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    • 3. 发明申请
    • TARGETING OF TUMOR VASCULATURE USING RADIOLABELLED ANTIBODY L19 AGAINST FIBRONECTIN ED-B
    • 使用放射性抗体L19对FIBRONECTIN ED-B进行肿瘤血管造影
    • WO2005023318A1
    • 2005-03-17
    • PCT/EP2004/009733
    • 2004-09-01
    • PHILOGEN S.P.ASCHERING AGBORSI, LauraCARNEMOLLA, BarbaraBALZA, EnricaCASTELLANI, PatriziaZARDI, LucianoFRIEBE, MatthiasHILGER, Christoph-Stephan
    • BORSI, LauraCARNEMOLLA, BarbaraBALZA, EnricaCASTELLANI, PatriziaZARDI, LucianoFRIEBE, MatthiasHILGER, Christoph-Stephan
    • A61K51/10
    • A61K51/1045
    • 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.
    • 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。