Methods of stimulating mitogenesis in glial cells using glial mitogenic factors

• US 6,232,286 B1
• Filed: 06/06/1995
• Issued: 05/15/2001
• Est. Priority Date: 04/10/1991
• Status: Expired due to Term

• Current Assignee: Acorda Therapeutics Incorporated
• Original Assignee: Ludwig Institute for Cancer Research, Ltd., CeNeS Pharmaceuticals, Inc. (PAION AG)
• Inventors: Hiles, Ian, Waterfield, Michael, Stroobant, Paul, Minghetti, Luisa, Marchioni, Mark, Chen, Mario Su, Goodearl, Andrew
• Primary Examiner(s): Kunz, Gary L.
• Assistant Examiner(s): Gucker, Stephen
• Application Number:
  US08/470,339
• Time in Patent Office: 2,170 Days
• Field of Search: 514/2, 514/12, 435/69.1
• US Class Current: 514/7.6
• 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: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4705 stimulating, promoting or activating activity
• CPC Class Codes: C07K 14/4756 Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
• CPC Class Codes: C07K 14/82 Translation products from oncogenes
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C12N 2799/026 where the vector is derived from a baculovirus

Abstract

The invention features methods for stimulating glial cell mitogenesis by contacting the glial cells with p185^erbB2 ligand polypeptides, including glial growth factor (GGF), a GGF splice variant comprised of segments E, B, A, C, and C/D or C/D′, a 35 kD polypeptide factor isolated from rat I-EJ transformed fibroblast cells, 75 kD polypeptide factor isolated from the LKBR-3 human breast cells, 44 kD polypeptide factor isolated from the rat I-EJ transformed fibroblast cells, 45 kD polypeptide factor isolated from MDA-MB 231 human breast cells, 7-14 kD polypeptide factor isolated from the ATL-2 human T-cells, 25 kD polypeptide factor isolated from activated mouse peritoneal macrophages, and 25 kD polypeptide factor isolated from bovine kidney.

Claims

1. A method of stimulating mitogenic activity in a glial cell, said glial cell being an oligodendrocyte, a microglial cell, or a myelinating glial cell, said method comprising applying 35 kD polypeptide factor isolated from the rat I-EJ transformed fibroblast cell line to said glial cell.

2. A method of stimulating mitogenic activity in a glial cell, said glial cell being an oligodendrocyte, a microglial cell, or a myelinating glial cell, said method comprising applying 75 kD polypeptide factor isolated from the SKR\BR-3 human breast cell line to said glial cell.

3. A method of stimulating mitogenic activity in a glial cell, said glial cell being an oligodendrocyte, a microglial cell, or a myelinating glial cell, said method comprising applying 44 kD polypeptide factor isolated from the rat I-IJ transformed fibroblast cell line to said glial cell.

4. A method of stimulating mitogenic activity in a glial cell, said glial cell being an oligodendrocyte, a microglial cell, or a myelinating glial cell, said method comprising applying 45 kD polypeptide factor isolated from the MDA-MB 231 human breast cell line to said glial cell.

5. A method of stimulating mitogenic activity in a glial cell, said glial cell being an oligodendrocyte, a microglial cell, or a myelinating glial cell, said method comprising applying 7 to 14 kD polypeptide factor isolated from the ATL-2 human T-cell line to said glial cell.

6. A method of stimulating mitogenic activity in a glial cell, said glial cell being an oligodendrocyte, a microglial cell, or a myelinating glial cell, said method comprising applying 25 kD polypeptide factor isolated from activated mouse peritoneal macrophages to said glial cell.

7. A method of stimulating mitogenic activity in a glial cell, said glial cell being an oligodendrocyte, a microglial cell, or a myelinating glial cell, said method comprising applying a 25 kD polypeptide factor isolated from bovine kidney to said glial cell.

8. A method of stimulating mitogenic activity in a glial cell, said method comprising applying ARIA polypeptide to said glial cell.