IP Library › Granted Patent US 7,390,781
Granted Patent B2
US 7,390,781 · App. 10/753,592 · Granted Jun 24, 2008

Methods of using truncated glial cell line-derived neurotrophic factor

Assignee: Amgen Inc.
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Quick Facts
Patent No.
US 7,390,781
App. No.
10/753,592
Granted
Jun 24, 2008
Kind
B2
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 (168)

1. A method for promoting the survival or function of dopaminergic neurons comprising administering to a patient a pharmaceutical composition comprising:

(a) a pharmaceutically acceptable vehicle, and

(b) a truncated glial cell line-derived neurotrophic factor (GDNF) protein product consisting of the amino acid sequence

Cys 41 through Cys 133 of SEQ ID NO:2.

2. A method for promoting the survival or function of dopaminergic neurons comprising administering a pharmaceutical composition comprising:

(a) a pharmaceutically acceptable vehicle, and

(b) a truncated GDNF protein product consisting of the formula: X-(Cys 41 -Cys 133 )-Y,

wherein

Cys 41 through Cys 133 is SEQ ID NO:2

Y is absent or a carboxy-terminus amino acid residue of Ile 134 , and

X is a methionylated or nonmethionylated amine group of Cys 41 or amino-terminus amino acid residue(s) selected from the group consisting of:

         G

        RG

       NRG

      KNRG

(SEQ ID NO:3)

     GKNRG

(SEQ ID NO:4)

    RGKNRG

(SEQ ID NO:5)

   QRGKNRG

(SEQ ID NO:6)

  GQRGKNRG

(SEQ ID NO:7)

 RGQRGKNRG

(SEQ ID NO:8)

RRGQRGKNRG

(SEQ ID NO:9)

         G

RRGQRGKNRG

(SEQ ID NO:10)

        KG

RRGQRGKNRG

(SEQ ID NO:11)

       GKG

RRGQRGKNRG

(SEQ ID NO:12)

      RGKG

RRGQRGKNRG

(SEQ ID NO:13)

     SRGKG

RRGQRGKNRG

(SEQ ID NO:14)

    NSRGKG

RRGQRGKNRG

(SEQ ID NO:15)

   ENSRGKG

RRGQRGKNRG

(SEQ ID NO:16)

  PENSRGKG

RRGQRGKNRG

(SEQ ID NO:17)

 NPENSRGKG

RRGQRGKNRG

(SEQ ID NO:18)

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:19)

         A

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:20)

        AA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:21)

       AAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:22)

      QAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:23)

     RQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:24)

    NRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:25)

   RNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:26)

  ERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:27)

 RERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:28)

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:29)

        P

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:30)

       LP

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:31)

      VLP

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:32)

     AVLP

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:33)

    MAVLP

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:34)

   QMAVLP

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:35)

  KQMAVLP

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:36)

 DKQMAVLP

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:37)

and

PDKQMAVLP

RRERNRQAAA

ANPENSRGKG

RRGQRGKNRG

(SEQ ID NO:38)

3. The method according to claim 2 wherein X is SEQ ID NO: 3.

4. The method according to claim 2 wherein X is SEQ ID NO: 7.

5. The method according to claim 2 wherein X is SEQ ID NO: 8.

6. The method according to claim 2 wherein X is SEQ ID NO: 14.

7. The method according to claim 2 wherein X is SEQ ID NO: 17.

8. The method according to claim 2 wherein X is SEQ ID NO: 51.

9. The method according to claim 2 wherein X is SEQ ID NO: 18.

10. The method according to claim 2 wherein X is SEQ ID NO: 24.

11. The method according to 2 wherein X is G, RG, or NRG.

12. A method for promoting the survival or function of dopaminergic neurons comprising administering to a patient a pharmaceutical composition comprising:

(a) a pharmaceutically acceptable vehicle, and

(b) a truncated GDNF protein product consisting of the amino acid sequence of SEQ ID NO:42.

13. A method for promoting the survival or function of dopaminergic neurons comprising administering to a patient a pharmaceutical composition comprising:

(a) a pharmaceutically acceptable vehicle, and

(b) a truncated GDNF protein product consisting of the amino acid sequence of SEQ ID NO:44.

14. A method for promoting the survival or function of dopaminergic neurons comprising administering to a patient a pharmaceutical composition comprising:

(a) a pharmaceutically acceptable vehicle, and

(b) a truncated GDNF protein product consisting of the amino acid sequence of SEQ ID NO:46.

15. The method according to claim 1 wherein said truncated GDNF protein product is glycosylated.

16. The method according to any of claims 2 - 14 wherein said truncated GDNF protein product is glycosylated.

17. The method according to claim 1 wherein said truncated GDNF protein product is conjugated to a water soluble polymer.

18. The method according to any of claims 2 - 14 wherein said truncated GDNF protein product is conjugated to a water soluble polymer.

19. The method according to claim 17 wherein said water soluble polymer is PEG.

20. The method according to claim 18 wherein said water soluble polymer is PEG.

Continuity (3)
Continuation 0968798400 · Oct 13, 2000
Division 0853568100 · Sep 28, 1995
Related Publication 20040127419A1 · Jul 1, 2004