IL-18 binding protein (IL-18BP) and antibodies for treating inflammatory diseases
The present invention provides means and methods for treating Interleukin 18 (IL-18)-associated diseases and disorders. In particular, the present invention discloses antibodies specific for free IL-18 and IL-18 Binding Protein (IL-18BP) for use in such treatments and for the diagnosis of the diseases and disorders.
1 . A method for the treatment of an IL-18 associated autoinflammatory disease or disorder and/or symptoms associated with said disease or disorder in a subject, said method comprising administering to said subject an IL-18 inhibitor, wherein the IL-18 inhibitor is an IL-18 binding protein (IL-18BP) or an active fragment thereof, wherein the IL-18BP or the active fragment thereof comprises N-terminal and/or C-terminal deletion variants of IL-18BP, which are present in an amount of less than 30%, wherein the IL-18 associated autoinflammatory disease or disorder is selected from juvenile idiopathic arthritis (JIA), systemic juvenile idiopathic arthritis (sJIA), systemic onset juvenile idiopathic arthritis (SoJIA), SoJIA with macrophage activation syndrome (SoJIA-MAS), or interstitial lung disease (ILD).
2 . The method of claim 1 , wherein the body fluids of said subject have been quantified to have abnormal levels of free IL-18, which exceed the level of free IL-18 in body fluids of a healthy control subject by 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or more than 100%.
3 . The method of claim 2 , wherein the level of free IL-18 in the body fluids has been determined to be ≥5 μg/mL as compared to ≤4 μg/mL in the healthy control subject.
4 . The method of claim 1 , wherein the IL18-BP is human IL-18BP.
5 . The method of claim 4 , wherein said human IL-18BP is selected from isoforms a, b, c and d of human IL-18BP.
6 . The method of claim 1 , wherein said deletion variants comprise deletions of between 1 and 5 amino acid residues at the C-terminal end of the IL-18BP and/or between 1 and 30 amino acid residues at the N-terminal end of the IL-18BP.
7 . The method of claim 1 , wherein the IL-18 associated autoinflammatory disease or disorder is accompanied by high levels of IL-18 and free IL-18.
8 . The method of claim 1 , wherein the IL-18 BP or the active fragment thereof is administered to the subject in need thereof in one or multiple doses/day, in one or multiple doses/week or in one or multiple doses/month.
9 . The method of claim 1 , wherein the IL-18 BP or the active fragment thereof is administered in one dose per week, in two doses per week, three doses per week, or four doses per week.
10 . The method of claim 9 , wherein a single dose comprises between 0.5 mg and 600 mg IL-18BP.
11 . The method of claim 9 , wherein a single dose comprises between 0.5 mg of IL-18BP/kg body weight and 10 mg of IL-18BP/kg body weight.
12 . The method of claim 9 , wherein a single dose of between 0.5 mg of IL-18BP/kg body weight and 5 mg of IL-18BP/kg body weight is administered every 24 or 48 hours.
13 . The method of claim 9 , wherein a single dose of 2 mg of IL-18BP/kg body weight is administered every 48 hours.
14 . The method of claim 1 , wherein the IL-18 BP or the active fragment thereof is administered every 24 hours to 48 hours.
15 . The method of claim 1 , wherein the IL-18 inhibitor is administered to the subject subcutaneously.
16 . The method of claim 1 , wherein the subject is a human.
17 . The method of claim 1 , wherein the IL-18 associated autoinflammatory disease or disorder is induced by viral infection.
18 . The method of claim 1 , further comprising administering to the subject a glucocorticoid.
19 . The method of claim 18 , wherein the glucocorticoid is dexamethasone.