Chondrocyte therapeutic delivery system

• US 8,394,369 B2
• Filed: 08/10/2006
• Issued: 03/12/2013
• Est. Priority Date: 09/08/2003
• Status: Expired due to Fees

• Current Assignee: DePuy Mitek Incorporated (Johnson & Johnson)
• Original Assignee: DePuy Mitek Incorporated (Johnson & Johnson)
• Inventors: Binette, Francois, Story, Brooks J.
• Primary Examiner(s): BERTOGLIO, VALARIE E
• Application Number:
  US11/463,708
• Publication Number:
  US 20080181954A1
• Time in Patent Office: 2,406 Days
• Field of Search: 424/93.1
• US Class Current: 424/93.21
• 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 method for expressing a therapeutic agent 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 the genetically altered chondrocyte into a target region of the subject, wherein the target region is in an atypical chondrocyte environment, wherein the genetically altered chondrocyte becomes a structural component of neither the target region nor the atypical chondrocyte environment surrounding the target region; and

expressing the therapeutic agent in the target region at a level higher than the baseline level of said therapeutic agent in the target region so as to modify the environment surrounding the target region.

2. The methods of claim 1, 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.

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

4. The method of claim 1, wherein the step of implanting the biocompatible substrate comprises implanting a gel matrix substrate.

5. The method of claim 4, wherein the gel matrix substrate is selected from the group consisting of alginate, polysaccharide, and agarose.

6. The method of claim 4, 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.

7. The method of claim 6, 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.

8. The method of claim 1, wherein the target region is associated with a disorder, the disorder being selected from the group consisting of a blood disorder, an autoimmune disorder, a hormonal disorder, an anti-inflammatory disorder, a fertility disorder, and a neurodegenerative disorder.

9. The method of claim 1, wherein the target region is associated with an injury, the injury being selected from the group consisting of a wound, and a skin wound.