Methods of reducing aggregation of IL-1ra

A method of reducing aggregation of an aggregating interleukin-1 receptor antagonist (IL-1ra) in an aqueous composition comprising

• incubating the aqueous composition comprising the IL-1ra with at least one accessory molecule at a concentration sufficient to reduce aggregation of the IL-1ra for at least two hours at 25 to 45° C., and
• determining reduced aggregation of the IL-1ra in the aqueous composition by measuring the optical density at 405 nm of the aqueous composition after at least two hours of incubation at 30 to 45° C., wherein the optical density of the aqueous composition comprising the IL-1ra is less than 60% of the optical density of an aqueous composition comprising the IL-1ra without incubating with the accessory molecule, and
• wherein the at least one accessory molecule is selected from the group consisting of (1) a sugar at a concentration of from 1 to 2 percent, wherein the sugar is sucrose, glycerol, or sorbitol, (2) a multiple-charge anion, wherein the multiple-charge anion is 1 to 20 mM pyrophosphate or 1 to 20 mM citrate, and (3) a lysine-reactive accessory molecule or an arginine-reactive accessory molecule, selected from the group consisting of the three compounds from 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoic acid (NBD-X), methyl acetyl phosphate (MAP), and citraconic anhydride.