Claims for Patent: 5,677,278

Summary for Patent: 5,677,278

Title:	Truncated keratinocyte growth factor (KGF) having increased biological activity
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 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 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.
Inventor(s):	Gospodarowicz; Denis J. (Lafayette, CA), Masiarz; Frank R. (San Francisco, CA)
Assignee:	Chiron Corporation (Emeryville, CA)
Application Number:	08/410,941
Patent Claims:	1. A keratinocyte growth factor fragment that exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant, full-length keratinocyte growth factor, wherein the fragment lacks the first 23 N-terminal amino acid residues of the mature, full-length keratinocyte growth factor but retains the remainder of the molecule. 2. The keratinocyte growth factor fragment as claimed in claim 1, wherein the fragment exhibits a 7-fold increase in mitogenic activity as compared to the mature, recombinant, full-length keratinocyte growth factor. 3. The keratinocyte growth factor fragment as claimed in claim 1, wherein the fragment exhibits a 10-fold increase in mitogenic activity as compared to the mature, recombinant, full-length keratinocyte growth factor. 4. The keratinocyte growth factor fragment as claimed in claim 1, wherein the fragment exhibits decreased cytotoxicity as compared to the mature, recombinant, full-length keratinocyte growth factor. 5. A composition comprising: (a) a keratinocyte growth factor fragment that exhibits at least a 2-fold increase in mitogenic activity as compared to the mature, recombinant, full-length keratinocyte growth factor, wherein the fragment lacks the first 23 N-terminal amino acid residues of the mature, full-length keratinocyte growth factor but retains the remainder of the molecule, and (b) a carrier. 6. The keratinocyte growth factor fragment as claimed in claim 1 having the amino acid sequence depicted at amino acid residues 24 to 163, inclusive, of FIG. 1 (amino acid residues 55-194, inclusive, of SEQ ID No: 1). 7. An analog of the keratinocyte growth factor fragment as claimed in claim 6, wherein the analog differs from its keratinocyte growth factor fragment of claim 6 in having at least one conservative substitution selected from the group of substitutions consisting of a substitution of a leucine with an isoleucine or an isoleucine with a leucine, a substitution of a leucine with a valine or a valine with a leucine, a substitution of an aspartic acid with a glutamic acid or a glutamic acid with an aspartic acid and a substitution of a threonine with a serine or a serene with a threonine and further wherein the analog exhibits the biological activity of the keratinocyte growth factor fragment. 8. An analog of the keratinocyte growth factor fragment as claimed in claim 6, wherein the analog differs from its keratinocyte growth factor fragment of claim 6 in having at least one cysteine residue substituted by another amino acid and further wherein the analog exhibits the biological activity of the keratinocyte growth factor fragment. 9. The analog as claimed in claim 8, wherein the cysteine residue is replaced with serine or threonine. 10. A composition comprising: (a) the keratinocyte growth factor fragment as claimed in claim 6, and (b) a carrier. 11. A composition comprising: (a) the analog as claimed in claim 7, and (b) a carrier. 12. A composition comprising: (a) the analog as claimed in claim 5, and (b) a carrier. 13. A composition comprising: (a) the analog as claimed in claim 9, and (b) a carrier.

Details for Patent 5,677,278

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Swedish Orphan Biovitrum Ab (publ)	KEPIVANCE	palifermin	For Injection	125103	12/15/2004		2039-03-29

International Patent Family for US Patent 5,677,278

Country	Patent Number	Estimated Expiration
Austria	278777
Australia	681405
Australia	6820894
Bulgaria	100236