Chondrocyte therapeutic delivery system

• US 7,927,599 B2
• Filed: 12/04/2008
• Issued: 04/19/2011
• Est. Priority Date: 09/08/2003
• Status: Expired due to Fees

• Current Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Binette, Francois, Brown, M. E. Liesbeth, Story, Brooks J.
• Primary Examiner(s): Ton; Thaian N
• Assistant Examiner(s): NOBLE, MARCIA STEPHENS
• Application Number:
  US12/328,083
• Publication Number:
  US 20090162386A1
• Time in Patent Office: 866 Days
• Field of Search: 424/184.1, 424/93.21
• US Class Current: 424/184.1
• 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, the housing having an interior and an exterior, the interior of the housing comprising;

(i) a cell chamber,

(ii) an auxiliary fluid chamber configured to house an auxiliary fluid, and

(iii) an expandable chamber;

the auxiliary fluid chamber being position between the cell chamber and the expandable chamber; and

(b) a genetically altered chondrocyte retained within the cell chamber, the genetically altered chondrocyte modified to express a therapeutic agent;

wherein the cell chamber includes a mechanism configured to allow selective release of the therapeutic agent;

wherein the auxiliary fluid chamber is configured to deliver auxiliary fluid to the cell chamber; and

wherein the expandable chamber includes an osmotic membrane configured to allow for the input of fluid to the expandable chamber such that auxiliary fluid is controllably introduced to the cell chamber in response to the expansion of the expandable chamber.

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

3. The therapeutic system of claim 1, further comprising a cap removably coupled to an end of the housing to allow for the introduction of the genetically altered chondrocytes to the cell chamber.

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

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

6. The therapeutic system of claim 1, wherein the cell chamber is sized such that a portion of the chondrocytes is a distance of at least about 1.5 mm from the exterior of the housing.

7. The therapeutic system of claim 1, wherein the expandable chamber is separated from the auxiliary fluid chamber by a piston.

8. The therapeutic system of claim 7, wherein the expandable chamber houses a water swellable agent adapted to supply a force to the piston in response to an input of water.

9. The therapeutic system of claim 1, wherein the auxiliary fluid includes cell nutrients.

10. The therapeutic system of claim 1, wherein the auxiliary fluid includes an agent capable of modifying an aspect of chondrocyte performance.

11. The therapeutic system of claim 1, 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.

12. The therapeutic system of claim 1, further comprising a entrance port adapted to allow for the introduction of chondrocytes to the cell chamber.

13. The therapeutic system of claim 12, wherein the entrance port is a rubber septum.

14. 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.

15. The therapeutic system of claim 1, wherein the therapeutic agent is an erythropoietin protein.

16. The therapeutic system of claim 1, wherein the therapeutic agent is an erythropoietin mimetibody.