Chondrocyte therapeutic delivery system

• US 7,897,384 B2
• Filed: 09/08/2003
• Issued: 03/01/2011
• Est. Priority Date: 09/08/2003
• Status: Active Grant

• Current Assignee: DePuy Mitek Holding Corporation (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Binette, Francois, Story, Brooks J.
• Primary Examiner(s): BERTOGLIO, VALARIE E
• Application Number:
  US10/657,516
• Publication Number:
  US 20050054595A1
• Time in Patent Office: 2,731 Days
• Field of Search: 435/325
• US Class Current: 435/325
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• 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 27/02 Ophthalmic agents
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/48 : of the pancreatic hormones
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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

Methods and compositions for producing therapeutic agents using chondrocytes are provided. The genetically engineered chondrocytes can be used to express the 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 composition comprising:

(a) a biocompatible substrate having a length in a range of about 10 cm to about 30 cm;

(b) a genetically altered chondrocyte cultured and modified to express a therapeutic agent in a target region associated with a disorder, the genetically altered chondrocyte not used for tissue repair or construction,

wherein the target region is an ectopic site and wherein the composition is capable of delivering the therapeutic agent at a level sufficient to ameliorate the disorder.

2. The composition of claim 1, wherein the composition does not become part of the ectopic target region.

3. The composition of claim 1, further being adapted to deliver the therapeutic agent to an environment surrounding a cell associated with a disorder, and being capable of modifying the environment surrounding the cell.

4. The composition of claim 1, wherein the chondrocyte produces a therapeutic agent selected from the group consisting of a protein, an antibody, a mimetibody, 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.

5. The composition of claim 1, wherein the therapeutic agent is an Erythropoietin protein.

6. The composition of claim 1, wherein the therapeutic agent is an Erythropoietin mimetibody.

7. The composition of claim 1, wherein the ectopic site is in a site 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.

8. The composition of claim 1, wherein the ectopic site is an aqueous environment selected from the group consisting of blood and plasma.

9. The composition of claim 1, wherein the biocompatible substrate is gel matrix substrate.

10. The composition of claim 9, wherein the gel matrix substrate is selected from the group consisting of alginate, polysaccharide, and agarose.

11. The composition of claim 9, wherein the dimensions of the implanted gel matrix substrate determines the concentration of chondrocytes within the gel matrix substrate that are available to express the therapeutic agent.

12. The composition of claim 9, wherein the concentration of chondrocytes in the gel matrix substrate is about 100,00 to 10 million cells per ml in a gel matrix volume of 0.05 ml to 10 ml.

21. The composition of claim 1, wherein the genetically altered chondrocyte is isolated from cartilage tissue.

13. A composition comprising:

(a) a biocompatible substrate; and

(b) a genetically altered chondrocyte cultured and modified to express a therapeutic agent in a target region associated with a disorder;

the genetically altered chondrocyte not used for tissue repair or construction,

wherein the target region is an ectopic site, and wherein the composition is capable of delivering the therapeutic agent at a level sufficient to ameliorate the disorder, and wherein the therapeutic agent is selected from the group consisting of Erythropoietin protein and Erythropoietin mimetibody.

14. The composition of claim 13, wherein the composition is not part of the ectopic target region.

15. The composition of claim 13, wherein the ectopic site is in a site 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.

16. The composition of claim 13, wherein the ectopic site is an aqueous environment selected from the group consisting of blood and plasma.

17. The composition of claim 13, wherein the biocompatible substrate is gel matrix substrate.

18. The composition of claim 17, wherein the gel matrix substrate is selected from the group consisting of alginate, polysaccharide, and agarose.

19. The composition of claim 17, wherein the dimensions of the implanted gel matrix substrate determines the concentration of chondrocytes within the gel matrix substrate that are available to express the therapeutic agent.

20. The composition of claim 17, wherein the concentration of chondrocytes in the gel matrix substrate is about 100,00 to 10 million cells per ml in a gel matrix volume of 0.05 ml to 10 ml.

22. The composition of claim 13, wherein the genetically altered chondrocyte is isolated from cartilage tissue.