# US 10,501,756 B2 · Gene-therapy vectors for treating cardiomyopathy

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- Number: US 10,501,756 B2
- Document ID: US10501756B2
- Status: Granted
- Kind: B2
- Application number: 14/785,188
- Filed: 2014-04-17
- Published: 2016-04-21
- Granted: 2019-12-10
- Earliest claimed: 2013-04-17
- Assignees: Universitätsklinikum Hamburg-Eppendorf; Ruprecht-Karls-UniversitäT Heidelberg; Sorbonne Universite; Association Institute De Myologie
- Applicants: UniversitäTsklinikum Hamburg-Eppendorf; Ruprecht-Karls-UniversitäT Heidelberg; Sorbonne Université; Association Institut De Myologie
- Inventors: Lucie Carrier; Thomas Eschenhagen; Thomas Voit; Giulia Mearini; Oliver Mueller; Doreen Stimpel; Julia Mourot-Filiatre
- Web page: https://patentgrep.com/patent/US10501756B2

## CPC

- C12N 15/86: Viral vectors
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 48/0058: {Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct}
- A61K 48/0066: {Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- C07K 14/4716: {Muscle proteins, e.g. myosin, actin}
- C12N 5/0657: {Cardiomyocytes; Heart cells}
- C12N 5/0696: {Artificially induced pluripotent stem cells, e.g. iPS}
- 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 2506/45: from artificially induced pluripotent stem cells
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2799/025: where the vector is derived from a parvovirus
- C12N 2830/007: cell cycle specific enhancer/promoter combination
- C12N 2830/008: cell type or tissue specific enhancer/promoter combination
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention relates to a gene therapy vector which is useful in the treatment or prevention of hypertrophic cardiomyopathy in a subject in need thereof. The gene therapy vector of the invention comprises a nucleic acid sequence encoding a cardiac sarcomeric protein and a cardiomyocyte-specific promoter which is operably linked to said nucleic acid sequence. The invention furthermore relates to a cell which comprises the gene therapy vector. Pharmaceutical compositions which comprise the gene therapy vector and/or a cell comprising said vector are also provided. In another aspect, the invention relates to a method for treating or preventing hypertrophic cardiomyopathy in a subject by introducing the gene therapy vector of the invention into a subject in need of treatment.

## Claims

### Claim 1

A method of treating hypertrophic cardiomyopathy in a human subject, said method comprising:
administering to said subject, by intravenous injection or infusion or by direct administration to the heart, a gene therapy vector for expressing an exogenous nucleic acid sequence comprising:
(a) a nucleic acid sequence encoding a functional cardiac sarcomeric protein, wherein said cardiac sarcomeric protein is cardiac myosin binding protein C (cMyBP-C), and
(b) a cardiomyocyte-specific promoter which is operably linked to said nucleic acid sequence,
wherein said gene therapy vector is an adeno-associated virus vector, wherein said subject carries a mutation in a gene encoding said cardiac sarcomeric protein which expresses a level of non-functional mutant versions of said protein and causes said hypertrophic cardiomyopathy, and wherein after said administering, said exogenous nucleic acid sequence expresses said functional cardiac sarcomeric protein in the subject and the level of non-functional mutant versions of said protein is reduced in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein said cardiomyocyte-specific promoter is the human cardiac troponin T promoter (hTNNT2).

### Claim 3 (depends on 2)

The method of claim 2, wherein the hTNNT2 promoter comprises the sequence of SEQ ID NO:5.

### Claim 4 (depends on 1)

The method of claim 1, wherein said cMyBP-C protein comprises the sequence of SEQ ID NO:2.

### Claim 5 (depends on 1)

The method of claim 1, wherein said vector is formulated for administration into the myocardium by intravenous or intracardiac injection or infusion.