# US 10,307,442 B2 · Pharmaceutical composition for the prevention or treatment of a pulmonary disorder comprising mesenchymal stem cells having improved proliferation and differentiation capacity

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- Number: US 10,307,442 B2
- Document ID: US10307442B2
- Status: Granted
- Kind: B2
- Application number: 15/540,334
- Filed: 2016-03-04
- Published: 2017-12-21
- Granted: 2019-06-04
- Earliest claimed: 2015-03-04
- Assignees: Medipost Co., Ltd.
- Applicants: Medipost Co., Ltd.
- Inventors: Yoon Sun Yang; Wonil Oh; Hye Jin Jin; Hong Bae Jeon; Miyeon Kim
- Web page: https://patentgrep.com/patent/US10307442B2

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- C12N 5/0605: {Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly}
- C12N 5/0663: {Bone marrow mesenchymal stem cells (BM-MSC)}
- C12N 5/0667: {Adipose-derived stem cells [ADSC]; Adipose stromal stem cells}
- C12N 5/0668: {Mesenchymal stem cells from other natural sources}
- 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

A pharmaceutical composition for the prevention or treatment of a pulmonary disorder is provided. The composition contains mesenchymal stem cells showing improved proliferation and differentiation capacity which are characterized by the expression or non-expression of one or more particular cell markers. Also, provided is a method for obtaining mesenchymal stem cells showing improved proliferation and differentiation capacity based on the expression or non-expression of such cell markers. The mesenchymal stem cells having improved proliferation and differentiation capacity can be easily obtained from mesenchymal stem cells of various origins based on the expression or non-expression of CD26, CD49f, CD146 and EGFR. The mesenchymal stem cells thus obtained can be effectively used for the prevention or treatment of a pulmonary disorder such as, for example, pulmonary emphysema.

## Claims

### Claim 1

A method for preventing and/or treating a pulmonary disorder in a subject in need thereof, comprising administering a composition comprising mesenchymal stem cells as an active ingredient to the subject,
wherein the mesenchymal stem cells do not express cluster of differentiation (CD) 26 as a cell marker, and
wherein the mesenchymal stem cells have a size of 8 μm or less.

### Claim 2 (depends on 1)

The method of claim 1, wherein the mesenchymal stem cells express at least one of CD49f, CD146, and epidermal growth factor receptor (EGFR) as a cell marker.

### Claim 3 (depends on 1)

The method of claim 1, wherein the mesenchymal stem cells express CD49f, CD146, and EGFR.

### Claim 4 (depends on 3)

The method of claim 3, wherein the mesenchymal stem cells express CD49f, CD146, and EGFR to levels which are higher by more than 50%, more than 90%, and more than 50%, respectively, as compared to mesenchymal stem cells expressing CD26.

### Claim 5 (depends on 1)

The method of claim 1, wherein the mesenchymal stem cells are derived from umbilical cord blood, bone marrow, lipid, muscle, skin, amniotic fluid, umbilical cord or tooth.

### Claim 6 (depends on 1)

The method of claim 1, wherein mesenchymal stem cells are obtained by
bringing a solution containing mesenchymal stem cells to be in contact with an agent which specifically binds to the CD26 to separate mesenchymal stem cells expressing CD26 from those not expressing CD26;
bringing a solution containing mesenchymal stem cells to be in contact with one or more of agents which each specifically bind to one of CD49f, CD146, and EGFR to separate mesenchymal stem cells expressing at least one of CD49f, CD146, and EGFR from those not expressing any of CD49f, CD146, and EGFR; and
subjecting the solution containing mesenchymal stem cells to a size separation to separate mesenchymal stem cells of 8 μm or less in size.

### Claim 7 (depends on 6)

The method of claim 6, wherein the agent which specifically binds to the CD26 is a CD26 antigen, and the one or more agents which each specifically bind to one of CD49f, CD146, and EGFR are one or more of CD49f antigen, CD146 antigen, and EGFR antigen.

### Claim 8 (depends on 1)

The method of claim 1, wherein the pulmonary disorder is damaged lung tissue.

### Claim 9

A method for regenerating pulmonary cells in a subject in need thereof, comprising administering a composition comprising mesenchymal stem cells as an active ingredient to the subject, wherein the mesenchymal stem cells do not express cluster of differentiation 26 (CD26) as a cell marker, and
wherein the size of the mesenchymal stem cells is 8 μm or less.

### Claim 10 (depends on 9)

The method of claim 9, wherein the mesenchymal stem cells express at least one selected from cluster of differentiation 49f (CD49f), cluster of differentiation 146 (CD146) and epidermal growth factor receptor (EGFR) as a cell marker.

### Claim 11 (depends on 9)

The method of claim 9, wherein the mesenchymal stem cells express CD49f, CD146, and EGFR as cell markers.

### Claim 12 (depends on 11)

The method of claim 11, wherein the mesenchymal stem cells express CD49f, CD146, and EGFR to levels which are higher by more than 50%, more than 90%, and more than 50%, respectively, as compared to mesenchymal stem cells expressing CD26.

### Claim 13 (depends on 9)

The method of claim 9, wherein the mesenchymal stem cells are derived from umbilical cord blood, bone marrow, lipid, muscle, skin, amniotic fluid, umbilical cord or tooth.

### Claim 14 (depends on 9)

The method of claim 9, wherein mesenchymal stem cells are obtained by
bringing a solution containing mesenchymal stem cells to be in contact with an agent which specifically binds to the CD26 to separate mesenchymal stem cells expressing CD26 from those not expressing CD26;
bringing a solution containing mesenchymal stem cells to be in contact with one or more of agents which each specifically bind to one of CD49f, CD146, and EGFR to separate mesenchymal stem cells expressing at least one of CD49f, CD146, and EGFR from those not expressing any of CD49f, CD146, and EGFR; and
subjecting the solution containing mesenchymal stem cells to a size separation to separate mesenchymal stem cells of 8 μm or less in size.

### Claim 15 (depends on 14)

The method of claim 14, wherein the agent which specifically binds to the CD26 is a CD26 antigen, and the one or more agents which each specifically bind to one of CD49f, CD146, and EGFR are one or more of CD49f antigen, CD146 antigen, and EGFR antigen.
