Human cystatin F

• US 6,066,617 A
• Filed: 01/29/1998
• Issued: 05/23/2000
• Est. Priority Date: 04/03/1996
• Status: Expired due to Term

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Gentz, Reiner L., Yu, Guo-Liang, Ni, Jian, Li, Haodong
• Primary Examiner(s): Wax, Robert A.
• Application Number:
  US09/019,485
• Time in Patent Office: 845 Days
• Field of Search: 514/12, 530/350
• US Class Current: 424/185.1
• CPC Class Codes: 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
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/8139 Cysteine protease (E.C. 3.4.22) inhibitors, e.g. cystatin
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The invention relates to Cystatin F polypeptides, polynucleotides encoding the polypeptides, methods for producing the polypeptides, in particular by expressing the polynucleotides, and agonists and antagonists of the polypeptides. The invention further relates to methods for utilizing such polynucleotides, polypeptides, agonists and antagonists for applications, which relate, in part, to research, diagnostic and clinical arts.

Claims

1. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:

(a) amino acid residue 1 to amino acid residue 145 as set forth in SEQ ID NO;

2;

(b) amino acid residue 2 to amino acid residue 145 as set forth in SEQ ID NO;

2;

(c) amino acid residue 19 to amino acid residue 145 as set forth in SEQ ID NO;

2; and

(d) a fragment of the amino acid sequence set forth in SEQ ID NO;

2,

wherein said fragment has Cystatin F activity or binds an antibody specific for Cystatin F.

2. The isolated polypeptide of claim 1 comprising amino acid residue 1 to amino acid residue 145 as set forth in SEQ ID NO:

2.

3. The isolated polypeptide of claim 1 comprising amino acid residue 2 to amino acid residue 145 as set forth in SEQ ID NO:

2.

4. The isolated polypeptide of claim 1 comprising amino acid residue 19 to amino acid residue 145 as set forth in SEQ ID NO:

2.

5. The isolated polypeptide of claim 1 comprising a fragment of the amino acid sequence set forth in SEQ ID NO:

2, wherein said fragment has Cystatin F activity or binds an antibody specific for Cystatin F.

6. The isolated polypeptide of claim 5 wherein said polypeptide has Cystatin F activity.

7. The isolated polypeptide of claim 5 wherein said polypeptide binds an antibody specific for Cystatin F.

47. The isolated polypeptide of claim 1, which further comprises a heterologous polypeptide.

53. A composition comprising the isolated polypeptide of claim 1, and a pharmaceutically acceptable carrier.

8. An isolated polypeptide comprising a member selected from the group consisting of:

(a) a full-length polypeptide having the amino acid sequence expressed by the human cDNA contained in ATCC Deposit No. 97463;

(b) a full-length polypeptide excepting the N-terminal methionine having the amino acid sequence expressed by the human cDNA contained in ATCC Deposit No. 97463;

(c) a mature polypeptide having the amino acid sequence expressed by the human cDNA contained in ATCC Deposit No. 97463; and

(d) a fragment of the full-length polypeptide having the amino acid sequence expressed by the human cDNA contained in ATCC Deposit No. 97463 wherein said fragment has Cystatin F activity or binds an antibody specific for Cystatin F.

9. The isolated polypeptide of claim 8 comprising a full-length polypeptide having the amino acid sequence expressed by the human cDNA contained in ATCC Deposit No. 97463.

10. The isolated polypeptide of claim 8 comprising a full-length polypeptide excepting the N-terminal methionine having the amino acid sequence expressed by the human cDNA contained in ATCC Deposit No. 97463.

11. The isolated polypeptide of claim 8 comprising a mature polypeptide having the amino acid sequence expressed by the human cDNA contained in ATCC Deposit No. 97463.

12. The isolated polypeptide of claim 8 comprising a fragment of the full-length polypeptide having the amino acid sequence expressed by the human cDNA contained in ATCC Deposit No. 97463 wherein said fragment has Cystatin F activity or binds an antibody specific for Cystatin F.

13. The isolated polypeptide of claim 12 wherein said polypeptide has Cystatin F activity.

14. The isolated polypeptide of claim 12 wherein said polypeptide binds an antibody specific for Cystatin F.

48. The isolated polypeptide of claim 8, which further comprises a heterologous polypeptide.

54. A composition comprising the isolated polypeptide of claim 8, and a pharmaceutically acceptable carrier.

15. An isolated first polypeptide comprising a second polypeptide selected from the group consisting of:

(a) a polypeptide comprising amino acid residue 1 to amino acid residue 145 as set forth in SEQ ID NO;

2, in which 1 to 5 amino acid residues are substituted, deleted or added, in any combination, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(b) a polypeptide comprising amino acid residue 1 to amino acid residue 145 as set forth in SEQ ID NO;

2, in which 5 to 10 amino acid residues are substituted, deleted or added, in any combination, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(c) a polypeptide comprising amino acid residue 19 to amino acid residue 145 as set forth in SEQ ID NO;

2, in which 1 to 5 amino acid residues are substituted, deleted or added, in any combination, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F; and

(d) a polypeptide comprising amino acid residue 19 to amino acid residue 145 as set forth in SEQ ID NO;

2, in which 5 to 10 amino acid residues are substituted, deleted or added, in any combination wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F.

