Active Variants of the Il-18 Binding Protein and Medical Uses Thereof

A composition of matter comprising:

• (a) an isolated IL-18 binding protein (IL-18BP) comprising an amino acid sequence selected from SEQ ID NO:
• 2, SEQ ID NO:
• 3, SEQ ID NO:
• 4, SEQ ID NO:
• 5, SEQ ID NO:
• 6, or SEQ ID NO:
• 7, or a functional derivative, fusion protein or salt thereof, said amino acid sequence not comprising SEQ ID NO:
• 1;
• (b) an isolated IL-18 binding protein (IL-18BP) according to (a), less the C-terminal glycine residue;
• (c) an isolated IL-18 binding protein (IL-18BP) consisting of the amino acid sequence of SEQ ID NO:
• 1 and being N-glycosylated at Asn 49, Asn 73 and Asn 117, but not at Asn 64, a functional derivative, fusion protein or salt thereof;
• (d) an isolated IL-18 binding protein (IL-18BP) according to (c), less the C-terminal glycine residue;
• (e) an isolated IL-18BP comprising a first polypeptide consisting of amino acids 1 to 30 of SEQ ID NO:
• 1 and a second polypeptide consisting of amino acids 31 to 164 or of amino acids 31 to 163, wherein the first and second polypeptide are linked by a disulfide bond;
• (f) an isolated IL-18BP comprising a first polypeptide consisting of amino acids 15 to 30 of SEQ ID NO:
• 1 and a second polypeptide consisting of amino acids 31 to 164 or of amino acids 31 to 163, wherein the first and second polypeptide are linked by a disulfide bond;
• (g) an isolated IL-18BP as set forth in (a) or (c), wherein said fusion protein comprises an immunoglobulin fusion;
• (h) an isolated IL-18BP as set forth in (a) or (c), wherein said functional derivative comprises at least one moiety attached to one or more functional groups, which occur as one or more side chains on the amino acid residues;
• (i) an isolated IL-18BP as set forth in (a) or (c), wherein said functional derivative comprises at least one polyethylene glycol (PEG) moiety attached to one or more functional groups, which occur as one or more side chains on the amino acid residues;
• (j) an isolated nucleic acid encoding a polypeptide as set forth in (a), (b), (c), (d), (e), or (f);
• (k) a host cell comprising an isolated nucleic acid encoding a polypeptide as set forth in (a), (b), (c), (d), (e), or (f);
• (j) an expression vector comprising a nucleic acid encoding a polypeptide as set forth in (a), (b), (c), (d), (e), or (f);
• (k) a composition comprising an IL-18BP as set forth in (a), (b), (c), (d), (e), or (f);
• (l) a composition comprising an IL-18BP as set forth in (a), (b), (c), (d), (e), or (f) in combination with an interferon or an inhibitor of tumor necrosis factor;
• or
• (m) a composition comprising an IL-18BP as set forth in (a), (b), (c), (d), (e), or (f) in combination with an interferon-β or soluble tumor necrosis factor receptor.

A method for production of an IL-18BP comprising culturing a host cell a host cell comprising an isolated nucleic acid encoding:

• (a) an IL-1 8 binding protein (IL-18BP) comprising an amino acid sequence selected from SEQ ID NO:
• 2, SEQ ID NO:
• 3, SEQ ID NO:
• 4, SEQ ID NO:
• 5, SEQ ID NO:
• 6, or SEQ ID NO:
• 7, or a functional derivative, fusion protein or salt thereof, said amino acid sequence not comprising SEQ ID NO:
• 1;
• (b) an IL-18 binding protein (IL-18BP) according to (a), less the C-terminal glycine residue;
• (c) an IL-18 binding protein (IL-18BP) consisting of the amino acid sequence of SEQ ID NO:
• 1 and being N-glycosylated at Asn 49, Asn 73 and Asn 117, but not at Asn 64, a functional derivative, fusion protein or salt thereof;
• (d) an IL-18 binding protein (IL-18BP) according to (c), less the C-terminal glycine residue;
• (e) an IL-p18BP comprising a first polypeptide consisting of amino acids 1 to 30 of SEQ ID NO:
• 1 and a second polypeptide consisting of amino acids 31 to 164 or of amino acids 31 to 163;
• (f) an IL-18BP comprising a first polypeptide consisting of amino acids 15 to 30 of SEQ ID NO:
• 1 and a second polypeptide consisting of amino acids 31 to 164 or of amino acids 31 to 163;
• or
• (g) an IL-18BP as set forth in (a) or (c), wherein said fusion protein comprises an immunoglobulin fusion;
• under conditions suitable for expression of said IL-18BP.