Oligonucleotides for treating inflammation and neoplastic cell proliferation

Abstract

There is provided oligonucleotides directed against the CCR3 receptor and the common beta sub-unit of IL-3, IL-5 and GMCSF receptors. The oligonucleotides are useful to inhibit general inflammation, including inflammation associated with asthma, COPD, allergy, Cystic fibrosis (CF), hypereosinophilia and neoplastic cell proliferation such as cancer.

1 . An oligonucleotide directed against a nucleic acid sequence coding for a protein selected from the group consisting of a CCR3 chemokine receptor and a common beta sub-unit of IL-3, IL-5 and GM-CSF receptors, wherein the oligonucleotide is one of (i) having a base sequence corresponding to any one of SEQ ID NOs. 1-698 and (ii) a modified oligonucleotide of any one of SEQ ID NOs. 1-698. 
     
     
         2 . The oligonucleotide of  claim 1 , wherein the oligonucleotide has the base sequence corresponding to any one of SEQ ID NOs. 1-698. 
     
     
         3 . The oligonucleotide of  claim 1 , wherein at least one adenosine nucleotide of the oligonucleotide is substituted with 2-amino-2′-deoxyadenosine (DAP) or an analog thereof. 
     
     
         4 . The oligonucleotide of  claim 1 , wherein at least one adenosine nucleotide of the oligonucleotide is substituted with 2-amino-2′ deoxyadenosine (DAP) or an analog thereof. 
     
     
         5 . The oligonucleotide of  claim 4 , wherein the arabinose modified nucleotide has a 2′ substituent selected from the group consisting of fluorine, hydroxyl, amino, azido, alkyl, alkoxy, and alkoxyalkyl groups. 
     
     
         6 .- 7 . (canceled) 
     
     
         8 . The oligonucleotide of  claim 4 , wherein the at least one arabinose modified nucleotide is 2′-deoxy-2′-fluoroarabinonucleotide (FANA). 
     
     
         9 . The oligonucleotide of  claim 8 , wherein the at least one arabinose modified nucleotide is at the 5′ end of the oligonucleotide. 
     
     
         10 . The oligonucleotide of  claim 8 , wherein the at least one arabinose modified nucleotide is at the 3′ end of the oligonucleotide. 
     
     
         11 . The oligonucleotide of  claim 8 , having at least two arabinose modified nucleotides at both the 5′ end and 3′ end of the oligonucleotide. 
     
     
         12 . The oligonucleotide of  claim 11 , having between 1-7 arabinose modified nucleotides independently at the 5′ end and 3′ end of the oligonucleotide. 
     
     
         13 . The oligonucleotide of  claim 11 , having between 1-6 arabinose modified nucleotides independently at the 5′ end and 3′ end of the oligonucleotide. 
     
     
         14 . The oligonucleotide of  claim 11 , having between 1-5 arabinose modified nucleotides independently at the 5′ end and 3′ end of the oligonucleotide. 
     
     
         15 . The oligonucleotide of  claim 11 , having between 1-4 arabinose modified nucleotides independently at the 5′ end and 3′ end of the oligonucleotide. 
     
     
         16 . The oligonucleotide of  claim 11 , having between 1-3 arabinose modified nucleotides independently at the 5′ end and 3′ end of the oligonucleotide. 
     
     
         17 . The oligonucleotide of  claim 1 , containing at least one internucleotide linkage selected from the group consisting of phosphodiester, phosphotriester, phosphorothioate, methylphosphonate, boranophosphate and any combination thereof. 
     
     
         18 . The oligonucleotide of  claim 1 , wherein the oligonucleotide is one of SEQ ID NOs. 1-698. 
     
     
         19 . The oligonucleotide of  claim 18 , wherein the oligonucleotide is one of SEQ ID NOs. 13 and 683. 
     
     
         20 . A pharmaceutical composition comprising at least one of the oligonucleotide of  claim 1  and pharmaceutically acceptable carrier. 
     
     
         21 .- 23 . (canceled) 
     
     
         24 . A method for treating and/or preventing at least one of asthma, COPD, allergy, CF, hypereosinophilia, general inflammation and cancer in a patient comprising administering to said patient the pharmaceutical composition of  claim 20 . 
     
     
         25 .- 72 . (canceled)