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1. 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。

2. 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.

3. 发明授权

EP1257297B1 Compositions and methods for treatemnt of angiogenesis in pathological lesions 有权
标题翻译：一起沉降在病理损伤治疗血管生成的方法
公开(公告)号：EP1257297B1
公开(公告)日：2006-07-26
申请号：EP01914085.4
申请日：2001-02-22
申请人： Philogen S.p.A.
发明人： ZARDI,L.,IST-Ist.Nazionale per la Ricerca sul Can: , NERI, D., c/oSwiss Fed Inst Tech Zurich, Dept Appl , CARNEMOLLA, Barbara , NILSSON, F., Swiss Fed Inst Tech Zurich, Dept Appl , TARLI, L. c/oSwiss Fed Inst Tech Zurich, Dept Appl , BORSI, Laura , HALIN, C. c/oSwiss Fed Inst Tech Zurich, Dept Appl
IPC分类号： A61K47/48 , C07K14/525 , C07K14/54 , C07K14/57 , A61P35/00
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-η (IFN-η), Tumor Necrosis Factor α(TNFα) or Tissue Factor protein (which may be truncated).

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