CHONDROCYTE THERAPEUTIC DELIVERY SYSTEM

• US 20090162386A1
• Filed: 12/04/2008
• Published: 06/25/2009
• Est. Priority Date: 09/08/2003
• Status: Active Grant

• Current Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Original Assignee: DePuy Mitek Incorporated (Johnson & Johnson)
• Inventors: Binette, Francois, Story, Brooks J., Brown, M. E. L.
• Granted Patent: US 7,927,599 B2
• Time in Patent Office: Days
• US Class Current: 424/184.100
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2533/74 Alginate
• CPC Class Codes: C12N 2533/76 : Agarose, agar-agar
• CPC Class Codes: C12N 5/0655 : Chondrocytes; Cartilage

Abstract

Systems and methods for modifying the environment of target cell using genetically altered chondrocytes are provided. The genetically engineered chondrocytes can be used to express a therapeutic agent in a subject, including in an environment typically associated with chondrocytes and in an environment not typically associated with chondrocytes.

Claims

1. A therapeutic system comprising:

(a) a housing configured to allow passage of a therapeutic agent; and

(b) a genetically altered chondrocyte retained within the housing, the genetically altered chondrocyte modified to express a therapeutic agent.

2. The therapeutic system of claim 1, wherein the housing comprises a cell chamber configured to retain chondrocytes.

3. The therapeutic system of claim 1, wherein the housing comprises a rigid material.

4. The therapeutic system of claim 3, wherein the housing further includes at least one semi-permeable port configured to allow passage of the therapeutic agent.

5. The therapeutic system of claim 1, further comprising a cap removably coupled to an end of the housing.

6. The therapeutic system of claim 1, further comprising a suture loop coupled to the housing, the suture loop configured to engage the device to a tissue.

7. The therapeutic system of claim 1, further comprising a radio-opaque marker.

8. The therapeutic system of claim 2, wherein the cell chamber is sized such that a portion of the chondrocytes are a distance of at least about 1.5 mm from an outer wall of the device.

9. The therapeutic system of claim 2, wherein the housing further includes an expandable chamber, the expandable chamber separated from the cell chamber by a piston element.

10. The therapeutic system of claim 9, wherein the expandable chamber houses a water swellable agent adapted to supply a force to the piston in response to an input of water.

11. The therapeutic system of claim 9, wherein the expandable chamber further includes a proximal end having an osmotic membrane thereby allowing for the input of water to the expandable chamber.

12. The therapeutic system of claim 8, further comprising an auxiliary fluid chamber positioned between the cell chamber and the expandable chamber, the auxiliary fluid chamber adapted to house an auxiliary fluid and the auxiliary fluid chamber separated from the cell chamber via a semi-permeable membrane.

13. The therapeutic system of claim 12, wherein the auxiliary fluid includes cell nutrients.

14. The therapeutic system of claim 12, wherein the auxiliary fluid includes an agent capable of modifying an aspect of chondrocyte performance.

15. The therapeutic system of claim 2, further comprising a delivery tube in communication with the housing such that the therapeutic agent can be delivered from the cell chamber to a distant location.

16. The therapeutic system of claim 2, further comprising an auxiliary fluid reservoir in communication with the cell chamber via a valve, the valve adapted to allow or prohibit the introduction of the auxiliary fluid to the cell chamber.

17. The therapeutic system of claim 16, further comprising a pump in communication with the fluid reservoir.

18. The therapeutic system of claim 2, further comprising a entrance port adapted to allow for the introduction of chondrocytes to the cell chamber.

19. The therapeutic system of claim 18, wherein the entrance port is a rubber septum.

20. The therapeutic system of claim 1, wherein the chondrocyte produces a therapeutic agent selected from the group consisting of a protein, an agonist or an antagonist of an antibody, an antigen, a hormone, an anti-inflammatory agent, an antiviral agent, an anti-bacterial agent, a growth factor, a cytokine, an oncogene, a tumor suppressor, a transmembrane receptor, an adhesion molecule, a neurotransmitter, a morphogenetic protein, a differentiation factor, an enzyme, and an extracellular matrix protein.

