Induction of immunological tolerance

• US 20040191227A1
• Filed: 04/13/2004
• Published: 09/30/2004
• Est. Priority Date: 10/26/1995
• Status: Active Grant

• Current Assignee: Paul P. Latta
• Original Assignee: Paul P. Latta
• Inventors: Latta, Paul P.
• Granted Patent: US 7,361,334 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• CPC Class Codes: A61K 2039/515 Animal cells
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 39/0008 Antigens related to auto-immune diseases; Preparations to induce self-tolerance
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• 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: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells

Abstract

A method of creating tolerance to transplanted cells, tissue, or organs without the need for continuous immunosuppression. A tolerizing dose of a cell or tissue within a membrane structure is implanted into a patient. Once the patient becomes tolerant to the cell or tissue, a tissue or organ is implanted which will no longer be recognized as foreign matter. The method makes animal organs practical for human use, prevents autoimmune destruction as well as immune rejection. It has applications in treatment and prevention of many mammalian diseases.

Claims

1. A method of treating diabetes in a mammal in need thereof, comprising the steps of:

implanting in said mammal a tolerizing dose of insulin-secreting cells from the same species as said mammal encapsulated in a biologically compatible permselective membrane;

then

administering to said mammal a curative dose of corresponding unencapsulated insulin-secreting cells.

2. The method of claim 1, wherein said mammal is a human, canine or feline.

3. The method of claim 1, wherein said tolerizing dose is one to two orders of magnitude less than said curative dose.

4. The method of claim 1, wherein said insulin-secreting cells are pancreatic islet cells.

5. The method of claim 1, wherein said membrane comprises polyethylene glycol.

6. The method of claim 1, wherein said tolerizing and curative doses are porcine.

7. The method of claim 1, further comprising the step of administering one or more anti-inflammatory agents to said mammal prior to, at the same time as, or subsequent to administration of said curative dose.

8. The method of claim 1, wherein said membrane has a molecular weight cutoff of about 150 kDa or less.

9. The method of claim 1, wherein said membrane has a pore size of less than about 0.4 μ

m.

10. The method of claim 9, wherein said membrane has a pore size of less than about 0.2 μ

m.

11. The method of claim 1, wherein said curative dose is between one and two orders of magniture higher that said tolerizing dose.

12. The method of claim 1, wherein said implanting step is subcapsular, subcutaneous, intraperitoneal or intraportal.

13. The method of claim 1, wherein said administering step is intraperitoneal, intraportal or subcutaneous.

14. The method of claim 1, wherein said tolerizing dose is administered incrementally.