Human rhinovirus assays, and compositions therefrom

• US 20020177125A1
• Filed: 11/16/2001
• Published: 11/28/2002
• Est. Priority Date: 03/04/1997
• Status: Abandoned Application

• Current Assignee: Deltagen Proteomics Incorporated
• Original Assignee: Deltagen Proteomics Incorporated
• Inventors: Poritz, Mark Aaron, Kamb, Carl Alexander, Teng, David Heng-Fai
• Application Number:
  US09/991,003
• Publication Number:
  US 20020177125A1
• Time in Patent Office: Days
• US Class Current: 435/5
• 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: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 16/1009 Picornaviridae, e.g. hepatitis A virus
• CPC Class Codes: C12N 15/1034 Isolating an individual clone by screening libraries
• CPC Class Codes: C12N 15/1055 Protein x Protein interaction, e.g. two hybrid selection
• CPC Class Codes: C12N 2770/32722 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12Q 1/6897 involving reporter genes operably linked to promoters
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/56983 Viruses

Abstract

Methods for assaying for viral-related activity are disclosed. The assays of the invention provide for the identification of biologically active phenotypic probes and cellular targets and fragments, variants and mimetics thereof.

Claims

1. An isolated polypeptide having viral activity comprising a polypeptide sequence selected from the group consisting of:

(a) the polypeptide sequence of FIG. 11 (cW985);

(b) biologically active modifications of (a); and

(c) biologically active fragments of (a).

2. The isolated polypeptide of claim 1 wherein said polypeptide sequence is the polypeptide sequence of FIG. 11 (cW985).

6. The isolated polypeptide of claim 1 wherein said isolated polypeptide comprises a sequence at least 99% identical to the polypeptide sequence of FIG. 11 (cW985).

7. The isolated polypeptide of claim 1 wherein said isolated polypeptide comprises a sequence at least 95% identical to the polypeptide sequence of FIG. 11 (cW985).

8. The isolated polypeptide of claim 1 wherein said isolated polypeptide comprises a sequence at least 90% identical to the polypeptide sequence of FIG. 11 (cW985).

9. The isolated polypeptide of claim 1 wherein said isolated polypeptide comprises a sequence at least 85% identical to the polypeptide sequence of FIG. 11 (cW985).

10. The isolated polypeptide of claim 1 wherein said isolated polypeptide comprises a sequence at least 80% identical to the polypeptide sequence of FIG. 11 (cW985).

11. The isolated polypeptide of claim 1 wherein said isolated polypeptide comprises a biologically active fragment of the polypeptide sequence of FIG. 11 (cW985) that displays viral activity.

12. The isolated polypeptide of claim 1 wherein said isolated polypeptide is a closely related analog of the polypeptide sequence of FIG. 11 (cW985), wherein said analog displays viral activity.

13. The isolated polypeptide of claim 1 wherein said isolated polypeptide is an antigenic analog of the polypeptide sequence of FIG. 11 (cW985), wherein said analog binds to an antibody specific for the polypeptide of FIG. 11 (cW985).

14. The isolated polypeptide of claim 1 wherein said isolated polypeptide is an N-terminal fragment of the polypeptide of FIG. 11 (cW985).

15. The isolated polypeptide of claim 14 wherein said N-terminal fragment comprises at least 10 amino acids of the polypeptide of FIG. 11 (cW985).

16. The isolated polypeptide of claim 1 wherein said isolated polypeptide is a C-terminal fragment of the polypeptide of FIG. 11 (cW985).

17. The isolated polypeptide of claim 16 wherein said C-terminal fragment comprises at least 10 amino acids of the polypeptide of FIG. 11 (cW985).

18. The polypeptide of claim 1 wherein said polypeptide is fused to heterologous sequence.

19. The polypeptide of claim 18 wherein said heterologous sequence is a scaffold.

20. The polypeptide of claim 19 wherein said scaffold is a fluorescent protein.

21. The polypeptide of claim 1 wherein said polypeptide is chemically modified.

22. The polypeptide of claim 21 wherein said polypeptide is radio labeled.

23. The polypeptide of claim 21 wherein said modification is selected from the group consisting of acetylation, glycosylation, or fluorescent tagging.

