Patent ID: 8278270

Claim:
A hepatocyte growth factor (HGF) precursor protein variant having an α-chain and a β-chain, in which amino acids in the HGF precursor protein variant are substituted with at least one protease recognition sequence, wherein the protein obtained by cleavage at said at least one protease recognition sequence results in a protein having hepatocyte proliferation activity; and wherein said substitution is selected from the group consisting of: a) the last four amino acids of the α-chain or the first four amino acids of the β-chain are substituted with Asp-Asp-Asp-Lys (SEQ ID NO: 3), Ile-Glu-Gly-Arg (SEQ ID NO: 4), Ile-Asp-Gly-Arg (SEQ ID NO: 5), Arg-Xaa-Lys-Arg (SEQ ID NO: 10), or Arg-Xaa-Arg-Arg (SEQ ID NO: 11), where Xaa represents any amino acid residue; b) the last six amino acids of the α-chain or the first six amino acids of the β-chain are substituted with Leu-Val-Pro-Arg-Gly-Ser (SEQ ID NO: 6), Pro-Gly-Ala-Ala-His-Tyr (SEQ ID NO: 12), or Pro-Gly-Ala-Ala-Tyr-His (SEQ ID NO: 13); c) the last seven amino acids of the α-chain or the first seven amino acids of the β-chain are substituted with Glu-Xaa-Xaa-Tyr-Phe-Gln-Ser (SEQ ID NO: 7) or Glu-Xaa-Xaa-Tyr-Phe-Gln-Gly (SEQ ID NO: 8), where Xaa represents any amino acid residue; d) the last eight amino acids of the α-chain or the first eight amino acids of the β-chain are substituted with Leu-Glu-Val-Leu-Phe-Gln-Gly-Pro (SEQ ID NO: 9); and e) the last two amino acids of the α-chain or the first two amino acids of the β-chain are substituted with His-Tyr or Tyr-His.