# US 10,481,147 B2 · Cardiac stem cells and methods of identifying and using the same

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- Number: US 10,481,147 B2
- Document ID: US10481147B2
- Status: Granted
- Kind: B2
- Application number: 15/657,635
- Filed: 2017-07-24
- Published: 2018-06-28
- Granted: 2019-11-19
- Earliest claimed: 2012-11-30
- Assignees: Vestion, Inc.
- Applicants: Vestion, Inc.
- Inventors: Joshua Hare; Konstantinos Chatzistergos
- Web page: https://patentgrep.com/patent/US10481147B2

## CPC

- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/02: Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- A61P 9/06: Antiarrhythmics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 13/12: of the kidneys
- A61P 35/00: Antineoplastic agents
- C12N 5/0657: {Cardiomyocytes; Heart cells}
- C12N 5/0662: {Stem cells}
- G01N 33/5073: {Stem cells}
- C12N 2506/02: from embryonic cells
- 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)
- 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)

## Abstract

Methods of isolating cardiac cells, including cardiac cells capable of regenerating cardiac tissue are provided. Compositions comprising cardiac cells, including cardiac cells capable of regenerating cardiac tissue are also provided. Methods of using cardiac cells, cardiac progenitor cells, including cardiac cells capable of regenerating cardiac tissue, are provided. Methods of identifying the prognosis of patients treated for heart disease and/or methods of predicting the regeneration of cardiac cells in a subject are also provided.

## Claims

### Claim 1

A method of treating a heart disease in a subject in need thereof comprising administering a pharmaceutical composition comprising a therapeutically effective amount of isolated composition of cardiac progenitor cells, wherein the composition of cardiac progenitor cells comprises cardiac progenitor cells that are phosphorylated retinoblastoma protein positive.

### Claim 2 (depends on 1)

The method of claim 1, wherein the phosphorylated retinoblastoma protein is hyperphosphorylated Rb.

### Claim 3 (depends on 1)

The method of claim 1, wherein the phosphorylated retinoblastoma is phosphorylated at position Ser 608 of Rb.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition of cardiac progenitor cells comprises cardiac progenitor cells that are positive for Gata4 (Gata4+).

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition of cardiac progenitor cells comprises cardiac progenitor cells that are negative for ARF (ARF−).

### Claim 6 (depends on 1)

The method of claim 1, wherein the composition of cardiac progenitor cells comprises cardiac progenitor cells that are positive for Gata4 (Gata4+) and negative for ARF (ARF−).

### Claim 7 (depends on 1)

The method of claim 1, wherein the composition of cardiac progenitor cells comprises cardiac progenitor cells that are phosphorylated retinoblastoma protein positive, positive for Gata4 (Gata4+), and negative for ARF (ARF−).

### Claim 8 (depends on 1)

The method of claim 1, wherein the heart disease is cardiovascular disease, cardiomyopathy, myocardial stunning, peripheral vascular disease, intermittent claudication, tachycardia, ischemia-reperfusion, myocardial infarction, acute renal failure, stroke, hypotension, embolism, or thromboembolism (blood clot).

### Claim 9 (depends on 1)

The method of claim 1, wherein the heart disease is cardiomyopathy.

### Claim 10 (depends on 1)

The method of claim 1, wherein the composition of cardiac progenitor cells comprises cardiac progenitor cells that are N-cadherinpos, connexin-43pos, Isl1pos, Wt1pos, CDK2pos, CDK4pos, CDK6pos, E2Fpos, phospho-p107pos, phospho-p130pos, CCNAPpos, CCND1pos, CCND2pos, CCND3posCCNEpos, c-kitpos, CD3neg, CD14neg, CD68neg, Nkx2.5pos, MITFpos, MEF2cpos, or any combination thereof.

### Claim 11 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition further comprises mesenchymal stem cells.

### Claim 12 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is suitable for parenteral administration.

### Claim 13 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is suitable for intravenous administration.

### Claim 14 (depends on 1)

The method of claim 1, wherein the heart disease is myocardial infarction.

### Claim 15 (depends on 1)

The method of claim 1, wherein the heart disease is hypotension.