Mixtures of polypeptides, compositions containing and processes for preparing same, and uses thereof

Abstract

The invention provides a composition comprising a mixture of polypeptides, wherein each polypeptide (a) is a copolymer of the amino acids L-glutamic acid, L-alanine, L-tyrosine, and L-lysine, and (b) may be in the form of a pharmaceutically acceptable salt; and wherein in the mixture (i) the polypeptides have an average molecular weight in the range 13,500 to 18,500 daltons, (ii) 13% to 38% of the polypeptides have a diethylamide group instead of a carboxyl group present at one end thereof, and (iii) 68% of the polypeptides have a molecular weight between 7,000 and 41,000 daltons. In an embodiment, the average molecular weight is 16,000 daltons, and processes for preparing and its uses.

1 . (canceled)  
     
     
         2 . The method of  claim 52 , wherein in the composition the average molecular weight is 16,000 daltons.  
     
     
         3 . The method of  claim 52 , wherein in the composition the amino acids are present in the mixture in an amount such that the average molar fraction of the amino acids is: L-glutamic acid 0.129-0.153; L-alanine 0.392-0.462; L-tyrosine 0.086-0.100; and L-lysine 0.300-0.374.  
     
     
         4 . The method of  claim 3 , wherein in the composition the amino acids are present in the mixture in an amount such that the average molar fraction of the amino acids is: L-glutamic acid 0.141; L-alanine 0.427; L-tyrosine 0.095; and L-lysine 0.338.  
     
     
         5 . The method of  claim 52 , wherein in the composition 19% to 28% of the polypeptides in the mixture have diethylamide at one end thereof.  
     
     
         6 . The method  claim 5 , wherein in the composition the remainder of polypeptides in the mixture have a carboxyl group at the C-terminus.  
     
     
         7 . The method of  claim 52 , wherein in the composition 35-45% of the polypeptides in the mixture have a L-alanine at the N-terminus.  
     
     
         8 . The method of  claim 52 , wherein in the composition less than 5% of the polypeptides in the mixture have a molecular weight below 4,700 daltons.  
     
     
         9 . (canceled)  
     
     
         10 . The method of  claim 52 , wherein in the composition the mixture of polypeptides has a circular dichroism value of 0.91.  
     
     
         11 . The method of  claim 52 , wherein in the composition the polypeptides are in the form of a pharmaceutically acceptable salt.  
     
     
         12 - 30 . (canceled)  
     
     
         31 . The method of  claim 78 , wherein the effective amount is 20 mg.  
     
     
         32 - 51 . (canceled)  
     
     
         52 . A method of treating a human subject afflicted with an autoimmune disease comprising administering to the subject a therapeutically effective amount of a composition comprising a mixture of polypeptides, wherein each polypeptide (a) is a copolymer of the amino acids L-glutamic acid, L-alanine, L-tyrosine, and L-lysine, and (b) may be in the form of a pharmaceutically acceptable salt; and wherein in the mixture (i) the polypeptides have an average molecular weight in the range 13,500 to 18,500 daltons, (ii) 13% to 38% of the polypeptides have a diethylamide group instead of a carboxyl group present at one end thereof, and (iii) 68% of the polypeptides have a molecular weight between 7,000 and 41,000 daltons, so as to thereby treat the human subject.  
     
     
         53 . A method of treating a human subject afflicted with an inflammatory non-autoimmune disease, an immune mediated disease, or a disease associated with demyelination comprising administering to the human subject a therapeutically effective amount of a composition comprising a mixture of polypeptides, wherein each polypeptide (a) is a copolymer of the amino acids L-glutamic acid, L-alanine, L-tyrosine, and L-lysine, and (b) may be in the form of a pharmaceutically acceptable salt; and wherein in the mixture (i) the polypeptides have an average molecular weight in the range 13,500 to 18,500 daltons, (ii) 13% to 38% of the polypeptides have a diethylamide group instead of a carboxyl group present at one end thereof, and (iii) 68% of the polypeptides have a molecular weight between 7,000 and 41,000 daltons, so as to thereby treat the human subject.  
     
     
         54 - 55 . (canceled)  
     
     
         56 . A method of promoting nerve regeneration or preventing or inhibiting secondary degeneration which may otherwise follow primary nervous system injury in a human subject comprising administering to the human subject a therapeutically effective amount of a composition comprising a mixture of polypeptides, wherein each polypeptide (a) is a copolymer of the amino acids L-glutamic acid, L-alanine, L-tyrosine, and L-lysine, and (b) may be in the form of a pharmaceutically acceptable salt; and wherein in the mixture (i) the polypeptides have an average molecular weight in the range 13,500 to 18,500 daltons, (ii) 13% to 38% of the polypeptides have a diethylamide group instead of a carboxyl group present at one end thereof, and (iii) 68% of the polypeptides have a molecular weight between 7,000 and 41,000 daltons.  
     
     
         57 - 60 . (canceled)  
     
     
         61 . The method of  claim 53 , wherein the neurodegenerative disease is glaucoma.  
     
     
         62 . The method of  claim 61 , wherein the method preserves the structural integrity of the optic nerve of the human subject afflicted with glaucoma.  
     
     
         63 - 64 . (canceled)  
     
     
         65 . The method of  claim 52 , further comprising administering to the subject of a second agent, wherein the second agent is glatiramer acetate, a pain reliever, a steroid, a muscle relaxant, prednisone, dexamethasone, an immunosuppressant, azathioprine, cyclophosphamide, an interferon, natalizumab, riluzole, alphacalcidol, calcitriol, rasagiline, minocycline, mitoxantrone, simvastatin or a combination thereof.  
     
     
         66 - 71 . (canceled)  
     
     
         72 . The method of  claim 52 , wherein the composition is administered once every week.  
     
     
         73 - 77 . (canceled)  
     
     
         78 . The method of  claim 52 , wherein the amount of the composition is 0.1 mg to 70 mg of the polypeptide mixture.  
     
     
         79 - 82 . (canceled)  
     
     
         83 . The method of  claim 52 , wherein the administration is through an intravenous, intraperitoneal, intramuscular, subcutaneous, oral, intranasal, buccal, vaginal, rectal, intraocular, intrathecal, topical or intradermal route.  
     
     
         84 - 103 . (canceled)  
     
     
         104 . The method of  claim 52 , wherein the composition is administered every 5 to 60 days.  
     
     
         105 - 149 . (canceled)