US Patent No. 10,052,374

COMPOSITIONS, METHODS AND USES FOR DENGUE VIRUS SEROTYPE-4 CONSTRUCTS


Patent No. 10,052,374
Issue Date August 21, 2018
Title Compositions, Methods And Uses For Dengue Virus Serotype-4 Constructs
Inventorship Jill A. Livengood, Fort Collins, CO (US)
Claire Kinney, Fort Collins, CO (US)
Timothy D. Powell, Fort Collins, CO (US)
Dan T. Stinchcomb, Fort Collins, CO (US)
Jorge Osorio, Mount Horeb, WI (US)
Assignee Takeda Vaccines, Inc., Cambridge, MA (US) The United States of America as ...

Claim of US Patent No. 10,052,374

1. A tetravalent dengue virus composition comprising:live, attenuated dengue viruses comprising a dengue-2/4 chimera, wherein the dengue-2/4 chimera comprises a live, attenuated dengue-2 virus backbone having one or more structural proteins from a dengue-4 virus, and wherein a nucleic acid construct encoding the live, attenuated dengue-2/4 chimera further comprises one or more mutations, the one or more mutations comprising:
a mutation in an envelope (E) protein at an amino acid position synonymous to amino acid 417 of dengue-4 when the E protein is from dengue-4, wherein the mutation in the E protein at the position synonymous to amino acid 417 changes glutamic acid to a positively charged amino acid residue;
a mutation in the capsid (C) protein at an amino acid position synonymous to amino acid 107 in the live, attenuated dengue-2 virus backbone, wherein the mutation in the C protein at the position synonymous to amino acid 107 changes cysteine to an aromatic amino acid residue in dengue-2 virus backbone; and
a mutation in nonstructural protein 4A (NS4A) at an amino acid position synonymous to amino acid 17 in the dengue-2 virus backbone; and
one or more live, attenuated flaviviruses or one or more flavivirus chimeras, wherein the composition comprises all four dengue virus serotypes, dengue-1, dengue-2, dengue-3 and dengue-4, wherein the dengue-4 virus is present in the composition in an amount that is at least one log greater than the amount of dengue-2 virus.