Preparation of interleukin-2, useful for combination therapy treatment of cancer, by adding sodium dodecyl sulfate to form microaggregates

摘要

Forming microaggregates by adding sodium dodecyl sulfate (SDS) to an interleukin-2 (IL-2) composition, is new. Preparation of IL-2 for pharmaceutical use comprises the following steps: (a) adding SDS to an IL-2 composition in order to give an SDS concentration of at least 500 microgrammes SDS per mg IL-2; and (b) reducing SDS concentration without completely removing all SDS so that an SDS concentration of 95-250 microgrammes per mg IL-2 is obtained. Independent claims are also included for: (1) preparing a composition (C1) containing IL-2 and SDS in the form of aggregates by adding SDS to an IL-2 composition so that IL-2 monomers become present in solution and then reducing the SDS concentration so that SDS/IL-2 aggregates are formed, so that the resulting formulation has a specific turbidity of less than 1.1 cm2>/g after freeze-drying and reconstitution; (2) composition (C2) containing SDS/IL-2 aggregates and having at least one property chosen from a specific turbidity less than 1.1 cm2>/g, aggregates with a mean hydrodynamic diameter of 8-20 nm and an SDS concentration of 95-250 microgrammes SDS per mg IL-2; (3) freeze-dried composition (C3) comprising SDS and IL-2, which can be reconstituted with an aqueous medium to form (C2); (4) freeze-dried pharmaceutical composition (C4) which can be reconstituted with 1.2 ml sterilized water prior to injection to form a product containing (per ml) 1.1 mg non-glycolysed human des-alanyl-1 serine-125-IL-2, 50 mg mannitol, 0.18 mg SDS, 0.17 mg monobasic sodium phosphate and 0.89 mg dibasic sodium phosphate, having a pH of 7.5, SDS and IL-2 being present in the form SDS/IL-2 aggregates so that the reconstituted product has a specific turbidity of less than 1.1 cm2>/g; (5) aqueous pharmaceutical product (C5) prepared by reconstituting (C4) with 1.2 ml sterilized water before injection; (6) combination of (C2), (C3), (C4) or (C5) and a second pharmaceutical agent for a simultaneous, separate or subsequent treatment; (7) kit comprising (C2), (C3), (C4) or (C5) and a second pharmaceutical agent; (8) using SDS/IL-2 microaggregates with a mean hydrodynamic diameter of 8- 20 nm for preparing medicine; (9) using (C2) for preparing a medicine; and (10) using SDS/IL-2 microaggregates with a mean hydrodynamic diameter of 8-20 nm for the preparation of a combination medicine. ACTIVITY : Cytostatic; Anti-HIV. No biological data is given. MECHANISM OF ACTION : None given.