Means and Methods for Treating Angiogenesis-Related Diseases
Endostatin is an antiangiogenic protein first discovered in Folkman's laboratory at Childrens Hospital, Harvard Medical School, and Boston. The antitumor properties of this pro-tein are well established. However, the amount of protein required for injection in pa-tients was beyond production feasibility due to the poor pharmacokinetics of endostatin mon-omer.
We have shown that the problem of poor pharmacokinetics can be solved by using the Fc domain of IgG being conjugated to en-dostatin, a component of all monoclonal anti-bodies approved for patients with a number of diseases including cancer. As a result of em-ploying Fc-endostatin, the half-life in mice was increased to 2 weeks instead of 2 hours for endostatin alone, consistent with pharmacoki-netics of monoclonal antibodies
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