METHODS FOR THE TREATMENT OF GOUT
Disclosed are methods for the treatment and/or prevention of gout, comprising administering to a subject an effective amount of anti-IL-1β antibody or fragment thereof.
1 . A method of treating gout in a subject, the method comprising administering an anti-IL-1β antibody or fragment thereof to the subject.
2 . The method of claim 1 , wherein the gout is chronic gout, or acute gout.
3 . (canceled)
4 . The method of claim 1 , wherein the antibody or antibody fragment binds to human IL-1β with a dissociation constant of about 10 nM or less, about 1 nM or less, about 100 pM or less, about 10 pM or less, about 1 pM or less, or about 0.3 pM or less.
5 - 9 . (canceled)
10 . The method of claim 1 , wherein the anti-IL-1β antibody or antibody fragment is a neutralizing antibody.
11 . The method of claim 1 , wherein the anti-IL-1β antibody or antibody fragment binds to an IL-1β epitope such that the bound antibody or fragment substantially permits the binding of IL-1β to IL-1 receptor I (IL-1RI).
12 . The method of claim 1 , wherein the antibody or antibody fragment does not detectably bind to IL-1α, IL-1R or IL-1Ra.
13 . The method of claim 1 , wherein the antibody or antibody fragment binds to an epitope contained in the sequence ESVDPKNYPKKKMEKRFVFNKIE.
14 . The method of claim 1 , wherein the antibody or fragment thereof competes with the binding of an antibody having the light chain variable region of SEQ ID NO:5 and the heavy chain variable region of SEQ ID NO: 6
15 . The method of claim 1 , wherein the antibody or antibody fragment binds to an epitope incorporating Glu64 of IL-1β.
16 . The method of claim 1 , wherein the antibody or antibody fragment binds to amino acids 1-34 of the N terminus of IL-1β.
17 . The method of claim 1 , wherein the antibody or antibody fragment is human engineered or humanized.
18 . The method of claim 1 , wherein the antibody or antibody fragment is human.
19 . The method of claim 1 , wherein the antibody or antibody fragment is administered in one or more doses of 3 mg/kg or less of antibody or fragment, 1 mg/kg or less of antibody or fragment, 0.3 mg/kg or less of antibody or fragment, 0.1 mg/kg or less of antibody or fragment, 0.03 mg/kg or less of antibody or fragment, or 0.01 mg/kg or less of antibody or fragment.
20 - 24 . (canceled)
25 . The method of claim 19 , wherein the one or more doses are at least 0.01 mg/kg of antibody or fragment.
26 . The method of claim 1 , wherein the antibody or antibody fragment is administered in one or more doses of 0.001 mg/kg to 1 mg/kg, 0.003 mg/kg to 1 mg/kg, or 0.003 mg/kg to 0.3 mg/kg.
27 - 28 . (canceled)
29 . The method of claim 1 , wherein the antibody or fragment is administered as a fixed dose, independent of a dose per subject weight ratio.
30 . The method of claim 29 , wherein the antibody or fragment is administered in one or more doses of 500 mg or less of antibody or fragment; 250 mg or less of antibody or fragment, 100 mg or less of antibody or fragment, 25 mg or less of antibody or fragment, 10 mg or less of antibody or fragment, or 1.0 mg or less of antibody or fragment.
31 - 35 . (canceled)
36 . The method of claim 29 , wherein the antibody or fragment is administered in one or more doses of at least 1.0 mg of antibody or fragment, or at least 10 mg of antibody or fragment.
37 . (canceled)
38 . The method of claim 1 , wherein the anti-IL-1β antibody or fragment is administered by subcutaneous, intravenous or intramuscular injection.
39 . The method of claim 1 , wherein administration of an initial dose of the antibody or antibody fragment is followed by the administration of one or more subsequent doses.
40 . The method of claim 1 , wherein administration of an initial dose of the antibody or antibody fragment is followed by the administration of one or more subsequent doses, and wherein said one or more subsequent doses are in an amount that is approximately the same or less than the initial dose.
41 . The method of claim 1 , wherein administration of an initial dose of the antibody or antibody fragment is followed by the administration of one or more subsequent doses, and wherein at least one of the subsequent doses is in an amount that is more than the initial dose.
42 . The method of claim 1 , wherein the dose of the antibody or fragment is sufficient to achieve at least a 50% reduction in joint pain, at least a 70% reduction in joint pain, or at least a 90% reduction in joint pain.
43 - 44 . (canceled)
45 . The method of claim 1 , wherein the dose of the antibody or fragment is sufficient to achieve at least a 20% decrease in CRP levels, at least a 30% decrease in CRP levels, at least a 40% decrease in CRP levels, or at least a 50% decrease in CRP levels.
46 - 48 . (canceled)
49 . The method of claim 1 , wherein the dose of the antibody or fragment is sufficient to achieve at least a 20% decrease in ESR, at least a 40% decrease in ESR, or at least a 60% decrease in ESR.
50 - 51 . (canceled)
52 . The method of claim 1 , wherein the dose of the antibody or fragment is sufficient to achieve at least a 50% reduction in joint pain, at least a 20% decrease in CRP and at least a 20% decrease in ESR, at least a 30% decrease in CRP and at least a 30% decrease in ESR, or at least a 40% decrease in CRP and at least a 40% decrease in ESR.
53 - 54 . (canceled)
55 . The method of claim 1 , wherein said method is in conjunction with at least one additional treatment method, said additional treatment method comprising administering at least one pharmaceutical composition comprising an active agent other than an IL-1β antibody or fragment.
56 . The method of claim 55 , wherein said at least one pharmaceutical composition comprising an active agent other than an IL-1β antibody or fragment is selected from the group consisting of a nonsteroidal anti-inflammatory drug (NSAID), a corticosteroid, an adrenocorticotropic hormone, and a colchicine.
57 . The method of claim 1 , wherein the antibody or fragment thereof has a lower IC 50 than an IL-1β receptor antagonist in a human whole blood IL-1β inhibition assay that measures IL-1β induced production of IL-8.
58 . The use of an anti-IL-1β antibody or fragment thereof which has a lower IC 50 than an IL-1β receptor antagonist in a human whole blood IL-1β inhibition assay that measures IL-1β induced production of IL-8, in the manufacture of a composition for use in the treatment of gout.
59 . The method of claim 57 , wherein the IL-1β receptor antagonist is anakinra.
60 . The use according to claim 58 , wherein the IL-1β receptor antagonist is anakinra.