# US 8,772,233 B2 · Method for promoting regeneration of pancreatic beta-cells by administering neurturin

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- Number: US 8,772,233 B2
- Document ID: US8772233B2
- Status: Granted
- Kind: B2
- Application number: 13/769,011
- Filed: 2013-02-15
- Published: 2013-06-13
- Granted: 2014-07-08
- Earliest claimed: 2003-11-27
- Assignees: Evotec International GmbH
- Applicants: DeveloGen Aktiengesellschaft
- Inventors: Matthias Austen; Ulrike Burk
- Web page: https://patentgrep.com/patent/US8772233B2

## CPC

- 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}
- A61K 38/1709: {from mammals}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C12N 5/0676: {Pancreatic cells}
- G01N 33/507: {Pancreatic cells}
- C12N 2501/13: Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
- C12N 2506/02: from embryonic cells
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## 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

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

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

### Claim 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.

### Claim 6 (depends on 5)

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

### Claim 7 (depends on 5)

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

### Claim 8 (depends on 5)

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

### Claim 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.

### Claim 10 (depends on 9)

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.

### Claim 11 (depends on 9)

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

### Claim 12 (depends on 9)

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

### Claim 13 (depends on 9)

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

### Claim 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.

### Claim 15 (depends on 14)

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.

### Claim 16 (depends on 14)

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

### Claim 17 (depends on 14)

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

### Claim 18 (depends on 14)

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