16. The isolated first polypeptide of claim 15, wherein said polypeptide has Cystatin F activity.

17. The isolated first polypeptide of claim 15, wherein said polypeptide binds an antibody specific for Cystatin F.

18. The isolated first polypeptide of claim 15, comprising second polypeptide (a).

19. The isolated first polypeptide of claim 15, comprising second polypeptide (b).

20. The isolated first polypeptide of claim 15, comprising second polypeptide (c).

21. The isolated first polypeptide of claim 20, wherein said polypeptide has Cystatin F activity.

22. The isolated first polypeptide of claim 20, wherein said polypeptide binds an antibody specific for Cystatin F.

23. The isolated first polypeptide of claim 15, comprising second polypeptide (d).

24. The isolated first polypeptide of claim 23, wherein said polypeptide has Cystatin F activity.

25. The isolated first polypeptide of claim 23, wherein said polypeptide binds an antibody specific for Cystatin F.

49. The isolated polypeptide of claim 15, which further comprises a heterologous polypeptide.

55. A composition comprising the isolated first polypeptide of claim 15, and a pharmaceutically acceptable carrier.

26. An isolated first polypeptide comprising a second polypeptide selected from the group consisting of:

(a) amino acid residue 30 to amino acid residue 39 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(b) amino acid residue 51 to amino acid residue 64 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(c) amino acid residue 58 to amino acid residue 66 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(d) amino acid residue 59 to amino acid residue 64 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(e) amino acid residue 63 to amino acid residue 66 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(f) amino acid residue 65 to amino acid residue 79 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(g) amino acid residue 67 to amino acid residue 72 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(h) amino acid residue 72 to amino acid residue 89 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(i) amino acid residue 84 to amino acid residue 98 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F;

(j) amino acid residue 100 to amino acid residue 120 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F; and

(k) amino acid residue 120 to amino acid residue 131 as set forth in SEQ ID NO;

2, wherein said polypeptide has Cystatin F activity or binds an antibody specific for Cystatin F.

27. The isolated first polypeptide of claim 26 comprising second polypeptide (a).

28. The isolated first polypeptide of claim 26 comprising second polypeptide (b).

29. The isolated first polypeptide of claim 26 comprising second polypeptide (c).

30. The isolated first polypeptide of claim 26 comprising second polypeptide (d).

31. The isolated first polypeptide of claim 26 comprising second polypeptide (e).

32. The isolated first polypeptide of claim 26 comprising second polypeptide (f).

33. The isolated first polypeptide of claim 26 comprising second polypeptide g).

34. The isolated first polypeptide of claim 26 comprising second polypeptide (h).

35. The isolated first polypeptide of claim 26 comprising second polypeptide (i).

36. The isolated first polypeptide of claim 26 comprising second polypeptide (j).

37. The isolated first polypeptide of claim 26 comprising second polypeptide (k).

38. The isolated polypeptide of claim 26, wherein said polypeptide has Cystatin F activity.

39. The isolated polypeptide of claim 26, wherein said polypeptide binds an antibody specific for Cystatin F.

50. The isolated polypeptide of claim 26, which further comprises a heterologous polypeptide.

56. A composition comprising the isolated first polypeptide of claim 26, and a pharmaceutically acceptable carrier.

40. An isolated polypeptide encoded by a nucleic acid molecule comprising a polynucleotide which hybridizes to the complement of the polynucleotide set forth in SEQ ID NO:

1 wherein said hybridization occurs under conditions comprising hybridization in a buffer consisting of 7% SDS, 0.5M NaPO₄, pH 7.4 overnight at 65°

C. and wash in a buffer consisting of 0.5×

SSC, 0.1% SDS at 60°

C.

41. The isolated polypeptide of claim 40, wherein said polypeptide has Cystatin F activity.

42. The isolated polypeptide of claim 40, wherein said polypeptide binds an antibody specific for Cystatin F.

51. The isolated polypeptide of claim 40, which further comprises a heterologous polypeptide.

57. A composition comprising the isolated first polypeptide of claim 40, and a pharmaceutically acceptable carrier.

43. An isolated polypeptide comprising 30 contiguous amino acids of SEQ ID NO:

2.

44. The isolated polypeptide of claim 43, comprising 50 contiguous amino acids of SEQ ID NO:

2.

45. The isolated polypeptide of claim 43, wherein said polypeptide has Cystatin F activity.

46. The isolated polypeptide of claim 43, wherein said polypeptide binds an antibody specific for Cystatin F.

52. The isolated polypeptide of claim 43, which further comprises a heterologous polypeptide.

58. A composition comprising the isolated first polypeptide of claim 43, and a pharmaceutically acceptable carrier.