CONJUGATE OF NATRIURETIC PEPTIDE AND ANTIBODY CONSTANT REGION
The present application describes a conjugate between a natriuretic peptide, such as urodilatin, and the constant region of an immunoglobulin or a fragment thereof. Also described are compositions comprising the conjugate and methods for using the conjugate.
1 . A conjugate comprising a natriuretic peptide and an antibody constant region, wherein the conjugate binds to a natriuretic peptide receptor.
2 . The conjugate of claim 1 , wherein the natriuretic peptide is urodilatin.
3 . The conjugate of claim 1 , wherein the natriuretic peptide receptor is NPR-A.
4 . The conjugate of claim 1 , wherein the natriuretic peptide and the antibody constant region is linked via a linker.
5 . The conjugate of claim 1 , which is a fusion polypeptide.
6 . The conjugate of claim 5 , wherein the fusion polypeptide further comprises a peptide linker.
7 . The conjugate of claim 5 , wherein the fusion polypeptide comprises the amino acid sequence of SEQ ID NO:6 or 12.
8 . The conjugate of claim 1 , wherein the antibody constant region is linked to the N-terminus of the natriuretic peptide.
9 . The conjugate of claim 1 , wherein the antibody constant region is linked to the C-terminus of the natriuretic peptide.
10 . The conjugate of claim 1 , wherein the natriuretic peptide is linked to an internal amino acid of the antibody constant region.
11 . The conjugate of claim 1 , which activates a natriuretic peptide receptor.
12 . The conjugate of claim 1 , which has a longer serum half-life compared with the natriuretic peptide.
13 . An isolated nucleic acid comprising a polynucleotide sequence encoding a fusion polypeptide that comprises a natriuretic peptide and an antibody constant region.
14 . The nucleic acid of claim 13 , wherein the fusion polypeptide further comprises a peptide linker.
15 . The nucleic acid of claim 13 , wherein the natriuretic peptide is urodilatin.
16 . The nucleic acid of claim 13 , which comprises the polynucleotide sequence of SEQ ID NO:5 or 11.
17 . An expression cassette comprising the nucleic acid of claim 13 .
18 . An isolated host cell transfected with the expression cassette of claim 17 .
19 . The host cell of claim 18 , which is a eukaryotic cell.
20 . A method for recombinantly producing a fusion polypeptide comprising a natriuretic peptide and an antibody constant region, comprising the steps of:
a. transfecting a host cell with the expression cassette of claim 17 ; and
b. culturing the cell under the condition that are suitable for the cell to express the fusion polypeptide.
21 . The method of claim 20 , wherein the natriuretic peptide is urodilatin.
22 . A composition comprising the conjugate of claim 1 and a pharmaceutically acceptable carrier.
23 . A method for treating bacterial infection, pulmonary and bronchial diseases, renal failure, or heart failure, comprising the step of administering to a patient in need thereof an effective amount of the conjugate of claim 1 .