IP Library › Granted Patent US 12,194,138
Granted Patent B2
US 12,194,138 · App. 17/736,579 · Granted Jan 14, 2025

Devices and methods for delivering therapeutics

Inventors: Christopher Thanos (Cumberland, RI); Yang Qiu (Providence, RI)
Assignee: Vertex Pharmaceuticals Incorporated
A61K9/00A61K9/0024A61K9/7007A61K35/39A61K38/18A61K38/43A61M31/002C12N5/0676C12N5/0678C12N5/0613C12N2537/10
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Quick Facts
Patent No.
US 12,194,138
App. No.
17/736,579
Granted
Jan 14, 2025
Kind
B2
Abstract

The present invention provides devices and methods for delivering a population of cells or a therapeutic agent to a subject in need thereof.

Claims (55)

1. A method of delivering a first molecule to a subject, the method comprising:

implanting an implantable device in the subject;

controlling diffusion of at least the first molecule and a second molecule across a porous polymeric membrane of the implantable device at least partially encapsulating a population of cells, wherein the population of cells comprises at least one selected from the group of pancreatic progenitor cells, endocrine cells, alpha cells, delta cells, and beta cells,

wherein the membrane includes a plurality of open pores, wherein the open pores have an average pore size equal to or less than 1 μm, and

wherein a ratio of D first /D second is equal to or greater than 2 and less than or equal to 50, wherein D first is a first diffusion coefficient across the membrane for the first molecule having a first molecular weight between or equal to 50 Da and 10 kDa, wherein D second is a second diffusion coefficient across the membrane for the second molecule having a second molecular weight between or equal to 50 kDa and 500 kDa, and wherein a ratio of said second molecular weight to said first molecular weight is equal to or greater than 10.

2. The method of claim 1 , wherein the implantable device is implanted in the subject for a period of more than six months.

3. The method of claim 1 , wherein the first molecule treats at least one condition selected from the group of diabetes, an ischemic tissue wound, and hypoparathyroidism.

4. The method of claim 1 , further comprising producing and releasing insulin when the implantable device is implanted into the subject.

5. The method of claim 1 , wherein the membrane has an average thickness of between 10 μm and 150 μm, and wherein the membrane has a tensile strength of at least 1 MPa.

6. The method of claim 1 , wherein said population of cells is encapsulated within said device in an amount of 10 4 to 10 6 cells per μL.

7. The method of claim 1 , wherein the ratio of D first /D second is measured using 4 kDa FITC-dextran and 500 kDa FITC-dextran.

8. The method of claim 1 , wherein the first molecule comprises a therapeutic agent.

9. The method of claim 1 , wherein the first molecule is insulin.

10. The method of claim 1 , wherein the second molecule comprises at least one selected from the group of pepsinogen, lipase 2, prolipase, angiotensinogen, amylase, and cholesterol esterase.

11. The method of claim 1 , wherein said population of cells comprises at least one insulin producing cell and at least one glucagon or somatostatin producing cell, and wherein said device, when implanted into the subject, releases said insulin at a different flux rate than said device releases said glucagon or said somatostatin.

12. The method of claim 1 , wherein the membrane comprises polyacrylonitrile (PAN), polysulfone (PSf), polytetrafluoroethylene (PTFE), polyurethane (PU), polyvinylidene fluoride (PVDF), or any combination thereof.

13. The method of claim 1 , wherein the population of cells comprises non-native beta cells.

14. The method of claim 1 , wherein the first molecule treats diabetes.

15. A method treating of delivering a first molecule to a subject, the method comprising:

implanting an implantable device in the subject;

controlling diffusion of at least the first molecule and a second molecule across a porous polymeric membrane of the implantable device at least partially encapsulating a population of human cells, wherein said population of human cells comprises at least one selected from the group of human pancreatic progenitor cells, human endocrine cells, human alpha cells, human delta cells, and human beta cells,

wherein the membrane includes a plurality of open pores, wherein the membrane has an average pore size equal to or less than 1 μm, wherein the membrane has an average thickness of between 10 μm and 150 μm,

wherein a ratio of D first /D second is equal to or greater than 2 and less than or equal to 50, wherein D first is a first diffusion coefficient across the membrane for the first molecule having a first molecular weight between or equal to 50 Da and 10 kDa, wherein D second is a second diffusion coefficient across the membrane for the second molecule having a second molecular weight between or equal to 50 kDa and 500 kDa, and wherein a ratio of said second molecular weight to said first molecular weight is equal to or greater than 10.

16. The method of claim 15 , wherein the membrane comprises polyacrylonitrile (PAN), polysulfone (PSf), polytetrafluoroethylene (PTFE), polyurethane (PU), polyvinylidene fluoride, or any combination thereof.