24. The isolated polypeptide of claim 1 wherein said polypeptide is chemically synthesized.

25. An isolated polynucleotide encoding a polypeptide of claim 1.

26. An isolated polynucleotide encoding a polypeptide of claim 1 wherein said polypeptide encodes the polypeptide sequence of FIG. 11 (cW985).

30. An isolated polynucleotide encoding a polypeptide of claim 6.

31. An isolated polynucleotide encoding a polypeptide of claim 7.

32. An isolated polynucleotide encoding a polypeptide of claim 8.

33. An isolated polynucleotide encoding a polypeptide of claim 9.

34. An isolated polynucleotide encoding a polypeptide of claim 10.

35. An isolated polynucleotide encoding a polypeptide of claim 14.

36. An isolated polynucleotide encoding a polypeptide of claim 16.

40. The isolated polynucleotide of claim 37 wherein said isolated polynucleotide comprises a sequence at least 99% identical to said polynucleotide.

41. The isolated polynucleotide of claim 37 wherein said isolated polynucleotide comprises a sequence at least 95% identical to said polynucleotide.

42. The isolated polynucleotide of claim 37 wherein said isolated polynucleotide comprises a sequence at least 90% identical to said polynucleotide.

43. The isolated polynucleotide of claim 37 wherein said isolated polynucleotide comprises a sequence at least 85% identical to said polynucleotide.

44. The isolated polynucleotide of claim 37 wherein said isolated polynucleotide comprises a sequence at least 80% identical to said polynucleotide.

45. A vector comprising the polynucleotide of any one of claims 25, 26, 38 or 39.

46. The vector of claim 45, wherein said vector provides inducible expression.

47. A gene therapy vector comprising the polynucleotide of claims 25, 26, 38 or 39.

48. A host cell comprising the vector of claim 45.

49. A polynucleotide that hybridizes under stringent conditions to the polynucleotide of any one of claims 25, 26, 38 or 39.

50. A method for producing a polypeptide having viral activity comprising culturing a population of host cells of claim 48 under conditions suitable for the expression of an encoded polypeptide and recovering expressed polypeptide from the host cell culture.

51. A composition comprising the polypeptide of claims 1, 2, 3 or 5 in a pharmaceutically acceptable carrier.

52. An antibody to the polypeptide of claims 1, 2, 3 or 5.

53. A method of identifying a cellular target that interacts with a polypeptide having viral activity, comprising the steps of exposing a polypeptide of claim 1 to putative target molecules and identifying a polypeptide/target interaction pair.

54. The method of claim 53 wherein said method is a yeast two-hybrid assay.

55. A method of screening for putative viral related therapeutics, comprising the steps of:

a) exposing a polypeptide/target interaction pair obtained by the method of claim 53 to a plurality of agents; and

b) recovering a subpopulation of disrupting agents which competitively displace said polypeptide from said target;

wherein said disrupting agents are putative viral related therapeutics.

56. The method of claim 55, wherein said plurality of agents is a combinatorial chemical library.

57. A method of treating a viral related condition, comprising the step of administering a therapeutically effective amount of the polypeptide of claim 1, or a pharmaceutically acceptable salt thereof.

3. The isolated polypeptide consisting essentially of the polypeptide sequence of FIG. 11 (cW985).

4. The isolated polypeptide of claim 3 wherein said isolated polypeptide comprises the polypeptide sequence of FIG. 11 (cW985) except for one or more conservative amino acid substitutions.

27. An isolated polynucleotide encoding a polypeptide of claim 3.

28. An isolated polynucleotide encoding a polypeptide of claim 4.

5. The isolated polypeptide consisting of the polypeptide sequence of FIG. 11 (cW985).

29. An isolated polynucleotide encoding a polypeptide of claim 5.

37. An isolated polynucleotide comprising the DNA sequence of FIG. 11 (cW985).

38. An isolated polynucleotide consisting essentially of the DNA sequence of FIG. 11 (cW985).

39. An isolated polynucleotide consisting of the DNA sequence of FIG. 11 (cW985).