Metalloproteinase binding proteins: WO2009097397.
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.
Itoh
Yoshifumi
Y
Kennedy Institute of Rheumatology, Imperial College London, Hammersmith, UK. y.itoh@imperial.ac.uk
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010330:Patents as Topic; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D008666:Metalloendopeptidases