Compound comprising an autoantigenic peptide and a carrier with a mhc binding motif

Abstract

The invention relates a compound comprising (a) a peptide and (b) a carrier, wherein said peptide having at least the motif X-X-X-X-X-X-X, wherein at least one amino acid residue X is glycosylated, said peptide being linked to the peptide binding protein and said carrier comprises at least a MHC binding motif being linked to said peptide as well as pharmaceutical compositions comprising said compound and the use of said compound or pharmaceutical composition for the treatment of a disease, such as an inflammatory joint disease. The subject matter of the application is exemplified with peptides derived from type II collagen such as peptides having at least the sequence AGFKGEA, or IAGFKGEQPKG, or the peptide AAAKAAA. Preferably a hydroxylysine in the peptides are glycosylated.

1 . A compound comprising (a) a peptide and (b) a carrier, wherein
 a. said peptide having at least the motif X-X-X-X-X-X-X, wherein at least one amino acid residue X is glycosylated, said peptide being linked to the peptide binding protein and   b. said carrier comprises at least a MHC binding motif being linked to said peptide.   
     
     
         2 . The compound according to  claim 1 , wherein at least one amino acid residue X of said peptide (a) is O-linked glycosylated. 
     
     
         3 . The compound according to  claim 2 , wherein the glycosylated amino acid reside X of said peptide (a) is hydroxylysine. 
     
     
         4 . The compound according to  claim 3 , wherein said peptide (a) comprises 4 to 50 amino acid residues. 
     
     
         5 . The compound according to  claim 4 , wherein said peptide (a) comprises X-F-K-X-X-X-X-X-X-X, wherein K is hydroxylysine. 
     
     
         6 . The compound according to  claim 5 , wherein said peptide (a) comprises X-F-K-X-E-X-X-X-X-X, wherein K is hydroxylysine. 
     
     
         7 . The compound according to  claim 6 , wherein at least one amino acid residue has been substituted. 
     
     
         8 . The compound according to  claim 1 , wherein said carrier comprises the variable region of an MHC class II molecule selected from the group consisting of DRB 1*0401/DRA, DRBI*0402/DRA, DRBI*0403/DRA, DRBI*0404/DRA, DRBI*0405/DRA, DRB I*0406/DRA, DRBI*0407/DRA, DRBI*0408/DRA, DRBI*0409/DRA, DRBI*0410/DRA, DRBI*0101/DRA, DRBI*0102/DRA and DRBI*1001/DRA, DRBI*1002/DRA. 
     
     
         9 . The compound according to  claim 8 , wherein at least one amino acid residue of the variable region has been substituted. 
     
     
         10 . The compound according to  claim 8 , wherein said variable region comprises a peptide having 80% identity to the polypeptide sequence in its full length shown in SEQ ID NO 1 and a second polypeptide having 80% identity in its full length to the polypeptide sequence shown in SEQ ID NO 2. 
     
     
         11 . The compound according to  claim 10 , wherein said variable region comprises a peptide having 90% identity to the polypeptide sequence in its full length shown in SEQ ID NO 1 and a second polypeptide having 90% identity in its full length to the polypeptide sequence shown in SEQ ID NO 2. 
     
     
         12 . The compound according to  claim 11 , wherein said variable region comprises a peptide having 95% identity to the polypeptide sequence in its full length shown in SEQ ID NO 1 and a second polypeptide having 95% identity in its full length to the polypeptide sequence shown in SEQ ID NO 2. 
     
     
         13 . The compound according to  claim 1 , wherein said peptide (a) is selected from the group consisting of A-G-F-K-G-E-A and A-A-A-K-A-A-A. 
     
     
         14 . The compound according to  claim 1 , wherein said peptide (a) is at least IAGFKGEQGPKG. 
     
     
         15 . The compound according to  claim 1 , wherein said peptide (a) is covalently bound to said carrier (b). 
     
     
         16 . The compound according to  claim 1 , wherein said peptide (a) is hydroxylated. 
     
     
         17 . The compound according to  claim 1 , wherein said carrier comprises a constant region being linked to said MHC binding motif. 
     
     
         18 . The compound according to  claim 17 , wherein said constant region being selected from the group consisting of the constant region of an MHC class II molecule or an immunoglobulin. 
     
     
         19 . The compound according to  claim 1 , wherein said constant region comprises a peptide having 80% identity to the polypeptide sequence in its full length shown in SEQ ID NO 3 and a second polypeptide having 80% identity in its full length to the polypeptide sequence shown in SEQ ID NO 4. 
     
     
         20 . The compound according to  claim 19 , wherein said constant region comprises a peptide having 90% identity to the polypeptide sequence in its full length shown in SEQ ID NO 3 and a second polypeptide having 90% identity in its full length to the polypeptide sequence shown in SEQ ID NO 4. 
     
     
         21 . The compound according to  claim 20 , wherein said constant region comprises a peptide having 95% identity to the polypeptide sequence in its full length shown in SEQ ID NO 3 and a second polypeptide having 95% identity in its full length to the polypeptide sequence shown in SEQ ID NO 4. 
     
     
         22 . The compound according to  claim 1 , wherein said constant region of said carrier comprises at least 25% of the polypeptide sequence shown in SEQ ID NO 3 and 4. 
     
     
         23 . The compound according to  claim 22 , wherein said constant region of said carrier comprises at least 30% of the polypeptide sequences shown in SEQ ID NO 3 and 4. 
     
     
         24 . A pharmaceutical composition comprising
 a compound comprising a peptide having at least the motif X-X-X-X-X-X-X, wherein at least one amino acid residue X is glycosylated, wherein said peptide being linked to the peptide binding protein, and a carrier comprising at least a MHC binding motif being linked to said peptide; and   a pharmaceutically acceptable carrier, excipient or diluter.   
     
     
         25 . A method of using a pharmaceutical composition for the treatment of a disease or disorder wherein the pharmaceutical composition comprising a compound comprising a peptide having at least the motif X-X-X-X-X-X-X, wherein at least one amino acid residue X is glycosylated, wherein said peptide being linked to the peptide binding protein, and a carrier comprising at least a MHC binding motif being linked to said peptide; and a pharmaceutically acceptable carrier, excipient or diluter. 
     
     
         26 . Method according to  claim 25  for the treatment of a disease or disorder selected from the group consisting of arthritis, reumatoid arthritis, ankylosing spondylitis, psoriasis arthritis, osteoarthritis, relapsing polychondritis and Menieres disease.