US2017369876A1PendingUtilityA1

Exon skipping compositions for treating muscular dystrophy

64
Assignee: SAREPTA THERAPEUTICS INCPriority: Mar 14, 2013Filed: Feb 1, 2017Published: Dec 28, 2017
Est. expiryMar 14, 2033(~6.7 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 21/00A61P 21/04C12N 2310/3233C12N 2310/3513C12N 2310/351A61K 47/60C12N 15/113C12N 2310/33C12N 15/111C12N 2320/33C12N 2310/11C12N 2310/3535A61K 31/713A61K 47/6455C12N 2320/30A61K 31/7088C12N 15/11Y02A50/30
64
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Claims

Abstract

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.

Claims

exact text as granted — not AI-modified
1 . An antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to a target region of exon 44 of the human dystrophin pre-mRNA, wherein the target region is the annealing site H44A(−07+15), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide induces exon 44 skipping;
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         2 . An isolated antisense oligonucleotide of 22 bases comprising the base sequence GAT CTG TCA AAT CGC CTG CAG G (SEQ ID NO: 5), in which thymine bases are optionally uracil bases;
 or a pharmaceutically acceptable salt thereof.   
     
     
         3 - 7 . (canceled) 
     
     
         8 . The antisense oligonucleotide of  claim 1 , wherein the oligonucleotide is chemically linked to a polyethylene glycol molecule. 
     
     
         9 . The antisense oligonucleotide of  claim 2 , wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol molecule. 
     
     
         10 - 15 . (canceled) 
     
     
         16 . An antisense oligonucleotide having the following structure: 
       
         
           
           
               
               
           
         
       
       wherein 
       
         
           
           
               
               
           
         
       
       and wherein ̂=the stereochemistry of the phosphorous center is not defined. 
     
     
         17 - 20 . (canceled) 
     
     
         21 . The antisense oligonucleotide of  claim 1 , wherein the antisense oligonucleotide is conjugated to a triethyleneglycol moiety via a piperazinyl moiety. 
     
     
         22 . The antisense oligonucleotide of  claim 2 , wherein the antisense oligonucleotide is conjugated to a triethyleneglycol moiety via a piperazinyl moiety. 
     
     
         23 . The antisense oligonucleotide of  claim 1 , wherein thymine bases are uracil bases. 
     
     
         24 . The antisense oligonucleotide of  claim 2 , wherein thymine bases are uracil bases. 
     
     
         25 . The antisense oligonucleotide of  claim 8 , wherein thymine bases are uracil bases. 
     
     
         26 . The antisense oligonucleotide of  claim 9 , wherein thymine bases are uracil bases. 
     
     
         27 . The antisense oligonucleotide of  claim 16 , wherein thymine bases are uracil bases. 
     
     
         28 . The antisense oligonucleotide of  claim 21 , wherein thymine bases are uracil bases. 
     
     
         29 . The antisense oligonucleotide of  claim 22 , wherein thymine bases are uracil bases. 
     
     
         30 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         31 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         32 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 8  and a pharmaceutically acceptable carrier. 
     
     
         33 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 9  and a pharmaceutically acceptable carrier. 
     
     
         34 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 16  and a pharmaceutically acceptable carrier. 
     
     
         35 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 21  and a pharmaceutically acceptable carrier. 
     
     
         36 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 22  and a pharmaceutically acceptable carrier. 
     
     
         37 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 23  and a pharmaceutically acceptable carrier. 
     
     
         38 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 24  and a pharmaceutically acceptable carrier. 
     
     
         39 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 25  and a pharmaceutically acceptable carrier. 
     
     
         40 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 26  and a pharmaceutically acceptable carrier. 
     
     
         41 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 27  and a pharmaceutically acceptable carrier. 
     
     
         42 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 28  and a pharmaceutically acceptable carrier. 
     
     
         43 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 29  and a pharmaceutically acceptable carrier. 
     
     
         44 . The pharmaceutical composition of  claim 30  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         45 . The pharmaceutical composition of  claim 31  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         46 . The pharmaceutical composition of  claim 32  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         47 . The pharmaceutical composition of  claim 33  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         48 . The pharmaceutical composition of  claim 34  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         49 . The pharmaceutical composition of  claim 35  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         50 . The pharmaceutical composition of  claim 36  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         51 . The pharmaceutical composition of  claim 37  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         52 . The pharmaceutical composition of  claim 38  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         53 . The pharmaceutical composition of  claim 39  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         54 . The pharmaceutical composition of  claim 40  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         55 . The pharmaceutical composition of  claim 41  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         56 . The pharmaceutical composition of  claim 42  for use in the treatment of Duchenne muscular dystrophy (DMD). 
     
     
         57 . The pharmaceutical composition of  claim 43  for use in the treatment of Duchenne muscular dystrophy (DMD).

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