Delivery of biologically active molecules using cells contained in biocompatible immunoisolatory capsules

• US 5,639,275 A
• Filed: 05/25/1995
• Issued: 06/17/1997
• Est. Priority Date: 08/12/1993
• Status: Expired due to Term

• Current Assignee: Neurotech USA, Inc. (Woodbrook Group Holdings, Inc.)
• Original Assignee: Cytotherapeutics, Inc.
• Inventors: Emerich, Dwaine F., Hammang, Joseph P., Gentile, Frank T., Baetge, Edward E., Lindner, Mark D., Winn, Shelley R.
• Primary Examiner(s): Ziska, Suzanne E.
• Application Number:
  US08/449,756
• Time in Patent Office: 754 Days
• Field of Search: 424/93.21, 424/408, 604/891.1
• US Class Current: 604/891.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• 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 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 14/48 Nerve growth factor [NGF]
• CPC Class Codes: C07K 14/70 Enkephalins
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

This invention provides improved devices and methods for long-term, stable expression of a biologically active molecule using a biocompatible capsule containing genetically engineered cells for the effective delivery of biologically active molecules to effect or enhance a biological function within a mammalian host. The novel capsules of this invention are biocompatible and are easily retrievable. This invention specifically provides improved methods and compositions which utilize cells transfected with recombinant DNA molecules comprising DNA sequences coding for biologically active molecules operatively linked to promoters that are not subject to down regulation in vivo upon implantation into a mammalian host. Furthermore, the methods of this invention allow for the long-term, stable and efficacious delivery of biologically active molecules from living cells to specific sites within a given mammal. In addition, this invention provides a general means for maintaining, for extended periods of time, the in vivo expression of transgenes.

Claims

1. A capsule comprising a semipermeable membrane, the membrane comprising an inner wall surface that is permselective, an outer non-permselective wall surface, and a trabecular wall therebetween, the outer wall surface containing macropores, the macropores comprising between about 2.0-20% of the total area of the outer wall surface, and ranging from about 5-15 μ

m in diameter.

2. The capsule of claim 1, wherein the capsule is shaped to form a cylindrical hollow fiber.

3. The capsule of claim 2 wherein the capsule is shaped to form a flat sheet.

4. The capsule according to any one of claims 1-3, wherein the macropores comprise about 2.5% of the total area of the outer wall surface.

5. The capsule according to any one of claims 1-3 wherein the macropores comprise about 10% of the total area of the outer wall surface.

6. The capsule according to any one of claims 1-3 wherein the macropores comprise about 12% of the outer wall surface.