Process for making biologically active polypeptides based on transforming growth factor-βsequences

Claim 1

A process for obtaining a polypeptide that inhibits the in vitro proliferation of a cultured established mink lung cell line CCL 64 or in nitro proliferation of human lymphocytes to an antigen or a mitogen comprising crosslinking a monomeric polypeptide at one of its termini with at least one polypeptide chain homologous to the polypeptide, so as to form a polymer of the monomeric polypeptide, wherein the monomeric polypeptide comprises an amino acid sequence of the formula: X-A-Arg-B-Leu-Tyr-Ile-Asp-Phe-H-I-Asp-Leu-Gly-Trp-Lys, wherein; X is Cys or a crosslinker moiety of a polypeptide that has at its C-terminus a Cys, and that, if greater than 15 residues, does not have the sequence of mature or precursor TGF-β at a homologous location in the mature or precursor TGF-β molecule; A is Val or Leu; B is Pro or Gln; H is Arg or Lys; and I is Lys, Arg, or Gln; or a physiologically acceptable salt or ester thereof; provided, however, that the polypeptide excludes (a) a full-length mature TFG-β molecule or precursor TGF-β molecule or deletion variants of mature or precursor TGF-β molecules in which from about 1 to 10 amino acid residues have been deleted, (b) a polypeptide of the sequence: Cys-Val-Arg-Gln-Leu-Tyr-Ile-Asp-Phe-Arg-Lys-Asp-Leu-Gly-Trp-Lys, and (c) a polypeptide of the sequence: Arg-Asn-Leu-Glu-Glu-Asn-Cys-Cys-Val-Arg-Pro-Leu-Tyr-Ile-Asp-Phe-Arg-Gln-Asp-Leu.