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

• US 6,264,941 B1
• Filed: 01/25/1999
• Issued: 07/24/2001
• Est. Priority Date: 08/12/1993
• Status: Expired due to Fees

• Current Assignee: Neurotech USA, Inc. (Woodbrook Group Holdings, Inc.)
• Original Assignee: Neurotech S.A. (LivaNova Plc)
• Inventors: Emerich, Dwaine F., Baetge, Edward E., Lindner, Mark D., Winn, Shelley R., Hammang, Joseph P., Gentile, Frank T.
• Primary Examiner(s): Nguyen, Dave Trong
• Application Number:
  US09/236,246
• Time in Patent Office: 911 Days
• Field of Search: 435/402, 435/320.1, 435/325, 424/473, 424/93.21, 424/451, 424/457, 424/460, 424/462, 424/422, 424/425, 424/226, 424/427
• 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: 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. An implantable biocompatible immunoisolatory capsule for providing long-term, stable expression of a biologically active molecule wherein the biologically active molecule is provided to the aqueous humor or vitreous humor of the eye of a mammalian host, the capsule comprising:

(a) a core comprising one or more cells dispersed in a biocompatible matrix, the cell or cells being transfected with a recombinant DNA molecule comprising

(i) a DNA sequence coding for the biologically active molecule

(ii) operatively linked to a promoter not subject to down regulation upon implantation in the host; and

(b) an external diffuisional surface jacket surrounding the core, wherein the jacket has a molecular weight cutoff below the molecular weight of substances essential for immunological rejection of the cells, but permitting therethrough, passage of substances between the eye of the mammalian host and the core,

wherein the capsule is implanted into the aqueous humor or vitreous humor of the eye of the mammalian host, and wherein the capsule provides 1-1500 ng/day of the biologically active molecule to the mammalian host.

2. The capsule according to claim 1 wherein the mammalian host is a human.