# US 8,784,802 B2 · Ischemic tissue cell therapy

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- Number: US 8,784,802 B2
- Document ID: US8784802B2
- Status: Granted
- Kind: B2
- Application number: 13/063,456
- Filed: 2009-09-14
- Published: 2011-11-10
- Granted: 2014-07-22
- Earliest claimed: 2008-09-12
- Assignees: Cryopraxis Criobiologia Ltda.; Universidade Federal de Sao Paulo - UNIFESP; University of South Florida
- Applicants: Paul R. Sanberg; Nelson Americo Hossne, Jr.; Alison E. Willing; Adriana Invitti
- Inventors: Paul R. Sanberg; Nelson Americo Hossne, Jr.; Alison E. Willing; Adriana Invitti
- Web page: https://patentgrep.com/patent/US8784802B2

## CPC

- A61K 35/51: Umbilical cord; Umbilical cord blood; Umbilical stem cells
- A61K 35/44: Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
- A61K 40/17: Monocytes; Macrophages
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/40: characterised by antigens that are targeted or presented by cells of the immune system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- 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 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/32: Alcohol-abuse
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 5/0605: {Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly}
- C12N 5/0634: {Cells from the blood or the immune system}
- C12N 5/0645: {Macrophages, e.g. Kuepfer cells in the liver; Monocytes}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2239/31: characterized by the route of administration
- 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

The present invention is directed to compositions and methods for treatment of ischemic diseases and conditions, particularly myocardial, CNS/brain and limb ischemia. More particularly, the present invention provides methods of treating disorders by administering monocytes obtained from blood, including umbilical cord blood, peripheral blood, or bone marrow to an individual in need of treatment, wherein the drug is administered to the individual at a time point specifically determined to provide therapeutic efficacy. In one embodiment, the cells are for injection into ischemic myocardium for the treatment of angina.

## Claims

### Claim 1

A method of treatment of ischemia in a subject comprising injecting a therapeutic cell population into the ischemic tissue of the subject, wherein the therapeutic cell population comprises a mononuclear cell population enriched for monocyte lineage cells and wherein the monocyte lineage cells comprise promonocytes.

### Claim 2 (depends on 1)

The method of claim 1 wherein the ischemia is cardiac ischemia and the ischemic tissue is ischemic myocardium.

### Claim 3 (depends on 2)

The method of claim 2 wherein the therapeutic cell population injected into the myocardium includes at least 107 monocyte lineage cells.

### Claim 4 (depends on 2)

The method of claim 2 wherein the therapeutic cell population is injected into the myocardium through at least two separate injections, at least three separate injections, at least four separate injections, at least five separate injections, at least ten separate injections, at least twenty separate injections, at least thirty separate injections, or at least forty separate injections.

### Claim 5 (depends on 1)

The method of claim 1 wherein an injection is between 0.05 ml and 0.3 ml.

### Claim 6 (depends on 5)

The method of claim 5 wherein the injection is about 0.2 ml.

### Claim 7 (depends on 1)

The method of claim 1 wherein the therapeutic cell population is autologous to the subject.

### Claim 8 (depends on 1)

The method of claim 1 wherein the therapeutic cell population is allogeneic to the subject.

### Claim 9 (depends on 1)

The method of claim 1 wherein the therapeutic cell population is a mononuclear cell population enriched for monocyte lineage cells and wherein the monocyte lineage cells comprise promonocytes.

### Claim 10 (depends on 1)

The method of claim 1, wherein the mononuclear cell population was obtained from bone marrow, cord blood or mobilized peripheral blood.

### Claim 11 (depends on 1)

The method of claim 1, wherein the mononuclear cell population was obtained from bone marrow.

### Claim 12 (depends on 1)

The method of claim 1, wherein the enrichment for monocyte lineage cells comprised isolating the therapeutic cells from a sample using a method that enriches monocyte lineage cells; culturing the therapeutic cell population under conditions that enriches monocyte lineage cells; and/or adding monocyte lineage cells to the therapeutic cell population.

### Claim 13

A method of improving perfusion in a subject comprising injecting a therapeutic cell population into a tissue of the subject in need of improved perfusion, wherein the therapeutic cell population comprises a mononuclear cell population enriched for monocyte lineage cells and wherein the monocyte lineage cells comprise promonocytes.

### Claim 14 (depends on 13)

The method of claim 13 wherein the perfusion is cardiac perfusion and the tissue is myocardium.

### Claim 15 (depends on 13)

The method of claim 13, wherein the mononuclear cell population was obtained from bone marrow, cord blood or mobilized peripheral blood.

### Claim 16 (depends on 13)

The method of claim 13, wherein the mononuclear cell population was obtained from bone marrow.

### Claim 17 (depends on 13)

The method of claim 13, wherein the enrichment for monocyte lineage cells comprised isolating the therapeutic cells from a sample using a method that enriches monocyte lineage cells; culturing the therapeutic cell population under conditions that enriches monocyte lineage cells; and/or adding monocyte lineage cells to the therapeutic cell population.