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1. 发明申请

WO03076469A2 SELECTIVE TARGETING OF TUMOR VASCULATURE USING ANTIBODY MOLECULES 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：WO03076469A2
公开(公告)日：2003-09-18
申请号：PCT/IB0301458
申请日：2003-03-11
申请人： PHILOGEN SRL , 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 , C07K16/00
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.
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. 发明申请

WO1997045544A1 ANTIBODIES TO THE ED-B DOMAIN OF FIBRONECTIN, THEIR CONSTRUCTION AND USES 审中-公开
标题翻译：抗纤维蛋白的ED-B抗体，其构建和用途
公开(公告)号：WO1997045544A1
公开(公告)日：1997-12-04
申请号：PCT/GB1997001412
申请日：1997-05-23
申请人： MEDICAL RESEARCH COUNCIL , INSTITUTO NAZIONALE PER LA RICERCA SUL CANCRO , UNIVERSITA' DI SIENA , NERI, Dario , CARNEMOLLA, Barbara , SIRI, Annalisa , BALZA, Enrica , CASTELLANI, Patrizia , PINI, Alessandro , ZARDI, Luciano , WINTER, Greg , NERI, Giovanni , BORSI, Laura
发明人： MEDICAL RESEARCH COUNCIL , INSTITUTO NAZIONALE PER LA RICERCA SUL CANCRO , UNIVERSITA' DI SIENA
IPC分类号： C12N15/13
CPC分类号： C07K16/28 , A61K38/00 , C07K14/78 , C07K16/18
摘要： According to the present invention there is provided a specific binding member which is specific for and binds directly to the ED-B oncofoetal domain of fibronectin (FN). The invention also provides materials and methods for the production of such binding members.
摘要翻译：根据本发明，提供了特异性结合成员，其特异性并直接结合纤连蛋白（FN）的ED-B骨架结构域。本发明还提供了用于生产这种结合构件的材料和方法。

3. 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。

4. 发明申请

WO2010066872A1 A MONOCLONAL ANTIBODY AND ITS USE FOR THE IDENTIFICATION OF THE ONCOFETAL ISOFORM OF FIBRONECTIN (B-FN) FOR DIAGNOSIS OR THERAPY 审中-公开
标题翻译：单克隆抗体及其用于鉴定FIBRONECTIN（B-FN）的ONCOFETAL ISOFORM用于诊断或治疗的用途
公开(公告)号：WO2010066872A1
公开(公告)日：2010-06-17
申请号：PCT/EP2009/066907
申请日：2009-12-11
申请人： CASTELLANI, Patrizia , SASSI, Francesca , CARNEMOLLA, M. Barbara , BORSI, Laura , BALZA, Enrica
发明人： CASTELLANI, Patrizia , SASSI, Francesca , CARNEMOLLA, M. Barbara , BORSI, Laura , BALZA, Enrica
IPC分类号： C07K16/18 , A61K39/395 , A61P35/00
CPC分类号： C07K16/18 , A61K2039/505 , C07K2317/30
摘要： Epitopes localized on FNIII-8 repeat that are normally cryptic but are unmasked by insertion of FNIII-B into the FN molecule and are recognized by specific ligands are described; antibodies or their fragments able to identify the above said epitope are also described.
摘要翻译：定位在FNIII-8重复上的表位通常是隐性的，但是通过将FNIII-B插入FN分子并被特异性配体识别而被掩盖; 还描述了能够鉴定上述表位的抗体或其片段。

5. 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。

6. 发明申请

WO0162298A2 COMPOSITIONS AND METHODS FOR TREATMENT OF ANGIOGENESIS IN PATHOLOGICAL LESIONS 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：WO0162298A2
公开(公告)日：2001-08-30
申请号：PCT/IB0100382
申请日：2001-02-22
申请人： PHILOGEN SRL , ZARDI LUCIANO , NERI DARIO , CARNEMOLLA BARBARA , NILSSON FREDRIK , TARLI LORENZO , BORSI LAURA , HALIN CORNELIA
发明人： ZARDI LUCIANO , NERI DARIO , CARNEMOLLA BARBARA , NILSSON FREDRIK , TARLI LORENZO , BORSI LAURA , HALIN CORNELIA
IPC分类号： A61K39/395 , A61K47/48 , A61P9/00 , A61P35/00 , C07K14/475 , C07K14/525 , C07K14/54 , C07K14/55 , C07K14/57 , C07K14/705 , C07K16/18 , C07K16/24
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： Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration, and angiomas. 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 may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12(IL-12), Interferon- gamma (IFN- gamma ), Tumor Necrosis Factor alpha (TNF alpha ) or Tissue Factor protein (which may be truncated).
摘要翻译：治疗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，年龄相关性肌肉退化和血管瘤。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）或组织因子蛋白被截断）。

7. 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.

8. 发明申请

WO0162298A9 COMPOSITIONS AND METHODS FOR TREATMENT OF ANGIOGENESIS IN PATHOLOGICAL LESIONS 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：WO0162298A9
公开(公告)日：2003-07-31
申请号：PCT/IB0100382
申请日：2001-02-22
申请人： PHILOGEN SRL , ZARDI LUCIANO , NERI DARIO , CARNEMOLLA BARBARA , NILSSON FREDRIK , TARLI LORENZO , BORSI LAURA , HALIN CORNELIA
发明人： ZARDI LUCIANO , NERI DARIO , CARNEMOLLA BARBARA , NILSSON FREDRIK , TARLI LORENZO , BORSI LAURA , HALIN CORNELIA
IPC分类号： A61K39/395 , A61K47/48 , A61P9/00 , A61P35/00 , C07K14/475 , C07K14/525 , C07K14/54 , C07K14/55 , C07K14/57 , C07K14/705 , C07K16/18 , C07K16/24
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： Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration, and angiomas. 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 may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12(IL-12), Interferon- gamma (IFN- gamma ), Tumor Necrosis Factor alpha (TNF alpha ) or Tissue Factor protein (which may be truncated).
摘要翻译：治疗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，年龄相关性肌肉退化和血管瘤。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）或组织因子蛋白被截断）。

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