Polypeptide comprising the amino acid of an N-terminal choline binding protein a truncate, vaccine derived therefrom and uses thereof

• US 6,858,706 B2
• Filed: 04/07/1998
• Issued: 02/22/2005
• Est. Priority Date: 04/07/1998
• Status: Expired due to Fees

• Current Assignee: St Jude Children's Research Hospital Incorporated (Abbott Laboratories), Medimmune Incorporated (Astrazeneca PLC)
• Original Assignee: St Jude Children's Research Hospital Incorporated (Abbott Laboratories), Medimmune Incorporated (Astrazeneca PLC)
• Inventors: Johnson, Leslie Sydnor, Wizemann, Theresa M., Koenig, Scott, Tuomanen, Elaine I., Masure, H. Robert
• Primary Examiner(s): MINNIFIELD, NITA M
• Application Number:
  US09/056,019
• Publication Number:
  US 20030096950A1
• Time in Patent Office: 2,513 Days
• Field of Search: 530/350, 530/324, 424/184.1, 424/185.1, 424/190.1, 424/244.1, 424/234.1
• US Class Current: 530/350
• 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 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07K 14/3156 from Streptococcus pneumoniae (Pneumococcus) Streptokinase C07K14/3153

Abstract

This invention provides an isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate in which the amino acid sequence is set forth in any of SEQ ID NOS: 1, 3-7, or 9-11, including fragments, mutants, variants, analogs, or derivatives, thereof. Also, this invention provides a isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate, wherein the amino acid is set forth in SEQ ID NO 24, wherein the polypeptide retains its native tertiary structure and methods of preparation. This invention provides an isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate, wherein the polypeptide has lectin activity and does not bind to choline. This invention provides an isolated immunogenic polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate. This invention provides an isolated nucleic acid encoding a polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate. Lastly, this invention provides pharmaceutical compositions, vaccines, and diagnostic and therapeutic methods of use.

Claims

1. An isolated polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:

5, wherein said polypeptide does not bind to choline.

2. The isolated polypeptide of claim 1, wherein said polypeptide comprises SEQ ID NO:

3.

3. The isolated polypeptide of claim 1, wherein said polypeptide comprises SEQ ID NO:

1.

4. The isolated polypeptide of claim 1, wherein said polypeptide comprises SEQ ID NO:

24.

5. The isolated polypeptide of claim 1, wherein said polypeptide is immunogenic.

6. The isolated polypeptide of claim 1, wherein said polypeptide comprises an amino acid sequence having up to 475 amino acids.

7. The isolated polypeptide of claim 6, wherein said polypeptide comprises an amino acid sequence having up to 460 amino acids.

8. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier, or diluent.

9. An isolated polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:

4, wherein said polypeptide does not bind to choline.

10. The isolated polypeptide of claim 9, wherein said polypeptide comprises SEQ ID NO:

22.

11. The isolated polypeptide of claim 9, wherein said polypeptide is immunogenic.

12. The isolated polypeptide of claim 9, wherein said polypeptide comprises an amino acid sequence having up to 475 amino acids.

13. The isolated polypeptide of claim 9, wherein said polypeptide comprises an amino acid sequence having up to 460 amino acids.

14. An isolated polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:

24, wherein said fragment does not bind to choline, and comprises at least 138 consecutive amino acids of SEQ ID NO;

24, wherein said polypeptide is immunogenic.

43. The isolated polypeptide of claim 14, wherein said polypeptide has lectin activity.

46. The isolated polypeptide of claim 14, wherein said polypeptide has lectin activity.

15. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

5, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, wherein said polypeptide does not bind choline, is immunogenic and said polypeptide comprises up to 398 amino acids.

19. The isolated polypeptide of claim 15, wherein said amino acid substitutions comprise conservative amino acid substitutions.

44. The isolated polypeptide of claim 15, wherein said polypeptide has lectin activity.

16. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

3, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline and wherein said polypeptide is immunogenic.

17. The isolated polypeptide of claim 16, wherein said polypeptide comprises the amino acid sequence set forth in SEQ ID NO:

1, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline and wherein said polypeptide is immunogenic.

18. The isolated polypeptide of claim 16, wherein said polypeptide comprises the amino acid sequence set forth in SEQ ID NO:

24, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline and wherein said polypeptide is immunogenic.

42. The isolated polypeptide of claim 16, wherein said amino acid substitutions comprise conservative amino acid substitutions.

45. The isolated polypeptide of claim 16, wherein said polypeptide has lectin activity.

47. The isolated polypeptide of claim 18, wherein said polypeptide has lectin activity.

20. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:

4, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, wherein said polypeptide does not bind choline and wherein said polypeptide is immunogenic and said polypeptide comprises up to 398 amino acids.

21. The isolated polypeptide of claim 20, wherein said polypeptide comprises the amino acid sequence set forth in SEQ ID NO:

22, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline and wherein said polypeptide is immunogenic.

48. The isolated polypeptide of claim 20, wherein said polypeptide has lectin activity.

49. The isolated polypeptide of claim 21, wherein said polypeptide has lectin activity.

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

a) an analog of the amino acid sequence set forth in SEQ ID NO;

5, wherein said polypeptide does not bind choline and is immunogenic;

b) an analog of the amino acid sequence set forth in SEQ ID NO;

4, wherein said polypeptide does not bind choline and is immunogenic;

c) an analog of the amino acid sequence set forth in SEQ ID NO;

11, wherein said polypeptide does not bind choline, is immunogenic, and comprise up to 328 amino acids;

d) an analog of the amino acid sequence set forth in SEQ ID NO;

9, wherein said polypeptide does not bind choline, is immunogenic, and comprises up to 376 amino acids; and

,

e) an analog of the amino acid sequence set forth in SEQ ID NO;

10, wherein said polypeptide does not bind choline, is immunogenic and comprises up to 328 amino acids.

