# US 8,784,891 B2 · Compositions for regenerating defective or absent myocardium

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- Number: US 8,784,891 B2
- Document ID: US8784891B2
- Status: Granted
- Kind: B2
- Application number: 13/732,805
- Filed: 2013-01-02
- Published: 2013-05-23
- Granted: 2014-07-22
- Earliest claimed: 2005-07-15
- Assignees: CorMatrixCardiovascular, Inc.
- Applicants: Francis Law Group
- Inventors: Robert G Matheny
- Web page: https://patentgrep.com/patent/US8784891B2

## CPC

- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/726: Glycosaminoglycans, i.e. mucopolysaccharides (chondroitin sulfate, dermatan sulfate A61K31/737)
- A61K 35/22: Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 35/37: Digestive system
- A61K 35/38: Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
- A61K 35/407: Liver; Hepatocytes
- A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
- A61K 35/545: Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
- A61K 38/1741: {alpha-Glycoproteins}
- A61K 38/1825: {Fibroblast growth factor [FGF]}
- A61K 38/1841: {Transforming growth factor [TGF]}
- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24}
- 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 27/3683: {subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment}
- A61L 27/3687: {characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents}
- A61L 27/3804: {characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney 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 27/3873: {Muscle tissue, e.g. sphincter}
- A61L 27/40: Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L 27/58: Materials at least partially resorbable by the body
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/711: Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61L 2300/412: Tissue-regenerating or healing or proliferative agents
- A61L 2300/414: Growth factors
- A61L 2300/426: Immunomodulating agents, i.e. cytokines, interleukins, interferons
- A61L 2300/45: Mixtures of two or more drugs, e.g. synergistic mixtures
- A61L 2300/64: Animal cells
- A61L 2400/06: Flowable or injectable implant compositions
- A61L 2430/20: for reconstruction of the heart, e.g. heart valves
- A61L 2430/30: for muscle reconstruction
- 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)
- 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)

## Abstract

Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition may also include an extracellular matrix scaffold component of any formulation, and further include added cells, proteins, or other components to optimize the regenerative process and restore cardiac function.

## Claims

### Claim 1

An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular heart extracellular matrix (ECM), said ECM comprising endogenous transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added glycosaminoglycan (GAG), said GAG comprising at least 0.1% by weight of said composition, said GAG being linked to said ECM, wherein said GAG stimulates angiogenic effects of FGF-2 and interacts with TGF-β to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.

### Claim 2 (depends on 1)

The composition of claim 1, wherein said composition further comprises an exogenously added cytokine.

### Claim 3

An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular stomach submucosa (SS), said SS comprising endogenous transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added glycosaminoglycan (GAG), said GAG comprising at least 0.1% by weight of said composition, said GAG being linked to said ECM, wherein said GAG stimulates angiogenic effects of FGF-2 and interacts with TGF-β to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.

### Claim 4 (depends on 3)

The composition of claim 3, wherein said composition further comprises an exogenously added cytokine.

### Claim 5

An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular liver basement submucosa (LBS), said LBS comprising endogenous transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added glycosaminoglycan (GAG), said GAG comprising at least 0.1% by weight of said composition, said GAG being linked to said ECM, wherein said GAG stimulates angiogenic effects of FGF-2 and interacts with TGF-β to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased cardiovascular tissue, said composition induces stein cell proliferation and differentiation of stein cells into cardiomyocytes.

### Claim 6 (depends on 5)

The composition of claim 5, wherein said composition further comprises an exogenously added cytokine.

### Claim 7

An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular liver basement membrane (LBM), said LBM comprising endogenous transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added glycosaminoglycan (GAG), said GAG comprising at least 0.1% by weight of said composition, said GAG being linked to said ECM, wherein said GAG stimulates angiogenic effects of FGF-2 and interacts with TGF-β to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.

### Claim 8 (depends on 7)

The composition of claim 7, wherein said composition further comprises an exogenously added cytokine.

### Claim 9

An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular placental extracellular matrix (ECM), said ECM comprising endogenous transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added glycosaminoglycan (GAG), said GAG comprising at least 0.1% by weight of said composition, said GAG being linked to said ECM, wherein said GAG stimulates angiogenic effects of FGF-2 and interacts with TGF-β to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.

### Claim 10 (depends on 9)

The composition of claim 9, wherein said composition further comprises an exogenously added cytokine.