IP Library › Granted Patent US 12,686,855
Granted Patent B2
US 12,686,855 · App. 17/602,177 · Granted Jul 21, 2026

Generation of pancreatic endoderm from stem cell derived definitive endoderm

Inventors: Dorthe Roenn Petersen (Slangerup, DK); Christian Honore (Vanloese, DK)
Assignee: ASPECT BIOSYSTEMS LTD.
C12N5/0676A61K35/39C12N2501/10C12N2501/115C12N2501/155C12N2501/385C12N2501/727C12N2506/45
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Quick Facts
Patent No.
US 12,686,855
App. No.
17/602,177
Filed
Oct 7, 2021
Granted
Jul 21, 2026
Kind
B2
Art Unit
1634
USPC
424/93.7
Abstract

The present invention relates to methods of efficiently generating pancreatic endoderm from human pluripotent stem (PS) cell derived human definitive endoderm. The present invention also relates to pancreatic endoderm cells obtained by the methods of the invention. Finally, the present invention relates to culture medium and composition comprising a RAR antagonist and uses of said RAR antagonist in the induction of pancreatic endoderm cells. The present invention provides a more homogenous and synchronised pancreatic cell population, with increased efficiency.

Claims (16)

1 . A method of differentiating definitive endoderm (DE) cells derived from human pluripotent stem cells into pancreatic endoderm (PE) cells, comprising,

culturing the DE cells in a culture medium comprising a retinoic acid receptor (RAR) antagonist to produce pancreatic endoderm precursor cells,

and culturing the pancreatic endoderm precursor cells in a cell culture medium comprising a RAR agonist to produce the PE cells;

wherein the PE cells are PDX1+/NKX6.1+ double positive; wherein the RAR antagonist is AGN193109; wherein the RAR agonist is selected from the group consisting of AM580, All-trans retinoic acid, 9-cis retinoic acid, AC 261066, AC 55649, Adapalene, AM 80, BMS 753, BMS 961, CD 1530, CD 2314, CD 437, Ch 55, Isotretinoin, Tazarotene, TTNPB, and EC19; and wherein the concentration of the RAR antagonist is in a range of 0.5-100 μM.

2 . The method according to claim 1 , wherein the concentration of the RAR antagonist is in a range of 7-12 μM.

3 . The method according to claim 1 , wherein the culturing of the DE cells is performed for a duration in the range from one hour to six days.

4 . The method according to claim 3 , wherein the culturing of the DE cells is performed for a duration in the range from one hour to six days.

5 . The method according to claim 1 , wherein the RAR agonist is AM580.

6 . The method according to claim 1 , wherein the RAR antagonist is AGN 193109, the concentration of the RAR antagonist is in a range of 7-12 μM, the culturing of the DE cells is performed for a duration in the range from one hour to six days and wherein the RAR agonist is AM580.

7 . A method for inducing pancreatic endoderm (PE) cells from human pluripotent stem cell-derived human definitive endoderm (DE) cells, which comprises:

a step of culturing the DE cells in a culture medium comprising a retinoic acid receptor (RAR) antagonist to obtain pancreatic endoderm precursor cells,

followed by a step of culturing the pancreatic endoderm precursor cells in a cell culture medium comprising a RAR agonist, thereby inducing PE cells, wherein said PE cells are PDX-1+/NKX6.1+ double positive, wherein said RAR antagonist is AGN193109.

8 . The method according to claim 7 , wherein the concentration of said RAR antagonist is 0.5-100 μM.

9 . The method according to claim 7 , wherein said step of culturing the definitive endoderm cells in a culture medium comprising the RAR antagonist to obtain pancreatic endoderm precursor cells, has the duration of one hour to six days.

10 . The method according to claim 9 , wherein the duration is 1 to 4 days.

11 . The method according to claim 10 , wherein the duration is two days.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 1, 2026
From: NOVO NORDISK A/S
To: ASPECT BIOSYSTEMS LTD.
Reel/Frame 075363/0935 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 14, 2021
From: PETERSEN, DORTHE ROENN; HONORE, CHRISTIAN
To: NOVO NORDISK A/S
Reel/Frame 057789/0017 →
Priority Claims (1)
EP 19167800 · Apr 8, 2019 · regional
Continuity (1)
Related Publication 20220177849A1 · Jun 9, 2022
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