Method of treatment using cysteine mutants of beta interferon

摘要

The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby. Also disclosed are therapeutic methods for using the cysteine variants of the invention.

主权项

1. A method to treat an animal with a disease or condition that can be treated by wild-type beta interferon, comprising administering to said animal a composition comprising a beta interferon cysteine mutein of SEQ ID NO:5, wherein a cysteine residue is substituted for an amino acid selected from the group consisting of: M1, S2, Q23, N25, G26, N80, E109, D110, F111, T112, R113, G114, K115 and N166, or wherein a cysteine residue is added following the last amino acid of the protein, and wherein said variant has biological activity in vitro, as measured by inhibition of proliferation of a cell line whose proliferation is inhibited in response to beta interferon.