US 12,338,464 B2
Clonal strains of attenuated vaccinia viruses and methods of use thereof
Aladar A. Szalay, Highland, CA (US); Nanhai G. Chen, San Diego, CA (US); Yong A. Yu, San Diego, CA (US); and Qian Zhang, San Diego, CA (US)
Assigned to Genelux Corporation, Westlake Village, CA (US)
Filed by GENELUX CORPORATION, Westlake Village, CA (US)
Filed on Sep. 3, 2021, as Appl. No. 17/466,381.
Application 17/466,381 is a continuation of application No. 13/506,369, filed on Apr. 13, 2012, granted, now 11,149,254, issued on Oct. 19, 2021.
Claims priority of provisional application 61/628,684, filed on Nov. 4, 2011.
Claims priority of provisional application 61/517,297, filed on Apr. 15, 2011.
Prior Publication US 2023/0008052 A1, Jan. 12, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 7/00 (2006.01); A61K 35/768 (2015.01); C07K 16/22 (2006.01)
CPC C12N 7/00 (2013.01) [A61K 35/768 (2013.01); C07K 16/22 (2013.01); C07K 2317/622 (2013.01); C12N 2710/24121 (2013.01); C12N 2710/24132 (2013.01); C12N 2710/24143 (2013.01)] 50 Claims
 
1. An isolated clonal LIVP strain, wherein:
the genome of the clonal LIVP strain is not modified to contain non-viral heterologous nucleic acid containing an open reading frame encoding a non-viral heterologous protein;
the genome of the clonal strain comprises the sequence of nucleotides selected from among:
a) nucleotides 2,256-181,114 of SEQ ID NO:1, nucleotides 11,243-182,721 of SEQ ID NO:2, nucleotides 6,264-181,390 of SEQ ID NO:4, nucleotides 7,044-181,820 of SEQ ID NO:5, nucleotides 6,674-181,409 of SEQ ID NO:6, nucleotides 6,716-181,367 of SEQ ID NO:7, or nucleotides 6,899-181,870 of SEQ ID NO:8; and
b) a sequence of nucleotides that has at least 95% sequence identity to the sequence of nucleotides 2,256-181,114 of SEQ ID NO:1, nucleotides 11,243-182,721 of SEQ ID NO:2, nucleotides 6,264-181,390 of SEQ ID NO:4, nucleotides 7,044-181,820 of SEQ ID NO:5, nucleotides 6,674-181,409 of SEQ ID NO:6, nucleotides 6,716-181,367 of SEQ ID NO:7, or nucleotides 6,899-181,870 of SEQ ID NO:8;
the clonal LIVP strain has greater anti-tumorigenicity or reduced toxicity or both compared to the strain designated GLV-1h68;
the genome of the clonal LIVP strain comprises a sequence of nucleotides that has at least 90% sequence identity with the sequence of nucleotides set forth in SEQ ID NO: 10 but does not comprise the sequence of nucleotides set forth in SEQ ID NO:10; and
the isolated clonal strain is produced by or obtainable by a method comprising:
(i) preparing a clonal isolate from an LIVP virus sample;
(ii) assaying the clonal isolate for toxicity;
(iii) assaying the clonal isolate for anti-tumorigenicity; and
(iv) selecting the clonal isolate that exhibits greater anti-tumorigenicity and/or reduced toxicity compared to GLV-1h68.