P
USRE45016EExpiredUtilityPatentIndex 83

Development of mutations useful for attenuating dengue viruses and chimeric dengue viruses

Assignee: US OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPT OF HEALTH AND HUMAN SERVICESPriority: May 22, 2001Filed: May 17, 2013Granted: Jul 15, 2014
Est. expiryMay 22, 2021(expired)· nominal 20-yr term from priority
Inventors:WHITEHEAD STEPHEN SMURPHY BRIAN RHANLEY KATHRYN ABLANEY JOSEPH ELAI CHING-JUH
A61P 31/14A61P 37/04G01N 2500/10A61K 2039/5256A61K 2039/5254C12N 7/00A61K 2039/575C12N 2770/24171A61K 2039/54C12N 2770/24121A61K 2039/5252C12Q 2600/156C12N 2770/24162C12N 2770/24134G01N 2333/18A61K 2039/70A61K 39/12C12N 2770/24161Y02A50/30C12Q 1/701C12N 2770/24163A61K 39/295C12N 2770/24151C12N 7/04
83
PatentIndex Score
4
Cited by
147
References
13
Claims

Abstract

A menu of mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccines.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A temperature-sensitive, host-range restricted mutant flavivirus, designated mutant 200, 201, wherein said virus comprises charge-cluster-to-alanine mutations at amino acids 2687 and 2688 of the NS5 gene, where amino acid position is given for the polyprotein of dengue virus type 4. 
     
     
       2. The flavivirus of  claim 1 , further comprising the Δ30 mutation. 
     
     
       3. The flavivirus of  claim 1 , wherein the flavivirus is a dengue virus type 1. 
     
     
       4. The flavivirus of  claim 1 , wherein the flavivirus is a dengue virus type 2. 
     
     
       5. The flavivirus of  claim 1 , wherein the flavivirus is a dengue virus type 3. 
     
     
       6. The flavivirus of  claim 1 , wherein the flavivirus is a dengue virus type 4. 
     
     
       7. The flavivirus of  claim 1 , wherein the flavivirus is a chimeric virus. 
     
     
       8. The chimeric virus of  claim 7  having a dengue 1 backbone. 
     
     
       9. The chimeric virus of  claim 7  having a dengue 2 backbone. 
     
     
       10. The chimeric virus of  claim 7  having a dengue 3 backbone. 
     
     
       11. The chimeric virus of  claim 7  having a dengue 4 backbone. 
     
     
       12. The flavivirus of  claim 1 , wherein the phenotype is temperature sensitivity in Vero cells or the human liver cell line HuH-7. 
     
     
       13. A pharmaceutical composition comprising a pharmacologically acceptable vehicle and a flavivirus according to any of  claims 1 - 12 .

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