US2022251156A1PendingUtilityA1

Adeno-associated virus vector delivery of b-sarcoglycan and microrna-29 and the treatment of muscular dystrophy

72
Assignee: RES INST NATIONWIDE CHILDRENS HOSPITALPriority: Apr 15, 2016Filed: Jan 20, 2022Published: Aug 11, 2022
Est. expiryApr 15, 2036(~9.7 yrs left)· nominal 20-yr term from priority
Inventors:Louise Rodino-KlapacJerry R. Mendell
C12N 15/86C07K 14/705C12N 2750/14143C12N 2800/22C12N 2750/14145A61K 48/0075C07K 14/47A61P 21/00A61P 25/00C12N 2830/008A61P 25/14A61K 48/0058C12N 15/85C07K 14/4716A61K 48/00C12N 5/0686C12N 5/0693C12N 5/0682C12N 5/0656C12N 5/0688A61K 48/0008C12N 2510/00
72
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Described herein are recombinant AAV vectors comprising a polynucleotide sequence comprising β-sarcoglycan and methods of using the recombinant vectors to reduce or prevent fibrosis in a mammalian subject suffering from a muscular dystrophy. Also described herein are combination therapies comprising administering AAV vector(s) expressing β-sarcoglycan and miR-29c to a mammalian subject suffering from a muscular dystrophy.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A recombinant AAV vector comprising a polynucleotide sequence encoding β-sarcoglycan. 
     
     
         2 . The recombinant AAV vector of  claim 1  wherein the polynucleotide sequence encoding β-sarcoglycan comprises a nucleotide sequence at least 95% identical to SEQ ID NO: 1. 
     
     
         3 . The recombinant AAV vector of  claim 1 , wherein the polynucleotide sequence encoding β-sarcoglycan comprises the nucleotide sequence set forth in SEQ ID NO: 1. 
     
     
         4 . The recombinant AAV vector of any one of  claims 1 - 3 , wherein the vector is of the serotype AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13 or AAV rh.74. 
     
     
         5 . The recombinant AAV vector of any one of  claims 1 - 4 , wherein the polynucleotide sequence is operably linked to a muscle-specific control element. 
     
     
         6 . The recombinant AAV vector of  claim 5 , wherein the muscle-specific control element is human skeletal actin gene element, cardiac actin gene element, myocyte-specific enhancer binding factor mef, muscle creatine kinase (MCK), truncated MCK (tMCK), myosin heavy chain (MHC), MHCK7, C5-12, murine creatine kinase enhancer element, skeletal fast-twitch troponin c gene element, slow-twitch cardiac troponin c gene element, the slow-twitch troponin i gene element, hypozia-inducible nuclear factors, steroid-inducible element or glucocorticoid response element (gre). 
     
     
         7 . The recombinant AAV vector of  claim 6 , wherein the muscle-specific control element is truncated MCK (tMCK). 
     
     
         8 . The recombinant AAV vector of  claim 6 , wherein the muscle-specific control element is MHCK7. 
     
     
         9 . The recombinant AAV vector of any of  claims 1 - 8  comprising the nucleotide sequence set forth in SEQ ID NO: 3 
     
     
         10 . The recombinant AAV vector of any of  claims 1 - 8  comprising the nucleotide sequence set forth in SEQ ID NO: 5. 
     
     
         11 . A composition comprising the recombinant AAV vector of any one of  claims 1 - 10 . 
     
     
         12 . A method of treating muscular dystrophy in a subject comprising administering to the subject a therapeutically effective amount of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11 . 
     
     
         13 . A method of increasing muscular force and/or muscle mass in a mammalian subject suffering from muscular dystrophy comprising administering to the subject a therapeutically effective amount of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11 . 
     
     
         14 . A method of reducing fibrosis in a subject suffering from muscular dystrophy comprising administering to the subject a therapeutically effective amount of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11 . 
     
     
         15 . A method of reducing contraction-induced injury in a subject suffering from muscular dystrophy comprising administering to the subject a therapeutically effective amount of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11 . 
     
     
         16 . A method of treating β-sarcoglycanopathy in a subject comprising administering to the subject a therapeutically effective amount of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11 . 
     
     
         17 . The method of claim any one of  claims 12 - 16 , wherein the subject is suffering from limb-girdle muscular dystrophy. 
     
     
         18 . The method of any one of  claims 12 - 17 , wherein the recombinant AAV vector or the composition is administered by intramuscular injection or intravenous injection. 
     
     
         19 . The method of any one of  claims 12 - 17 , wherein the recombinant AAV vector or the composition is administered systemically. 
     
     
         20 . The method of  claim 19 , where the recombinant AAV vector or the composition is parentally administration by injection, infusion or implantation. 
     
     
         21 . The method of any one of  claims 12 - 20 , further comprising administering a second recombinant AAV vector comprising a polynucleotide sequence comprising miR29C. 
     
