# US 2021/0275599 A1 · Mitochondrial augmentation therapy of brain diseases

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- Number: US 2021/0275599 A1
- Document ID: US20210275599A1
- Status: Published application
- Kind: A1
- Application number: 17/254,770
- Filed: 2019-07-22
- Published: 2021-09-09
- Earliest claimed: 2018-07-22
- Assignees: Minovia Therapeutics Ltd.
- Applicants: Minovia Therapeutics Ltd.
- Inventors: Natalie Yivgi Ohana; Uriel Halavee; Shmuel Bukshpan; Noa Sher; Moriya Blumkin
- Web page: https://patentgrep.com/patent/US20210275599A1

## CPC

- A61K 35/545: Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/33: Fibroblasts
- A61K 35/38: Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
- A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
- A61K 35/51: Umbilical cord; Umbilical cord blood; Umbilical stem cells
- A61K 40/10: characterised by the cell type used
- A61K 40/40: characterised by antigens that are targeted or presented by cells of the immune system
- A61K 40/414: {Nervous system antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/16: Anti-Parkinson drugs
- 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
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- 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

## Abstract

The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating brain diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.

## Claims

### Claim at position 1

-3. (canceled)

### Claim 4 (depends on 28)

The method of claim 28, wherein the human exogenous mitochondria are syngeneic or allogeneic.

### Claim at position 3

-6. (canceled)

### Claim 7 (depends on 28)

The method of claim 28, wherein the disease or disorder is selected from the group consisting of Parkinson Disease (PD), Alzheimer Disease (AD), stroke, epilepsy, multiple sclerosis (MS), dementia, adrenoleukodystrophy (ALD), Huntington Disease (HD), Guillain Barre Syndrome (GBS), autism and Friedreich's ataxia.

### Claim 8 (depends on 28)

The method of claim 28, wherein the symptom is selected from the group consisting of impaired ability to execute commands, impaired ability to speak, impaired response time, impaired motor skills, impaired learning, impaired ability to walk, impaired ability to climb stairs, impaired EEG, seizures, impaired ability to draw, impaired language skills, and impaired memory.

### Claim 9 (depends on 28)

The method of claim 28, wherein said pharmaceutical composition is administered directly to the central nervous system (CNS).

### Claim at position 7

-12. (canceled)

### Claim 13 (depends on 28)

The method of claim 28, wherein the mitochondrially-enriched human stem cells have at least one of:
an increased mitochondrial DNA content;
(ii) an increased level of citrate synthase (CS) activity;
(iii) an increased content of at least one mitochondrial protein selected from SDHA and COX1;
(iv) an increased rate of O2 consumption;
(v) an increased rate of ATP production; or
(vi) any combination thereof,
relative to the corresponding level in the stem cells prior to mitochondrial enrichment.

### Claim at position 9

-16. (canceled)

### Claim 17 (depends on 28)

The method of claim 28, wherein the human stem cells are hematopoietic stem cells, mesenchymal stem cells, pluripotent stem cells (PSCs), induced pluripotent stem cells (iPSCs), or CD34+ cells.

### Claim at position 11

-21. (canceled)

### Claim 22 (depends on 28)

The method of claim 28, wherein the human stem cells are isolated, derived or obtained from cells of the bone marrow, adipose tissue, oral mucosa, skin fibroblasts, blood or umbilical cord blood.

### Claim 23 (depends on 28)

The method of claim 28, wherein the human exogenous mitochondria are isolated or obtained from placenta, placental cells grown in culture or blood cells.

### Claim 24

(canceled)

### Claim 25 (depends on 28)

The method of claim 28, wherein the human exogenous mitochondria constitute at least between 1% and 30% of the total mitochondria in the mitochondrially-enriched human stem cells.

### Claim 26 (depends on 25)

The method of claim 25, wherein the human exogenous mitochondria constitute 1%, 3%, 5%, 7%, 10%, 15%, 20%, 25%, or 30% of the total mitochondria in the mitochondrially-enriched human stem cells.

### Claim 27 (depends on 28)

The method of claim 28, further comprising non-enriched stem cells, megakaryocytes, erythrocytes, mast cells, myeloblasts, basophils, neutrophils, eosinophils, monocytes, macrophages, natural killer (NK) cells, small lymphocytes, T lymphocytes, B lymphocytes, plasma cells, reticular cells, or any combination thereof.

### Claim 28

A method of treating a brain disease, disorder or a symptom thereof in a human patient in need of such treatment comprising administering a pharmaceutical composition to the patient, the pharmaceutical composition comprising at least about 5×105 to 5×109 human stem cells, wherein the human stem cells are enriched with human exogenous mitochondria, wherein the brain disease or disorder is not a primary mitochondrial disease or disorder caused by a pathogenic mutation in mitochondrial DNA or by a pathogenic mutation in nuclear DNA encoding a mitochondrial protein.

### Claim 29 (depends on 28)

The method of claim 28, wherein said administering the pharmaceutical composition is directly to the central nervous system (CNS), intrathecally or systemically.

### Claim at position 20

-31. (canceled)

### Claim 32 (depends on 28)

The method of claim 28, wherein the human stem cells are obtained or derived from the patient before enrichment with the exogenous mitochondria.

### Claim 33 (depends on 28)

The method of claim 28, wherein the human stem cells are obtained or derived from a donor different than the patient before enrichment with the exogenous mitochondria.

### Claim 34

(canceled)

### Claim 35 (depends on 33)

The method of claim 33, further comprising a step of administering to the patient an agent which prevents, delays, minimizes or abolishes an adverse immunogenic reaction between the patient and the mitochondrially-enriched human stem cells.

### Claim 36 (depends on 35)

The method of claim 35, wherein the adverse immunogenic reaction is a graft-versus-host disease (GvHD).

### Claim 37 (depends on 28)

The method of claim 28, further comprising administering to the subject non-enriched stem cells, megakaryocytes, erythrocytes, mast cells, myeloblasts, basophils, neutrophils, eosinophils, monocytes, macrophages, natural killer (NK) cells, small lymphocytes, T lymphocytes, B lymphocytes, plasma cells, reticular cells, or any combination thereof.

### Claim 38 (depends on 13)

The method of claim 13, wherein increased mitochondrial DNA content is from endogenous and/or exogenous mitochondria.

### Claim 39 (depends on 26)

The method of claim 26, wherein the human exogenous mitochondria constitute at least 1% of the total mitochondria in the mitochondrially enriched human stem cells.