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AssigneeChiron Corporation
InventorsDenis J. Gospodarowicz, Frank R. Masiarz
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The present invention relates to a keratinocyte growth factor fragment, KGFdes1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGF163 N-terminus. The present invention also relates to a DNA molecule encoding KGFdes1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGFdes1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGFdes1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGFdes1-23 and a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.
An isolated polynucleotide comprising a coding sequence encoding a polypeptide having at least 95% sequence identity to the contiguous sequence of amino acids 55–194 of SEQ ID NO:1 and optionally including a methionine residue at the N-terminus thereof, wherein said polypeptide exhibits an increase in bioactivity relative to mature, full-length, human KGF depicted at amino acids 32–194 of SEQ ID NO:1 as determined by the Balb/MK bioactivity assay, and further wherein any deviation from the secquence of amino acids 55–194 of SEQ ID NO:1 is due to one or more amino acid substitutions.
A non-human host cell that expresses a polypeptide having at least 95% sequence identity to the contiguous sequence of amino acids 55–194 of SEQ ID NO:1 and optionally including a methionine residue at the N-terminus thereof, wherein said polypeptide exhibits an increase in bioactivity relative to mature, full-length, human KGF depicted at amino acids 32–194 of SEQ ID NO:1 as determined by the Balb/MK bioactivity assay, and further wherein any deviation from the sequence of amino acids 55–194 of SEQ ID NO:1 is due to one or more amino acid substitutions.
Dependencies are inferred from the claim text.