# US 10,118,957 B2 · Method for treating heart disease by inhibiting the Coxsackievirus-Adenovirus Receptor

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- Number: US 10,118,957 B2
- Document ID: US10118957B2
- Status: Granted
- Kind: B2
- Application number: 14/419,413
- Filed: 2013-08-05
- Published: 2015-11-05
- Granted: 2018-11-06
- Earliest claimed: 2012-08-03
- Assignees: Max-DelbrüCk-Centrum FüR Molekulare Medizin (Mdc) Berlin-Buch
- Applicants: Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch
- Inventors: Michael Gotthardt; Fabian Freiberg
- Web page: https://patentgrep.com/patent/US10118957B2

## CPC

- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)}
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C12N 15/1138: {against receptors or cell surface proteins}
- G01N 33/6887: {from muscle, cartilage or connective tissue}
- C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/3233: Morpholino-type ring
- C12N 2320/31: Combination therapy
- G01N 2800/324: Coronary artery diseases, e.g. angina pectoris, myocardial infarction
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention pertains to a means for downregulating or inhibiting or mislocalizing CAR in a cardiac cell for treating/curing a patient who has suffered or is predisposed to suffering a myocardial infarction (MI) or preventing myocardial infarction or complications thereof.

## Claims

### Claim 1

A method for down-regulating or inhibiting Coxsackievirus-Adenovirus Receptor (CAR) in a heart of a subject not suffering from myocarditis, comprising administering to the subject at least one of:
a CAR protein ligand or a CAR protein ligand fragment, wherein the heart is a heart subjected to inadequate perfusion.

### Claim 2 (depends on 1)

The method of claim 1, wherein the down-regulating or inhibiting Coxsackievirus-Adenovirus Receptor (CAR) in the heart of a subject comprises administering to the subject at least one of an antibody specifically binding to the CAR, a specifically binding fragment of the antibody, a CAR-Fc-fusion protein, fibronectin, a CAR ligand fusion protein and a fusion protein of any of the before-mentioned proteins.

### Claim 3

A method for down-regulating or inhibiting Coxsackievirus-Adenovirus Receptor (CAR) in a cardiac cell of a subject not suffering from myocarditis, comprising:
functionally inhibiting a CAR protein by administering to the subject a CAR protein ligand, wherein the cardiac cell is a cardiac cell subjected to inadequate perfusion.

### Claim 4 (depends on 3)

The method of claim 3, wherein the functional inhibition of the CAR protein is achieved using at least one of an antibody specifically binding to the CAR, a specifically binding fragment of the antibody, a CAR-Fc-fusion protein, and fibronectin.

### Claim 5

A method for down-regulating or inhibiting Coxsackievirus-Adenovirus Receptor (CAR) in a heart of a subject not suffering from myocarditis, comprising administering to the subject at least one of:
a CAR protein ligand or a CAR protein ligand fragment, wherein the heart is a heart subjected to ischemia.