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

a) a derivative of the amino acid sequence set forth in SEQ ID NO;

5, wherein said polypeptide does not bind choline and is immunogenic;

b) a derivative of the amino acid sequence set forth in SEQ ID NO;

4, wherein said polypeptide does not bind choline and is immunogenic;

c) a derivative of the amino acid sequence set forth in SEQ ID NO;

11, wherein said polypeptide does not bind choline, is immunogenic, and comprise up to 328 amino acids;

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

9, wherein said polypeptide does not bind choline, is immunogenic, and comprises up to 376 amino acids; and

,

e) a derivative of the amino acid sequence set forth in SEQ ID NO;

10, wherein said polypeptide does not bind choline, is immunogenic and comprises up to 328 amino acids.

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

a) the amino acid sequence set forth in SEQ ID NO;

5 wherein said amino acid sequence comprises at least one to 57 amino acid substitutions and said polypeptide comprises up to 398 amino acids, does not bind choline and is immunogenic, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide;

b) the amino acid sequence set forth in SEQ ID NO;

4 wherein said amino acid sequence comprises at least one to 57 amino acid substitutions and said polypeptide comprises up to 398 amino acids, does not bind choline and is immunogenic, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide;

c) the amino acid sequence set forth in SEQ ID NO;

11 wherein said amino acid sequence comprises at least one to 57 amino acid substitutions and said polypeptide, does not bind choline and is immunogenic, and comprise up to 328 amino acids, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide;

d) the amino acid sequence set forth in SEQ ID NO;

9 wherein said amino acid sequence comprises at least one to 57 amino acid substitutions and said polypeptide does not bind choline and is immunogenic, and comprises up to 376 amino acids, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide;

e) the amino acid sequence set forth in SEQ ID NO;

10 wherein said amino acid sequence comprises at least one to 57 amino acid substitutions and said polypeptide does not bind choline, is immunogenic and comprises up to 147 amino acids, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide; and

,

f) the amino acid sequence set forth in SEQ ID NO;

3 wherein said amino acid sequence comprises at least one to 57 amino acid substitutions and said polypeptide, does not bind choline and is immunogenic, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide.

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

a) the amino acid sequence set forth in SEQ ID NO;

5, wherein said polypeptide does not bind choline, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide;

b) the amino acid sequence set forth in SEQ ID NO;

4, wherein said polypeptide does not bind choline, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CpbA polypeptide;

c) the amino acid sequence set forth in SEQ ID NO;

11, wherein said polypeptide does not bind choline, is immunogenic and comprise up to 328 amino acids, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide;

d) the amino acid sequence set forth in SEQ ID NO;

9, wherein said polypeptide does not bind choline, is immunogenic and comprises up to 376 amino acids, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with the full-length CbpA polypeptide; and

,

e) the amino acid sequence set forth in SEQ ID NO;

10, wherein said polypeptide does not bind choline, is immunogenic and comprises up to 328 amino acids, wherein said polypeptide interacts with an antibody, said antibody is capable of interacting with a full-length CbpA polypeptide.

26. An isolated polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:

11, wherein said polypeptide does not bind to choline and comprises up to 328 amino acids.

29. The isolated polypeptide of claim 26, wherein said polypeptide is immunogenic.

31. A pharmaceutical composition comprising the polypeptide of claim 26, and a pharmaceutically acceptable carrier, or diluent.

27. An isolated polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:

9, wherein said polypeptide does not bind to choline and comprises up to 376 amino acids.

28. The isolated polypeptide of claim 27, wherein said polypeptide comprises SEQ ID NO:

7.

30. The isolated polypeptide of claim 27, wherein said polypeptide is immunogenic.

41. A pharmaceutical composition comprising the polypeptide of claim 27, and a pharmaceutically acceptable carrier, or diluent.

32. An isolated polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:

10, wherein said polypeptide does not bind to choline, and said polypeptide comprises up to 328 amino acids.

33. The isolated polypeptide of claim 32, wherein said polypeptide comprises SEQ ID NO:

23.

34. The isolated polypeptide of claim 32, wherein said polypeptide is immunogenic.

35. An isolated polypeptide comprising an amino acid sequence set forth in SEQ ID NO:

11, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline, is immunogenic and comprises up to 328 amino acids.

36. The isolated polypeptide of claim 35, wherein said polypeptide comprises the amino acid sequence set forth in SEQ ID NO:

9, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline and is immunogenic.

37. The isolated polypeptide of claim 36, wherein said polypeptide comprises the amino acid sequence set forth in SEQ ID NO:

7, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline and is immunogenic.

38. The isolated polypeptide of claim 35, wherein said amino acid substitutions comprise conservative amino acid substitutions.

50. The isolated polypeptide of claim 35, wherein said polypeptide has lectin activity.

51. The isolated polypeptide of claim 36, wherein said polypeptide has lectin activity.

52. The isolated polypeptide of claim 37, wherein said polypeptide has lectin activity.

39. An isolated polypeptide comprising an amino acid sequence set forth in SEQ ID NO:

10, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline, is immunogenic and comprises up to 147 amino acids.

40. The isolated polypeptide of claim 39, wherein said polypeptide comprises the amino acid sequence set forth in SEQ ID NO:

23, wherein said amino acid sequence comprises at least one to 57 amino acid substitutions, and said polypeptide does not bind choline and is immunogenic.

53. The isolated polypeptide of claim 39, wherein said polypeptide has lectin activity.

54. The isolated polypeptide of claim 40, wherein said polypeptide has lectin activity.