Method of generating cartilage

• US 6,719,970 B1
• Filed: 07/10/2000
• Issued: 04/13/2004
• Est. Priority Date: 07/10/2000
• Status: Expired due to Fees

• Current Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc), University Of Massachusetts
• Original Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc), University Of Massachusetts
• Inventors: Costantino, Henry R., Bonassar, Lawrence J., Tracy, Mark A.
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/612,744
• Time in Patent Office: 1,373 Days
• Field of Search: 435/174, 435/177, 435/180, 435/395, 424/422, 424/423, 424/93.7
• US Class Current: 424/93.7
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 2531/00 Microcarriers
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage

Abstract

The invention relates to an improved method for administering live cells to a patient and compositions useful in the method. The composition comprises live cells and biocompatible, biodegradable polymer microparticles. The cells and microparticles of the cell/microparticle composition can be contacted immediately prior to administration, or can be contacted in culture for a specified period of time prior to administration. In the method of the invention, an effective amount of the cell/microparticle composition is administered to a patient in need thereof by injection to a treatment site of the patient to provide a therapeutic effect in the patient. The therapeutic effect can be, for example, the formation of new tissue at the treatment site, or the production and secretion of a biologically active secretory molecule at the treatment site. The composition comprising lives cells and biocompatible, biodegradable polymer microparticles can further comprise a biologically active agent. In a preferred embodiment, the biologically active agent is incorporated into the microparticle. The biologically active agent can be, for example, factors which modulate cell growth.

Claims

1. A method of generating cartilage tissue in a patient in need thereof consisting essentially of administering by injection to a treatment site of the patient without open surgery to expose the treatment site an effective amount of a composition consisting essentially of live chondrocytes and biocompatible, biodegradable polymer microparticles wherein, the microparticles are injected in an amount sufficient to provide a surface for the chondrocytes to grow and generate said tissue.

2. The method of claim 1 wherein the the biocompatible, biodegradable polymer of the microparticle is selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, polycarbonates, polyesteramides, polyanydrides, poly(amino acids), polyorthoesters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, polyurethanes, blends thereof, and copolymers thereof.

3. The method of claim 2 wherein the biocompatible, biodegradable polymer is a poly(lactide-co-glycolide).

4. The method of claim 1 wherein the composition further consisting essentially of a pharmaceutically acceptable carrier.

5. The method of claim 1 wherein the composition further consisting essentially of a biologically active agent.

6. The method of claim 5 wherein the biologically active agent has cartilage regeneration inductive properties.

7. The method of claim 5 wherein the biologically active agent is a growth factor or differentiating factor.

8. The method of claim 7 wherein the growth factor is selected from basic fibroblast growth factor (bFGF), platelet-derived growth factors (PDGF), transforming growth factors (TGF-α

, TGF-β

), cementum growth factors, epidermal growth factor (EGF), hepatocyte growth factor, heparin binding factor, insulin-like growth factors I or II (IGF-I, IGF-II), erythropoietin, and nerve growth factor (NGF).

9. The method of claim 7 wherein the differentiating factor is a morphogenic protein.

10. The method of claim 9 wherein the morphogenic protein is selected from OP-1, OP-2, OP-3, BMP2, BMP3, BMP4, BMP5, BMP6 and active fragments and derivatives thereof.

11. The method of claim 1 wherein the concentration of cells in the composition is from about 0.5×

10⁶ cells/mL to about 50×

10⁶ cells/mL.

12. The method of claim 1 wherein the treatment site is the articular space of a joint of the patient.