Compositions and methods for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules

• US 5,676,943 A
• Filed: 05/25/1995
• Issued: 10/14/1997
• 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:
  US08/450,316
• Time in Patent Office: 873 Days
• Field of Search: 424/93.21, 424/408, 424/425, 514/44
• US Class Current: 424/93.21
• 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 method for delivering nerve growth factor to the central nervous system of a mammalian host, the method comprising implanting at least one biocompatible capsule into the host, each capsule comprising

(a) a core comprising living cells secreting a dosage of nerve growth factor effective for preventing degeneration of, or inducing sprouting of, cholinergic basal forebrain neurons, and

(b) a biocompatible jacket surrounding the core, the jacket comprising a permselective membrane permitting passage of nerve growth factor thereacross into the host.

2. The method of claim 1 wherein the cells are xenogeneic to the host.

3. The method according to claim 1 wherein the cells are BHK cells wherein said cells are transfected with the gene encoding human nerve growth factor.

4. The method of claim 1 wherein the jacket material is selected from the group consisting of polyacrylates, polyvinylidenes, polyvinylchloride copolymers, polyurethanes, polystyrenes, polyamides, cellulose acetates, cellulose nitrates, polysulfones, polyphosphazenes, polyacrilonitriles, poly(acrilonitrile/covinyl chloride), and derivatives, copolymers and mixtures thereof.

5. The method of claim 1 wherein the jacket is shaped to form a hollow fiber.

6. The method of claim 1 wherein between one and six capsules are implanted in the central nervous system of the host.

7. The method of claim 1 wherein the neurons are trkA-positive neurons or p75-positive neurons.