US2011313144A1PendingUtilityA1

iRNA Agents Targeting CCR5 Expressing Cells And Uses Thereof

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Assignee: MANOHARAN MUTHIAHPriority: Nov 21, 2006Filed: Aug 23, 2011Published: Dec 22, 2011
Est. expiryNov 21, 2026(~0.4 yrs left)· nominal 20-yr term from priority
C07D 211/96C07D 401/12C07D 405/12C07D 211/24C07D 471/10C07D 309/14C07D 401/14C07H 21/00C07D 407/12C07D 409/12C07D 211/58
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Claims

Abstract

The invention relates to iRNA agents that preferably include a modification that targets CC chemokine receptor 5 (CCR5). The invention also relates to methods of making and using such modified iRNA agents.

Claims

exact text as granted — not AI-modified
1 . A compound having structure: 
       
         
           
           
               
               
           
         
         wherein, 
         A is H, a hydroxyl protecting group, a phosphate group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, a nucleotide, or an oligonucleotide; 
         B is H, a hydroxyl protecting group, a phosphate group, an activated phosphate group, an activated phosphate group, a phosphoramidite, a solid support, a nucleotide, or an oligonucleotide; 
         Z is a CCR5-binding ligand; 
         Q is —(CH 2 ) n NH—, —C(O)(CH 2 ) n NH—, —(CH 2 ) n ONH—, —C(O)(CH 2 ) n ONH—, —C(O)—(CH 2 ) n —, —(CH 2 ) n NHNH 2 —, —C(O)(CH 2 ) n NHNH 2 —, —C(O)—O—, —(CH 2 ) n —C(O)—, —C(O)—NH—, —C(O)—, —C(O)—(CH 2 ) n —C(O)—, —C(O)—(CH 2 ) n —C(O)O—, —C(O)—(CH 2 ) n —NH—C(O)—, —(CH 2 ) n —C(O)O—, —C(O)(CH 2 ) n NHC(O)(CH 2 ) m —, —C(O)(CH 2 ) n NHC(O)(CH 2 ) m NH—, —(CH 2 ) n —NH—C(O)—, or —(CH 2 ) n —, 
         n is 1-20; and 
         m is 1-6. 
       
     
     
         2 . The compound of  claim 1 , wherein A is an activated phosphite group, a phosphoramidite, or a solid support. 
     
     
         3 . The compound of  claim 1 , wherein B is a hydroxyl protecting group. 
     
     
         4 . The compound of  claim 1 , wherein Q is —C(O)(CH 2 ) n NHC(O)(CH 2 ) m NH—, —C(O)(CH 2 ) n NHC(O)(CH 2 ) m —, —C(O)(CH 2 ) n NH—, or. 
     
     
         5 . The compound of  claim 4 , wherein Q is —C(O)(CH 2 ) n NHC(O)(CH 2 ) m NH—. 
     
     
         6 . The compound of  claim 1 , wherein the CCR5-binding ligand is a CCR5 antagonist. 
     
     
         7 . The compound of  claim 6 , wherein the CCR5 antagonist is an antagonist listed in column 1 of Table 1. 
     
     
         8 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         19 . The compound of  claim 7 , wherein the CCR5 antagonist has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         20 . The compound of  claim 1 , wherein A is an oligonucleotide. 
     
     
         21 . The compound of  claim 20 , wherein the oligonucleotide is double stranded. 
     
     
         22 . The compound of  claim 1 , wherein B is an oligonucleotide. 
     
     
         23 . The compound of  claim 22 , wherein the oligonucleotide is double stranded. 
     
     
         24 . The compound of  claim 1 , wherein A is an oligonucleotide and B is an oligonucleotide. 
     
     
         25 . The compound of  claim 24 , wherein oligonucleotide is double stranded.

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