GIP derivative, long-acting conjugate thereof, and pharmaceutical composition comprising same
Provided are a GIP derivative, a pharmaceutically acceptable salt or solvate thereof, or a long-acting conjugate thereof, or a pharmaceutical composition including the same for preventing or treating inflammatory or autoimmune disease.
1 . A peptide comprising any one amino acid sequence
selected from the group consisting of SEQ ID NOs: 1 to 26.
2 . The peptide of claim 1 , wherein the peptide has activity on a glucose-dependent insulinotropic peptide (GIP) receptor.
3 . The peptide of claim 1 , wherein the peptide comprises any one amino acid sequence selected from the group consisting of SEQ ID NOs: 11, 17, and 19 to 26.
4 . The peptide of claim 1 , wherein the peptide comprises any one amino acid sequence selected from the group consisting of SEQ ID NOs: 11, 17, 21, and 24.
5 . The peptide of claim 1 , wherein the C-terminus of the peptide is not modified or is amidated.
6 . The peptide of claim 1 , wherein the peptide is conjugated to a moiety that increases half-life in vivo.
7 . The peptide of claim 6 , wherein the moiety is selected from the group consisting of polyethylene glycol, polypropylene glycol, ethylene glycol-propylene glycol copolymer, polyoxyethylated polyol, polyvinyl alcohol, polysaccharide, polyvinyl ethyl ether, a biodegradable polymer, a lipid polymer, chitin, hyaluronic acid, fatty acid, cholesterol, albumin or fragment thereof, an albumin-binding molecule, a polymer of repeating units of specific amino acid sequences, an antibody, an antibody fragment, an FcRn-binding molecule, fibronectin, transferrin, a saccharide, heparin, elastin, and combination thereof.
8 . The peptide of claim 6 , wherein the moiety is an FcRn-binding molecule.
9 . The peptide of claim 8 , wherein the FcRn-binding molecule is an immunoglobulin Fc region.
10 . The peptide of claim 9 , wherein the immunoglobulin Fc region is selected from the group consisting of: (a) a heavy-chain constant region 1 (CH1) domain, a heavy-chain constant region 2 (CH2) domain, a heavy-chain constant region 3 (CH3) domain, and a heavy-chain constant region 4 (CH4) domain; (b) a CH1 domain and a CH2 domain; (c) a CH1 domain and a CH3 domain; (d) a CH2 domain and a CH3 domain; (e) a combination between one or two or more domains among a CH1 domain, a CH2 domain, a CH3 domain, and a CH4 domain, and an immunoglobulin hinge region or a part of the hinge region; and (f) a dimer between each domain of the heavy chain constant region and the light chain constant region.
11 . The peptide of claim 9 , wherein the immunoglobulin Fc region is aglycosylated.
12 . The peptide of claim 9 , wherein the immunoglobulin Fc region is an immunoglobulin G4 (IgG4) Fc region.
13 . The peptide of claim 9 , wherein the immunoglobulin Fc region is aglycosylated Fc region derived from human IgG4.
14 . The peptide of claim 6 , wherein the peptide is linked to the moiety via a linker.
15 . The peptide of claim 14 , wherein the linker is selected from the group consisting of a peptide, a fatty acid, a saccharide, a polyethylene glycol, a polypropylene glycol, an ethylene glycol-propylene glycol copolymer, a polyoxyethylated polyol, a polyvinyl alcohol, a polysaccharide, a polyvinyl ethyl ether, a biodegradable polymer, a lipid polymer, chitin, hyaluronic acid, an oligonucleotide, and a combination thereof.
16 . The peptide of claim 14 , wherein the linker comprises an ethylene glycol repeating unit.
17 . The peptide of claim 16 , wherein the ethylene glycol repeating unit has a molecular weight in a range of 1 kDa to 100 kDa.
18 . A pharmaceutical composition comprising the peptide of claim 1 , a pharmaceutically acceptable salt thereof or a solvate thereof.
19 . The pharmaceutical composition of claim 18 , wherein the peptide is conjugated to a moiety that increases half-life in vivo.
20 . A method for treating vasculitis, rheumatoid arthritis, or diabetes mellitus in a subject in need thereof, wherein the method comprises administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a peptide comprising any one amino acid sequence selected from the group consisting of SEQ ID NOs: 11, 17, 21 and 24.
21 . The method of claim 20 , wherein the vasculitis is one selected from the group consisting of: giant cell arteritis; Takayasu's arteritis; aortitis in Cogan's syndrome; aortitis in spondylarthropathies; isolated aortitis; Kawasaki disease; polyarteritis nodosa; antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis; granulomatosis with polyangiitis; microscopic polyangiitis; eosinophilic granulomatosis with polyangiitis; primary angiitis of the central nervous system; IgA vasculitis; vasculitis associated with rheumatoid arthritis, vasculitis associated with systemic lupus erythematosus, vasculitis associated with Sjogren's syndrome; cryoglobulinemic vasculitis; and drug-induced vasculitis.
22 . The method of claim 20 , wherein the peptide is conjugated to a moiety that increases half-life in vivo.