# US 12,178,833 B2 · Use of mesenchymal stem cells in treating immune-related diseases

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- Number: US 12,178,833 B2
- Document ID: US12178833B2
- Status: Granted
- Kind: B2
- Application number: 17/434,417
- Filed: 2019-09-25
- Published: 2022-05-05
- Granted: 2024-12-31
- Earliest claimed: 2019-05-21
- Assignees: Emo Biomedicine Corp.
- Applicants: Emo Biomedicine Corp.
- Inventors: Shing-Mou Lee; Hung-Hsuan Chen; Wan-Ling Lai; San-Ni Yu
- Web page: https://patentgrep.com/patent/US12178833B2

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C12N 5/0667: {Adipose-derived stem cells [ADSC]; Adipose stromal stem cells}
- G01N 33/5073: {Stem cells}
- C12N 2501/24: Interferons [IFN]
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Disclosed herein is a method of identifying a plurality of mesenchymal stem cells (MSCs) that are therapeutic to a subject having an immune-related disease, for example, arthritis. According to embodiments of the present disclosure, the MSCs exhibiting to the immune-related disease are characterized in having an immunosuppressive protein binding value (IPBv) greater than 170 toward indoleamine 2,3-dioxygenase (IDO) after being exposed to 50-800 U/ml of IFN-γ. Also disclosed herein are uses of the identified MSCs for the manufacture of a medicament, and methods of treating an immune-related disease by use of the identified MSCs or medicament.

## Claims

### Claim 1

A method of treating a subject having an immune-related disease, comprising administering to the subject a therapeutically effective amount of a composition comprising activated mesenchymal stem cells (MSCs), wherein the activated MSCs are made by incubating them with IFN-γ at a dose of 50-800 U/ml, wherein the activated MSCs have having an immunosuppressive protein binding value (IPBv) greater than 170 toward indoleamine 2,3-dioxygenase (IDO), and wherein the IPBv of the activated MSCs is determined by:
(a) adding a first antibody to the MSCs, wherein the first antibody is specific to the IDO, and has a fluorescent molecule conjugated therewith;
(b) providing a plurality of microbead populations, wherein each microbead in each population of the plurality of microbead populations has a second antibody coupled thereto, wherein the number of second antibodies coupled to each microbead in each population is the same within one population but is different from the number of coupled second antibodies in each different population in the plurality of populations, and wherein the second antibody is specific to the first antibody;
(c) adding the MSC-first antibody composition made in step (a) to the mixture of microbead populations of step (b);
(d) measuring the fluorescence intensity of each microbead population made in step (c);
(e) constructing a calibration plot of the number of the second antibody coupled to the microbead populations as a function of the fluorescence intensity determined in step (d); and
(f) determining the IPBv of the activated MSCs from the calibration plot of step (e) based on the fluorescence intensity determined in step (d).

### Claim 2 (depends on 1)

The method of claim 1, wherein the immune-related disease is arthritis.

### Claim 3 (depends on 1)

The method of claim 1, wherein the MSCs are autologous to the subject.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject is a human.
