# US 2021/0162020 A1 · Systemic gene replacement therapy for treatment of x-linked myotubular myopathy (xlmtm)

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- Number: US 2021/0162020 A1
- Document ID: US20210162020A1
- Status: Published application
- Kind: A1
- Application number: 16/935,437
- Filed: 2020-07-22
- Published: 2021-06-03
- Earliest claimed: 2013-03-01
- Assignees: Wake Forest University Health Sciences; Genethon; Children's Medical Center Corporation
- Applicants: Wake Forest University Health Sciences; Genethon; Children's Medical Center Corporation
- Inventors: Martin K. Childers; Alan H. Beggs; Ana Maria Buj Bello
- Web page: https://patentgrep.com/patent/US20210162020A1

## CPC

- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 9/16: acting on ester bonds (3.1)
- C12Y 301/03: Phosphoric monoester hydrolases (3.1.3)
- C12Y 301/03064: Phosphatidylinositol-3-phosphatase (3.1.3.64)
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

The present invention provides compositions and methods for treating a myopathy. In certain embodiments, the invention provides compositions and methods for treating, improving muscle function, and prolonging survival in a subject with X-linked myotubular myopathy (XLMTM). The present invention provides a method comprising systemic administration of a composition that induces the increased expression of myotubularin in the muscle of a subject. The invention provides sustained regional and global increases in muscle function.

## Claims

### Claim at position 1

1-64. (canceled)

### Claim 65

A method of making a Myotubularin 1 recombinant viral vector (rViral-MTM1) for treating an X-linked myotubular myopathy (XLMTM) in a mammal in need thereof, the method comprising:
a. generating a first recombinant baculovirus comprising a viral rep gene and a viral cap gene or any combination thereof;
b. generating a second recombinant baculovirus comprising an insert that comprises an MTM1 cDNA cloned downstream of a muscle specific promoter wherein the insert is flanked by viral inverted terminal repeats (ITRs), and;
c. infecting a cell with the first and second recombinant baculoviruses, wherein when the first and second recombinant baculoviruses are expressed in the cell, rViral-MTM1 vector particles are generated.

### Claim 66 (depends on 65)

The method of claim 65, wherein the cell is an insect cell.

### Claim 67 (depends on 65)

The method of claim 65, wherein the insect cell is Sf9.

### Claim 68 (depends on 65)

The method of claim 65, wherein the viral vector, the viral rep gene, the viral cap gene and the viral ITRs are from a virus selected from the group consisting of a lentivirus, a retrovirus, an adenovirus, and an adeno-associated virus (AAV).

### Claim 69 (depends on 68)

The method of claim 68, wherein the AAV comprises a serotype selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, and AAV9.

### Claim 70 (depends on 65)

The method of claim 65, wherein the muscle specific promoter is a desmin promoter.

### Claim 71 (depends on 65)

The method of claim 65, wherein the mammal is a human.

### Claim 72

A method of making a Myotubularin 1 recombinant viral vector (rViral-MTM1) for treating an X-linked myotubular myopathy (XLMTM) in a mammal in need thereof, the method comprising:
a. generating a first expression plasmid comprising a viral rep gene and a viral cap gene or any combination thereof;
b. generating a second expression plasmid comprising an insert that comprises an MTM1 cDNA cloned downstream of a muscle specific promoter wherein the insert is flanked by viral inverted terminal repeats (ITRs), and;
c. transfecting a cell with the first and second expression plasmids and with a third viral helper plasmid, wherein when the first and second plasmids are expressed in the cell, rViral-MTM1 vector particles are generated.

### Claim 73 (depends on 72)

The method of claim 72, wherein the cell is a mammalian cell.

### Claim 74 (depends on 73)

The method of claim 73, wherein the mammalian cell is HEK293.

### Claim 75 (depends on 72)

The method of claim 72, wherein the viral vector, the viral rep gene, the viral cap gene, the viral ITRs and the viral helper plasmid are from a virus selected from the group consisting of a lentivirus, a retrovirus, an adenovirus, and an adeno-associated virus (AAV).

### Claim 76 (depends on 75)

The method of claim 75, wherein the AAV comprises a serotype selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, and AAV9.

### Claim 77 (depends on 72)

The method of claim 72, wherein the muscle specific promoter is a desmin promoter.

### Claim 78 (depends on 72)

The method of claim 72, wherein the mammal is a human.