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1. 发明授权

US08703143B2 Antibodies of the ED-B domain of fibronectin, their construction and uses 有权
标题翻译：纤连蛋白的ED-B结构域的抗体，其构建和用途
公开(公告)号：US08703143B2
公开(公告)日：2014-04-22
申请号：US11842774
申请日：2007-08-21
申请人： Dario Neri , Barbara Carnemolla , Luciano Zardi , Gregory Paul Winter
发明人： Dario Neri , Barbara Carnemolla , Luciano Zardi , Gregory Paul Winter
IPC分类号： A61K31/00 , A61K38/00 , A61K39/00 , A61K39/395
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。

2. 发明申请

US20080274099A1 ANTIBODIES OF THE ED-B DOMAIN OF FIBRONECTIN, THEIR CONSTRUCTION AND USES 有权
标题翻译：吡虫啉的ED-B抗体，其构建和用途
公开(公告)号：US20080274099A1
公开(公告)日：2008-11-06
申请号：US11842774
申请日：2007-08-21
申请人： Dario Neri , Barbara Carnemolla , Enrica Balza , Patrizia Castellani , Luciano Zardi , Gregory Paul Winter , Giovanni Neri , Laura Borsi , Alessandro Pini
发明人： Dario Neri , Barbara Carnemolla , Enrica Balza , Patrizia Castellani , Luciano Zardi , Gregory Paul Winter , Giovanni Neri , Laura Borsi , Alessandro Pini
IPC分类号： A61K39/395 , C07K16/18 , C12N15/13 , C12N1/21 , C12N1/19 , C12N5/10 , C12P21/00
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

US20130189735A1 Process for engineering polyvalent, polyspecific fusion proteins using uteroglobin as skeleton and so obtained products. 审中-公开
标题翻译：使用子宫肌钙蛋白作为骨架和所得产物来工程化多价，多特异性融合蛋白的工艺。
公开(公告)号：US20130189735A1
公开(公告)日：2013-07-25
申请号：US13145245
申请日：2010-01-18
申请人： Luciano Zardi
发明人： Luciano Zardi
IPC分类号： C07K19/00
CPC分类号： C07K19/00 , C07K14/4721 , C07K16/18 , C07K16/241 , C07K16/468 , C07K2317/31 , C07K2317/622 , C07K2317/76 , C07K2319/00
摘要： It is described a processes for generating stable and soluble polyvalent and polyspecific fusion proteins based on the use of uteroglobin (UG) as a reaction skeleton; proteins as above defined produced with said process are also described.
摘要翻译：描述了基于使用子宫红素（UG）作为反应骨架产生稳定和可溶性多价和多特异性融合蛋白的方法; 还描述了用所述方法制备的如上定义的蛋白质。

4. 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。

5. 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。

6. 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。

7. 发明授权

US08623373B2 Compositions and methods for treatment of angiogenesis in pathological lesions 有权
标题翻译：用于治疗病理损伤中血管生成的组合物和方法
公开(公告)号：US08623373B2
公开(公告)日：2014-01-07
申请号：US10204581
申请日：2001-02-22
申请人： Luciano Zardi , Dario Neri , Barbara Carnemolla , Fredrik Nilsson , Lorenzo Tarli , Laura Borsi , Cornelia Halin
发明人： Luciano Zardi , Dario Neri , Barbara Carnemolla , Fredrik Nilsson , Lorenzo Tarli , Laura Borsi , Cornelia Halin
IPC分类号： A61K39/44 , C07K16/00
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-γ (IFN-γ), Tumor Necrosis Factor α(TNFα) 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，类风湿关节炎，糖尿病性视网膜病变，年龄相关性肌肉退变。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（TNFalpha）或组织因子蛋白（可能是截断）。

8. 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。

9. 发明授权

US07109301B1 Tenascin-C isoform as marker for neoplasias 有权
标题翻译：腱生蛋白C同种型作为肿瘤标志物
公开(公告)号：US07109301B1
公开(公告)日：2006-09-19
申请号：US09959373
申请日：2000-04-19
申请人： Luciano Zardi
发明人： Luciano Zardi
IPC分类号： C12P21/08 , C07K16/00 , C07K17/00 , G01N33/53 , A61K39/395
CPC分类号： G01N33/6887 , C07K16/18 , C07K2317/21 , C07K2317/622 , G01N33/574
摘要： Diagnostic method for the identification of human neoplasias based on the determination of the CTN-C isoform of TN-C, fragments antibodies and their conjugates used in said method, and their therapeutic use.
摘要翻译：基于TN-C的CTN-C同种型的测定，所述方法中使用的片段抗体及其缀合物及其治疗用途来鉴定人类肿瘤的诊断方法。

10. 发明授权

US08784824B2 Compositions and methods for treatment of angiogenesis in pathological lesions 有权
标题翻译：用于治疗病理损伤中血管生成的组合物和方法
公开(公告)号：US08784824B2
公开(公告)日：2014-07-22
申请号：US12835854
申请日：2010-07-14
申请人： Luciano Zardi , Dario Neri , Barbara Carnemolla , Fredrik Nilsson , Lorenzo Tarli , Laura Borsi , Cornelia Halin
发明人： Luciano Zardi , Dario Neri , Barbara Carnemolla , Fredrik Nilsson , Lorenzo Tarli , Laura Borsi , Cornelia Halin
IPC分类号： A61K39/44 , C07K16/00
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-γ (IFN-γ), Tumor Necrosis Factor α (TNFα) 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）或组织因子蛋白截断）。

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