IP Library › Granted Patent US 10,196,636
Granted Patent B2
US 10,196,636 · App. 14/853,517 · Granted Feb 5, 2019

Recombinant virus products and methods for inhibition of expression of myotilin

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 10,196,636
App. No.
14/853,517
Granted
Feb 5, 2019
Kind
B2
Abstract

The present invention relates to RNA interference-based methods for inhibiting the expression of the myotilin gene. Recombinant adeno-associated viruses of the invention deliver DNAs encoding microRNAs that knock down the expression of myotilin. The methods have application in the treatment of muscular dystrophies such as Limb Girdle Muscular Dystrophy Type 1A.

Claims (20)

1. A recombinant adeno-associated virus comprising a MYOT miRNA-encoding DNA set out in SEQ ID NO: 2, 11286, 11287 or 11288, wherein the recombinant adeno-associated virus lacks rep and cap genes.

2. A composition comprising the recombinant adeno-associated virus of claim 1 and a pharmaceutically acceptable carrier.

3. The recombinant adeno-associated virus of claim 1 wherein expression of the miRNA-encoding DNA is under the control of a CMV promoter, a muscle creatine kinase (MCK) promoter, an alpha-myosin heavy chain enhancer-/MCK enhancer-promoter (MHCK7) or a desmin promoter.

4. The recombinant adeno-associated virus of claim 1 that is a recombinant AAV-6.

5. The recombinant adeno-associated virus of claim 4 that is a self-complementary AAV-6.

6. A method of inhibiting expression of the MYOT gene in a cell comprising contacting the cell with a recombinant adeno-associated virus of claim 1 , wherein the recombinant adeno-associated virus lacks rep and cap genes.

7. A method of delivering a MYOT miRNA-encoding DNA to an animal in need thereof, comprising administering to the animal a recombinant adeno-associated virus comprising the MYOT miRNA-encoding DNA set out in SEQ ID NO: 2, 11286, 11287 or 11288, wherein the recombinant adeno-associated virus lacks rep and cap genes.

8. A method of treating limb girdle muscular dystrophy type 1A comprising administering a recombinant adeno-associated virus comprising the MYOT miRNA-encoding DNA set out in SEQ ID NO: 2, 11286, 11287 or 11288, wherein the recombinant adeno-associated virus lacks rep and cap genes.

9. The method of any one of claims 6 - 8 wherein expression of the miRNA-encoding DNA is under the control of a CMV promoter, a muscle creatine kinase (MCK) promoter, an alpha-myosin heavy chain enhancer-/MCK enhancer-promoter (MHCK7) or a desmin promoter.

10. The method of any one of claims 6 - 8 wherein the recombinant adeno-associated virus is a self-complementary AAV-6.

11. A recombinant adeno-associated virus encoding an MYOT miRNA comprising an antisense guide strand set out SEQ ID NO: 7592, 7736, 7767, 7875, 8843 or 8874, wherein the recombinant adeno-associated virus lacks rep and cap genes.

12. A composition comprising the recombinant adeno-associated virus of claim 11 and a pharmaceutically acceptable carrier.

13. The recombinant adeno-associated virus of claim 11 wherein expression of the miRNA-encoding DNA is under the control of a CMV promoter, a muscle creatine kinase (MCK) promoter, an alpha-myosin heavy chain enhancer-/MCK enhancer-promoter (MHCK7) or a desmin promoter.

14. The recombinant adeno-associated virus of claim 11 that is a recombinant AAV-6.

15. The recombinant adeno-associated virus of claim 14 that is a self-complementary AAV-6.

16. A method of inhibiting expression of the MYOT gene in a cell comprising contacting the cell with a recombinant adeno-associated virus of claim 11 , wherein the recombinant adeno-associated virus lacks rep and cap genes.

17. A method of delivering a MYOT miRNA-encoding DNA to an animal in need thereof, comprising administering to the animal a recombinant adeno-associated virus encoding an MYOT miRNA comprising an antisense guide strand set out in one of SEQ ID NO: 7592, 7736, 7767, 7875, 8843 or 8874, wherein the recombinant adeno-associated virus lacks rep and cap genes.

18. A method of treating limb girdle muscular dystrophy type 1A comprising administering a recombinant adeno-associated virus encoding an MYOT miRNA comprising an antisense guide strand set out in one of SEQ ID NO: 7592, 7736, 7767, 7875, 8843 or 8874, wherein the recombinant adeno-associated virus lacks rep and cap genes.

19. The method of any one of claims 16 - 18 wherein the recombinant adeno-associated virus is a self-complementary AAV-6.

20. The method of claim 9 wherein the recombinant adeno-associated virus is a self-complementary AAV-6.

Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT SERIAL NUMBER PCT/US14/47999 FILED 07/24/2014 SHOULD BE PCT/US12/47999 FILED 07/24/2012 PREVIOUSLY RECORDED ON REEL 063643 FRAME 0786. ASSIGNOR(S) HEREBY CONFIRMS THE THE CORRECT SERIAL NUMBER AND ASSIGNMENT DOC ID 507906702. Recorded May 24, 2023
From: NATIONWIDE CHILDREN'S HOSPITAL, INC.
To: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Reel/Frame 063743/0208 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2023
From: NATIONWIDE CHILDREN'S HOSPITAL, INC.
To: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Reel/Frame 063643/0786 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 18, 2018
From: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
To: NATIONWIDE CHILDREN'S HOSPITAL, INC.
Reel/Frame 045576/0669 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME (RECEIVING PARTY) PREVIOUSLY RECORDED AT REEL: 037571 FRAME: 0180. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Feb 16, 2016
From: HARPER, SCOTT QUENTON; LIU, JIAN
To: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Reel/Frame 037825/0636 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 25, 2016
From: HARPER, SCOTT QUENTON; LIU, JIAN
To: NATIONWIDE CHILDREN'S HOSPITAL
Reel/Frame 037571/0180 →