Human Notch3 based fusion proteins as decoy inhibitors of Notch3 signaling
This invention provides a fusion protein comprising a signal peptide, EGF repeats 1-X of the extracellular domain of human Notch3 receptor protein wherein X is any integer from 12 to 34, and an Fc portion of an antibody bound thereto. This invention also provides a method for treating a subject having a tumor, a method for inhibiting angiogenesis in a subject, a method for treating a subject having ovarian cancer, and a method for treating a subject having a metabolic disorder, comprising administering to the subject an amount of the above fusion protein effective to treat the subject. This invention further provides uses of the above fusion protein for the preparation of a pharmaceutical composition for the treatment of a subject having a tumor, for inhibiting angiogenesis in a subject, for treating a subject having ovarian cancer, and for treating a subject having a metabolic disorder.
1. A fusion protein the sequence of which (a) is identical to a sequence consisting of EGF repeats 1-X of the extracellular domain of human Notch3 receptor protein, wherein X is any integer from 12 to 33, followed by (b) a sequence identical to the sequence of an Fc portion of an antibody, wherein (b) is located to the carboxy terminal side of (a) and wherein (b) is attached to (a) either directly or by means of a linker sequence wherein the fusion protein has Notch3 ligand binding activity.
2. The fusion protein of claim 1 , wherein the Fc portion of the antibody is the Fc portion of a human antibody.
3. The fusion protein of claim 1 , wherein (b) is attached directly to (a).
4. The fusion protein of claim 1 , wherein (b) is attached to (a) by means of a linker sequence.