21. The therapeutic system of claim 1, wherein the therapeutic agent is an Erythropoietin protein.

22. The therapeutic system of claim 1, wherein the therapeutic agent is an Erythropoietin mimetibody.

23. A method for modifying an environment of a target cell associated with a disorder using a genetically altered chondrocyte, comprising:

providing a housing configured to retain a genetically altered chondrocyte;

providing a genetically altered chondrocyte retained within the housing, the genetically altered chondrocyte altered to express a therapeutic agent;

delivering the housing and genetically altered chondrocyte to the environment of a target cell associated with a disorder; and

expressing the therapeutic agent to a level sufficient to modify the environment surrounding the target cell.

24. The method of claim 23, wherein the target cell associated with the disorder is in an atypical chondrocyte environment.

25. The method of claim 24, wherein the atypical chondrocyte environment is in an organ selected from the group consisting of the brain, heart, liver, kidney, gastro-intestinal tract, spleen, smooth muscles, skeletal muscles, eye, ganglions, lungs, gonads, and pancreas.

26. The therapeutic system of claim 24, wherein the atypical chondrocyte environment is an aqueous environment selected from the group consisting of blood and plasma.

27. The method of claim 23, wherein the target cell associated with the disorder is in a typical chondrocyte environment.

28. The method of claim 27, wherein the typical chondrocyte environment is selected from the group consisting of bone, tendon and cartilage.

29. The method of claim 23, wherein the target cell associated with the disorder is a cell selected from the group consisting of a cell associated with a blood disorder, a cell associated with a cardiovascular disorder, a cell associated with an endocrine disorder, a cell associated with an autoimmune disorder, a cell associated with a neurological disorder, a cell associated with a skin disorder, a cell associated with fertility disorder, and a cell associated with reproduction.

30. The method of claim 23, wherein the housing comprises a rigid material.

31. The method of claim 23, wherein the housing further includes at least one semi-permeable port configured to allow passage of the therapeutic agent.

32. The method of claim 23, wherein the genetically altered chondrocyte, is genetically altered to produce a therapeutic agent selected from the group consisting of a protein, an agonist or an antogonist of an antibody, an antigen, a hormone, an anti-inflammatory agent, an antiviral agent, and anti-bacterial agent, a growth factor, a cytokine, an oncogene, a tumor suppressor, a transmembrane receptor, an adhesion molecule, a neurotransmitter, a morphogenetic protein, a differentiation factor, an enzyme, and an extracellular matrix protein.

33. The method of claim 23, wherein the therapeutic agent is an Erythropoietin protein.

34. The method of claim 23, wherein the therapeutic agent is an Erythropoietin mimetibody.

35. A method for ameliorating a disorder or injury in a subject, comprising:

providing a housing configured to retain a genetically altered chondrocyte;

providing a genetically altered chondrocyte retained within the housing, the genetically altered chondrocyte altered to express a therapeutic agent;

delivering the housing and genetically altered chondrocyte into a target region of the subject; and

expressing the therapeutic agent in the target region at a level sufficient to ameliorate the disorder.

36. The method of claim 35, wherein the genetically altered chondrocyte is not structurally functional in the target region or an environment surrounding the target region.

37. The method of claim 35, wherein the target region is in an atypical chondrocyte environment.

38. The method of claim 37, wherein the atypical chondrocyte environment is in an organ selected from the group consisting of the brain, heart, liver, kidney, gastro-intestinal tract, spleen, smooth and skeletal muscles, eye, ganglions, lungs, gonads, and pancreas.

39. The method of claim 37, wherein the atypical chondrocyte environment is an aqueous environment selected from the group consisting of blood and plasma.

40. The method of claim 35, wherein the target region is in a typical chondrocyte environment.

41. The method of claim 40, wherein the typical chondrocyte environment is selected from the group consisting of bone, tendon, and cartilage.

42. The method of claim 35, wherein the disorder is selected from the group consisting of a blood disorder, an autoimmune disorder, a hormonal disorder, an anti-inflammatory disorder, a fertility disorder, and an neurodegenerative disorder.

43. The method of claim 35, wherein the injury is selected from the group consisting of a wound, a bone defect, a cartilage defect, a skin wound, and a torn ligament.

44. The method of claim 35, wherein the housing comprises a rigid material.

45. The method of claim 35, wherein the housing further includes at least one semi-permeable port configured to allow passage of the therapeutic agent.