IP Library › Patent Application 18022538
Patent Application
App. No. 18/022,538

METHOD FOR SCREENING IN VITRO POPULATION OF STEM CELL DERIVED BETA LIKE CELLS AND NOVEL MARKERS THEREOF

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Patent No.
US None
App. No.
18/022,538
Abstract

The present invention relates to a method for screening for beta like cells in an in vitro cell population of pluripotent stem cell derived cells, wherein the method comprises a step of identifying the beta like cells expressing specific markers or combinations thereof for predicting the in vivo functionality of said cells prior to transplantation. The present invention also relates to an in vitro population of pluripotent stem cell derived beta like cells, wherein the beta like cell comprises one or more markers that is absent in native human beta cell or the expression level of said marker is different than in native human beta cells.

Claims (53)

1 .- 15 . (canceled)

16 . An in vitro population of beta like cells expressing NKX6.1 in combination with one or more markers selected from the group consisting of ACVR1C, MARCKSL1, BASP1, STARD10, AMBP, ST6GALNAC5, HMGCS1, SOX11, FREM2, and DCC;

wherein the expression level of each marker is at least about 1 average log fold change more than the expression level of the marker in a native human beta cell; and

wherein the cells are capable of maintaining insulin expression and secretion after in vivo transplantation.

17 . The beta like cells according to claim 16 , wherein the beta like cells express one or more markers selected from the group consisting of ACVR1C, MARCKSL1, BASP, STARD10, AMBP, ST6GALNAC5, and HMGCS1.

18 . The beta like cells according to claim 16 , wherein the beta like cells express one or more markers selected from the group consisting of SOX11, FREM2, and DCC.

19 . The beta like cells according to claim 16 , wherein the beta like cells further express G6PC2.

20 . The beta like cells according to claim 16 , wherein the beta like cells express ACVR1C, MARCKSL1, BASP, STARD10, AMBP, ST6GALNAC5, HMGCS1, SOX11, FREM2, and DCC.

21 . The beta like cells according to claim 20 , wherein the beta like cells further express G6PC2.

22 . The beta like cells according to claim 16 , wherein at least 95% of the beta like cells express ACVR1C.

23 . The beta like cells according to claim 22 , wherein the expression level of ACVR1C is at least about 2 average log fold change more than the expression of ACVR1C in a native human beta cell.

24 . The beta like cells according to claim 16 , wherein at least 95% of the beta like cells express MARCKSL1.

25 . The beta like cells according to claim 24 , wherein the expression level of MARCKSL1 is at least about 2 average log fold change more than the expression of MARCKSL1 in a native human beta cell.

26 . The beta like cells according to claim 16 , wherein at least 75% of the beta like cells express BASP1.

27 . The beta like cells according to claim 16 , wherein at least 95% of the beta like cells express STARD10.

28 . The beta like cells according to claim 16 , wherein at least 90% of the beta like cells express AMBP.

29 . The beta like cells according to claim 28 , wherein the expression level of AMBP is at least about 2 average log fold change more than the expression of AMBP in a native human beta cell.

30 . The beta like cells according to claim 16 , wherein at least 85% of the beta like cells express ST6GALNAC5.

31 . The beta like cells according to claim 16 , wherein at least 80% of the beta like cells express HMGCS1.

32 . The beta like cells according to claim 16 , wherein at least 85% of the beta like cells express SOX11.

33 . The beta like cells according to claim 16 , wherein at least 75% of the beta like cells comprise FREM2.

34 . The beta like cells according to claim 16 , wherein at least 85% of the beta like cells comprise DCC.

35 . The beta like cells according to claim 16 , wherein at least 95% of the beta like cells express ACVR1C, wherein at least 95% of the beta like cells express MARCKSL1, wherein at least 75% of the beta like cells express BASP1, wherein at least 95% of the beta like cells express STARD10, wherein at least 90% of the beta like cells express AMBP, wherein at least 85% of the beta like cells express ST6GALNAC5, wherein at least 80% of the beta like cells express HMGCS1, wherein at least 85% of the beta like cells express SOX11, wherein at least 75% of the beta like cells comprise FREM2, and wherein at least 85% of the beta like cells comprise DCC.

36 . The beta like cells according to claim 16 , wherein at least 80% of the beta like cells express ACVR1C, MARCKSL1, STARD10, AMBP, ST6GALNAC5, and HMGCS1.

