IP Library › Granted Patent US 12,312,599
Granted Patent B2
US 12,312,599 · App. 17/667,934 · Granted May 27, 2025

Methods, compositions, and kits for producing beige adipocytes and treating metabolic disorders

Inventor: Aaron C. Brown (Portland, ME)
Assignee: MaineHealth
C12N5/0653A61K35/35A61K38/2026A61K45/06A61P3/04A61P3/06A61P3/10C12N2501/2304C12N2501/999
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Quick Facts
Patent No.
US 12,312,599
App. No.
17/667,934
Granted
May 27, 2025
Kind
B2
Abstract

Provided herein are, inter alia, methods, compositions, and kits for producing adipocyte populations such as beige adipocyte populations. Also included are methods and compositions for increasing the level of adipocyte populations (e.g., beige adipocyte populations) in a subject, as well as methods and compositions for treating subjects who are overweight, obese, or who have diabetes.

Claims (19)

1. A method of treating obesity in a subject in need thereof, the method comprising administering to the subject an effective amount of a population of beige adipocytes, or a factor obtained from the population of beige adipocytes, wherein the population of beige adipocytes are produced by contacting a mesenchymal stem cell (MSC) population with an effective amount of

(i) interleukin 4 (IL-4); and

(ii) a transforming growth factor beta (TGF-β) inhibitor.

2. The method of claim 1 , wherein the MSC population is contacted with the IL-4 and the TGF-β inhibitor concurrently.

3. The method of claim 1 , comprising culturing the MSC population in a cell culture medium that comprises the IL-4 and the TGF-β inhibitor.

4. The method of claim 1 , wherein the TGF-β inhibitor is a small molecule, an antibody or a fragment thereof, an oligonucleotide, an aptamer, or a peptide.

5. The method of claim 1 , wherein the TGF-β inhibitor is lerdelimumab, metelimumab, fresolimumab, LY2382770, trabedersen, lucanix, disitertide, galunisertib, TEW-7197, PF-03446962, LY3022859, or SB431542.

6. The method of claim 1 , further comprising contacting the MSC population with an adipogenic differentiation compound.

7. The method of claim 6 , wherein the MSC population is contacted with the TGF β inhibitor and the IL-4 to produce a preadipocyte population, and the preadipocyte population is contacted with the adipogenic differentiation compound.

8. The method of claim 6 , wherein the adipogenic differentiation compound comprises a PPARγ activator.

9. The method of claim 6 , wherein the adipogenic differentiation compound comprises 3,3′,5-Triiodo-L-thyronine (T3), insulin, rosiglitazone, 3-isobutyl-1-methylxanthine (IBMX), or dexamethasone.

10. The method of claim 6 , wherein the adipogenic differentiation compound comprises a compound that induces or increases adipogenesis.

11. The method of claim 1 , wherein cells of the beige adipocyte population express uncoupling protein 1 (UCP1).

12. The method of claim 1 , wherein cells of the beige adipocyte population secrete an anti-diabetic factor.

13. The method of claim 12 , wherein the anti-diabetic factor is fibroblast growth factor 21 (FGF21), neuregulin 4 (NRG4), interleukin 6 (IL6), or Adiponectin, C1Q and Collagen Domain Containing (ADIPOQ) protein.

14. A method of treating obesity in a subject in need thereof, the method comprising administering to the subject an effective amount of IL-4 and a TGF-B inhibitor.

15. The method of claim 14 , wherein the IL-4 and the TGF-β inhibitor are injected into adipose tissue of the subject.

16. A method of increasing the level of a beige adipocyte population in a subject in need thereof, the method comprising administering to the subject an effective amount of IL-4 and a TGF-β inhibitor.

17. The method of claim 16 , wherein the IL-4 and the TGF-β inhibitor are injected into adipose tissue of the subject.

Assignments (3)
CHANGE OF NAME Recorded Apr 29, 2025
From: MAINE MEDICAL CENTER RESEARCH INSTITUTE
To: MAINE MEDICAL CENTER
Reel/Frame 071109/0575 →
CHANGE OF NAME Recorded Apr 29, 2025
From: MAINE MEDICAL CENTER
To: MAINEHEALTH
Reel/Frame 071109/0607 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2022
From: BROWN, AARON C.
To: MAINE MEDICAL CENTER RESEARCH INSTITUTE
Reel/Frame 061025/0039 →
Continuity (3)
Continuation 16245298 · Jan 11, 2019
Provisional Application 62616507 · Jan 12, 2018
Related Publication 20220162557A1 · May 26, 2022
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