EXTRACORPOREAL CELL-BASED THERAPEUTIC DEVICE AND DELIVERY SYSTEM

• US 20070269489A1
• Filed: 02/01/2007
• Published: 11/22/2007
• Est. Priority Date: 02/02/2006
• Status: Active Grant

• Current Assignee: Seastar Medical, Inc. (LMF Acquisition Opportunities, Inc.)
• Original Assignee: Innovative Biotherapies, Inc.
• Inventors: Humes, H.
• Granted Patent: US 8,048,419 B2
• Time in Patent Office: Days
• US Class Current: 424/430
• CPC Class Codes: A61M 1/3489 by biological cells, e.g. bioreactor
• CPC Class Codes: A61M 1/3655 Arterio-venous shunts or fistulae
• CPC Class Codes: A61M 1/3687 Chemical treatment A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/3689 by biological cells
• CPC Class Codes: A61M 2202/09 Body tissue
• CPC Class Codes: A61M 5/14 Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Extracorporeal cell-based therapeutic devices and delivery systems are disclosed which provide a method for therapeutic delivery of biologically active molecules produced by living cells in response to a dynamic physiologic environment. Exemplary designs are disclosed. In a first exemplary embodiment the device includes long hollow fibers in which a layer of cells are grown within the intraluminal volume or within a double hollow-filled chamber. In another exemplary embodiment the device includes a wafer or a series of wafers forms a substrate onto which cells are grown. The wafer(s) are then inserted into a device. The devices are intended to be extracorporeal. Disclosed is a device for delivering a pre-selected molecule, for example, a hormone, into a mammal'"'"'s systemic circulation. The device may also deliver a member of different cell products. The device comprises an anchoring element that can be anchored to an inner wall of an extracorporeal tube for blood. The device also comprises a capsule that is held in place within the extracorporeal tube for blood or fluid by an anchor. The device is adapted to secure viable cells which produce and secrete the pre-selected molecule into blood or fluid passing the capsule. The invention also provides a minimally invasive method for percutaneously introducing into a preselected blood vessel or body cavity the device of the invention.

Claims

1. An extracorporeal cell based therapeutic device comprising:

(a) an anchor system which is capable of attaching the device to an extracorporeal tube, which when attached to the inner wall of the tube permits blood in the tube to pass therethrough; and

(b) a capsule including a plurality of pores and having viable cells disposed therein, wherein the capsule, when introduced into the tube, is retained within the tube by the anchor system and the pores permit nutrients to enter the capsule to maintain viability of the cells disposed therein.

2. The device of claim 1, wherein the capsule is defined by a semi-permeable membrane.

3. The device of claim 2, wherein the semi-permeable membrane comprises a material selected from the group consisting of polyvinylidene fluoride, polyvinylchloride, polyurethane, polyalginate, polystyrene, polyurethane, polyvinyl alcohol, polyacrylonitrile, polyamide, polymethylmethacrylate, polyethylene oxide, polytetrafluorethylene, isocyanate, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose nitrate, polysulfone, and mixtures thereof.

4. The device of claim 1, wherein the viable cells are disposed on a plurality of filaments.

5. The device of claim 4, wherein the filaments are metallic.

6. The device of claim 1, wherein the pores are dimensioned to prevent passage of antibodies therethrough.

7. The device of claim 1, wherein the cells are disposed on at least one disk.

8. The device of claim 1, wherein the cells are eukaryotic cells.

9. The device of claim 8, wherein the cells are mammalian cells.

10. The device of claim 1, wherein the capsule is adapted to be separated from the tube by attaching and detaching the anchor system from the tube.

11. The device of claim 1, wherein the capsule includes at least one hollow fiber.

12. The device of claim 1, wherein the pores permit solutes less than 150 kD to pass therethrough.

13. The device of claim 1, wherein the device is configured to provide a therapeutically significant amount of a molecule without using an artificial blood pump.

14. An extracorporeal cell based therapeutic device comprising:

(a) an attachment system anchorable to an inner wall of an extracorporeal tube adapted to provide a conduit for blood, which when anchored to the inner wall of a tube permits blood to circulate; and

(b) a capsule defining a plurality of pores and having viable cells disposed therein, wherein the capsule is retained within the tube by the attachment system and the pores permit nutrients to enter the capsule to maintain viability of the cells disposed therein.

