US2008026011A1PendingUtilityA1

Immunostimulatory nucleic acid molecules

Assignee: UNIV IOWA RES FOUNDPriority: Jul 15, 1994Filed: Jun 5, 2007Published: Jan 31, 2008
Est. expiryJul 15, 2014(expired)· nominal 20-yr term from priority
A61P 31/04A61P 35/00A61P 37/06A61P 37/02A61P 31/10A61P 33/00A61P 31/00A61P 37/04A61P 31/12A61P 7/00A61P 37/08A61P 43/00A61P 11/06A61P 1/04A61P 1/16A61P 17/06A61P 17/00A61P 1/00A61P 19/02A61P 1/02C12N 15/117C12N 2310/17C12Q 1/68A61K 31/711C07H 21/00A61K 31/00A61K 31/4706A61K 39/39A61K 2039/55561A61K 31/7048C12N 2310/315A61K 31/7125A61K 39/00Y02A50/30
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Claims

Abstract

Nucleic acids containing unmethylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response and to redirect a Th2 response to a Th1 response in a subject are disclosed. Methods for treating atopic diseases, including atopic dermatitis, are disclosed.

Claims

exact text as granted — not AI-modified
1 . A method for treating atopic dermatitis, comprising 
 administering to a subject in need of treatment of atopic dermatitis an immunostimulatory oligonucleotide 8 to 100 nucleotides long, comprising:      5′ X 1 CGX 2  3′   wherein the C is unmethylated and wherein X 1  and X 2  are nucleotides, wherein X 1  is selected from the group consisting of A, G, and T, and wherein X 2  is selected from the group consisting of C and T, in an effective amount to treat the atopic dermatitis.    
     
     
         2 . The method of  claim 1 , further comprising administering to the subject an allergen in conjunction with the administering of the immunostimulatory oligonucleotide.  
     
     
         3 . The method of  claim 1 , wherein the immunostimulatory oligonucleotide is a synthetic nucleic acid molecule.  
     
     
         4 . The method of  claim 1 , wherein the immunostimulatory oligonucleotide is 8 to 40 nucleotides in length.  
     
     
         5 . The method of  claim 1 , wherein the immunostimulatory oligonucleotide is a stabilized nucleic acid molecule.  
     
     
         6 . The method of  claim 5 , wherein the immunostimulatory oligonucleotide includes a phosphate backbone modification which is a phosphorothioate or phosphorodithioate modification.  
     
     
         7 . The method of  claim 1 , wherein the immunostimulatory oligonucleotide is administered to the subject orally.  
     
     
         8 . The method of  claim 1 , wherein the immunostimulatory oligonucleotide is administered to the subject transdermally.  
     
     
         9 . The method of  claim 1 , wherein the immunostimulatory oligonucleotide is administered to the subject by injection.  
     
     
         10 . The method of  claim 1 , wherein the immunostimulatory oligonucleotide comprises a sequence GTCGTT.  
     
     
         11 . The method of  claim 1 , wherein the immunostimulatory oligonucleotide comprises a sequence GTCGTT and wherein the subject is a human.  
     
     
         12 . A method for treating atopic dermatitis, comprising 
 administering to a subject in need of treatment of atopic dermatitis an immunostimulatory oligonucleotide 8 to 100 nucleotides long, comprising:      5′ X 1 X 2 CGX 3 X 4  3′   wherein the C is unmethylated and wherein X 1 , X 2 , X 3 , and X 4  are nucleotides, in an effective amount to treat the atopic dermatitis.    
     
     
         13 . The method of  claim 12 , wherein X 1 X 2  is selected from the group consisting of GpT, GpG, GpA and ApA.  
     
     
         14 . The method of  claim 12 , wherein X 3 X 4  is selected from the group consisting of TpT and CpT.  
     
     
         15 . The method of  claim 12 , wherein X 1 X 2  is selected from the group consisting of GpT, GpG, GpA and ApA and wherein X 3 X 4  is selected from the group consisting of TpT and CpT.  
     
     
         16 . The method of  claim 12 , wherein 5′ X 1 X 2 CGX 3 X 4  3′ is not a palindrome.  
     
     
         17 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide comprises a sequence selected from the group consisting of  
       
         
           
                 
                 
               
                     
                 
                   (SEQ ID NO:37) 
                     
                 
                 
                 
                 
               
                     
                   TCCATGTCGGTCCTGATGCT, 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:38) 
                     
                 
                 
                 
                 
               
                     
                   TCCATGCCGGTCCTGATGCT, 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:39) 
                     
                 
                 
                 
                 
               
                     
                   TCCATGGCGGTCCTGATGCT, 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:40) 
                     
                 
                 
                 
                 
               
                     
                   TCCATGACGGTCCTGATGCT, 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:42) 
                     
                 
                 
                 
                 
               
                     
                   TCCATGTCGCTCCTGATGCT, 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:43) 
                     
                 
                 
                 
                 
               
                     
                   TCCATGTCGTTCCTGATGCT, 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:44) 
                     
                 
                 
                 
                 
               
                     
                   TCCATGACGTTCCTGATGCT, 
                     
                 
                     
                   and 
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:45) 
                     
                 
                 
                 
                 
               
                     
                   TCCATAACGTTCCTGATGCT. 
                     
                 
                     
                     
                 
             
                
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
               
            
           
         
       
     
     
         18 . The method of  claim 12 , further comprising administering to the subject an allergen in conjunction with the administering of the immunostimulatory oligonucleotide.  
     
     
         19 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide is a synthetic nucleic acid molecule.  
     
     
         20 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide is 8 to 40 nucleotides in length.  
     
     
         21 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide is a stabilized nucleic acid molecule.  
     
     
         22 . The method of  claim 21 , wherein the immunostimulatory oligonucleotide includes a phosphate backbone modification which is a phosphorothioate or phosphorodithioate modification.  
     
     
         23 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide is administered to the subject orally.  
     
     
         24 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide is administered to the subject transdermally.  
     
     
         25 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide is administered to the subject by injection.  
     
     
         26 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide comprises a sequence GTCGTT.  
     
     
         27 . The method of  claim 12 , wherein the immunostimulatory oligonucleotide comprises a sequence GTCGTT and wherein the subject is a human.

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