Semi-soft c-class immunostimulatory oligonucleotides

Abstract

The invention relates to specific C-Class semi-soft CpG immunostimulatory oligonucleotides that are useful for stimulating an immune response. In particular the oligonucleotides are useful for treating allergy, such as allergic rhinitis and asthma, cancer and infectious disease, such as hepatitis B and hepatitis C.

1 .- 24 . (canceled) 
     
     
         25 . An oligonucleotide comprising:
 5′ TC_GTC_GTN 1 TC_GGCGCN 1 GCCG 3′ (SEQ ID NO: 27), wherein the oligonucleotide includes at least 2 stabilized internucleotide linkages and_represents phosphodiester or phosphodiester-like internucleotide linkage and wherein N 1  is 0-3 nucleotides in length, with N referring to any nucleotide.   
     
     
         26 . The oligonucleotide of  claim 25 , wherein N 1  is 3 nucleotides in length. 
     
     
         27 . The oligonucleotide of  claim 25 , wherein N 1  is 0 nucleotides in length. 
     
     
         28 . An oligonucleotide comprising:
 5′ TTC_GTC_GTTTX 1— GTC_GTT 3′ (SEQ ID NO: 25), wherein the oligonucleotide includes at least 2 stabilized internucleotide linkages and_represents phosphodiester or phosphodiester-like internucleotide linkage and wherein X 1  is a pyrimidine.   
     
     
         29 . The oligonucleotide of  claim 28 , wherein X 1  is T. 
     
     
         30 . The oligonucleotide of  claim 29 , wherein the oligonucleotide comprises 5′ T*T*C_G*T*C_G*T*T*T*T_G*T*C_G*T*T 3′ (SEQ ID NO: 5), wherein * represents a stabilized internucleotide linkage. 
     
     
         31 . The oligonucleotide of  claim 29 , wherein the oligonucleotide is 5′ T*T*C_G*T*C_G*T*T*T*T_G*T*C_G*T*T 3′ (SEQ ID NO: 5), wherein * represents a stabilized internucleotide linkage, wherein 5′ refers to the free 5′ end of the oligonucleotide and 3′ refers to the free 3′ end of the oligonucleotide. 
     
     
         32 . The oligonucleotide of  claim 28 , wherein X 1  is C 
     
     
         33 . The oligonucleotide of  claim 32 , wherein the oligonucleotide comprises 5′ T*T*T*C_G*T*C_G*T*T*T*C _G*T*C_G*T*T 3′ (SEQ ID NO: 6), wherein * represen stabilized internucleotide linkage. 
     
     
         34 . The oligonucleotide of  claim 32 , wherein the oligonucleotide is 5′ T*T*T*C_G*T*C_G*T*T*T*C_G*T*C_G*T*T 3′ (SEQ ID NO: 6), wherein * represents a stabilized internucleotide linkage, wherein 5′ refers to the free 5′ end of the oligonucleotide and 3′ refers to the free 3′ end of the oligonucleotide. 
     
     
         35 . An oligonucleotide comprising: T*C_G*T*C_G*T*C, wherein * represents a stabilized internucleotide linkage and _ represents phosphodiester or phosphodiester-like internucleotide linkage. 
     
     
         36 . The oligonucleotide of  claim 35 , wherein the oligonucleotide is 5′ T*C_G*T*C_G*T*C_G*T*T*C_G*G*C*G*C 3′ (SEQ ID NO.: 22), wherein 5′ refers to the free 5′ end of the oligonucleotide and 3′ refers to the free 3′ end of the oligonucleotide. 
     
     
         37 . An oligonucleotide comprising: T*C_G*T*T*C_G*G, wherein * represents a stabilized internucleotide linkage and _ represents phosphodiester or phosphodiester-like internucleotide linkage. 
     
     
         38 . A pharmaceutical composition comprising an oligonucleotide of  claim 25  and a pharmaceutically acceptable carrier. 
     
     
         39 . The pharmaceutical composition of  claim 38 , further comprising a nebulizer. 
     
     
         40 . The pharmaceutical composition of  claim 38 , further comprising an inhaler. 
     
     
         41 . The pharmaceutical composition of  claim 40  wherein the inhaler is a metered dose inhaler. 
     
     
         42 . The pharmaceutical composition of  claim 40 , wherein the inhaler is a powder inhaler. 
     
     
         43 . The pharmaceutical composition of  claim 38 , further comprising a chemotherapeutic agent. 
     
     
         44 . The pharmaceutical composition of  claim 38 , further comprising an anti-viral agent. 
     
     
         45 . The pharmaceutical composition of  claim 38 , wherein the pharmaceutically acceptable carrier is formulated for subcutaneous administration. 
     
     
         46 . The pharmaceutical composition of  claim 38 , wherein the pharmaceutically acceptable carrier is formulated for oral administration. 
     
     
         47 . The pharmaceutical composition of  claim 38 , wherein the pharmaceutically acceptable carrier is formulated for intranasal administration. 
     
     
         48 . A method for modulating an immune response, comprising administering to a subject an oligonucleotide of  claim 25 , in an effective amount to modulate an immune response.