US 12,258,417 B2
Adenovirus armed with bispecific T cell engager
Brian Robert Champion, Abingdon (GB); Alice Claire Noel Bromley, Abingdon (GB); Joshua David Freedman, Chigwell (GB); Kerry David Fisher, Witney (GB); and Leonard William Seymour, Wootton by Woodstock (GB)
Assigned to AKAMIS BIO LIMITED, Oxfordshire (GB)
Appl. No. 16/329,125
Filed by AKAMIS BIO LIMITED, Abingdon (GB)
PCT Filed Aug. 29, 2017, PCT No. PCT/EP2017/071655
§ 371(c)(1), (2) Date Feb. 27, 2019,
PCT Pub. No. WO2018/041827, PCT Pub. Date Mar. 8, 2018.
Claims priority of application No. 1614607 (GB), filed on Aug. 29, 2016; application No. 1700663 (GB), filed on Jan. 13, 2017; application No. 1706219 (GB), filed on Apr. 19, 2017; and application No. 1713765 (GB), filed on Aug. 28, 2017.
Prior Publication US 2019/0233536 A1, Aug. 1, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/30 (2006.01); A61K 35/761 (2015.01); A61K 39/395 (2006.01); A61P 35/00 (2006.01); C07K 14/52 (2006.01); C07K 16/28 (2006.01); C07K 16/40 (2006.01); C12N 15/86 (2006.01); C12N 15/861 (2006.01); A61K 35/768 (2015.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/30 (2013.01) [A61K 35/761 (2013.01); A61K 39/39558 (2013.01); A61P 35/00 (2018.01); C07K 14/521 (2013.01); C07K 16/2809 (2013.01); C07K 16/40 (2013.01); C12N 15/86 (2013.01); C12N 15/861 (2013.01); A61K 35/768 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5256 (2013.01); A61K 2039/585 (2013.01); A61K 2300/00 (2013.01); C07K 2317/31 (2013.01); C07K 2317/56 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/75 (2013.01); C07K 2319/92 (2013.01); C12N 2710/10332 (2013.01); C12N 2710/10343 (2013.01); C12N 2830/60 (2013.01); C12N 2840/44 (2013.01)] 23 Claims
 
1. An oncolytic adenovirus comprising a sequence of formula (I):
5′ITR-B1-BA-B2-BX-BB-BY-B3-3′ITR  (I)
wherein:
B1 is a bond or comprises: E1A, E1B or E1A-E1B;
BA comprises: E2B-L1-L2-L3-E2A-L4;
B2 is a bond or comprises: E3;
BX is a bond or a DNA sequence comprising: a restriction site, one or more transgenes or both;
BB comprises: L5;
BY is a bond or a DNA sequence comprising: a restriction site, one or more transgenes or both;
B3 is a bond or comprises: E4;
wherein the adenovirus encodes:
a tumour antigen-specific Bispecific T cell Engager comprising at least two binding domains, Bd1 and Bd2, wherein at least one of the binding domains is specific to a component of a T-cell receptor complex (TCR) and at least one of the binding domains is specific to a tumour antigen, and
a tumour stromal antigen-specific Bispecific T cell Engager comprising at least two binding domains, Bd3 and Bd4, wherein at least one of the binding domains is specific to a component of a T-cell receptor complex (TCR) and at least one of the binding domains is specific to a tumour stromal antigen;
wherein both Bispecific T cell Engagers are encoded in position BY; and
the adenovirus is Enadenotucirev (EnAd) or serotype 11 adenovirus (Ad11).