Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation

US7879319B2 · kind B2 · utility

Assignee

• Merk Patent GMBH · DE

Inventors

• Stephen D. Gillies · Carlisle, US
• Kin-Ming Lo · Lexington, US
• Yan Lan · Belmont, US

Key dates

• Filing date: Jul 7, 2009
• Grant date: Feb 1, 2011
• Expiry date: Jul 7, 2029

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ratio of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to one ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.