37 . The beta like cells according to claim 16 , wherein at least 90% of the beta like cells express ACVR1C, MARCKSL1, STARD10, and AMBP.

38 . The beta like cells according to claim 16 , wherein at least 55% of the beta like cells express SOX11, FREM2, and DCC.

39 . The beta like cells according to claim 16 , wherein at least 75% of the beta like cells express SOX11, FREM2, and DCC.

40 . A method for screening beta like cells in an in vitro population of pluripotent stem cell derived cells, comprising identifying beta like cells expressing NKX6.1 in combination with one or more markers selected from the group consisting of ACVR1C, MARCKSL1, BASP1, STARD10, AMBP, ST6GALNAC5, HMGCS1, SOX11, FREM2, and DCC;

wherein the expression level of each marker is at least about 1 average log fold change more than the expression level of the marker in a native human beta cell; and

wherein the cells are capable of maintaining insulin expression and secretion after in vivo transplantation.

41 . The method according to claim 40 , wherein the beta like cells express one or more markers selected from the group consisting of ACVR1C, MARCKSL1, BASP, STARD10, AMBP, ST6GALNAC5, and HMGCS1.

42 . The beta like cells according to claim 40 , wherein the beta like cells express one or more markers selected from the group consisting of SOX11, FREM2, and DCC.

43 . The beta like cells according to claim 40 , wherein the beta like cells further express G6PC2.

44 . The beta like cells according to claim 40 , wherein the beta like cells express ACVR1C, MARCKSL1, BASP, STARD10, AMBP, ST6GALNAC5, HMGCS1, SOX11, FREM2, and DCC.

45 . The beta like cells according to claim 44 , wherein the beta like cells further express G6PC2.

46 . The method according to claim 40 , wherein at least 95% of the beta like cells express ACVR1C.

47 . The method according to claim 46 , wherein the expression level of ACVR1C is at least about 2 average log fold change more than the expression of ACVR1C in a native human beta cell.

48 . The method according to claim 40 , wherein at least 95% of the beta like cells express MARCKSL1.

49 . The method according to claim 48 , wherein the expression level of MARCKSL1 is at least about 2 average log fold change more than the expression of MARCKSL1 in a native human beta cell.

50 . The method according to claim 40 , wherein at least 75% of the beta like cells express BASP1.

51 . The method according to claim 40 , wherein at least 95% of the beta like cells express STARD10.

52 . The method according to claim 40 , wherein at least 90% of the beta like cells express AMBP.

53 . The method according to claim 52 , wherein the expression level of AMBP is at least about 2 average log fold change more than the expression of AMBP in a native human beta cell.

54 . The method according to claim 40 , wherein at least 85% of the beta like cells express ST6GALNAC5.

55 . The method according to claim 40 , wherein at least 80% of the beta like cells express HMGCS1.

56 . The method according to claim 40 , wherein at least 85% of the beta like cells express SOX11.

57 . The method according to claim 40 , wherein at least 75% of the beta like cells comprise FREM2.

58 . The method according to claim 40 , wherein at least 85% of the beta like cells comprise DCC.

59 . The method according to claim 40 , wherein at least 95% of the beta like cells express ACVR1C, wherein at least 95% of the beta like cells express MARCKSL1, wherein at least 75% of the beta like cells express BASP1, wherein at least 95% of the beta like cells express STARD10, wherein at least 90% of the beta like cells express AMBP, wherein at least 85% of the beta like cells express ST6GALNAC5, wherein at least 80% of the beta like cells express HMGCS1, wherein at least 85% of the beta like cells express SOX11, wherein at least 75% of the beta like cells comprise FREM2, and wherein at least 85% of the beta like cells comprise DCC.

60 . The method according to claim 40 , wherein at least 80% of the beta like cells express ACVR1C, MARCKSL1, STARD10, AMBP, ST6GALNAC5, and HMGCS1.

61 . The method according to claim 40 , wherein at least 90% of the beta like cells express ACVR1C, MARCKSL1, STARD10, and AMBP.

62 . The method according to claim 40 , wherein at least 55% of the beta like cells express SOX11, FREM2, and DCC.

63 . The method according to claim 40 , wherein at least 75% of the beta like cells express SOX11, FREM2, and DCC.

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 Apr 10, 2023
From: KIRKEGAARD, JEANNETTE SCHLICHTING; LU, TESS TSAI-HSIU
To: NOVO NORDISK A/S
Reel/Frame 063270/0717 →