Methods and compositions for modulating the immune system with arginase i

Abstract

Methods and compositions comprising recombinant Arginase I proteins which are capable of depleting the plasma arginine levels in a subject are disclosed. The methods and compositions can be used to modulate the activity of the immune system in a subject. Modulation of the immune system is useful in the treatment of immune disorders and in preventing rejection of a transplanted organ, tissue, or cell. The methods and compositions can also be used to treat a bone condition of a subject.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising, a recombinant human Arginase I or a functional fragment thereof, wherein the recombinant human Arginase I inhibits T-cell polarization when administered to a subject. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the recombinant human Arginase I comprises at least one polyethylene glycol (PEG) oligomer. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the recombinant human Arginase I comprises at least two polyethylene glycol oligomers. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein at least one of the two polyethylene glycol oligomers weighs from about 20 kilodaltons and about 40 kilodaltons. 
     
     
         5 . The pharmaceutical composition of  claim 2 , wherein the recombinant human Arginase I comprises from about 4 polyethylene glycol oligomers to about 13 polyethylene glycol oligomers. 
     
     
         6 . The pharmaceutical composition of  claim 2 , wherein the polyethylene glycol oligomer weighs about 5 kilodaltons. 
     
     
         7 . The pharmaceutical composition of  claim 2 , wherein the total molecular weight of the polyethylene glycol oligomer conjugated with each molecule of said recombinant human Arginase I is about 20-120 kilodaltons. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the total molecular weight of the PEG oligomer conjugated with each molecule of said recombinant human Arginase I is about 30-60 kilodaltons. 
     
     
         9 . The pharmaceutical composition of  claim 2 , wherein the polyethylene glycol oligomer is conjugated to a cysteine residue of the recombinant human Arginase I. 
     
     
         10 . The pharmaceutical composition of  claim 2 , wherein the polyethylene glycol oligomer is conjugated to an amine residue of the recombinant human Arginase I protein. 
     
     
         11 . The pharmaceutical composition of  claim 2 , wherein the polyethylene glycol oligomer is conjugated to the N-terminus of the recombinant human Arginase I protein. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is packaged as a kit. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein said recombinant human Arginase I protein comprises SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7. SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises from about 5 mg to about 1000 mg of the recombinant human Arginase I. 
     
     
         15 . The pharmaceutical composition of  claim 1 , wherein the subject is afflicted with an inflammatory disease. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the inflammatory disease is multiple sclerosi s. 
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein the inflammatory disease is rheumatoid arthritis. 
     
     
         18 . The pharmaceutical composition of  claim 1 , wherein the recombinant human Arginase I suppresses the immune system of the subject when administered to said subject. 
     
     
         19 . The pharmaceutical composition of  claim 1 , wherein the subject is afflicted with a bone condition selected from the group consisting of osteoporosis, inflammation in the bone, Paget's disease, osteogenesis imperfecta, fibrous dysplasis, and osteomyelitis. 
     
     
         20 . The pharmaceutical composition of  claim 1 , wherein the recombinant human Arginase I is formulated for parenteral administration to the subject. 
     
     
         21 . The pharmaceutical composition of  claim 1 , wherein the subject is an infant, a toddler, a child, a pre-adolescent, or an adolescent human. 22, The pharmaceutical composition of  claim 1 , wherein the subject is an adult human.