Modified immunoglobulin Fc-fusion protein and use thereof
The present invention relates to a novel immunoglobulin Fc domain variant protein and use thereof, and when expressed in the form of a fusion protein with another biologically active protein, an immunoglobulin Fc domain variant protein according to an embodiment of the present invention can prolong the half-life in vivo of the biologically active protein as well as effectively suppress effector functions such as ADCC or CDC to minimize unexpected side effects.
1 . An immunoglobulin Fc domain variant protein comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 5 to 9.
2 . A fusion protein, wherein at least one biologically active protein is linked to an N-terminus and/or a C-terminus of the immunoglobulin Fc domain variant protein of claim 1 .
3 . The fusion protein of claim 2 , wherein the biologically active protein is linked to the N-terminus or the C-terminus of the immunoglobulin Fc domain variant protein through a linker peptide or a hinge region of an antibody.
4 . The fusion protein of claim 2 , wherein the biologically active protein is a cytokine, an enzyme, a blood coagulation factor, an extracellular domain of a membrane receptor, a growth factor, a peptide hormone, or an antibody mimetic.
5 . A polynucleotide which encodes the immunoglobulin Fc domain variant protein of claim 1 or the fusion protein of claim 2 .
6 . A recombinant vector comprising the polynucleotide of claim 5 .
7 . A homodimer comprising the fusion protein of claim 2 .
8 . A heterodimer comprising the fusion protein of claim 2 .
9 . The heterodimer of claim 8 , wherein the immunoglobulin Fc domain variant protein has a knobs-into-holes structure.
10 . A composition comprising, as an active ingredient, at least one selected from the group consisting of the fusion protein of claim 2 , the homodimer of claim 7 , and the heterodimer of claim 8 .
11 . A method for prolonging the half-life in vivo of a biologically active protein, the method comprising a step for administering, to a subject, a fusion protein obtained by fusing the biologically active protein to the immunoglobulin Fc domain variant protein of claim 1 , or a homodimer or a heterodimer which contains the fusion protein,
wherein the immunoglobulin Fc domain variant protein prolongs the half-life in vivo of the biologically active protein compared to the Fc region of conventional IgG1 or IgG4.