Granted Patent
B2
US 12,465,639 · App. 18/462,133 · Granted Nov 11, 2025
Modified oncolytic virus
Assignee:
Replimune Limited GB
A61K39/39558A61K35/763A61K39/3955A61K45/06A61P35/00C07K14/005C07K14/535C07K16/2818C12N7/00A61K2039/505C12N2710/16621C12N2710/16622C12N2710/16632C12N2710/16633C12N2710/16643C12N2740/13022
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Abstract
The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene and (ii) an immune stimulatory molecule-encoding gene.
Claims (29)
1 . An oncolytic herpes simplex virus (HSV) comprising inserted in its genome: (i) a heterologous gene encoding a fusogenic glycoprotein from gibbon ape leukemia virus (GALV) from which the R peptide has been mutated or removed (GALV-R-), (ii) a heterologous gene encoding an anti-CTLA-4 antibody or an antigen binding fragment thereof, and (iii) one or more heterologous genes encoding any of a CD40 ligand, 4-1-BB ligand, GITR ligand, OX40 ligand, ICOS ligand and flt3 ligand.
2 . The oncolytic virus of claim 1 , wherein the oncolytic virus comprises a heterologous gene encoding GALV-R-, a heterologous gene encoding an anti-CTLA-4 antibody or an antigen binding fragment thereof, a heterologous gene encoding a CD40 ligand and a heterologous gene encoding a 4-1-BB ligand.
3 . The oncolytic virus of claim 1 , wherein GALV-R- has the amino acid sequence as set out in SEQ ID NO: 9.
4 . The oncolytic virus of claim 1 , wherein the CD40 ligand has the amino acid sequence as set out in SEQ ID NO: 11, 13 or 17.
5 . The oncolytic virus of claim 1 , wherein the sequence of one or more of the heterologous genes is codon optimised so as to increase expression levels in target cells.
6 . The oncolytic virus of claim 5 , wherein the heterologous gene encoding GALV-R-comprises the nucleotide sequence as set out in SEQ ID NO: 8, or the nucleotide sequence from position 4 to position 2013 as set out in SEQ ID NO: 8.
7 . The oncolytic virus of claim 5 , wherein the heterologous gene encoding the CD40 ligand comprises the nucleotide sequence as set out in SEQ ID NO: 10, 12 or 16.
8 . The oncolytic virus of claim 5 , wherein the heterologous gene encoding the 4-1-BB ligand comprises the nucleotide sequence as set out in SEQ ID NO: 21 or 23.
9 . The oncolytic virus of claim 1 , wherein each of the heterologous genes is under the control of a promoter sequence.
10 . The oncolytic virus of claim 9 , wherein the promoter is a viral promoter.
11 . The oncolytic virus of claim 10 , wherein the promoter is a CMV promoter, a RSV promoter, a retroviral LTR promoter, or a SV40 promoter.
12 . The oncolytic virus of claim 11 , wherein the retroviral LTR promoter is from MMLV.
13 . The oncolytic virus of claim 1 , wherein one or more of the heterologous genes is inserted into the ICP34.5 encoding locus, either by insertion, or partial or complete deletion, each under separate regulatory control.
14 . The oncolytic virus of claim 13 , wherein the heterologous genes encoding GALV-R- and an anti-CTLA-4 antibody are inserted into the ICP34.5 encoding locus, either by insertion, or partial or complete deletion, each under separate regulatory control.
15 . The oncolytic virus of claim 1 , wherein two or more of the heterologous genes are inserted into the oncolytic virus genome in a back to back orientation in relation to each other.
16 . The oncolytic virus of claim 15 , wherein the heterologous genes encoding GALV-R- and an anti-CTLA-4 antibody are inserted into the oncolytic virus genome in a back to back orientation in relation to each other.
17 . The oncolytic virus of claim 15 , wherein the heterologous genes encoding CD40 ligand and 4-1-BB ligand are inserted into the oncolytic virus genome in a back to back orientation in relation to each other.
18 . The oncolytic virus of claim 1 , wherein multiple copies of one or more of the heterologous genes are inserted into the oncolytic virus genome.
19 . The oncolytic virus of claim 1 , wherein two copies of the heterologous gene encoding GALV-R- and two copies of the heterologous gene encoding an anti-CTLA-4 antibody are inserted into the oncolytic virus genome.
20 . The oncolytic virus of claim 1 , which is a HSV1.
21 . The oncolytic virus of claim 20 , which is a modified HSV1 strain RH018A having the accession number ECACC 16121904.
22 . The oncolytic virus of claim 20 , wherein the oncolytic virus:
(a) does not express functional ICP34.5;
(b) does not express functional ICP47; and/or
(c) expresses the US11 gene as an immediate early gene.
23 . The oncolytic virus of claim 22 , wherein the ICP47-encoding gene is deleted such that the US11 gene is under the control of the ICP-47 immediate early gene promoter.
24 . A pharmaceutical composition comprising the oncolytic virus of claim 1 and a pharmaceutically acceptable carrier or diluent.
25 . An oncolytic herpes simplex virus (HSV), which is a modified HSV1 strain RH018A having the accession number ECACC 16121904, comprising inserted in its genome a heterologous gene encoding a fusogenic glycoprotein from gibbon ape leukemia virus (GALV) from which the R peptide has been mutated or removed (GALV-R-), a heterologous gene encoding an anti-CTLA-4 antibody or an antigen binding fragment thereof, a heterologous gene encoding a CD40 ligand and a heterologous gene encoding a 4-1-BB ligand, wherein the heterologous genes encoding GALV-R- and an anti-CTLA-4 antibody are inserted into the ICP34.5 encoding locus of the oncolytic virus genome such that the oncolytic virus does not express functional ICP34.5, and wherein the ICP47-encoding gene is deleted such that the US11 gene is under the control of the ICP-47 immediate early gene promoter.
26 . A pharmaceutical composition comprising the oncolytic virus of claim 25 and a pharmaceutically acceptable carrier or diluent.
Assignments (2)
SECURITY INTEREST
Recorded Jan 30, 2026
From: REPLIMUNE GROUP, INC.; REPLIMUNE, INC.; REPLIMUNE LIMITED
To: HERCULES CAPITAL, INC.
Reel/Frame 073644/0641 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 6, 2023
From: COFFIN, ROBERT
To: REPLIMUNE LIMITED
Reel/Frame 064818/0172 →
Priority Claims (3)
GB 1600380
· Jan 8, 2016
· national
GB 1600381
· Jan 8, 2016
· national
GB 1600382
· Jan 8, 2016
· national
Continuity (4)
Continuation
16068816
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