Granted Patent B2

US 12,653,852 · App. 18/583,342 · Granted Jun 16, 2026

Inventors: Brian Robert Champion (Oxfordshire, GB); Alice Claire Noel Brown (Oxfordshire, GB); Kerry David Fisher (Oxfordshire, GB); Tamara Nicolson (Oxfordshire, GB)

Assignee: Akamis Bio, Inc.

A61K35/761A61K39/0011C12N7/00A61K2039/5256C12N2710/10332C12N2710/10343

Abstract

Claims (28)

1 . A replication competent group B oncolytic adenovirus comprising a sequence of formula (I):

5′ITR-B 1 -B A -B 2 -B X -B B -B Y -B 3 -3′ITR

wherein:

B 1 is absent or comprises: E1A, E1B or E1A-E1B;

B A comprises: E2B-L1-L2-L3-E2A-L4;

B 2 is absent or comprises: E3;

B X is absent or a DNA sequence comprising: a restriction site, one or more transgenes, or both;

B B comprises: L5;

B Y comprises: a transgene cassette comprising two or more transgenes; and

B 3 is absent or comprises: E4,

wherein the transgene cassette is under the control of an endogenous major late promoter.

2 . The adenovirus of claim 1 , wherein B Y further comprises the sequence set forth in SEQ ID NO: 11 or a DNA sequence that hybridizes thereto under stringent conditions.

3 . The adenovirus of claim 1 , wherein B Y further comprises a splice acceptor sequence.

4 . The adenovirus of claim 3 , wherein the splice acceptor sequence is selected from CAGG, SEQ ID NO: 17, and SEQ ID NO: 18.

5 . The adenovirus of claim 1 , wherein the transgene cassette further comprises an internal ribosome entry sequence or a high self-cleavage efficiency 2A peptide.

6 . The adenovirus of claim 1 , wherein the transgene cassette further comprises a Kozak sequence.

7 . The adenovirus of claim 6 , wherein the Kozak sequence is located at the start of a protein coding sequence.

8 . The adenovirus of claim 1 , wherein the transgene cassette further comprises a polyadenylation sequence.

9 . The adenovirus of claim 1 , wherein the transgene cassette further comprises a restriction site at the 3′ end or the 5′ end.

10 . The adenovirus of claim 1 , wherein the transgene cassette encodes at least one monocistronic mRNA and/or one polycistronic mRNA.

11 . The adenovirus of claim 1 , wherein the transgene cassette comprises a therapeutic gene encoding an RNAi, an antibody or binding fragment thereof, a chemokine, a cytokine, an immunomodulator, an enzyme, or a combination thereof.

12 . The adenovirus of claim 11 , wherein the antibody or binding fragment thereof specifically binds to OX40, OX40 ligand, CD27, CD28, CD30, CD40, CD40 ligand, CD70, CD137, GITR, 4-1BB, ICOS, ICOS ligand, CTLA-4, PD-1, PD-L1, PD-L2, VISTA, B7-H3, B7-H4, HVEM, ILT-2, ILT-3, ILT-4, TIM-3, LAG-3, BTLA, LIGHT, and/or CD160.

13 . The adenovirus of claim 11 , wherein the cytokine is selected from IL-1α, IL-1β, IL-6, IL-9, IL-12, IL-13, IL-17, IL-18, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-33, IL-35, IL-2, IL-4, IL-5, IL-7, IL-10, IL-15, IL-21, IL-25, IL-1RA, IFNα, IFNβ, IFNγ, TNFα, TGFβ, lymphotoxin α (LTA) and GM-CSF.

14 . The adenovirus of claim 11 , wherein the chemokine is selected from IL-8, CCL5, CCL17, CCL20, CCL22, CXCL9, CXCL10, CXCL11, CXCL13, CXCL12, CCL2, CCL19, CCL21, CXCR2, CCR2, CCR4, CCR5, CCR6, CCR7, CCR8, CXCR3, CXCR4, CXCR5, CRTH2, and a receptor of any of the above.

15 . The adenovirus of claim 1 , wherein the transgene cassette encodes a reporter gene.

16 . The adenovirus of claim 1 , wherein the adenovirus is Ad11.

17 . The adenovirus of claim 1 , wherein the adenovirus is chimeric EnAd.

18 . A composition comprising the adenovirus of claim 1 and a pharmaceutically acceptable carrier or excipient.

Assignments (3)

Priority Claims (5)

Continuity (4)

References Cited (306)