Method for promoting regeneration of pancreatic beta-cells by administering neurturin

• US 8,772,233 B2
• Filed: 02/15/2013
• Issued: 07/08/2014
• Est. Priority Date: 11/27/2003
• Status: Expired due to Fees

• Current Assignee: Evotec International GmbH (Evotec SE)
• Original Assignee: Evotec International GmbH (Evotec SE)
• Inventors: Austen, Matthias, Burk, Ulrike
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US13/769,011
• Publication Number:
  US 20130150293A1
• Time in Patent Office: 508 Days
• Field of Search: None
• US Class Current: 514/8.3
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 2501/13 Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: G01N 33/507 Pancreatic cells

Abstract

The present invention relates generally to methods for preventing and/or treating pancreatic disorders, particularly those related to diabetes, by administering a neurturin protein product.

Claims

1. A method for promoting regeneration of pancreatic beta-cells in a mammal having impaired beta-cell function, comprising the step of:

administering a neurturin product to said mammal in an amount sufficient to increase neurturin concentration relative to an untreated mammal having impaired beta-cell function, wherein the number of functional beta-cells in said mammal administered the neurturin product are increased;

wherein the neurturin product comprises a biologically active neurturin polypeptide;

wherein the biologically active neurturin polypeptide is capable of dimerizing with another neurturin polypeptide and activating RET signaling; and

wherein the biologically active neurturin polypeptide shares at least 90% sequence identity with;

a) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO;

7;

or

b) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO;

7.

2. The method of claim 1, wherein said mammal having impaired beta-cell function suffers from diabetes type I.

3. The method of claim 1, wherein said mammal having impaired beta-cell function suffers from diabetes type II.

4. The method of claim 1, wherein said mammal having impaired beta-cell function suffers from latent autoimmune diabetes in adults.

5. A method for treating a mammal having impaired beta-cell function, wherein said method comprises the steps of:

a) administering a neurturin product to said mammal in an amount sufficient to increase neurturin concentration relative to an untreated mammal having impaired beta-cell function;

wherein the neurturin product comprises a biologically active neurturin polypeptide;

wherein the biologically active neurturin polypeptide is capable of dimerizing with another neurturin polypeptide and activating RET signaling; and

wherein the biologically active neurturin polypeptide shares at least 90% sequence identity with;

i) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO;

7;

or

ii) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO;

7;

b) administering to said mammal an immunosuppressive agent.

6. The method of claim 5, wherein said mammal having impaired beta-cell function suffers from diabetes type I.

7. The method of claim 5, wherein said mammal having impaired beta-cell function suffers from diabetes type II.

8. The method of claim 5, wherein said mammal having impaired beta-cell function suffers from latent autoimmune diabetes in adults.

9. A method for promoting regeneration of pancreatic beta-cells in a mammal having impaired beta-cell function, comprising the step of:

administering a neurturin product to said mammal in an amount sufficient to increase neurturin concentration relative to an untreated mammal having impaired beta-cell function, wherein the number of functional beta-cells in said mammal administered the neurturin product are increased;

wherein the neurturin product comprises a biologically active neurturin polypeptide;

wherein the biologically active neurturin polypeptide is capable of dimerizing with another neurturin polypeptide, wherein the biologically active neurturin polypeptide shares at least 95% sequence identity with;

a) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO;

7;

or

b) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO;

7.

10. The method of claim 9, wherein the biologically active neurturin polypeptide shares 100% sequence identity with:

a) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO;

7;

or

b) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO;

7.

11. The method of claim 9, wherein said mammal having impaired beta-cell function suffers from diabetes type I.

12. The method of claim 9, wherein said mammal having impaired beta-cell function suffers from diabetes type II.

13. The method of claim 9, wherein said mammal having impaired beta-cell function suffers from latent autoimmune diabetes in adults.

14. A method for treating a mammal having impaired beta-cell function, wherein said method comprises the steps of:

administering a neurturin product to said mammal in an amount sufficient to increase neurturin concentration relative to an untreated mammal having impaired beta-cell function, wherein the number of functional beta-cells in said mammal administered the neurturin product are increased;

wherein the neurturin product comprises a biologically active neurturin polypeptide;

wherein the biologically active neurturin polypeptide is capable of dimerizing with another neurturin polypeptide, wherein the biologically active neurturin polypeptide shares at least 95% sequence identity with;

a) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO;

7;

or

b) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO;

7.

15. The method of claim 14, wherein the biologically active neurturin polypeptide shares 100% sequence identity with:

a) the human neurturin precursor protein having the amino acid sequence set forth in SEQ ID NO;

7;

or

b) the mature neurturin protein product that results from the cleavage of the human neurturin protein precursor having an amino acid sequence set forth in SEQ ID NO;

7.

16. The method of claim 14, wherein said mammal having impaired beta-cell function suffers from diabetes type I.

17. The method of claim 14, wherein said mammal having impaired beta-cell function suffers from diabetes type II.

18. The method of claim 14, wherein said mammal having impaired beta-cell function suffers from latent autoimmune diabetes in adults.