# US 10,864,233 B2 · Compositions and methods for treatment of cardiovascular disorders

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,864,233 B2
- Document ID: US10864233B2
- Status: Granted
- Kind: B2
- Application number: 15/877,803
- Filed: 2018-01-23
- Published: 2018-05-31
- Granted: 2020-12-15
- Earliest claimed: 2011-12-16
- Assignees: CorMatrix Cardiovascular, Inc.
- Applicants: CorMatrix Cardiovascular, Inc.
- Inventors: Robert G Matheny
- Web page: https://patentgrep.com/patent/US10864233B2

## CPC

- A61K 35/35: Fat tissue; Adipocytes; Stromal cells; Connective tissues (adipose-derived stem cells A61K35/28; collagen A61K38/39)
- A61M 60/216: including a rotating member acting on the blood, e.g. impeller
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 35/44: Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
- A61K 38/18: Growth factors; Growth regulators
- A61K 38/1808: {Epidermal growth factor [EGF] urogastrone}
- A61K 38/1841: {Transforming growth factor [TGF]}
- A61K 38/185: {Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3}
- A61K 38/1866: {Vascular endothelial growth factor [VEGF]}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61L 27/3604: {characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel}
- A61L 27/3629: {Intestinal tissue, e.g. small intestinal submucosa}
- A61L 27/3633: {Extracellular matrix [ECM]}
- A61L 27/367: {Muscle tissue, e.g. sphincter}
- A61L 27/3826: {Muscle cells, e.g. smooth muscle cells}
- A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61M 60/148: in line with a blood vessel using resection or like techniques, e.g. permanent endovascular heart assist devices
- A61M 60/178: drawing blood from a ventricle and returning the blood to the arterial system via a cannula external to the ventricle, e.g. left or right ventricular assist devices
- A61M 60/80: Constructional details other than related to driving
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61L 2300/414: Growth factors
- A61L 2300/434: of enzymes
- A61L 2300/64: Animal cells
- A61L 2430/20: for reconstruction of the heart, e.g. heart valves
- A61M 2205/05: combined with other kinds of therapy
- 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)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods for treating cardiovascular disorders that include administration of an ECM based composition to damaged cardiovascular tissue in conjunction with a treatment remedy, such as ventricular assistance and transmyocardial revascularization (TMR), which induces enhanced bioremodeling of the damaged cardiovascular tissue and regeneration of new cardiovascular tissue and associated structures with site-specific structural and functional properties.

## Claims

### Claim 1

A method for treating damaged cardiovascular tissue of a subject, the method comprising the steps of:
providing a mixed liquid exosome augmented extracellular matrix (ECM) composition, said exosome augmented ECM composition comprising acellular ECM from a mammalian tissue source and a plurality of exogenous exosomes isolated from mesenchymal stem cells (MSCs),
said acellular ECM adapted to induce a first level of stem cell proliferation, bioremodeling of damaged cardiovascular tissue and regeneration of new cardiovascular tissue, when said acellular ECM is disposed proximate said damaged cardiovascular tissue,
said plurality of exogenous exosomes adapted to induce a second level of stem cell proliferation, bioremodeling of said damaged cardiovascular tissue and regeneration of new cardiovascular tissue, when said plurality of exogenous exosomes is disposed proximate said damaged cardiovascular tissue;
providing a left ventricular assist device (LVAD) that supports heart function by reducing mechanical load on a left ventricle of a subject's heart when said LVAD is in communication with said subject's left ventricle; and
delivering said exosome augmented ECM composition proximate said damaged cardiovascular tissue associated with said subject's cardiovascular disorder in conjunction with providing said support of said subject's heart function with said LVAD, wherein, a third level of stem cell proliferation, bioremodeling of said damaged cardiovascular tissue and regeneration of new cardiovascular tissue is induced, said third level of induced stem cell proliferation, bioremodeling of said damaged cardiovascular tissue and regeneration of new cardiovascular tissue being greater than the sum of said first level of induced stem cell proliferation, bioremodeling of said damaged cardiovascular tissue and regeneration of new cardiovascular tissue, and said second level of induced stem cell proliferation, bioremodeling of said damaged cardiovascular tissue and regeneration of new cardiovascular tissue.

### Claim 2 (depends on 1)

The method of claim 1, wherein said mammalian tissue source comprises mammalian tissue selected from the group consisting of small intestine submucosa, urinary bladder submucosa, stomach submucosa, cardiac tissue, placental tissue, omentum tissue and kidney tissue.

### Claim 3 (depends on 1)

The method of claim 1, wherein said plurality of exogenous exosomes comprise an encapsulated growth factor selected from the group consisting of exogenous bFGF, TGF-β, and VEGF.

### Claim 4 (depends on 1)

The method of claim 1, wherein said plurality of exogenous exosomes comprise an encapsulated inflammation modulating agent selected from the group consisting of an interleukin, transcription factor RNA and micro RNA (miRNA).

### Claim 5 (depends on 1)

The method of claim 1, wherein said delivery of said exosome augmented ECM composition and said provision of said heart function support are performed within a first period of time of less than 10 minutes of each other.

### Claim 6 (depends on 1)

The method of claim 1, wherein said method further comprises the step of providing a needle-based injection system that is adapted to induce a biological insult in tissue when in communication therewith.

### Claim 7 (depends on 6)

The method of claim 6, wherein said biological insult is induced in said damaged cardiovascular tissue with said needle-based injection system in conjunction with said delivery of said exosome augmented ECM composition and said provision of said heart function support.

### Claim 8 (depends on 7)

The method of claim 7, wherein said biological insult comprises piercing said subject's damaged cardiovascular tissue.

### Claim 9 (depends on 7)

The method of claim 7, wherein said delivery of said exosome augmented ECM composition, said induced biological insult and said heart function support are performed within a first period of time in the range of 5-60 minutes of each other.