US2023381216A1PendingUtilityA1

Exon skipping oligomer conjugates for muscular dystrophy

Assignee: SAREPTA THERAPEUTICS INCPriority: Dec 19, 2016Filed: Mar 9, 2023Published: Nov 30, 2023
Est. expiryDec 19, 2036(~10.4 yrs left)· nominal 20-yr term from priority
A61K 31/712A61K 31/7125A61P 21/00C12N 15/113A61K 47/645C12N 2310/111
81
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 51 skipping are described.

Claims

exact text as granted — not AI-modified
1 . An antisense oligomer conjugate of Formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 each Nu is a nucleobase which taken together form a targeting sequence; and 
 T is a moiety selected from: 
 
       
         
           
           
               
               
           
         
         R 1  is C 1 -C 6  alkyl; 
         wherein the targeting sequence is complementary to an exon 51 annealing site in the dystrophin pre-mRNA designated as H51A(+66+95). 
       
     
     
         2 . The antisense oligomer conjugate of  claim 1 , wherein each Nu is independently selected from cytosine (C), guanine (G), thymine (T), adenine (A), 5-methylcytosine (5 mC), uracil (U), and hypoxanthine (I). 
     
     
         3 . The antisense oligomer conjugate of  claim 1 , wherein the targeting sequence is SEQ ID NO: 1 (5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′), wherein each thymine (T) is optionally uracil (U). 
     
     
         4 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and the targeting sequence is SEQ ID NO: 1
 (5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′), wherein each thymine (T) is optionally uracil (U). 
 
     
     
         5 . (canceled) 
     
     
         6 . An antisense oligomer conjugate of Formula (II): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein each Nu from 1 to 30 and 5′ to 3′ is (SEQ ID NO. 1): 
       
         
           
                 
                 
               
                     
                 
                   Position No. 5′ to 3′ 
                   Nu 
                 
                     
                 
                     
                 
                 
                 
               
                   1 
                   C 
                 
                   2 
                   X 
                 
                   3 
                   C 
                 
                   4 
                   C 
                 
                   5 
                   A 
                 
                   6 
                   A 
                 
                   7 
                   C 
                 
                   8 
                   A 
                 
                   9 
                   X 
                 
                   10 
                   C 
                 
                   11 
                   A 
                 
                   12 
                   A 
                 
                   13 
                   G 
                 
                   14 
                   G 
                 
                   15 
                   A 
                 
                   16 
                   A 
                 
                   17 
                   G 
                 
                   18 
                   A 
                 
                   19 
                   X 
                 
                   20 
                   G 
                 
                   21 
                   G 
                 
                   22 
                   C 
                 
                   23 
                   A 
                 
                   24 
                   X 
                 
                   25 
                   X 
                 
                   26 
                   X 
                 
                   27 
                   C 
                 
                   28 
                   X 
                 
                   29 
                   A 
                 
                   30 
                   G 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and wherein A is 
       
         
           
           
               
               
           
         
       
       C is 
       
         
           
           
               
               
           
         
       
       G is 
       
         
           
           
               
               
           
         
       
       and each X is 
       
         
           
           
               
               
           
         
       
     
     
         7 . (canceled) 
     
     
         8 . The antisense oligomer conjugate of  claim 6 , wherein the antisense oligomer is of Formula (IIA): 
       
         
           
           
               
               
           
         
       
       wherein each Nu from 1 to 30 and 5′ to 3′ is (SEQ ID NO. 1): 
       
         
           
                 
                 
               
                     
                 
                   Position No. 5′ to 3′ 
                   Nu 
                 
                     
                 
                     
                 
                 
                 
               
                   1 
                   C 
                 
                   2 
                   X 
                 
                   3 
                   C 
                 
                   4 
                   C 
                 
                   5 
                   A 
                 
                   6 
                   A 
                 
                   7 
                   C 
                 
                   8 
                   A 
                 
                   9 
                   X 
                 
                   10 
                   C 
                 
                   11 
                   A 
                 
                   12 
                   A 
                 
                   13 
                   G 
                 
                   14 
                   G 
                 
                   15 
                   A 
                 
                   16 
                   A 
                 
                   17 
                   G 
                 
                   18 
                   A 
                 
                   19 
                   X 
                 
                   20 
                   G 
                 
                   21 
                   G 
                 
                   22 
                   C 
                 
                   23 
                   A 
                 
                   24 
                   X 
                 
                   25 
                   X 
                 
                   26 
                   X 
                 
                   27 
                   C 
                 
                   28 
                   X 
                 
                   29 
                   A 
                 
                   30 
                   G 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and wherein A is 
       
         
           
           
               
               
           
         
       
       C is 
       
         
           
           
               
               
           
         
       
       G is 
       
         
           
           
               
               
           
         
       
       and X is 
       
         
           
           
               
               
           
         
       
     
     
         9 - 26 . (canceled) 
     
     
         27 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and
 R 1  is C 1 -C 6  alkyl; and 
 the targeting sequence is SEQ ID NO: 1 
 
       (5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′), wherein each thymine (T) is uracil (U). 
     
     
         28 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and
 R 1  is C 1 -C 6  alkyl; and 
 the targeting sequence is SEQ ID NO: 1 
 
       
         
           
                 
                 
               
                     
                   (5'-CTCCAACATCAAGGAAGATGGCATTTCTAG-3'). 
                 
             
                
               
            
           
         
       
     
     
         29 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and
 R 1  is C 1 -C 6  alkyl; and 
 the targeting sequence is SEQ ID NO: 1 
 
       (5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′), wherein each thymine (T) is uracil (U) and the antisense oligomer conjugate is a pharmaceutically acceptable 6HCl salt. 
     
     
         30 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and
 R 1  is C 1 -C 6  alkyl; and the targeting sequence is SEQ ID NO: 1 
 
       (5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′) and the antisense oligomer conjugate is a pharmaceutically acceptable 6 HCl salt. 
     
     
         31 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and
 the targeting sequence is SEQ ID NO: 1 
 
       (5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′), wherein each thymine (T) is uracil (U). 
     
     
         32 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and
 the targeting sequence is SEQ ID NO: 1 
 
       
         
           
                 
                 
               
                     
                   (5'-CTCCAACATCAAGGAAGATGGCATTTCTAG-3'). 
                 
             
                
               
            
           
         
       
     
     
         33 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and
 the targeting sequence is SEQ ID NO: 1 
 
       (5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′), wherein each thymine (T) is uracil (U) and the antisense oligomer conjugate is a pharmaceutically acceptable 6HCl salt. 
     
     
         34 . The antisense oligomer conjugate of  claim 1 , wherein T is 
       
         
           
           
               
               
           
         
       
       and
 the targeting sequence is SEQ ID NO: 1 
 
       (5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′) and the antisense oligomer conjugate is a pharmaceutically acceptable 6HCl salt. 
     
     
         35 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         36 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 27 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         37 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 28 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         38 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 29  and a pharmaceutically acceptable carrier. 
     
     
         39 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 30  and a pharmaceutically acceptable carrier. 
     
     
         40 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 31 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         41 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 32 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         42 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 33  and a pharmaceutically acceptable carrier. 
     
     
         43 . A pharmaceutical composition, comprising an antisense oligomer conjugate of  claim 34  and a pharmaceutically acceptable carrier.

Join the waitlist — get patent alerts

Track US2023381216A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.