Chondrocyte therapeutic delivery system

• US 20050054595A1
• Filed: 09/08/2003
• Published: 03/10/2005
• Est. Priority Date: 09/08/2003
• Status: Active Grant

• Current Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Binette, Francois, Story, Brooks J.
• Granted Patent: US 7,897,384 B2
• Time in Patent Office: Days
• US Class Current: 514/44.R
• 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 genetically altered chondrocyte used for expressing a therapeutic agent, wherein the genetically altered chondrocyte is effective to be delivered to a cell associated with a disorder and to express the therapeutic agent to modify an environment surrounding the cell, such that the genetically altered chondrocyte is not structurally functional in the environment surrounding the cell.

2. The genetically altered chondrocyte 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.

3. The genetically altered chondrocyte of claim 1, wherein the therapeutic agent is an Erythropoietin protein.

4. The genetically altered chondrocyte of claim 1, wherein the therapeutic agent is an Erythropoietin mimetibody.

6. The genetically altered chondrocyte of claim 1, wherein the atypical chondrocyte environment is in an organ selected from the group consisting of the brain, heart, liver, kidney, gastrointestinal tract, spleen, smooth muscles, skeletal muscles, eye, ganglions, lungs, gonads, and pancreas.

7. The genetically altered chondrocyte of claim 1, wherein the atypical chondrocyte environment is an aqueous environment selected from the group consisting of blood and plasma.

8. The genetically altered chondrocyte of claim 1, wherein the cell associated with a disorder is in a typical chondrocyte environment.

9. The genetically altered chondrocyte of claim 8, wherein the typical chondrocyte environment is selected from the group consisting of bone, tendon and cartilage.

10. The genetically altered chondrocyte of claim 1, further comprising a biocompatible substrate mixed therewith.

11. The genetically altered chondrocyte of claim 10, wherein the biocompatible substrate is gel matrix substrate.

12. The genetically altered chondrocyte of claim 1, wherein the cell associated with a 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.

5. The genetically altered chondrocyte of claim 5, wherein the cell associated with a disorder is in an atypical chondrocyte environment.

13. A genetically altered chondrocyte used for expressing a therapeutic agent in a target region associated with a disorder, wherein the genetically altered chondrocyte is effective to be delivered to the target region and to express the therapeutic agent to modify the target region or an environment surrounding the target region, such that the genetically altered chondrocyte does not become structurally functional in the target region or the environment surrounding the target region.

14. The genetically altered chondrocyte of claim 13, 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 genetically altered chondrocyte of claim 13, wherein the therapeutic agent is an Erythropoietin protein.

16. The genetically altered chondrocyte of claim 13, wherein the therapeutic agent is an Erythropoietin mimetibody.

17. The genetically altered chondrocyte of claim 13, wherein the target region is in an atypical chondrocyte environment.

18. The genetically altered chondrocyte of claim 17, 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.

19. The genetically altered chondrocyte of claim 17, wherein the atypical chondrocyte environment is an aqueous environment selected from the group consisting of blood and plasma.

20. The genetically altered chondrocyte of claim 13, wherein the target region is in a typical chondrocyte environment.

21. The genetically altered chondrocyte of claim 20, wherein the typical chondrocyte environment is selected from the group consisting of bone, tendon, and cartilage.

22. The genetically altered chondrocyte of claim 13, further comprising a biocompatible substrate mixed therewith.

23. The genetically altered chondrocyte of claim 22, wherein the biocompatible substrate is gel matrix substrate.

24. The genetically altered chondrocyte of claim 13, wherein the disorder is selected from the group consisting of a blood disorder;

a cardiovascular disorder;

an endocrine disorder;

an autoimmune disorder;

a neurological disorder;

a skin disorder;

a fertility disorder and reproduction.

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

providing a genetically altered chondrocyte, wherein the genetically altered chondrocyte has been altered to express a therapeutic agent;

delivering the genetically altered chondrocyte to the environment of a cell with a disorder such that the genetically altered chondrocyte does not become structurally functional in the environment surrounding the cell; and

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

26. The method of claim 25, 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.

27. The method of claim 25, wherein the therapeutic agent is an Erythropoietin protein.

28. The method of claim 25, wherein the therapeutic agent is an Erythropoietin mimetibody.

29. The method of claim 25, wherein the cell associated with the disorder is in an atypical chondrocyte environment.

30. The method of claim 29, 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.

31. The method of claim 29, wherein the atypical chondrocyte environment is an an aqueous environment selected from the group consisting of blood and plasma.

32. The method of claim 25, wherein the target region is in a typical chondrocyte environment.

33. The method of claim 32, wherein the typical chondrocyte environment is selected from the group consisting of bone, tendon, and cartilage.

34. The method of claim 25 further comprising mixing the genetically altered chondrocyte with a biocompatible substrate.

35. The method of claim 34, wherein the biocompatible substrate is a gel matrix substrate.

36. A method for ameliorating a disorder or injury in a subject using a genetically altered chondrocyte, comprising:

providing a genetically altered chondrocyte, wherein the genetically altered chondrocyte has been altered to express a therapeutic agent;

implanting a biocompatible substrate comprising a genetically altered chondrocyte into a target region of the subject, wherein the genetically altered chondrocyte is not structurally functional in the target region or an environment surrounding the target region; and

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

37. The method of claim 36, wherein the target region is in an atypical chondrocyte environment.

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

40. The method of claim 36, 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 36, wherein the step of implanting the biocompatible substrate comprises implanting a gel matrix substrate.

43. The method of claim 42, wherein the gel matrix substrate is selected from the group consisting of alginate, polysaccharide, and agarose.

44. The method of claim 42, 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.

45. The method of claim 44, wherein the concentration of chondrocytes in the gel matrix substrate is about 100,00 to 10 millions cells per ml in a gel matrix volume of 0.05 ml to 10 ml.

46. The method of claim 36, 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.

47. The method of claim 36, 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.