Methods for treating rheumatoid arthritis using ctla4-pon1 fusion proteins

A method for treating rheumatoid arthritis, the method comprising:

• administering to a subject having rheumatoid arthritis an effective amount of a dimeric protein comprising a first fusion polypeptide and a second fusion polypeptide, wherein each of the first and second fusion polypeptides is a fusion polypeptide comprising, from an amino terminal position to a carboxyl terminal position, T-L1-X-L2-P, wherein:
• T is a biologically active cytotoxic T-lymphocyte associated molecule-4 (CTLA-4) extracellular domain;
• L1 is a first polypeptide linker, wherein L1 is optionally present;
• X is an immunoglobulin heavy chain constant region, wherein the immunoglobulin heavy chain constant region is capable of forming dimers and specifically binding the neonatal Fc receptor (FcRn);
• L2 is a second polypeptide linker comprising at least eight amino acid residues;
• and
• P is a biologically active paraoxonase, wherein the paraoxonase has at least 95% identity with the amino acid sequence shown in residues 16-355 or 26-355 of SEQ ID NO:
• 6, and wherein the paraoxonase does not contain an amino terminal leader sequence corresponding to residues 1-15 of SEQ ID NO:6;
• wherein each of the first and second fusion polypeptides comprises an amino acid sequence having at least 95% identity with the amino acid sequence shown in residues 21-736 of SEQ ID NO:66.