# US 10,370,458 B2 · Therapeutic use of mitochondria and combined mitochondrial agent

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- Number: US 10,370,458 B2
- Document ID: US10370458B2
- Status: Granted
- Kind: B2
- Application number: 15/803,543
- Filed: 2017-11-03
- Published: 2018-03-01
- Granted: 2019-08-06
- Earliest claimed: 2016-01-15
- Assignees: Children's Medical Center Corporation and Beth Israel; Deaconess Medical Center, Inc.
- Applicants: Children's Medical Center Corporation; Beth Israel Deaconess Medical Center, Inc.
- Inventors: James D. McCully; Sidney Levitsky; Douglas B. Cowan; Pedro J. del Nido; Sitaram M. Emani
- Web page: https://patentgrep.com/patent/US10370458B2

## CPC

- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- A61B 6/42: Arrangements for detecting radiation specially adapted for radiation diagnosis
- 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 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 47/6901: {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
- A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents}
- A61K 49/1821: {coated or functionalised microparticles or nanoparticles}
- A61K 49/1896: {not provided for elsewhere, e.g. cells, viruses, ghosts, red blood cells, virus capsides}
- A61K 51/0421: {having six-membered rings with one oxygen as the only ring hetero atom}
- A61K 51/1203: {in a form not provided for by groups A61K51/1206 - A61K51/1296, e.g. cells, cell fragments, viruses, virus capsides, ghosts, red blood cells, viral vectors}
- A61K 51/1282: {Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents}
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 25/16: Anti-Parkinson drugs
- C12N 15/11: DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity}
- A61B 6/503: {for diagnosis of the heart}
- A61B 8/0883: {for diagnosis of the heart}
- A61K 2039/505: {comprising antibodies}
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- 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 disclosure relates to compositions comprising isolated mitochondria or combined mitochondrial agents, and methods of treating disorders using such compositions.

## Claims

### Claim 1

A method of delivering an agent to a target site of a human subject, the method comprising administering to the subject a composition comprising isolated viable mitochondria and an agent, to thereby deliver the agent to the target site of the subject, wherein the agent is linked to, attached to, embedded in, or encapsulated by the mitochondria, and the composition is administered into a blood vessel that carries blood to the target site, wherein the agent is 18F-Rhodamine 6G or iron oxide nanoparticle.

### Claim 2 (depends on 1)

The method of claim 1, wherein the target site is heart, kidney, pancreas, lung, optic nerve, brain, or skeletal muscle of the subject.

### Claim 3 (depends on 1)

The method of claim 1, wherein the agent is linked to mitochondria by a covalent bond.

### Claim 4 (depends on 1)

The method of claim 1, wherein the agent is embedded in mitochondrial membrane.

### Claim 5 (depends on 1)

The method of claim 1, wherein the mitochondria are autogeneic to the subject.

### Claim 6 (depends on 5)

The method of claim 5, wherein the autogeneic mitochondria have exogenous mitochondrial DNA (mtDNA).

### Claim 7 (depends on 1)

The method of claim 1, wherein the mitochondria are allogeneic to the subject.

### Claim 8 (depends on 1)

The method of claim 1, wherein the mitochondria are xenogeneic to the subject.

### Claim 9 (depends on 1)

The method of claim 1, wherein the agent is 18F-Rhodamine 6G.

### Claim 10 (depends on 1)

The method of claim 1, wherein the agent is iron oxide nanoparticle.

### Claim 11 (depends on 1)

The method of claim 1, wherein the blood vessel is the coronary artery of the subject or the greater pancreatic artery of the subject.

### Claim 12 (depends on 1)

The method of claim 1, wherein the composition does not cause an immune response.

### Claim 13

A method of delivering an agent to a target site of a human subject, the method comprising administering to the subject isolated viable mitochondria and an agent, to thereby deliver the agent to the target site of the subject, wherein the agent is 18F-Rhodamine 6G or iron oxide nanoparticle and the agent is linked to, attached to, embedded in or encapsulated by the mitochondria.

### Claim 14 (depends on 13)

The method of claim 13, wherein the agent is 18F-Rhodamine 6G.

### Claim 15 (depends on 13)

The method of claim 13, wherein the agent is iron oxide nanoparticle.