Antisense Formulation

Abstract

A room temperature stable and minimal aggregate liquid formulation comprises an oligonucleotide comprising Seq ID No. 1: or comprising a variant oligonucleotide in which no more than 3 non-sequential bases are different from Seq. ID NO. 1 and an aqueous carrier comprising a aggregation-preventing compound selected from the group consisting of mono and disaccharides and/or sugar alcohols.

1 - 12 . (canceled) 
     
     
         13 . A liquid formulation comprising
 (a) an oligonucleotide comprising Seq ID No. 1: or comprising a variant oligonucleotide in which no more than 3 non-sequential bases are different from Seq. ID NO. 1 and   (b) an aqueous carrier comprising an aggregation-preventing compound selected from the group consisting of mono and disaccharides and/or sugar alcohols, wherein the amount of the aggregation-preventing compound is sufficient to solubilize the oligonucleotide and maintain it in solution without aggregation for a period in excess of 6 hours at room temperature.   
     
     
         14 . The formulation of  claim 13 , wherein the carrier further comprises a phosphate buffer. 
     
     
         15 . The formulation of  claim 13 , wherein the carrier further comprises Tris buffer. 
     
     
         16 . The formulation of  claim 13  wherein the aggregation preventing compound is mannitol. 
     
     
         17 . The formulation of  claim 16 , wherein the mannitol is present in the aqueous carrier in an amount of 5% by weight. 
     
     
         18 . The formulation of  claim 13 , wherein the aggregation-preventing compound is dextrose. 
     
     
         19 . The formulation of  claim 18 , wherein the dextrose is present in the aqueous carrier in an amount of 5% by weight. 
     
     
         20 . The formulation of  claim 13  wherein said antisense oligonucleotide consists of Seq. ID No. 1, or a variant oligonucleotide in which no more than 3 non-sequential bases are different from Seq. ID No. 1. 
     
     
         21 . The formulation of  claim 20 , wherein the oligonucleotide consists of Seq ID No. 1 with modifications as follows: 
       
         
           
                 
                 
               
                     
                   5′- GGGA   Me CG Me CGG Me CG Me CT Me CG   U Me CA Me U -3′ 
                 
             
                
               
            
           
         
         wherein the underlined nucleosides (G, A, MeC, and MeU) denote 2′-O-methoxyethyl (2′ MOE) modifications of the ribonucleosides guanosine, adenosine, 5-methylcytidine and 5-methyluridine; wherein the G, MeC, and T represent the deoxyribonucleosides 2′-deoxyguanosine, 2′-deoxy-5-methylcytidine, and 2′-deoxythymidine; and wherein the internucleotide linkages are phosphorothioate diesters (sodium salts). 
       
     
     
         22 . The formulation of  claim 21 , wherein the aggregation preventing compound is mannitol. 
     
     
         23 . The formulation of  claim 22 , wherein the mannitol is present in the aqueous carrier in an amount of 5% by weight. 
     
     
         24 . The formulation of  claim 21 , wherein the aggregation-preventing compound is dextrose. 
     
     
         25 . The formulation of  claim 24 , wherein the dextrose is present in the aqueous carrier in an amount of 5% by weight. 
     
     
         26 . The formulation of  claim 20 , wherein the aggregation preventing compound is mannitol. 
     
     
         27 . The formulation of  claim 26 , wherein the mannitol is present in the aqueous carrier in an amount of 5% by weight. 
     
     
         28 . The formulation of  claim 20 , wherein the aggregation-preventing compound is dextrose. 
     
     
         29 . The formulation of  claim 28 , wherein the dextrose is present in the aqueous carrier in an amount of 5% by weight.