PHARMACEUTICAL COMPOSITION COMPRISING IMMUNOGLOBULIN FC-FUSED INTERLEUKIN-7 FUSION PROTEIN FOR PREVENTING OR TREATING HUMAN PAPILLOMAVIRUS-CAUSED DISEASES
The present invention relates to a pharmaceutical composition comprising an immunoglobulin Fc region and an IL-7 fusion protein. Specifically, when a fusion protein comprising the immunoglobulin Fc region and IL-7 is administered to an affected area, a strong immune response is induced in the body and thus allows human papillomavirus-caused diseases to be prevented or treated.
1 . A pharmaceutical composition comprising an interleukin-7 (IL-7) fusion protein, wherein the IL-7 fusion protein comprises an IL-7 protein and an immunoglobulin Fc region.
2 . The pharmaceutical composition of claim 1 , wherein the IL-7 protein is conjugated to the N-terminus or C-terminus of the immunoglobulin Fc region.
3 . The pharmaceutical composition of claim 1 ,
wherein the IL-7 fusion protein further comprises an oligopeptide.
4 . The pharmaceutical composition of claim 1 , wherein the IL-7 protein comprises an amino acid sequence which has at least about 70% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOS: 1 to 6.
5 . The pharmaceutical composition of claim 3 , wherein the oligopeptide is selected from the group consisting of methionine, glycine, methionine-methionine, glycine-glycine, methionine-glycine, glycine-methionine, methionine-methionine-methionine, methionine-methionine-glycine, methionine-glycine-methionine, glycine-methionine-methionine, methionine-glycine-glycine, glycine-methionine-glycine, glycine-glycine-methionine, methionine-methionine-methionine, and glycine-glycine-glycine.
6 - 7 . (canceled)
8 . The pharmaceutical composition of claim 1 , wherein the immunoglobulin Fc region comprises a CH2 domain and a CH3 domain in the N-terminus to C-terminus direction, wherein the CH2 domain comprises a portion of an amino acid residue of CH2 domain of human IgD and human IgG4, and the CH3 domain comprises a portion of an amino acid residue of human IgG4 CH3 domain.
9 . The pharmaceutical composition of claim 1 , wherein the immunoglobulin Fc region comprises the amino acid sequence set forth in any one of SEQ ID NOS: 9 to 14.
10 . (canceled)
11 . A method of preventing or treating a genital disease in a subject in need thereof comprising administering to the subject an interleukin-7 (IL-7) fusion protein, wherein the IL-7 fusion protein comprises an IL-7 protein and an immunoglobulin Fc region.
12 - 14 . (canceled)
15 . The pharmaceutical composition of claim 1 , wherein the IL-7 protein does not comprise a signal peptide.
16 . The pharmaceutical composition of claim 1 , wherein the IL-7 protein comprises: (a) amino acid residues 26-177 of the amino acid sequence set forth in SEQ ID NO: 1, (b) amino acid residues 26-154 of the amino acid sequence set forth in SEQ ID NO: 2; (c) amino acid residues 26-154 of the amino acid sequence set forth in SEQ ID NO: 3; (d) amino acid residues 26-177 of the amino acid sequence set forth in SEQ ID NO: 4; (e) amino acid residues 26-176 of the amino acid sequence set forth in SEQ ID NO: 5; or (f) amino acid residues 26-176 of the amino acid sequence set forth in SEQ ID NO: 6.
17 . The pharmaceutical composition of claim 1 , wherein the IL-7 fusion protein comprises the amino acid sequence set forth in any one of SEQ ID NOs: 21-27.
18 . A method of increasing an immune response within a mucosal tissue of a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 1 .
19 . A modified interleukin-7 (IL-7) fusion protein comprising an IL-7 protein and an immunoglobulin Fc region.
20 . The modified IL-7 fusion protein of claim 19 , which further comprises an oligopeptide.
21 . The modified IL-7 fusion protein of claim 19 , wherein the IL-7 protein does not comprise a signal peptide.
22 . The modified IL-7 fusion protein of claim 19 , wherein the IL-7 protein comprises: (a) amino acid residues 27-177 of the amino acid sequence set forth in SEQ ID NO: 1, (b) amino acid residues 26-154 of the amino acid sequence set forth in SEQ ID NO: 2; (c) amino acid residues 26-154 of the amino acid sequence set forth in SEQ ID NO: 3; (d) amino acid residues 26-177 of the amino acid sequence set forth in SEQ ID NO: 4; (e) amino acid residues 26-176 of the amino acid sequence set forth in SEQ ID NO: 5; or (f) amino acid residues 26-176 of the amino acid sequence set forth in SEQ ID NO: 6.
23 . The modified IL-7 fusion protein of claim 19 , which comprises the amino acid sequence set forth in any one of SEQ ID NOs: 21-27.
24 . The modified IL-7 fusion protein of claim 20 , wherein the oligopeptide is selected from the group consisting of methionine, glycine, methionine-methionine, glycine-glycine, methionine-glycine, glycine-methionine, methionine-methionine-methionine, methionine-methionine-glycine, methionine-glycine-methionine, glycine-methionine-methionine, methionine-glycine-glycine, glycine-methionine-glycine, glycine-glycine-methionine, methionine-methionine-methionine, and glycine-glycine-glycine.
25 . A method of producing the modified IL-7 fusion protein of claim 19 , comprising transforming a cell with a polynucleotide comprising a first nucleic acid sequence encoding the IL-7 protein and a second nucleic acid sequence encoding the immunoglobulin Fc region, and culturing the cell after the transforming such that the IL-7 fusion protein is produced.
26 . The method of claim 25 , wherein the first nucleic acid sequence is codon-optimized.