17. The method of claim 15 , wherein the implantable device is implanted in the subject for a period of more than six months.

18. The method of claim 15 , wherein the first molecule treats at least one condition selected from the group of diabetes, an ischemic tissue wound, and hypoparathyroidism.

19. The method of claim 15 , further comprising producing and releasing insulin when the implantable device is implanted into the subject.

20. The method of claim 15 , wherein the membrane has a tensile strength of at least 1 MPa.

21. The method of claim 15 , wherein said population of cells is encapsulated within said device in an amount of 10 4 to 10 6 cells per μL.

22. The method of claim 15 , wherein the ratio of D first /D second is measured using 4 kDa FITC-dextran and 500 kDa FITC-dextran.

23. The method of claim 15 , wherein the first molecule comprises a therapeutic agent.

24. The method of claim 15 , wherein the first molecule is insulin.

25. The method of claim 15 , wherein the second molecule comprises at least one selected from the group of pepsinogen, lipase 2, prolipase, angiotensinogen, amylase, and cholesterol esterase.

26. The method of claim 15 , wherein said population of cells comprises at least one insulin producing cell and at least one glucagon or somatostatin producing cell, and wherein said device, when implanted into the subject, releases said insulin at a different flux rate than said device releases said glucagon or said somatostatin.

27. The method of claim 15 , wherein the population of cells comprises non-native beta cells.

28. The method of claim 15 , wherein the first molecule treats diabetes.

29. A method of delivering a first molecule to a subject, the method comprising:

implanting an implantable device in the subject;

controlling diffusion of at least the first molecule and a second molecule across a porous crosslinked electrospun polymeric membrane of the implantable device at least partially encapsulating a population of cells,

wherein the membrane includes a plurality of open pores, wherein the membrane has an average pore size equal to or less than 1 μm, wherein the membrane has an average thickness of between 10 μm and 150 μm,

wherein a ratio of D first /D second is equal to or greater than 2 and less than or equal to 50, wherein D first is a first diffusion coefficient across the membrane for the first molecule having a first molecular weight between or equal to 50 Da and 10 kDa, wherein D second is a second diffusion coefficient across the membrane for the second molecule having a second molecular weight between or equal to 50 kDa and 500 kDa, and wherein a ratio of said second molecular weight to said first molecular weight is equal to or greater than 10.

30. The method of claim 29 , wherein the membrane comprises polyacrylonitrile (PAN), polysulfone (PSf), polytetrafluoroethylene (PTFE), polyurethane (PU), polyvinylidene fluoride (PVDF), or any combination thereof.

31. The method of claim 29 , wherein the membrane has an average fiber diameter of equal to or less than 1000 nm, and wherein the membrane is hydrophilic.

32. The method of claim 29 , wherein the implantable device is implanted in the subject for a period of more than six months.

33. The method of claim 29 , wherein the first molecule treats at least one condition selected from the group of diabetes, an ischemic tissue wound, and hypoparathyroidism.

34. The method of claim 29 , further comprising producing and releasing insulin when the implantable device is implanted into the subject.

35. The method of claim 29 , wherein the membrane has a tensile strength of at least 1 MPa.

36. The method of claim 29 , wherein said population of cells is encapsulated within said device in an amount of 10 4 to 10 6 cells per μL.

37. The method of claim 29 , wherein the ratio of D first /D second is measured using 4 kDa FITC-dextran and 500 kDa FITC-dextran.

38. The method of claim 29 , wherein the first molecule comprises a therapeutic agent.

39. The method of claim 29 , wherein the first molecule is insulin.

40. The method of claim 29 , wherein the second molecule comprises at least one selected from the group of pepsinogen, lipase 2, prolipase, angiotensinogen, amylase, and cholesterol esterase.

41. The method of claim 29 , wherein said population of cells comprises at least one insulin producing cell and at least one glucagon or somatostatin producing cell, and wherein said device, when implanted into the subject, releases said insulin at a different flux rate than said device releases said glucagon or said somatostatin.

42. The method of claim 29 , wherein the population of cells comprises non-native beta cells.

43. The method of claim 29 , wherein the first molecule treats diabetes.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 22, 2022
From: THANOS, CHRISTOPHER; QIU, YANG
To: SEMMA THERAPEUTICS, INC.
Reel/Frame 061180/0787 →
MERGER AND CHANGE OF NAME Recorded Sep 22, 2022
From: SEMMA THERAPEUTICS, INC.; VERTEX PHARMACEUTICALS INCORPORATED
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 061180/0894 →
Continuity (4)
Continuation 16294631 · Mar 6, 2019
Continuation PCTUS2018037637 · Jun 14, 2018
Provisional Application 62519702 · Jun 14, 2017
Related Publication 20220331234A1 · Oct 20, 2022
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