Apelin fusion proteins and uses thereof
The invention provides a fusion protein or polypeptide comprising an apelin peptide fused to a multimerizing component. The invention also provides a fusion protein or polypeptide comprising an apelin peptide fused to an Fc domain, a fragment of an Fc domain, or a variant of an Fc domain. Apelin Fc-fusion polypeptides are capable of binding to the apelin receptor (APLNR). Apelin Fc-fusion polypeptides are capable of activating the APLNR and have improved pharmacokinetic properties compared to apelin peptides that are not fused to an Fc or an Fc fragment. Apelin Fc-fusion polypeptides are useful in diseases and conditions related to cardiovascular function, diabetes, cancer, obesity and other apelin-related conditions.
1. A polypeptide comprising the amino acid sequence of SEQ ID NO: 2.
2. A composition comprising the polypeptide of claim 1 and at least one pharmaceutically acceptable carrier or diluent.
3. A nucleic acid molecule encoding the polypeptide of claim 1 .
4. The nucleic acid molecule of claim 3 linked to a nucleotide sequence encoding a signal peptide.
5. The nucleic acid molecule of claim 4 comprising the nucleotide sequence consisting of SEQ ID NO: 25.
6. A vector comprising the nucleic acid molecule of claim 5 .
7. A cell comprising the vector of claim 6 .
8. A cell comprising the nucleic acid molecule of claim 5 .
9. The cell of claim 8 , wherein the nucleic acid is stably integrated into the genome of the cell.
10. The cell of claim 9 , wherein the cell is a eukaryotic cell.
11. The cell of claim 10 , wherein the cell is selected from the group consisting of CHO, COS, retinal cell, Vero, CV1, 293, MDCK, HaK, BHK, HeLa, HepG2, WI38, MRC 5, Colo 25, HB 8065, HL-60, Jurkat, Daudi, A431 (epidermal), CV-1, U937, 3T3, L cell, C127 cell, SP2/0, NS-0, MMT cell, and tumor cell.
12. The cell of claim 11 , wherein the cell is an animal cell.
13. The cell of claim 12 , wherein the cell is a mammalian cell.
14. The cell of claim 13 , wherein the cell is a CHO cell.
15. The cell of claim 14 , wherein the cell is a CHO-K1 cell.