HUMAN PROTEINS BASED ON HUMAN NOTCH3 AS NOTCH3 SIGNAL TRAFFIC INHIBITORS

摘要

1. A hybrid protein comprising a signal peptide, EGF repeats of the 1-X extracellular domain of the human Notch3 receptor protein, and the Fc portion of an antibody linked to 1-X EGF repeats, wherein X is any integer from 1 to 10 or 12 to 34.! 2. The hybrid protein according to claim 1, comprising a signal peptide of at least 12 EGF repeats of the extracellular domain of the human Notch3 receptor. ! 3. The hybrid protein of claim 1 or 2, wherein the Fc portion of the antibody is the Fc portion of a human antibody. ! 4. The fusion protein of claim 1 or 2, wherein the signal peptide is a Notch3 signal peptide or an IgG antibody heavy chain signal peptide. ! 5. The hybrid protein according to claim 1 or 2, comprising EGF repeats 1-34 of the extracellular domain of human Notch3. ! 6. The hybrid protein according to claim 1 or 2, which includes sequential amino acids, the sequence of which is defined in SEQ ID NO: 32 or SEQ ID NO: 33. ! 7. The use of a hybrid protein according to any one of claims 1 to 6 for the preparation of a pharmaceutical composition for treating a subject suffering from a tumor or metabolic disorder. ! 8. The use according to claim 7, where the tumor is ovarian cancer or breast cancer. ! 9. The use according to claim 7, where the metabolic disorder is diabetes, obesity, atherosclerosis, ischemia, stroke or cardiovascular disease. ! 10. The use of the hybrid protein according to any one of claims 1 to 6 for the preparation of a pharmaceutical composition for inhibiting angiogenesis, physiological lymphangiogenesis, pathological lymphangiogenesis, tumor metastasis, growth of a secondary tumor, or the use of blood vessels by the tumor for its own purposes. ! 11. The use of a hybrid protein according to any one of claims 1 to 6 for the preparation of a pharmaceutical