Claims for Patent: 5,690,928

Summary for Patent: 5,690,928

Title:	Method of treating bladder cancer cells
Abstract:	Methods and compositions for treating bladder cancer using TGF-alpha or EGF fused to PE.sub.40 or cysteine modified derivatives are taught. Also, a method of producing TGF-alpha-PE.sub.40 derivatives of enhanced potency is described.
Inventor(s):	Heimbrook; David C. (Ringoes, NJ), Oliff; Allen I. (Gwynedd Valley, PA), Stirdivant; Steven M. (Warrington, PA), Ahern; Janet (Horsham, PA)
Assignee:	Merck & Co., Inc. (Rahway, NJ)
Application Number:	08/224,422
Patent Claims:	1. A method of treating bladder cancer comprising administering to a patient having bladder cancer a therapeutically effective amount of a hybrid protein selected from the group consisting of TGF-alpha-PE.sub.40 Ab, TGF-alpha-PE.sub.40 aB and TGF-alpha-PE.sub.40 ab, wherein "a" and "b" represent substitution of the cysteine residues at the A and B locus, respectively, with alanine or glycine residues. 2. A method according to claim 1 wherein the hybrid protein is in the form of a solution or suspension in a physiologically acceptable liquid. 3. A method according to claim 2 wherein the liquid comprises sterile water, water for injection, saline or buffered saline. 4. A method according to claim 3 wherein the liquid comprises buffered saline and additionally comprises a carrier protein. 5. A method according to claim 4 wherein the liquid is phosphate buffered saline and the carrier protein is human serum albumin. 6. A method according to claim 5 wherein the phosphate buffered saline contains from about 0.1 mg to about 10 mg of hybrid protein per 60 ml. 7. A method according to claim 5 wherein the phosphate buffered saline contains from about 0.5 mg to about 5 mg of the hybrid protein per 60 ml. 8. A method according to claim 5 wherein the phosphate buffered saline contains from about 2 mg to about 4 mg of the hybrid protein per 60 ml. 9. A method according to claim 2 wherein the physiologically acceptable liquid contains from about 0.1 mg to about 10 mg of the hybrid protein per 60 ml. 10. A method according to claim 2 wherein the physiologically acceptable liquid contains from about 0.5 mg to about 5 mg of the hybrid protein per 60 ml. 11. A method according to claim 2 wherein the physiologically acceptable liquid contains from about 2 mg to about 4 mg of the hybrid protein per 60 ml. 12. A method according to claim 2 wherein the administering is continued for a period of from about 30 minutes to about 4 hours. 13. A method according to claim 2 wherein the administering takes place at physiological temperature. 14. The method according to claim 1 wherein the hybrid protein is prepared by a urea-free process that comprises the purification step of precipitating the crude hybrid protein from a solution with ammonium sulfate. 15. A urea-free process for the preparation of a TGF-alpha-PE.sub.40 hybrid protein comprising the steps of harvesting a sufficient quantity of cells expressing a hybrid protein selected from the group consisting of TGF-alpha-PE.sub.40 Ab, TGF-alpha-PE.sub.40 aB and TGF-alpha-PE.sub.40 ab wherein "a" and "b" represent substitution of the cysteine residues at the A and B locus, respectively, with alanine or glycine residues; precipitating the expressed hybrid protein with ammonium sulfate; solublizing the precipitated protein; and purifying the soluble protein by affinity chromatography using a metal chelating chromatography column. 16. A hybrid protein prepared by the process of claim 15. 17. The hybrid protein of claim 16, wherein said hybrid protein is either TGF-alpha-PE.sub.40 ab or TGF-alpha-PE.sub.40 aB. 18. The method of claim 15 wherein the expressed hybrid protein is TGF-alpha-PE.sub.40 aB. 19. The method of claim 15 wherein the expressed hybrid protein is TGF-alpha-PE.sub.40 ab. 20. The method of claim 15 wherein the expressed hybrid protein is TGF-alpha-PE.sub.40 Ab.

Details for Patent 5,690,928

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2014-11-25