Conjugates comprising truncated keratinocyte growth factor (KGF)

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Hormones – e.g. – prolactin – thymosin – growth factors – etc.

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530350, 530402, 514 2, 435 691, 435 697, C07K 14475, C12N 1500

Patent

active

057735867

ABSTRACT:
The present invention relates to a keratinocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks i 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 KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host The present invention further relates to a conjugate of KGF.sub.des1-23 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 KGF.sub.des1-23 and a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.

REFERENCES:
Ron et al. 1993. J. Biol. Chem. 268:2984-2988.
Bellosta et al. 1993. J. Cell. Biol. 121: 705-713.
Bowie et al. 1990. Science 247: 1306:1310.

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