Oncolytic vaccinia virus with modified B5R gene for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-12509704-B2
Application number	US-201917284169-A
Country	US
Kind code	B2
Filing date	Oct 10, 2019
Priority date	Oct 10, 2018
Publication date	Dec 30, 2025
Grant date	Dec 30, 2025

Abstract

The present invention relates to a vaccinia virus vector comprising a nucleic acid sequence encoding a SCR1−, SCR2−, SCR3−, and SCR4− domain deleted B5R gene (B5R SCR1− SCR2− SCR3− SCR4−) inserted into the TK gene of the vaccinia virus. The invention also relates to compositions comprising the vaccinia virus vector, methods of treatment using the compositions, medical uses of the compositions and kits comprising the vaccinia virus vector. The invention also relates to a nucleic acid sequence encoding a SCR1−, SCR2−, SCR3−, and SCR4− domain deleted B5R gene (B5R SCR1− SCR2− SCR3− SCR4−) of vaccinia virus.

First claim

The invention claimed is:

1 . A vaccinia virus vector comprising an intact native B5R gene and a nucleic acid sequence encoding a SCR1−, SCR2−, SCR3−, and SCR4− domain deleted B5R gene (B5R SCR1−SCR2−SCR3−SCR4) having at least 90% sequence identity with the nucleic acid sequence of SEQ ID NO:68 inserted into the TK gene of the vaccinia virus, and wherein the vaccinia virus produces 10- to 30-fold more infectious extracellular enveloped virus (EEV) than a native vaccinia virus while the total replication of the vaccinia virus is not attenuated.

2 . A vaccinia virus vector according to claim 1 which further comprises a nucleic acid sequence encoding a biologically active protein inserted into the NIL gene of the vaccinia virus.

3 . A vaccinia virus vector according to claim 2 , in which the biologically active protein is selected from the group consisting of cytokines, antibodies, antibody fragments, cytokine receptors and cytokine receptor fragments.

4 . A vaccinia virus vector according to claim 3 , in which the biologically active protein is a cytokine.

5 . A vaccinia virus vector according to claim 4 , in which the cytokine is selected from the group consisting of IL-21, GM-CSF, IL-2, IL-7, IL-12, IL-15, IL-18 and IFN-α, or any combinations thereof.

6 . A vaccinia virus vector according to claim 3 , in which the biologically active protein is an immune checkpoint inhibitor molecule.

7 . A vaccinia virus vector according to claim 6 , in which the immune checkpoint inhibitor molecule is selected from the group consisting of soluble PD1, soluble PD-L1, soluble TIM-3, soluble CTLA-4, or any combinations thereof.

8 . A vaccinia virus vector according to claim 6 , in which the nucleic acid sequence encoding a SCR1−, SCR2−, SCR3−, and SCR4− domain deleted B5R gene (B5R SCR1−SCR2−SCR3−SCR4−) is SEQ ID NO:68.

9 . A composition comprising a vaccinia virus vector according to claim 6 .

10 . A kit comprising a vaccinia virus vector according to claim 6 and a pharmaceutically acceptable adjuvant, diluent and/or buffer.

11 . A composition comprising a vaccinia virus vector according to claim 1 .

12 . A kit comprising a vaccinia virus vector according to claim 1 and a pharmaceutically acceptable adjuvant, diluent and/or buffer.

13 . A vaccinia virus vector according to claim 1 , wherein the nucleic acid sequence encoding a SCR1−, SCR2−, SCR3−, and SCR4− domain deleted B5R gene (B5R SCR1−SCR2−SCR3−SCR4) has at least 95% sequence identity with the nucleic acid sequence of SEQ ID NO:68.

Assignees

• Univ London Queen Mary

Inventors

• Wang Yaohe
• Yuan Ming

Classifications

• C12N2710/24143

  viral genome or elements thereof as genetic vector · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C07K14/70532

  B7 molecules, e.g. CD80, CD86 · CPC title

• C07K14/70521

  CD28, CD152 · CPC title

• C07K14/5434

  IL-12 · CPC title