Treatment of diseases by site specific instillation of cells or site specific transformation of cells and kits therefor

• US 7,226,589 B2
• Filed: 12/10/1999
• Issued: 06/05/2007
• Est. Priority Date: 03/31/1989
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Nabel, Gary J., Nabel, Elizabeth G.
• Primary Examiner(s): WEHBE, ANNE MARIE SABRINA
• Application Number:
  US09/458,610
• Publication Number:
  US 20020197236A1
• Time in Patent Office: 2,734 Days
• Field of Search: 424/93.2, 424/93.21, 435/325, 435/320.1
• US Class Current: 424/93.21
• CPC Class Codes: A61B 17/22 Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for dilators A61M29/00
• CPC Class Codes: A61B 2017/22038 with a guide wire
• CPC Class Codes: A61B 2017/22054 with two balloons
• CPC Class Codes: A61B 2017/22082 after introduction of a substance
• CPC Class Codes: A61B 2017/22084 stone- or thrombus-dissolving
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• 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 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence

Abstract

A method for the direct treatment towards the specific sites of a disease is disclosed. This method is based on the delivery of proteins by catheterization to discrete blood vessel segments using genetically modified or normal cells or other vector systems. Endothelial cells expressing recombinant therapeutic agent or diagnostic proteins are situated on the walls of the blood vessel or in the tissue perfused by the vessel in a patient. This technique, provides for the transfer of cells or vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of diseases.

Claims

1. A method of treating a vascular injury in a mammal, comprising delivering to a blood vessel at the site of injury in the mammal a transformed vascular smooth muscle or endothelial cell, wherein the transformed vascular cell (i) originates from the mammal or is syngeneic to the mammal, (ii) comprises an exogenous nucleic acid encoding basic fibroblast growth factor;

and (iii) expresses sufficient amounts of basic fibroblast growth factor when implanted in the mammal to treat said vascular injury.

2. The method of claim 1, wherein the transformed cells are delivered to the blood vessel with a catheter.

3. The method of claim 2, wherein the catheter comprises a balloon.

4. The method of claim 3, wherein the balloon comprises two spaced apart inflatable members.

5. The method of claim 4, wherein the balloon further comprises an instillation port positioned between the inflatable members.

6. The method of claim 3, wherein the balloon further comprises an inflatable member near the distal end of the catheter.

7. The method of claim 6, wherein the balloon further comprises an instillation port proximal to the inflatable member.

8. The method of claim 1, wherein the transformed cells are surgically delivered to the blood vessel.

9. The method of claim 1, wherein the transformed cells are delivered to the blood vessel by injection.

10. The method of claim 9, wherein the injection occurs in a capillary bed.

11. The method of claim 1, wherein delivering to a blood vessel occurs at an angioplasty site following an angioplasty procedure.