Hoffmann-La Roche Inc.

Hauke Lilie

Kay-Gunnar Stubenrauch

Rainer Rudolph

Susanne Richter

A chimeric polypeptide has a first and a second polypeptide chain chemically linked via 1 to 3 cysteine-based disulfide bridges. The first polypeptide chain consists of 1 to 3 cysteines and 4 to 12 basic amino acids preferably selected from the group consisting of arginine, lysine and ornithine. The second polypeptide chain consists of 1 to 3 cysteines and 4 to 12 acidic amino acids selected from the group consisting of glutamate and aspartate. Each polypeptide chain is linked at its C- or N-terminus to a biologically active compound, and is useful as a multimeric pharmaceutical agent. A method for producing such chimeric polypeptide involves contacting the first polypeptide chain with the second polypeptide chain under conditions such that the basic amino acids on the first polypeptide chain ionically interact with the acidic amino acids on the second polypeptide chain and then treating the first polypeptide chain and the second polypeptide chain with an oxidizing agent under conditions such that the 1 to 3 cysteines of the first polypeptide chain form disulfide bridges with the 1 to 3 cysteines of the second polypeptide chain thereby forming the chimeric polypeptide.

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Halle, Germany

Hauke Lilie