Method of treatment with modified arginine deiminase
The present invention is directed to arginine deiminase modified with polyethylene glycol, to methods of treating cancer, and to methods of treating and/or inhibiting metastasis.
1. A method of enhancing the circulating half life of arginine deiminase comprising modifying said arginine deiminase by covalently bonding said arginine deiminase via a linking group to polyethylene glycol,
wherein the arginine deiminase is derived from a microorganism of the genus selected from the group consisting of: Steptococcus, Borrelia, Qiardia, Clostridium, Enterococcus, Lactobacillus , and Bacillus;
wherein the polyethylene glycol has a total weight average molecular weight of from about 1,000 to about 40,000, and
wherein the linking group is selected from the group consisting of a succinimide group, an amide group, an imide group, a carbarmate group, an ester group, an epoxy group, a carboxyl group, a hydroxyl group, a carbohydrate, a tyrosine group, a cysteine group, a histidine group and combinations thereof.
2. A method of treating a tumor in a patient comprising administering to said patient a compound comprising arginine deiminase covalently bonded via a linking group to polyethylene glycol,
wherein the arginine deiminase is derived from a microorganism of the genus selected from the group consisting of: Steptococcus, Borrelia, Qiardia, Clostridium, Enterococcus, Lactobacillus , and Bacillus;
wherein the polyethylene glycol has a total weight average molecular weight of from about 1,000 to about 40,000, and
wherein the linking group is selected from the group consisting of a succinimide group, an amide group, an imide group, a carbamate group, an ester group, an epoxy group, a carboxyl group, a hydroxyl group, a carbohydrate, a tyrosine group, a cysteine group, a histidine group and combinations thereof.
3. The method of claim 2 , wherein said tumor is a melanoma.
4. The method of claim 3 , wherein said polyethylene glycol has a total weight average molecular weight of about 20,000.
5. The method of claim 3 , wherein said linking group is a succinimide group.
6. The method of claim 5 , wherein said succinimide group is succinimidyl succinate, succinimidyl propionate, succinimidyl carboxymethylate, succinimidyl succinamide, N-hydroxy succinimide or combinations thereof.
7. The method of claim 2 , wherein said tumor is a hepatoma.
8. The method of claim 7 , wherein said polyethylene glycol has a total weight average molecular weight of about 20,000.
9. The method of claim 7 , wherein said linking group is a succinimide group.
10. The method of claim 9 , wherein said succinimide group is succinimidyl succinate, succinimidyl propionate, succinimidyl carboxymethylate, succinimidyl succinamide, N-hydroxy succinimide or combinations thereof.
11. The method of claim 2 , wherein said tumor is a sarcoma.