Neurotrophic factors and methods of use thereof

• US 8,217,146 B2
• Filed: 12/07/2009
• Issued: 07/10/2012
• 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: Sah, Dinah W. Y., Johansen, Teit E., Rossomando, Anthony
• Primary Examiner(s): LANDSMAN, ROBERT S
• Application Number:
  US12/632,517
• Publication Number:
  US 20100292142A1
• Time in Patent Office: 946 Days
• Field of Search: None
• US Class Current: 530/350
• 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. An isolated polypeptide that possesses neurotrophic activity and is at least 95% identical to amino acids 37-140 of SEQ ID NO:

9, wherein the polypeptide consists of 104 amino acids.

2. The polypeptide of claim 1, wherein the polypeptide is at least 98% identical to amino acids 37-140 of SEQ ID NO:

9.

3. The polypeptide of claim 1, wherein the polypeptide is at least 99% identical to amino acids 37-140 of SEQ ID NO:

9.

4. The polypeptide of claim 1, wherein the polypeptide is glycosylated.

5. The polypeptide of claim 2, wherein the polypeptide is glycosylated.

6. The polypeptide of claim 3, wherein the polypeptide is glycosylated.

7. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.

8. A pharmaceutical composition comprising the polypeptide of claim 2 and a pharmaceutically acceptable carrier.

9. A pharmaceutical composition comprising the polypeptide of claim 3 and a pharmaceutically acceptable carrier.

10. A pharmaceutical composition comprising the polypeptide of claim 4 and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising the polypeptide of claim 5 and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising the polypeptide of claim 6 and a pharmaceutically acceptable carrier.

13. A method of treating neuropathic pain in a mammal, comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising (a) the polypeptide of claim 1, and (b) a pharmaceutically acceptable carrier.

14. A method of treating a peripheral neuropathy in a mammal, comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising (a) the polypeptide of claim 1, and (b) a pharmaceutically acceptable carrier.

15. The method of claim 14, wherein the peripheral neuropathy is diabetic peripheral neuropathy.

16. The method of claim 13, wherein the pharmaceutical composition is administered systemically.

17. The method of claim 13, wherein the mammal is a human.

18. The method of claim 14, wherein the pharmaceutical composition is administered systemically.

19. The method of claim 14, wherein the mammal is a human.

20. The method of claim 15, wherein the pharmaceutical composition is administered systemically.

21. The method of claim 15, wherein the mammal is a human.

22. A method of treating neuropathic pain in a mammal, comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising (a) the polypeptide of claim 2, and (b) a pharmaceutically acceptable carrier.

23. A method of treating a peripheral neuropathy in a mammal, comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising (a) the polypeptide of claim 2, and (b) a pharmaceutically acceptable carrier.

24. The method of claim 23, wherein the peripheral neuropathy is diabetic peripheral neuropathy.

25. The method of claim 22, wherein the pharmaceutical composition is administered systemically.

26. The method of claim 22, wherein the mammal is a human.

27. The method of claim 23, wherein the pharmaceutical composition is administered systemically.

28. The method of claim 23, wherein the mammal is a human.

29. The method of claim 24, wherein the pharmaceutical composition is administered systemically.

30. The method of claim 24, wherein the mammal is a human.

31. 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 possesses neurotrophic activity and is a homodimer consisting of two polypeptides each of which consists of an amino acid sequence that is 104 amino acids in length and is at least 95% identical to amino acids 37-140 of SEQ ID NO:

9.

32. The method of claim 31, wherein the cell is a nerve or neuronal cell.

33. The method of claim 31, wherein the cell is a human cell.