US 12,350,304 B2
Recombinant oncolytic virus composition and use thereof
Chao Tian, Beijing (CN); Xiaopeng Li, Beijing (CN); Chunyang Sun, Beijing (CN); Hua Zhou, Beijing (CN); Jiajia Liu, Beijing (CN); and Jingshu Zhao, Beijing (CN)
Assigned to BEIJING WELLGENE COMPANY LTD., Beijing (CN)
Appl. No. 17/044,074
Filed by BEIJING WELLGENE COMPANY LTD., Beijing (CN)
PCT Filed Mar. 21, 2019, PCT No. PCT/CN2019/078999
§ 371(c)(1), (2) Date Sep. 30, 2020,
PCT Pub. No. WO2019/196617, PCT Pub. Date Oct. 17, 2019.
Claims priority of application No. 201810331305.9 (CN), filed on Apr. 13, 2018.
Prior Publication US 2021/0138008 A1, May 13, 2021
Int. Cl. A61K 35/763 (2015.01); A61P 35/00 (2006.01); C07K 14/535 (2006.01); C07K 14/54 (2006.01); C07K 14/55 (2006.01); C07K 16/28 (2006.01); C12N 7/00 (2006.01)
CPC A61K 35/763 (2013.01) [A61P 35/00 (2018.01); C07K 14/535 (2013.01); C07K 14/5434 (2013.01); C07K 14/55 (2013.01); C07K 16/2818 (2013.01); C12N 7/00 (2013.01); C12N 2710/16632 (2013.01); C12N 2710/16643 (2013.01)] 11 Claims
 
1. A recombinant oncolytic virus composition, characterized in that the composition comprises:
a first herpes simplex virus vector 1 (HSV-1) with a deletion of the genes encoding ICP34.5 and ICP47 and a first exogenous gene inserted in a position where the gene encoding ICP34.5 is deleted; wherein the first exogenous gene is selected from the group consisting of a gene encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), a gene encoding Interleukin-2 (IL-2), and a gene encoding Interleukin-12 (IL-12); and
a second herpes simplex virus vector 1 (HSV-1) with a deletion of the genes encoding ICP34.5 and ICP47 and a second exogenous gene inserted in a position where the gene encoding ICP34.5 is deleted; wherein the second exogenous gene is a gene encoding cytokine GM-CSF, or a gene encoding a programmed cell death protein 1 (PD-1) blocking monoclonal antibody,
wherein, the first herpes simplex virus vector and the second herpes simplex virus vector are the same or different from each other, and the selected first exogenous gene is different from the selected second exogenous gene; and
wherein, in terms of pfu, if the second exogenous gene is a gene encoding a cytokine, the mixing ratio of the first recombinant oncolytic virus to the second recombinant oncolytic virus is 0.5:1-1:0.5, if the second exogenous gene is a gene encoding a monoclonal antibody, the mixing ratio of the first recombinant oncolytic virus to the second recombinant oncolytic virus is 1:1-1:4.