Metalloproteinase binding proteins: WO2009097397

Abstract

MMPs are a group of metalloendopeptidases whose major role is in extracellular matrix (ECM) catabolism under physiological and pathological conditions. ECM catabolism is often associated with different diseases, and accumulated studies support the causal relationship between MMPs and different diseases especially with cancer and arthritis. Therefore, MMPs have been considered as therapeutic target molecules. However, multiple failures of MMP inhibitor drugs in clinical trials from late 1990s to early 2000s resulted in the consideration that wide inhibitory spectrum inhibitors of metalloproteinases may not be desirable for treatment of diseases. On the other hand, developing low molecular mass selective inhibitor(s) targeting the active site is not a very easy task. One way to overcome this problem is to develop biologic inhibitors, namely antibodies. In this patent application, Dyax Corp. reported that a binding protein (such as an antibody) against metalloproteinases, especially membrane-type 1 MMP (MMP-14) can be used as a therapeutic drug against different diseases including cancer. They succeeded in generating a selective MMP-14 inhibitory antibody with a K_i of 0.6 nM, which showed significant suppression of different tumour growth in mice. Further development of such an antibody as a drug may fulfil an unmet area of disease treatment targeting uncontrolled cell invasion and tissue destruction.

Keywords::

• antibody
• MMP
• MT1-MMP
• phage display

Acknowledgement

I thank L Troeberg for the critical reading of the manuscript. This paper was sponsored by a Cancer Research UK project grant and Arthritis Research UK core grant to the Kennedy Institute of Rheumatology.