MMP-Selective Antibody Inhibitors

Tech ID: 25155 / UC Case 2015-758-0

Patent Status

Country Type Number Dated Case
United States Of America Published Application 20190185581 06/20/2019 2015-758
 

Background

For more than 20 years, scientists have been developing drugs that block a family of matrix metalloproteinases (MMPs) in order to treat a variety of diseases ranging from cancer to inflammatory diseases. But clinical trials on a variety of promising small molecules have failed because these drugs lack the specificity needed to target faulty MMPs while still allowing "good" MMPs to perform their regular cellular duties.

Clinical trial failures indicate that selective, rather than broad-based, MMP inhibitors are required for successful MMP therapies. However achieving this selectivity with small-molecule inhibitors is difficult. As a result, broad-spectrum small molecule inhibitors have failed in clinical trials due to their low efficacy and deleterious side effects.

Brief Description

Prof. Xin Ge and his colleagues at the University of California, Riverside have developed a library of human, selective MMP-14 antibody inhibitors with nanomolar activities. Unlike known MMP inhibitors, n-TIMP-2 and GM6001, that inhibit a broad spectrum of the MMP family these antibody inhibitors do not exhibit off-target effects with other MMP family members such as MMP-2/MMP-9.

first

Fig. 1 shows inhibition selectivity tests of Fab 3A2, GM6001 and n-TIMP-2. Unlike n-TIMP-2 and GM6001, Fab3A2 shows selectivity for MMP-14 and did not inhibit MMP-2 or MMP-9.

 

 

Second

Fig. 2 shows the weight and number of the pulmonary metastic lesions in B16F1 (Mock) and B16F1 MT-MMP (mMT1) mouse models. The mMT1 mouse model treated with the 3A2 (mMT+3A2) antibody showed a reduction in the weight and number of pulmonary metastatic lesions.

Suggested uses

  • Antibodies may be developed as therapeutics for MMP-14 affected diseases
  • Antibodies may be used as research tools to further investigate MMP functionality.

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Keywords

inhibitory antibody, human antibody, monoclonal antibody, complementarity determining region, CDR, CDR library, matrix metalloproteinase, MMP, arthritis, atherosclerosis, cardiovascular, stroke

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