Fusion polypeptide containing GLP and immunoglobulin hybrid Fc and use thereof
The present invention relates to a fusion polypeptide containing a glucagon-like peptide (GLP) and an immunoglobulin hybrid Fc, and more specifically, to a fusion polypeptide with an increased half-life and improved efficacy compared to the conventional fusion polypeptide based on the discovery of an immunoglobulin hybrid Fc suitable for GLP or analogs thereof, and a pharmaceutical composition for treating diabetes, inflammatory bowel disease, endoenteritis or diarrhea caused by anticancer chemotherapy, or short bowel syndrome, containing the fusion polypeptide. The fusion polypeptide of the present invention has an increased half-life and improved resistance to DPP-4 enzyme compared to those of GLP-1 and GLP-2, and it thus has improved drug efficacy in treating diabetes, inflammatory bowel disease, endoenteritis or diarrhea caused by anticancer chemotherapy, or short bowel syndrome, compared to those of the conventional drugs. Accordingly, the fusion polypeptide of the present invention can be effectively applied to pharmaceutical drugs.
1. A fusion polypeptide comprising (a) glucagon-like peptide-1 (GLP-1) or an analog thereof, and (b) an immunoglobulin Fc polypeptide,
wherein the immunoglobulin Fc polypeptide (b) comprises
(i) an isolated IgD hinge region consisting of 35 to 49 consecutive amino acid residues from the C-terminus of SEQ ID NO: 25; and
(ii) a CH2 domain and a CH3 domain of the immunoglobulin Fc polypeptide.
2. The fusion polypeptide of claim 1 , wherein the GLP-1 consists of an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 13.
3. The fusion polypeptide of claim 1 , wherein the analog of the GLP-1 comprises a modification in a site, which may be cleaved by DPP-4 enzyme, and consists of the amino acid sequence selected from the group consisting of SEQ ID NOs: 2 to 12 and SEQ ID NOs: 14 to 24.
4. The fusion polypeptide of claim 1 , wherein the IgD hinge region consists of the amino acid sequence selected from the group consisting of SEQ ID NOs: 26 to 28.
5. The fusion polypeptide of claim 1 , wherein the fusion polypeptide exhibits an increased half-life compared to the polypeptide which is not fused with the immunoglobulin Fc polypeptide.
6. The fusion polypeptide of claim 1 , wherein the fusion polypeptide consists of the amino acid sequence selected from the group consisting of SEQ ID NOs: 30 to 32.
7. A pharmaceutical composition comprising the fusion polypeptide of claim 1 as an active ingredient.
8. A method for treating diabetes comprising administering the pharmaceutical composition of claim 7 to a subject in need thereof.
9. A polynucleotide encoding the fusion polypeptide according to claim 1 .
10. The polynucleotide of claim 9 , wherein the polynucleotide consists of the nucleic acid sequence selected from the group consisting of SEQ ID NOs: 41 to 43.
11. An expression vector comprising the polynucleotide of claim 9 .
12. A host cell comprising the expression vector of claim 11 .