15. The device of claim 14, wherein the capsule is defined by a semi-permeable membrane.

16. The device of claim 15, wherein the semi-permeable membrane comprises a material selected from the group consisting of polyvinylidene fluoride, polyvinylchloride, polyurethane, polyalginate, polystyrene, polyurethane, polyvinyl alcohol, polyacrylonitrile, polyamide, polymethylmethacrylate, polyethylene oxide, polytetrafluorethylene, isocyanate, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose nitrate, polysulfone, and mixtures thereof.

17. The device of claim 14, wherein the pores are dimensioned to exclude an agent in the blood which is detrimental to cell viability.

18. The device of claim 17, wherein the pores are dimensioned to prevent passage of antibodies therethrough.

19. The device of claim 14, wherein the cells are eukaryotic cells.

20. The device of claim 19, wherein in the cells are mammalian cells.

21. The device of claim 14, wherein the anchor is metallic.

22. The device of claim 14, wherein the capsule when introduced into the tube is retained upstream of the attachment system.

23. The device of claim 14, wherein the capsule includes at least one disk.

24. The device of claim 14, wherein the pores permit solutes less than 150 kD to pass therethrough.

25. The device of claim 14, wherein the cells are genetically engineered cells.

26. A method of introducing an extracorporeal cell-based therapeutic device into the circulatory system of a mammal, the method comprising the steps of:

(a) anchoring an attachment system to an inner wall of an extracorporeal tube adapted to provide a conduit for bodily fluid, which when anchored to the inner wall of a tube permits the bodily fluid to circulate; and

(b) inserting a capsule defining a plurality of pores and having viable cells disposed therein, wherein the capsule is retained within the tube by the attachment system and the pores permit nutrients to enter the capsule to maintain viability of the cells disposed therein.

27. The method of claim 26, wherein in step (a), the attachment system is introduced into the tube via a catheter.

28. The method of claim 26, wherein in step (b), the capsule is introduced into the tube via a catheter.

29. The method of claim 26, wherein the viable cells are disposed on at least one disk.

30. The method of claim 26, wherein the device is used to deliver a therapeutic amount of a molecule in the conduit without the use of an artificial body fluid pump.

31. The method of claim 26, wherein the conduit is attached to the peritoneum and the peritoneal fluid passes through the conduit.

32. An extracorporeal cell based therapeutic device comprising:

(a) an attachment system anchorable to an inner wall of an extracorporeal tube adapted to provide a conduit for a bodily fluid, which when anchored to the inner wall of a tube permits the bodily fluid to circulate; and

(b) a capsule defining a plurality of pores and having viable cells disposed therein, wherein the capsule, when introduced into the tube, is retained within the tube by the attachment system and the pores permit nutrients to enter the capsule to maintain viability of the cells disposed therein.

33. The device of claim 32, wherein the capsule is defined by a semi-permeable membrane.

34. The device of claim 33, wherein the semi-permeable membrane comprises a material selected from the group consisting of polyvinylidene fluoride, polyvinylchloride, polyurethane, polyalginate, polystyrene, polyurethane, polyvinyl alcohol, polyacrylonitrile, polyamide, polymethylmethacrylate, polyethylene oxide, polytetrafluorethylene, isocyanate, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose nitrate, polysulfone, and mixtures thereof.

35. The device of claim 34, wherein the pores are dimensioned to prevent passage of antibodies therethrough.

36. The device of claim 32, wherein the tube is adapted to be connected to the peritoneum and the bodily fluid includes peritoneal fluid.

37. The device of claim 32, wherein the tube is adapted to be connected to blood vessels and the bodily fluid includes blood.

38. The device of claim 32, wherein the attachment system separable from the tube.

39. The device of claim 32, wherein the capsule when introduced into the tube is retained upstream of the attachment system.

40. The device of claim 32, wherein the capsule includes at least one disk.

41. The device of claim 32, wherein the pores permit solutes less than 150 kD to pass therethrough.