IP Library › Granted Patent US 8,119,114
Granted Patent B2
US 8,119,114 · App. 12/163,425 · Granted Feb 21, 2012

Polymer conjugates of mutated neublastin

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Quick Facts
Patent No.
US 8,119,114
App. No.
12/163,425
Granted
Feb 21, 2012
Kind
B2
Abstract

A dimer comprising a mutated neublastin polypeptide coupled to a polymer is disclosed. Such dimers exhibit prolonged bioavailability and, in preferred embodiments, prolonged biological activity relative to wild-type forms of neublastin.

Claims (60)

1. A polymer-conjugated homodimer comprising two polypeptides, wherein each polypeptide comprises an amino acid sequence at least 90% identical to amino acids 8-113 of SEQ ID NO:1, wherein the polypeptide comprises an amino acid other than arginine substituted at the position corresponding to position 14 in SEQ ID NO:1, wherein the polymer-conjugated homodimer binds to GFRalpha3 and stimulates tyrosine phosphorylation of RET receptor tyrosine kinase, and wherein a non-naturally occurring polymer is conjugated to the amino acid substituted at the position corresponding to position 14 in SEQ ID NO:1.

2. The polymer-conjugated homodimer of claim 1 , wherein the amino acid sequence is at least 95% identical to amino acids 8-113 of SEQ ID NO:1.

3. The polymer-conjugated homodimer of claim 1 , wherein the amino acid sequence is at least 95% identical to amino acids 8-113 of SEQ ID NO:2.

4. The polymer-conjugated homodimer of claim 1 , wherein the polymer is a polyalkylene glycol.

5. The polymer-conjugated homodimer of claim 2 , wherein the polymer is a polyalkylene glycol.

6. The polymer-conjugated homodimer of claim 3 , wherein the polymer is a polyalkylene glycol.

7. The polymer-conjugated homodimer of claim 4 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 14 in SEQ ID NO:1.

8. The polymer-conjugated homodimer of claim 5 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 14 in SEQ ID NO:1.

9. The polymer-conjugated homodimer of claim 6 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 14 in SEQ ID NO:1.

10. The polymer-conjugated homodimer of claim 4 , wherein the polyalkylene glycol is polyethylene glycol.

11. The polymer-conjugated homodimer of claim 5 , wherein the polyalkylene glycol is polyethylene glycol.

12. The polymer-conjugated homodimer of claim 6 , wherein the polyalkylene glycol is polyethylene glycol.

13. The polymer-conjugated homodimer of claim 7 , wherein the polyalkylene glycol is polyethylene glycol.

14. The polymer-conjugated homodimer of claim 8 , wherein the polyalkylene glycol is polyethylene glycol.

15. The polymer-conjugated homodimer of claim 9 , wherein the polyalkylene glycol is polyethylene glycol.

16. A polymer-conjugated homodimer comprising two polypeptides, wherein each polypeptide comprises an amino acid sequence at least 90% identical to amino acids 8-113 of SEQ ID NO:1, wherein the polypeptide comprises an amino acid other than arginine substituted at the position corresponding to position 39 in SEQ ID NO:1, wherein the polymer-conjugated homodimer binds to GFRalpha3 and stimulates tyrosine phosphorylation of RET receptor tyrosine kinase, and wherein a non-naturally occurring polymer is conjugated to the amino acid substituted at the position corresponding to position 39 in SEQ ID NO:1.

17. The polymer-conjugated homodimer of claim 16 , wherein the amino acid sequence is at least 95% identical to amino acids 8-113 of SEQ ID NO:1.

18. The polymer-conjugated homodimer of claim 16 , wherein the amino acid sequence is at least 95% identical to amino acids 8-113 of SEQ ID NO:2.

19. The polymer-conjugated homodimer of claim 16 , wherein the polymer is a polyalkylene glycol.

20. The polymer-conjugated homodimer of claim 17 , wherein the polymer is a polyalkylene glycol.

21. The polymer-conjugated homodimer of claim 18 , wherein the polymer is a polyalkylene glycol.

22. The polymer-conjugated homodimer of claim 19 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 39 in SEQ ID NO:1.

23. The polymer-conjugated homodimer of claim 20 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 39 in SEQ ID NO:1.

24. The polymer-conjugated homodimer of claim 21 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 39 in SEQ ID NO:1.

25. The polymer-conjugated homodimer of claim 19 , wherein the polyalkylene glycol is polyethylene glycol.

26. The polymer-conjugated homodimer of claim 20 , wherein the polyalkylene glycol is polyethylene glycol.

27. The polymer-conjugated homodimer of claim 21 , wherein the polyalkylene glycol is polyethylene glycol.

28. The polymer-conjugated homodimer of claim 22 , wherein the polyalkylene glycol is polyethylene glycol.

29. The polymer-conjugated homodimer of claim 23 , wherein the polyalkylene glycol is polyethylene glycol.

30. The polymer-conjugated homodimer of claim 24 , wherein the polyalkylene glycol is polyethylene glycol.

31. A polymer-conjugated homodimer comprising two polypeptides, wherein each polypeptide comprises an amino acid sequence at least 90% identical to amino acids 8-113 of SEQ ID NO:1, wherein the polypeptide comprises an amino acid other than arginine substituted at the position corresponding to position 68 in SEQ ID NO:1, wherein the polymer-conjugated homodimer binds to GFRalpha3 and stimulates tyrosine phosphorylation of RET receptor tyrosine kinase, and wherein a non-naturally occurring polymer is conjugated to the amino acid substituted at the position corresponding to position 68 in SEQ ID NO:1.

