IP Library › Granted Patent US 12,589,128
Granted Patent B2
US 12,589,128 · App. 17/371,546 · Granted Mar 31, 2026

Oncolytic adenovirus compositions

Inventors: Clodagh O'Shea (San Diego, CA); Shigeki Miyake-Stoner (La Jolla, CA)
Assignee: Salk Institute for Biological Studies
A61K35/761A61K35/768C12N7/00C12N15/86C12N2710/10021C12N2710/10032C12N2710/10043
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Quick Facts
Patent No.
US 12,589,128
App. No.
17/371,546
Granted
Mar 31, 2026
Kind
B2
Abstract

An adenovirus comprising an E1A polypeptide comprising one or more modifications and comprising an E4orf6/7 polypeptide comprising one or more modifications is described. Compositions and kits comprising the modified adenoviruses are also described. Further described is a method of treating a proliferative disorder in a subject comprising administering to the subject an adenovirus comprising the E1A polypeptide comprising one or more modifications and comprising the E4orf6/7 polypeptide comprising one or more modifications.

Claims (18)

1 . A method of inducing cytotoxicity in an Rb-deficient tumor cell in a tumor comprising contacting the tumor cell with a recombinant adenovirus by local administration of the recombinant adenovirus to the tumor, wherein the recombinant adenovirus comprises a genome comprising:

(i) an adenovirus E1A promoter operably linked to a nucleic acid sequence encoding an E1A protein comprising a modification in a first Rb-binding site; and

(ii) an adenovirus E4 promoter operably linked to an E4orf6/7 gene product coding sequence comprising a deletion or modification of at least one of the two E4orf6/7 exons, wherein the deletion or the modification impairs E4orf6/7 gene product activity and/or expression,

wherein the recombinant adenovirus induces cytotoxicity in the Rb-deficient tumor cell in the tumor.

2 . The method of claim 1 , wherein the E4orf6/7 gene product coding sequence comprises a deletion or modification of only one of the two E4orf6/7 exons.

3 . The method of claim 1 , wherein the E1A protein modification is selected from:

a deletion of the LXCXE motif;

a deletion of amino acid residues 122-126; a deletion of amino acid residues 2-11;

a substitution at residue Y47;

a substitution at residue C124;

and any combination of the above.

4 . The method of claim 3 , wherein the substitution at residue Y47 is a Y47H substitution, or the substitution at residue C124 is a C124G substitution, or both.

5 . The method of claim 3 , wherein the E1A protein modification comprises a deletion of the LXCXE motif.

6 . The method of claim 5 , wherein the adenovirus is serotype 5.

7 . The method of claim 1 , wherein the E1A protein further comprises a modification in a second Rb-binding site.

8 . The method of claim 1 , wherein the deletion or modification of at least one of the two E4orf6/7 exons comprises a deletion or modification of both of the E4orf6/7 exons.

9 . The method of claim 1 , wherein the genome comprises a nucleic acid encoding an E4orf6 polypeptide.

10 . The method of claim 1 , wherein the adenovirus is serotype 5.

Assignments (3)
SECOND AMENDED AND RESTATED PATENT SECURITY AGREEMENT Recorded Mar 2, 2026
From: UROGEN PHARMA LTD.
To: BIOPHARMA CREDIT PLC, AS COLLATERAL AGENT
Reel/Frame 074994/0338 →
AMENDED AND RESTATED PATENT SECURITY AGREEMENT Recorded Mar 6, 2025
From: UROGEN PHARMA LTD.
To: BIOPHARMA CREDIT PLC [COLLATERAL AGENT]
Reel/Frame 070434/0319 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 12, 2021
From: O'SHEA, CLODAGH; MIYAKE-STONER, SHIGEKI
To: SALK INSTITUTE FOR BIOLOGICAL STUDIES
Reel/Frame 056830/0176 →
Continuity (4)
Division 14852981 · Sep 14, 2015
Continuation PCTUS2014029587 · Mar 14, 2014
Provisional Application 61782932 · Mar 14, 2013
Related Publication 20220096577A1 · Mar 31, 2022
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