US 12,257,300 B2
Replication-competent controlled alpha-herpesvirus vectors and uses therefore
Richard W Voellmy, La Tour-de-Peilz (CH)
Assigned to HSF PHARMACEUTICALS S.A., La Tour-de-Peilz (CH)
Appl. No. 17/300,287
Filed by HSF Pharmaceuticals SA, La Tour-de-Peilz (CH)
PCT Filed Nov. 4, 2019, PCT No. PCT/EP2019/080138
§ 371(c)(1), (2) Date May 12, 2021,
PCT Pub. No. WO2020/104180, PCT Pub. Date May 28, 2020.
Claims priority of provisional application 62/917,066, filed on Nov. 19, 2018.
Claims priority of application No. 18207121 (EP), filed on Nov. 19, 2018.
Prior Publication US 2023/0270846 A1, Aug. 31, 2023
Int. Cl. A61K 39/245 (2006.01); A61K 39/00 (2006.01); A61P 31/12 (2006.01); C12N 15/86 (2006.01)
CPC A61K 39/245 (2013.01) [A61K 39/0011 (2013.01); A61P 31/12 (2018.01); C12N 15/86 (2013.01); A61K 2039/5254 (2013.01); C12N 2710/16621 (2013.01); C12N 2710/16634 (2013.01); C12N 2710/16643 (2013.01); C12N 2710/16651 (2013.01); C12N 2710/16662 (2013.01); C12N 2710/16671 (2013.01); C12N 2830/002 (2013.01)] 12 Claims
 
1. A heat-controlled or heat- and small-molecule regulators-controlled replication-competent controlled alpha-herpesvirus whose replication can be transiently activated in nonneural cells infected with said replication-competent controlled alpha-herpesvirus but that cannot be transiently activated in neural cells infected with said replication-competent controlled alpha-herpesvirus, wherein the replication-competent controlled alpha-herpesvirus is a recombinant alpha-herpesvirus derived from a virus of the group consisting of a herpes simplex virus type 1 (HSV-1), a herpes simplex virus type 2 (HSV-2) and a varicella-zoster virus, said replication-competent controlled alpha-herpesvirus comprising:
(a) a first heterologous promoter that is a nucleic acid sequence that acts as a heat shock promoter, the first heterologous promoter controlling the expression of a first replication-essential gene of the replication-competent controlled alpha-herpesvirus, wherein
(1) the first heterologous promoter is functionally linked to the first replication-essential gene of the replication-competent controlled alpha-herpesvirus, or
(2) the first heterologous promoter is functionally linked to a gene for a heterologous, unregulated or small-molecule-regulated transactivator that has been inserted in the genome of the replication-competent controlled alpha-herpesvirus and the first replication-essential gene is functionally linked to a promoter that is responsive to the transactivator, and
(b) a second heterologous promoter that is known to be active in nonneural cells of a mammalian subject to which the replication-competent controlled alpha-herpesvirus is to be administered but is also known to be essentially inactive in neural cells of the mammalian subject, the second heterologous promoter being functionally linked to a second replication-essential gene of the replication-competent controlled alpha-herpesvirus.