Implantable device containing GDNF secreting cells for treating nerve damage and methods of use

• US 6,015,572 A
• Filed: 05/30/1995
• Issued: 01/18/2000
• Est. Priority Date: 09/20/1991
• Status: Expired due to Term

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Doherty, Daniel H., Lin, Leu-Fen H., Lile, Jack, Collins, Franklin D., Bektesh, Susan
• Primary Examiner(s): Hutzell, Paula K.
• Assistant Examiner(s): Gucker, Stephen
• Application Number:
  US08/453,176
• Time in Patent Office: 1,694 Days
• Field of Search: 435/182, 435/69.1, 424/424, 530/350, 530/399, 514/2, 514/12, 514/21, 604/891.1, 935/66
• US Class Current: 424/424
• 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 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• 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: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: Y10S 530/809 Fused cells, e.g. hybridoma
• CPC Class Codes: Y10S 530/839 Nerves; brain

Abstract

A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process. An implantable device containing recombinant GDNF secreting cells encapsulated in a semipermeable membrane may be used to treat nerve damage in patients suffering from disorders such as Parkinson'"'"'s disease.

Claims

1. A device for treating nerve damage by implantation in a patient comprising:

a membrane, and

one or more cells modified to express and secrete glial cell line-derived neurotrophic factor encapsulated within said membrane, provided however, said one or more cells are not B49 glioblastoma cells,

wherein said membrane is permeable to said glial cell line-derived neurotrophic factor, and impermeable to immune system materials from said patient which are detrimental to said cells, and

wherein said glial cell line-derived neurotrophic factor is a polypeptide comprising the amino acid sequence set forth in SEQ ID NO;

4 or SEQ ID NO;

6 or a polypeptide which is at least 70% identical to an amino acid sequence set forth in SEQ ID NO;

4 or SEQ ID NO;

6 when four gaps in a length of 100 amino acids may be introduced to assist in that alignment, and wherein said glial cell line-derived neurotrophic factor has the ability to promote the survival or function of nerve cells.

2. The device of claim 1 wherein said cells contain an expression regulatory element operatively linked to a nucleic acid sequence encoding said glial cell line-derived neurotrophic factor.

3. The device of claim 1 wherein said glial cell line-derived neurotrophic factor comprises a polypeptide which is at least 70% identical to an amino acid sequence set forth in SEQ ID NO:

4 OR SEQ ID NO;

6 when four gaps in a length of 100 amino acids may be introduced to assist in that alignment.

4. The device of claim 1 wherein said glial cell line-derived neurotrophic factor comprises the amino acid sequence of SEQ ID NO:

6.

7. A method for treating nerve damage comprising implanting a device according to claims 1 or 5 into a patient in need thereof.

8. The method of claim 7 wherein said patient is suffering from Parkinson'"'"'s disease.

9. The method of claim 7 wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:

6.

5. A device for treating nerve damage by implantation in a patient, comprising:

a membrane; and

one or more cells contained within said membrane, wherein said cells express and secrete a glial cell line-derived neurotrophic factor comprising the amino acid sequence set forth in SEQ ID NO;

6, provided however, said one or more cells are not B49 glioblastoma cells, and

wherein said membrane is permeable to said glial cell line-derived neurotrophic factor.

6. The device of claim 5, wherein said membrane is suitable for implantation in the central nervous system of the patient.