32. The polymer-conjugated homodimer of claim 31 , wherein the amino acid sequence is at least 95% identical to amino acids 8-113 of SEQ ID NO:1.

33. The polymer-conjugated homodimer of claim 31 , wherein the amino acid sequence is at least 95% identical to amino acids 8-113 of SEQ ID NO:2.

34. The polymer-conjugated homodimer of claim 31 , wherein the polymer is a polyalkylene glycol.

35. The polymer-conjugated homodimer of claim 32 , wherein the polymer is a polyalkylene glycol.

36. The polymer-conjugated homodimer of claim 33 , wherein the polymer is a polyalkylene glycol.

37. The polymer-conjugated homodimer of claim 34 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 68 in SEQ ID NO:1.

38. The polymer-conjugated homodimer of claim 35 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 68 in SEQ ID NO:1.

39. The polymer-conjugated homodimer of claim 36 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 68 in SEQ ID NO:1.

40. The polymer-conjugated homodimer of claim 34 , wherein the polyalkylene glycol is polyethylene glycol.

41. The polymer-conjugated homodimer of claim 35 , wherein the polyalkylene glycol is polyethylene glycol.

42. The polymer-conjugated homodimer of claim 36 , wherein the polyalkylene glycol is polyethylene glycol.

43. The polymer-conjugated homodimer of claim 37 , wherein the polyalkylene glycol is polyethylene glycol.

44. The polymer-conjugated homodimer of claim 38 , wherein the polyalkylene glycol is polyethylene glycol.

45. The polymer-conjugated homodimer of claim 39 , wherein the polyalkylene glycol is polyethylene glycol.

46. A polymer-conjugated homodimer comprising two polypeptides, wherein each polypeptide comprises an amino acid sequence at least 90% identical to amino acids 8-113 of SEQ ID NO:1, wherein the polypeptide comprises an amino acid other than asparagine substituted at the position corresponding to position 95 in SEQ ID NO:1, wherein the polymer-conjugated homodimer binds to GFRalpha3 and stimulates tyrosine phosphorylation of RET receptor tyrosine kinase, and wherein a non-naturally occurring polymer is conjugated to the amino acid substituted at the position corresponding to position 95 in SEQ ID NO:1.

47. The polymer-conjugated homodimer of claim 46 , wherein the amino acid sequence is at least 95% identical to amino acids 8-113 of SEQ ID NO:1.

48. The polymer-conjugated homodimer of claim 46 , wherein the amino acid sequence is at least 95% identical to amino acids 8-113 of SEQ ID NO:2.

49. The polymer-conjugated homodimer of claim 46 , wherein the polymer is a polyalkylene glycol.

50. The polymer-conjugated homodimer of claim 47 , wherein the polymer is a polyalkylene glycol.

51. The polymer-conjugated homodimer of claim 48 , wherein the polymer is a polyalkylene glycol.

52. The polymer-conjugated homodimer of claim 49 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 95 in SEQ ID NO:1.

53. The polymer-conjugated homodimer of claim 50 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 95 in SEQ ID NO:1.

54. The polymer-conjugated homodimer of claim 51 , wherein the polyalkylene glycol is conjugated to a lysine residue substituted at the position corresponding to position 95 in SEQ ID NO:1.

55. The polymer-conjugated homodimer of claim 49 , wherein the polyalkylene glycol is polyethylene glycol.

56. The polymer-conjugated homodimer of claim 50 , wherein the polyalkylene glycol is polyethylene glycol.

57. The polymer-conjugated homodimer of claim 51 , wherein the polyalkylene glycol is polyethylene glycol.

58. The polymer-conjugated homodimer of claim 52 , wherein the polyalkylene glycol is polyethylene glycol.

59. The polymer-conjugated homodimer of claim 53 , wherein the polyalkylene glycol is polyethylene glycol.

60. The polymer-conjugated homodimer of claim 54 , wherein the polyalkylene glycol is polyethylene glycol.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 26, 2019
From: GLORIANA THERAPEUTICS SARL
To: GLORIANA THERAPEUTICS, INC.
Reel/Frame 049005/0877 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 6, 2017
From: BIOGEN MA INC.
To: GLORIANA THERAPEUTICS SARL
Reel/Frame 041887/0117 →
CHANGE OF NAME Recorded May 4, 2015
From: BIOGEN IDEC MA INC.
To: BIOGEN MA INC.
Reel/Frame 035571/0926 →
CHANGE OF NAME Recorded Sep 12, 2008
From: BIOGEN, INC.
To: BIOGEN IDEC MA INC.
Reel/Frame 021522/0679 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 9, 2008
From: SAH, DINAH WEN-YEE; PEPINSKY, R. BLAKE; BORIACK-SJODIN, PAULA ANN; MILLER, STEPHAN S.; ROSSOMANDO, ANTHONY; SILVIAN, LAURA
To: BIOGEN, INC.
Reel/Frame 021504/0960 →