IP Library › Granted Patent US 9,683,022
Granted Patent B2
US 9,683,022 · App. 14/410,461 · Granted Jun 20, 2017

Complexes of cytomegalovirus proteins

Inventors: Andrea Carfi (Cambridge, MA); Yingxia Wen (Acton, MA)
Assignee: GLAXOSMITHKLINE BIOLOGICALS S.A.
C07K14/005A61K39/12A61K39/245C12N7/00A61K2039/53A61K2039/545A61K2039/55555A61K2039/55566A61K2039/55588A61K2039/572C12N2710/16122C12N2710/16134C12N2710/16151
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Quick Facts
Patent No.
US 9,683,022
App. No.
14/410,461
Granted
Jun 20, 2017
Kind
B2
Abstract

An isolated human cytomegalovirus (HCMV) membrane protein complex that comprises gH, gL and at least one more HCMV glycoprotein is provided. In some embodiments the complex consists of gH, gL and gO. In other embodiments the complex consists of gH, gL, pUL128, pUL130 and pUL131A. Processes for expressing and purifying such complexes, and subsequent uses of such complexes in immunogenic compositions and vaccines, are also provided.

Claims (54)

1. A composition comprising a purified human Cytomegalovirus (HCMV) pentameric complex comprising: a pentamer-forming fragment of HCMV gH having a truncated transmembrane (TM) domain and a truncated ectodomain as compared to wild-type HCMV gH; HCMV gL or pentamer-forming fragment thereof; HCMV pUL128 or pentamer-forming fragment thereof; HCMV pUL130 or pentamer-forming fragment thereof; and HCMV pUL131A or pentamer-forming fragment thereof, wherein the truncated TM domain consists of an amino acid sequence having a deletion of the amino acids corresponding to residues 718 to 736 of wild-type sequence SEQ ID NO: 1, and wherein the truncated ectodomain consists of an amino acid sequence having a deletion of the amino acids corresponding to residues 716 and 717 of wild-type sequence SEQ ID NO: 1.

2. The composition of claim 1 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 7-9 and 31.

3. The composition of claim 1 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence selected from the group consisting of SEQ ID NOs: 7-9 and 31.

4. The composition of claim 1 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 13-15 and 33.

5. The composition of claim 1 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence selected from the group consisting of SEQ ID NOs: 13-15 and 33.

6. The composition of claim 1 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 16, 17, and 34.

7. The composition of claim 1 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence selected from the group consisting of SEQ ID NOs: 16, 17, and 34.

8. The composition of claim 1 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 18-20, and 35.

9. The composition of claim 1 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence selected from the group consisting of SEQ ID NOs: 18-20, and 35.

10. The composition of claim 1 , that is a pharmaceutical comprising the purified HCMV pentameric complex and an adjuvant.

11. The pharmaceutical of claim 10 , wherein the adjuvant comprises an aluminum salt, an oil-in-water emulsion, or a combination thereof.

12. The pharmaceutical of claim 11 , wherein the adjuvant comprising an aluminum salt comprises aluminum hydroxide, aluminum oxyhydroxide, aluminum hydroxide adsorbed to a TLR7 agonist, or a combination thereof.

13. The pharmaceutical of claim 11 , wherein the oil-in-water emulsion comprises MF59, AS03, or a combination thereof.

14. The composition of claim 1 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 4, 6, 29, and 30.

15. The composition of claim 14 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 6, 29, and 30.

16. The composition of claim 15 , wherein said pentamer-forming fragment of HCMV gH comprises the sequence SEQ ID NO: 6.

17. A purified human Cytomegalovirus (HCMV) pentameric complex comprising: a pentamer-forming fragment of HCMV gH having a truncated transmembrane (TM) domain and a truncated ectodomain as compared to wild-type HCMV gH; HCMV gL or pentamer-forming fragment thereof; HCMV pUL128 or pentamer-forming fragment thereof; HCMV pUL130 or pentamer-forming fragment thereof; and HCMV pUL131A or pentamer-forming fragment thereof, wherein the truncated TM domain consists of an amino acid sequence having a deletion of the amino acids corresponding to residues 718 to 736 of wild-type sequence SEQ ID NO: 1, and wherein the truncated ectodomain consists of an amino acid sequence having a deletion of the amino acids corresponding to residues 716 and 717 of wild-type sequence SEQ ID NO: 1.

