# US 2017/0281685 A1 · Noble gas augmentation of regenerative cell activity

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- Number: US 2017/0281685 A1
- Document ID: US20170281685A1
- Status: Published application
- Kind: A1
- Application number: 15/465,514
- Filed: 2017-03-21
- Published: 2017-10-05
- Earliest claimed: 2016-03-29
- Assignees: Noblis Therapeutics, Inc.
- Applicants: Noblis Therapeutics, Inc.
- Inventors: Vlad Bogin; Thomas Ichim
- Web page: https://patentgrep.com/patent/US20170281685A1

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- C12N 5/0663: {Bone marrow mesenchymal stem cells (BM-MSC)}
- C12N 5/0668: {Mesenchymal stem cells from other natural sources}
- C12N 2500/02: Atmosphere, e.g. low oxygen conditions
- C12N 2500/05: Inorganic components
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The current invention discloses compositions of matter, therapeutic protocols, and combination therapies utilizing previously unknown activity of Xenon alone or in combination with other Noble gases to augment therapeutic activity of regenerative cells, in one embodiment said regenerative cells comprising of mesenchymal stem cells. In one embodiment the invention provides use of xenon-pretreatment of cells prior to in vivo application in order to allow for enhanced efficacy of said cells. In other embodiments xenon alone, or in combination with other gases is utilized to modulate regenerative activity of cells in vivo.

## Claims

### Claim 1

A method of generating mesenchymal stem cells with enhanced therapeutic activity, said method comprising treatment of mesenchymal stem cells with one or more Noble gases at a concentration and frequency sufficient to induce more than 5% increase in HIF-1 alpha expression in said mesenchymal stem cell.

### Claim 2 (depends on 1)

The method of claim 1, wherein said mesenchymal stem cells are selected from a group comprising of: a) bone marrow; b) perivascular tissue; c) adipose tissue; d) placental tissue; e) amniotic membrane; f) omentum; g) tooth; h) umbilical cord tissue; i) fallopian tube tissue; j) hepatic tissue; k) renal tissue; l) cardiac tissue; m) tonsillar tissue; n) testicular tissue; o) ovarian tissue; p) neuronal tissue; q) auricular tissue; r) colonic tissue; s) submucosal tissue; t) hair follicle tissue; u) pancreatic tissue; v) skeletal muscle tissue; and w) subepithelial umbilical cord tissue.

### Claim 3 (depends on 1)

The method of claim 1, wherein said mesenchymal stem cells express a marker selected from a group comprising of: a) CD73; b) CD90; and c) CD105.

### Claim 4 (depends on 1)

The method of claim 1, wherein said mesenchymal stem cells lack expression of a marker selected from a group comprising of: a) CD14; b) CD45; and c) CD34.

### Claim 5 (depends on 1)

The method of claim 1, wherein said efficacy reflects enhanced ability to induce clinical response in a disease condition.

### Claim 6 (depends on 6)

The method of claim 6, wherein said disease condition is selected from a group comprising of: a) neurological disease; b) inflammatory conditions; c) psychiatric disorders; d) inborn errors of metabolisms; e) vascular disease; f) cardiac disease; g) renal disease; h) hepatic disease; i) pulmonary disease; j) ocular conditions; k) gastrointestinal disorders; l) orthopedic disorders; m) dermal disorders; n) neoplasia; o) predisposition to neoplasia; p) hematopoietic disorders; q) reproductive disorders; r) gynecological disorders; s) urological disorders; t) immunological disorders; u) olfactory disorders; and v) auricular disorders.

### Claim 7 (depends on 1)

The method of claim 1, wherein said mesenchymal stem cells selected for enhanced efficacy are utilized as a source of conditioned media.

### Claim 8 (depends on 7)

The method of claim 7, wherein conditioned media is used therapeutically in the treatment of a disorder.

### Claim 9 (depends on 8)

The method of claim 8, wherein said disorder is selected from a group comprising of a) neurological disease; b) inflammatory conditions; c) psychiatric disorders; d) inborn errors of metabolisms; e) vascular disease; f) cardiac disease; g) renal disease; h) hepatic disease; i) pulmonary disease; j) ocular conditions; k) gastrointestinal disorders; l) orthopedic disorders; m) dermal disorders; n) neoplasia; o) predisposition to neoplasia; p) hematopoietic disorders; q) reproductive disorders; r) gynecological disorders; s) urological disorders; t) immunological disorders; u) olfactory disorders; and v) auricular disorders.

### Claim 10 (depends on 1)

The method of claim 1, wherein said Noble gas is xenon.

### Claim 11 (depends on 1)

The method of claim 1, wherein said Noble gas is a mixture, said mixture containing one or more of the following gases: a) nitrogen; b) helium; c) Nitric Oxide; d) krypton; e) argon; and f) neon.

### Claim 12 (depends on 1)

The method of claim 1, wherein said mesenchymal stem cells are treated with said Noble gas containing mixture by incubating said cells in an atmosphere containing said gases.

### Claim 13 (depends on 1)

The method of claim 1, wherein said Noble gas mixture containing said Noble gas is administered into culture media by dissolving of said Noble gas or mixture containing said Noble gas into said culture media.

### Claim 14 (depends on 1)

The method of claim 1, wherein said noble gas containing mixture is comprised of a gas mixture containing oxygen and a proportion by volume of 20 to 70% of xenon.

### Claim 15 (depends on 65)

The method of claim 65, wherein said proportion of xenon is between 22 and 60% by volume to oxygen.

### Claim 16 (depends on 65)

The method of claim 65, wherein said proportion of xenon is between 25 and 60% by volume to oxygen.

### Claim 17 (depends on 1)

The method of claim 1, wherein said noble gas containing mixture consists only of a) oxygen and xenon or b) air and xenon.

### Claim 18 (depends on 1)

The method of claim 1, wherein said noble gas containing mixture also contains nitrogen, helium, Nitric Oxide, krypton, argon or neon.

### Claim 19 (depends on 1)

The method of claim 1, wherein said noble gas containing mixture contains a proportion by volume of oxygen of between 15 and 25%.