Philogen S.p.a.

Bayer Schering Pharma Ag

Luciano Zardi

Barbara Carnemolla

Dario Neri

Gregory Paul Winter

Laura Borsi

Fredrik Nilsson

Lorenzo Tarli

Cornelia Halin

Matthias Friebe

Christoph-Stephan Hilger

Patrizia Castellani

Enrica Balza

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.

Antibodies of the ED-B domain of fibronectin, their construction and uses

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-&#x3b3; (IFN-&#x3b3;), Tumor Necrosis Factor &#x3b1; (TNF&#x3b1;) or Tissue Factor protein (which may be truncated).

Compositions and methods for treatment of angiogenesis in pathological lesions

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-&#x3b3; (IFN-&#x3b3;), Tumor Necrosis Factor &#x3b1;(TNF&#x3b1;) or Tissue Factor protein (which may be truncated).

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.

Selective targeting of tumor vasculature using antibody molecules

A specific binding member is specific for and binds directly to the ED&#x2014;B oncofoetal domain of fibronectin (FN).

Antibodies to the ED-B domain of fibronectin, their construction and uses

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.

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Genoa, Italy

Luciano Zardi