18. The purified HCMV pentameric complex of claim 17 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 7-9 and 31.

19. The purified HCMV pentameric complex of claim 17 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 13-15 and 33.

20. The purified HCMV pentameric complex of claim 17 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 16, 17, and 34.

21. The purified HCMV pentameric complex of claim 17 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 18-20, and 35.

22. The purified HCMV pentameric complex of claim 17 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 4, 6, 29, and 30.

23. The purified HCMV pentameric complex of claim 22 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 6, 29, and 30.

24. The purified HCMV pentameric complex of claim 23 , wherein said pentamer-forming fragment of HCMV gH comprises the sequence SEQ ID NO: 6.

25. The composition of claim 1 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 7-9 and 31.

26. The composition of claim 1 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 7-9 and 31.

27. The composition of claim 1 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 7-9 and 31.

28. The composition of claim 1 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 13-15 and 33.

29. The composition of claim 1 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 13-15 and 33.

30. The composition of claim 1 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 13-15 and 33.

31. The composition of claim 1 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 16, 17, and 34.

32. The composition of claim 1 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 16, 17, and 34.

33. The composition of claim 1 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 16, 17, and 34.

34. The composition of claim 1 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 18-20, and 35.

35. The composition of claim 1 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 18-20, and 35.

36. The composition of claim 1 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 18-20, and 35.

37. The composition of claim 1 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 4, 6, 29, and 30.

38. The composition of claim 1 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 4, 6, 29, and 30.

39. The composition of claim 1 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 4, 6, 29, and 30.

40. The purified HCMV pentameric complex of claim 17 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 7-9 and 31.

41. The purified HCMV pentameric complex of claim 17 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 7-9 and 31.

42. The purified HCMV pentameric complex of claim 17 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 7-9 and 31.

43. The purified HCMV pentameric complex of claim 17 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 13-15 and 33.

44. The purified HCMV pentameric complex of claim 17 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 13-15 and 33.

45. The purified HCMV pentameric complex of claim 17 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 13-15 and 33.

46. The purified HCMV pentameric complex of claim 17 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 16, 17, and 34.

47. The purified HCMV pentameric complex of claim 17 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 16, 17, and 34.

48. The purified HCMV pentameric complex of claim 17 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 16, 17, and 34.

49. The purified HCMV pentameric complex of claim 17 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 18-20, and 35.

50. The purified HCMV pentameric complex of claim 17 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 18-20, and 35.

51. The purified HCMV pentameric complex of claim 17 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 18-20, and 35.

52. The purified HCMV pentameric complex of claim 17 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 4, 6, 29, and 30.

53. The purified HCMV pentameric complex of claim 17 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 4, 6, 29, and 30.

54. The purified HCMV pentameric complex of claim 17 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 4, 6, 29, and 30.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 16, 2016
From: NOVARTIS VACCINES AND DIAGNOSTICS INC
To: NOVARTIS AG
Reel/Frame 039688/0696 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 16, 2016
From: CARFI, ANDREA; WEN, YINGXIA
To: NOVARTIS VACCINES AND DIAGNOSTICS INC
Reel/Frame 039688/0716 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 22, 2016
From: NOVARTIS AG
To: GLAXOSMITHKLINE BIOLOGICALS SA
Reel/Frame 038986/0292 →
Continuity (3)
Provisional Application 61668975 · Jul 6, 2012
Provisional Application 61770257 · Feb 27, 2013
Related Publication 20160159864A1 · Jun 9, 2016