HUMAN NOTCH1 BASED FUSION PROTEINS AS DECOY INHIBITORS OF JAGGED-NOTCH SIGNALING AND DLL-NOTCH SIGNALING

摘要

This invention provides a fusion protein, the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of amino acids in: (a) an extracellular domain of a human Notch1 receptor protein, followed by (b) an Fc portion of an antibody, wherein the extracellular domain of the human Notch1 receptor protein (i) commences with the amino acid present at the N-terminus of EGF-like repeat 10 and (ii) extends to and includes the C-terminal amino acid of EGF-like repeat 18 or 20. Also provided is a composition comprising the any of the fusion proteins of this invention and a pharmaceutically acceptable carrier, a method of treating a subject suffering from age-related macular degeneration (AMD), diabetic retinopathy, or cancer which comprises administering to the subject any of the compositions of this invention in an amount effective to treat the subject's cancer.