US 12,480,097 B2
Syncytial oncolytic herpes simplex mutants as potent cancer therapeutics
Timothy P. Cripe, Columbus, OH (US); Kevin A. Cassady, Columbus, OH (US); Pin-Yi Wang, Columbus, OH (US); and Julia K. Halley, Columbus, OH (US)
Assigned to Research Institute at Nationwide Children's Hospital, Columbus, OH (US)
Appl. No. 17/438,877
Filed by RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL, Columbus, OH (US)
PCT Filed Mar. 13, 2020, PCT No. PCT/US2020/022806
§ 371(c)(1), (2) Date Sep. 13, 2021,
PCT Pub. No. WO2020/186238, PCT Pub. Date Sep. 17, 2020.
Claims priority of provisional application 62/932,725, filed on Nov. 8, 2019.
Claims priority of provisional application 62/818,577, filed on Mar. 14, 2019.
Prior Publication US 2022/0154149 A1, May 19, 2022
Int. Cl. C12N 15/869 (2006.01); A61K 35/763 (2015.01); A61P 35/00 (2006.01); C12N 7/00 (2006.01); C12N 15/86 (2006.01)
CPC C12N 7/00 (2013.01) [A61K 35/763 (2013.01); A61P 35/00 (2018.01); C12N 15/86 (2013.01); C12N 15/8695 (2013.01); C12N 2710/00052 (2013.01); C12N 2710/16621 (2013.01); C12N 2710/16622 (2013.01); C12N 2710/16632 (2013.01); C12N 2710/16643 (2013.01); C12N 2710/16651 (2013.01)] 16 Claims
 
1. A non-natural herpes simplex virus (“HSV”), wherein the virus comprises at least one mutation in a virulence gene selected from:
(a) an alanine-to-threonine mutation at position 151 of the gE protein, wherein the alanine-to-threonine mutation at position 151 is with respect to SEQ ID NO: 19,
(b) an arginine-to-histidine mutation at position 258 of the ICP0 protein, wherein the arginine-to-histidine mutation at position 258 is with respect to SEQ ID NO: 26,
(c) an alanine-to-threonine mutation at position 376 of the DNA packaging terminase subunit 1 protein, wherein the alanine-to-threonine mutation at position 376 is with respect to SEQ ID NO: 42, or
(d) a threonine-to-methionine mutation at position 1155 of the ICP8 protein, wherein the threonine-to-methionine mutation at position 1155 is with respect to SEQ ID NO: 34;
and wherein the non-natural HSV has improved lytic activity compared to an HSV that does not comprise the at least one mutation.