DLL4-binding molecules

Abstract

DII4-binding molecules, preferably DII4-binding immunoglobulin single variable domains like VHHs and VHs, pharmaceutical compositions containing same and their use in the treatment of diseases that are associated with DII4-mediated effects on angiogenesis. Bispecific DII4-binding molecules that also bind to VEGF-A. Nucleic acids encoding DII4-binding molecules, host cells and methods for preparing same.

Description

field of invention [0001] The present invention relates to the field of human therapy, especially cancer therapy, as well as medicaments and compositions suitable for use in this therapy. Background of the invention [0002] As outlined in US 2008 / 0014196, angiogenesis is implicated in the pathogenesis of many diseases including solid tumors and metastasis. In the case of tumor growth, angiogenesis appears to be critical for the transition from hyperplasia to neoplasia and for providing nutrients for tumor growth and metastasis (Folkman et al., Nature 339-58 (1989)), which makes tumor cells phase Gain a growth advantage over normal cells. Therefore, anti-angiogenic therapy has become an important treatment option for several types of tumors. These treatments have focused on blocking the VEGF pathway (Ferrara et al., Nat Rev Drug Discov. 2004 May;3(5):391-400). [0003] The Notch signaling pathway is critical for cell-cell communication and is involved in gene regulatory m...

AI Technical Summary

Problems solved by technology

[0007] However, prior art monoclonal antibodies (MAbs) and fusion proteins have several disadvantages in view of their therapeutic applications: they must be stored at temperatures close to freezing in order to prevent their degradation

Furthermore, it is not suitable for oral administration because of its rapid digestion in the digestive tract

Another major limitation of MAbs for cancer therapy is poor transport, which results in lower concentrations and inability to target all cells in the tumor

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