# US 7,611,865 B2 · Polynucleotides encoding truncated glial cell line-derived neurotrophic factor

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- Number: US 7,611,865 B2
- Document ID: US7611865B2
- Status: Granted
- Kind: B2
- Application number: 10/855,820
- Filed: 2004-05-26
- Published: 2004-12-16
- Granted: 2009-11-03
- Earliest claimed: 1995-09-28
- Assignees: Amgen Inc.
- Inventors: Shaw-Fen Sylvia Hu
- Web page: https://patentgrep.com/patent/US7611865B2

## CPC

- C07K 14/475: Growth factors; Growth regulators
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Disclosed are novel proteins, referred to as truncated glial cell line-derived neurotrophic factor (truncated GDNF) proteins, that promote dopamine uptake by dopaminergic cells and promote the survival of nerve cells. Also disclosed are processes for obtaining the truncated GDNF proteins by recombinant genetic engineering techniques.

## Claims

### Claim 1

A polynucleotide encoding a truncated glial cell line-derived neurotrophic factor (GDNF) protein product of the formula:
X-[Cys41-Cys133]-Y
wherein
[Cys41-Cys133] is Cys41 through Cys133 of SEQ ID NO: 2,
Y is absent or a carboxy-terminus amino acid residue of Ile134, and
X represents a methionylated or nonmethionylated amine group of Cys41 or amino-terminus amino acid residue(s) selected from the group:
RG
NRG
(SEQ ID NO:3)
KNRG
(SEQ ID NO:4)
GKNRG
(SEQ ID NO:5)
RGKNRG
(SEQ ID NO:6)
QRGKNRG
(SEQ ID NO:7)
GQRGKNRG
(SEQ ID NO:8)
RGQRGKNRG
(SEQ ID NO:9)
RRGQRGKNRG
(SEQ ID NO:10)
G RRGQRGKNRG
(SEQ ID NO:11)
KG RRGQRGKNRG
(SEQ ID NO:12)
GKG RRGQRGKNRG
(SEQ ID NO:13)
RGKG RRGQRGKNRG
(SEQ ID NO:14)
SRGKG RRGQRGKNRG
(SEQ ID NO:15)
NSRGKG RRGQRGKNRG
(SEQ ID NO:16)
ENSRGKG RRGQRGKNRG
(SEQ ID NO:17)
PENSRGKG RRGQRGKNRG
(SEQ ID NO:51)
SPENSRGKG RRGQRGKNRG
(SEQ ID NO:18)
NPENSRGKG RRGQRGKNRG
(SEQ ID NO:19)
ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:20)
A ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:21)
AA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:22)
AAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:23)
QAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:24)
RQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:25)
NRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:26)
RNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:27)
ERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:28)
RERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:29)
RRERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:30)
P RRERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:31)
LP RRERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:32)
VLP RRERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:33)
AVLP RRERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:34)
MAVLP RRERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:35)
QMAVLP RRERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:36)
KQMAVLP RRERNRQAAA ANPENSRGKG RRGQRGKNRG
(SEQ ID NO:37)
DKQMAVLP RRERNRQAAA ANPENSRGKG RRGQRGKNRG
and
(SEQ ID NO:38)
PDKQMAVLP RRERNRQAAA ANPENSRGKG RRGQRGKNRG;
wherein said protein product has a neurotrophic effect on dopaminergic nerve cells.

### Claim 2 (depends on 1)

The polynucleotide according to claim 1 wherein X is selected from the group consisting of SEQ ID NOS: 3, 7, 8, 14, 17, 18, 24, and 51.

### Claim 3 (depends on 1)

The polynucleotide according to claim 1 wherein X is G, RG or NRG.

### Claim 4 (depends on 1, 2)

A vector comprising a polynucleotide of claim 1, 2, or 3, operatively linked to an expression control sequence.

### Claim 5 (depends on 1, 2)

A prokaryotic or eukaryotic host cell transformed or transfected with a polynucleotide of claim 1, 2, or 3.

### Claim 6 (depends on 5)

A method for producing a truncated GDNF protein, comprising growing host cells of claim 5 in a suitable nutrient medium and, optionally, isolating said truncated GDNF from said cells or said nutrient medium.

### Claim 7 (depends on 6)

The method according to claim 6 wherein said host cells are E. coli.

### Claim 8 (depends on 6)

The method according to claim 6 wherein said host cells are Chinese hamster ovary cells.

### Claim 9 (depends on 4)

A method for the production of a truncated glial cell line-derived neurotrophic factor (GDNF) protein, comprising the steps of:
(a) culturing a prokaryotic or eukaryotic host cell transformed or transfected with a vector of claim 4;
(b) maintaining said host cell under conditions allowing the expression of truncated GDNF protein by said host cell; and
(c) optionally, isolating the truncated GDNF protein expressed by said host cell.