     
         22 . The method of  claim 21 , wherein the second recombinant vector comprises the nucleotide sequence set forth in SEQ ID NO: 9 or the nucleotide sequence set forth in SEQ ID NO: 8. 
     
     
         23 . The method of  claim 21  or  22  wherein the second recombinant AAV vector is administered by intramuscular injection or intravenous injection. 
     
     
         24 . A composition comprising the recombinant AAV vector of any one of  claims 1 - 10  for reducing fibrosis in a mammalian subject in need thereof. 
     
     
         25 . The composition of  claim 24 , wherein the subject is suffering from muscular dystrophy. 
     
     
         26 . A composition comprising the recombinant AAV vector of any one of  claims 1 - 10  for treating a β-sarcoglycanopathy in a mammalian subject in need thereof. 
     
     
         27 . The composition of  claim 26 , wherein the subject is suffering from muscular dystrophy. 
     
     
         28 . A composition comprising the recombinant AAV vector of any one of  claims 1 - 10  for increasing muscular force in a mammalian subject suffering from muscular dystrophy. 
     
     
         29 . A composition comprising the recombinant AAV vector of any one of  claims 1 - 10  for treatment of muscular dystrophy. 
     
     
         30 . The composition of any one of  claims 24 - 29 , wherein the muscular dystrophy is limb-girdle muscular dystrophy. 
     
     
         31 . The composition of any one of  claims 24 - 30  further comprising a second recombinant AAV vector comprising the miR-29 nucleotide sequence. 
     
     
         32 . The composition of  claim 31  wherein the second rAAV comprises wherein the second recombinant vector comprises the nucleotide sequence set forth in SEQ ID NO: 9 or the nucleotide sequence set forth in SEQ ID NO: 8. 
     
     
         33 . The composition of any one of  claims 24 - 32  that is formulated for intramuscular injection or intravenous injection. 
     
     
         34 . The composition of any one of  claims 24 - 34  that is formulation for systemic administration. 
     
     
         35 . The composition of  claim 34 , wherein the systemic administration is parenteral administration by injection, infusion or implantation. 
     
     
         36 . Use of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11  in the preparation of a medicament for reducing fibrosis in a mammalian subject in need thereof. 
     
     
         37 . Use of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11  in the preparation of a medicament for increasing muscular force in a mammalian subject in need thereof. 
     
     
         38 . The use of  claim 36  or  claim 37 , wherein the subject is suffering from muscular dystrophy. 
     
     
         39 . Use of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11  in the preparation of a medicament for treating muscular dystrophy in a mammalian subject. 
     
     
         40 . The use of  claim 38  or  39 , wherein the muscular dystrophy is limb-girdle muscular dystrophy. 
     
     
         41 . The use of any one of  claims 36 - 40 , wherein the medicament further comprises a second recombinant AAV vector comprising the miR-29 nucleotide sequence. 
     
     
         42 . Use of the recombinant AAV vector of any one of  claims 1 - 10  or the composition of  claim 11  in combination with a second recombinant AAV vector comprising a polynucleotide sequence comprising miR29C in the preparation of a medicament for reducing fibrosis in a mammalian subject in need thereof. 
     
     
         43 . The use of  claim 41  or  42 , wherein the second recombinant vector comprises the nucleotide sequence set forth in SEQ ID NO: 9 or the nucleotide sequence set forth in SEQ ID NO: 8. 
     
     
         44 . Use of the recombinant AAV vector of any one of  claims 1 - 10  of the composition of  claim 11  in combination with a second recombinant AAV vector comprising a polynucleotide sequence comprising a miR-29c in the preparation of a medicament for increasing muscular force in a mammalian subject in need thereof. 
     
     
         45 . The use of  claim 44 , wherein the second recombinant vector comprises the nucleotide sequence set forth in SEQ ID NO: 9 or the nucleotide sequence set forth in SEQ ID NO: 8. 
     
     
         46 . The use of any one of  claim 39 - 45 , wherein the subject is suffering from muscular dystrophy. 
     
     
         47 . Use of the recombinant AAV vector of any one of  claims 1 - 10  of the composition of  claim 11  in combination with a second recombinant AAV vector comprising a polynucleotide sequence comprising a miR-29c in the preparation of a medicament for treating muscular dystrophy in a mammalian subject. 
     
     
         48 . The use of  claim 47 , wherein the second recombinant vector comprises the nucleotide sequence set forth in SEQ ID NO: 9 or the nucleotide sequence set forth in SEQ ID NO: 8. 
     
     
         49 . The use of  claim 47  or  48 , wherein the muscular dystrophy is limb-girdle muscular dystrophy.

Join the waitlist — get patent alerts

Track US2022251156A1 — get alerts on status changes and closely related new filings.

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