Methods of activating RET receptor tyrosine kinase using neurotrophic factors

• US 7,655,463 B2
• Filed: 02/12/2008
• Issued: 02/02/2010
• Est. Priority Date: 03/12/2001
• Status: Expired due to Fees

• Current Assignee: NsGene A/S, Sinfonia Biotherapeutics AB
• Original Assignee: Biogen Idec MA Inc. (Biogen, Inc.), NsGene A/S
• Inventors: Rossomando, Anthony, Johansen, Teit E., Sah, Dinah W. Y.
• Primary Examiner(s): LANDSMAN, ROBERT S
• Application Number:
  US12/029,917
• Publication Number:
  US 20080233647A1
• Time in Patent Office: 721 Days
• Field of Search: None
• US Class Current: 435/375
• 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 21/04 for myasthenia gravis
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/48 Nerve growth factor [NGF]

Abstract

The invention relates to neublastin neurotrophic factor polypeptides, nucleic acids encoding neublastin polypeptides, and antibodies that bind specifically to neublastin polypeptides, as well as methods of making and methods of using the same.

Claims

1. A method of activating a Rearranged During Transfection (RET) receptor tyrosine kinase, the method comprising contacting a cell expressing RET and Glial Cell Line-Derived Neurotrophic Factor Family Receptor Alpha-3 (GFRalpha3) with an amount of a dimerized protein effective to bind to a complex comprising RET and GFRalpha3 and induce dimerization and autophosphorylation of RET, thereby activating the RET receptor tyrosine kinase, wherein the dimerized protein is a homodimer consisting of two polypeptides each of which consists of an amino acid sequence selected from the group consisting of amino acids 37-140 of SEQ ID NO:

9 (NBN

     104), amino acids 39-140 of SEQ ID NO;

9 (NBN

     102), and amino acids 42-140 of SEQ ID NO;

9 (NBN

     99).

2. The method of claim 1, wherein each of the polypeptides consists of amino acids 37-140 of SEQ ID NO:

9 (NBN

     104).

3. The method of claim 1, wherein each of the polypeptides consists of amino acids 39-140 of SEQ ID NO:

9 (NBN

     102).

4. The method of claim 1, wherein each of the polypeptides consists of amino acids 42-140 of SEQ ID NO:

9 (NBN

     99).

5. The method of claim 1, wherein the cell is a nerve or neuronal cell.

6. The method of claim 2, wherein the cell is a nerve or neuronal cell.

7. The method of claim 3, wherein the cell is a nerve or neuronal cell.

8. The method of claim 4, wherein the cell is a nerve or neuronal cell.

9. The method of claim 1, wherein the cell is a human cell.

10. The method of claim 2, wherein the cell is a human cell.

11. The method of claim 3, wherein the cell is a human cell.

12. The method of claim 4, wherein the cell is a human cell.

13. The method of claim 5, wherein the cell is a human cell.

14. The method of claim 6, wherein the cell is a human cell.

15. The method of claim 7, wherein the cell is a human cell.

16. The method of claim 8, wherein the cell is a human cell.