of 76B r, 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 domai n, and a VH domain comprising a VH CDR1, a VH CDR2 and a VH CDR3, wherein the V H CDR3 is the L19 VH CDR3 of SEQ ID NO. 3, the VH CDR1 is optionally L19 VH CD R1 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 a nd dimerized or comprises a whole IgG1 antibody molecule; also methods and uses employing sucha specific binding member.

5. 发明专利

BRPI0414272A 未知
公开(公告)号：BRPI0414272A
公开(公告)日：2006-11-07
申请号：BRPI0414272
申请日：2004-09-01
申请人： PHILOGEN SPA , SCHERING AG
发明人： BORSI LAURA , CARNEMOLLA BARBARA , BALZA ENRICA , CASTELLANI PATRIZIA , ZARDI LUCIANO , FRIEBE MATTHIAS , HILGER CHRISTOPH-STEPHAN
IPC分类号： A61K51/00 , A61K51/10 , A61P35/00 , C07K16/46
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 CDR3of 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.

6. 发明专利

CA2536256C TARGETING OF TUMOR VASCULATURE USING RADIOLABELLED ANTIBODY L19 AGAINST FIBRONECTIN ED-B 未知
公开(公告)号：CA2536256C
公开(公告)日：2013-02-26
申请号：CA2536256
申请日：2004-09-01
申请人： PHILOGEN SPA , SCHERING AG
发明人： BORSI LAURA , CARNEMOLLA BARBARA , BALZA ENRICA , CASTELLANI PATRIZIA , ZARDI LUCIANO , FRIEBE MATTHIAS , HILGER CHRISTOPH-STEPHAN
IPC分类号： A61K51/10 , A61K51/00 , A61P35/00 , C07K16/46
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.

7. 发明专利

AU2004269897A1 Targeting of tumor vasculature using radiolabelled antibody L19 against fibronectin ED-B 未知
公开(公告)号：AU2004269897A1
公开(公告)日：2005-03-17
申请号：AU2004269897
申请日：2004-09-01
申请人： SCHERING AG , PHILOGEN SPA
发明人： BALZA ENRICA , FRIEBE MATTHIAS , BORSI LAURA , HILGER CHRISTOPH-STEPHAN , CASTELLANI PATRIZIA , CARNEMOLLA BARBARA , ZARDI LUCIANO
IPC分类号： A61K51/10 , A61K51/00 , A61P35/00 , C07K16/46
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 CDR3of 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. 发明专利

JP2009268470A Selective targeting of tumor vasculature using antibody molecule 审中-公开
标题翻译：使用抗体分子选择性定位肿瘤血管
公开(公告)号：JP2009268470A
公开(公告)日：2009-11-19
申请号：JP2009183370
申请日：2009-08-06
申请人： Bayer Schering Pharma Ag , Philogen Spa , バイエル・シエーリング・ファーマアクチエンゲゼルシャフト , フィロジェンソチエタペルアツィオニ
发明人： BORSI LAURA , CARNEMOLLA BARBARA , BALZA ENRICA , CASTELLANI PATRIZIA , ZARDI LUCIANO , FRIEBE MATTHIAS , HILGER CHRISTOPH-STEPHAN
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61K51/10 , A61P3/10 , A61P9/00 , A61P9/10 , A61P19/02 , A61P27/02 , A61P29/00 , A61P35/00 , A61P43/00 , C07K16/18 , C07K16/44 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/13 , C12P21/00 , C12P21/08
CPC分类号： A61K51/1018 , C07K16/18 , C07K2317/21 , C07K2317/52 , C07K2317/565 , C07K2317/622 , C07K2319/00
摘要： PROBLEM TO BE SOLVED: To provide a specific binding member binding human ED-B, containing an antigen-binding part comprising an antibody VH domain and an antibody VL domain. SOLUTION: Provided are 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 having the variable regions of L19 is employed. In other embodiments 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 is employed. 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. COPYRIGHT: (C)2010,JPO&INPIT
摘要翻译：要解决的问题：提供结合人ED-B的特异性结合成员，其含有包含抗体VH结构域和抗体VL结构域的抗原结合部分。提供了使用人重组scFv（L19）选择性靶向肿瘤血管的血管发生标志物纤连蛋白的ED-B结构域。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。版权所有（C）2010，JPO＆INPIT

9. 发明专利

RS20060176A CILJANJE VASKULATURE TUMORA UPOTREBOM RADIOOZNAČENOG ANTITELA L19 SPRAM FIBRONEKTIN ED-B 未知
公开(公告)号：RS20060176A
公开(公告)日：2008-08-07
申请号：YUP17606
申请日：2004-09-01
申请人： PHILOGEN SPA , SCHERING AG
发明人： BORSI LAURA , CARENEMOLLA BARBARA , BALZA ENRICA , CASTELLANI PATRIZIA , ZARDI LUCIANO , FRIEBE MATTHIAS , HILGER CHRISTOPH-STEPHAN
IPC分类号： A61K51/10 , A61K51/00 , A61P35/00 , C07K16/46
摘要： Specifični vezujući član koji vezuje humani ED-B, pri čemu je specifični vezujući član označen izotopom odabrano od grupe koja se sastoji od 76Br, 77Br, 123J, 124J, 131J i 211At i sadrži antigen-vezujući položaj koji sadrži VH domen anti tela i VL domen anti tela , pri čemu je VH domen antitela odabran od grupe koja se sastoji od L19 VH domena, i VH domen se sastoji od VH CDR1, VH CDR2 i VH CDR3, pri čemu VH CDR3 je L19 VH CDR3 sa SEQ ID NO. 3, VH CDR1 je opciono L19 VH CDR1 sa SEQ ID NO. 1, i VH CDR2 je opciono L19 VH CDR2 sa SEQ ID NO. 2; i pri čemu je VL domen antitela opciono odabran od grupe koja se sastoji od L19' VL domena, i VL domen se sastoji od VL CDR1, VL CDR2 i VL CDR3, pri čemu VL CDR3 je L19 VL CDR3 sa SEQ ID NO. 6, VL CDR1 je opciono L19 VL CDR1 sa SEQ ID NO. 4, i VL COR2 je opciono L19 VL COR2 sa SEQ ID NO. 5; gde su L19 VH domen i L19 VL domen sekvence otkrivene u Pini et al., (1998) J. Biol. Chem. 273: 21769-21776; pri čemu specifični vezujući član sadrži mini imunoglobulin koji sadrži navedeni VH domen anti tela i VL domen anti tela spojen sa εS2-CH4 i dimerizovan ili sadrži celi IgG1 antitelo molekul; takođe postupci i upotrebe upošljavanja takvog specifičnog vezujućeg člana.

10. 发明专利

PL374386A1 SELECTIVE TARGETING OF TUMOR VASCULATURE USING ANTIBODY MOLECULES 未知
公开(公告)号：PL374386A1
公开(公告)日：2005-10-17
申请号：PL37438603
申请日：2003-03-11
申请人： PHILOGEN SPA , SCHERING AG
发明人： BORSI LAURA , CARNEMOLLA BARBARA , BALZA ENRICA , CASTELLANI PATRIZIA , ZARDI LUCIANO , FRIEBE MATTHIAS , HILGER CHRISTOPH-STEPHAN
IPC分类号： A61K38/00 , A61K39/395 , A61K51/10 , A61P9/00 , C12N15/09 , A61P35/00 , A61P43/00 , C07K16/18 , C07K16/44 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/13 , C12P21/00 , 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.

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