IP Library › Granted Patent US 12,414,973
Granted Patent B2
US 12,414,973 · App. 17/058,379 · Granted Sep 16, 2025

Antigenically stealthed oncolytic viruses

Inventors: Joseph C. Glorioso, III (Pittsburgh, PA); Gary H. Cohen (Havertown, PA); Doina Atanasiu (Norwood, PA); Tina Marie Cairns (Warminster, PA); Bonnie Lynn Hall (Allison Park, PA); Justus B. Cohen (Allison Park, PA); Ceren Tuzmen (Pittsburgh, PA)
Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education; The Trustees of the University of Pennsylvania
A61K35/763C12N7/00C12N2710/16621C12N2710/16622C12N2710/16632C12N2710/16645
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Quick Facts
Patent No.
US 12,414,973
App. No.
17/058,379
Granted
Sep 16, 2025
Kind
B2
Abstract

Provided herein are antigenically stealthed HSV particles, and methods of use of the antigenically-stealthed HSV particles.

Claims (27)

1. A retargeted herpes simplex virus (HSV) particle, comprising a genome, a capsid, tegument, and an envelope comprising an antigenically-modified glycoprotein D (gD) protein, wherein one or more of amino acids 10-20, 54, 75-79, 132, 140, 213, 216, 222-224, and 262-279 of SEQ ID NO: 1 or SEQ ID NO: 2, or one or more amino acids corresponding to amino acids 10-20, 54, 75-79, 132, 140, 213, 216, 222-224, and 262-279 of SEQ ID NO: 1 or SEQ ID NO: 2, are modified in the gD glycoprotein of the virus particle, and

wherein the modifications:

reduce or eliminate neutralization of the retargeted virus particle by antibodies that recognize the gD glycoprotein, and

permit gD glycoprotein-mediated infection of a target cell by the retargeted virus particle.

2. The virus particle of claim 1 , wherein one or both of amino acids P54 and T213 of SEQ ID NO: 1 or SEQ ID NO: 2, or one or both amino acids corresponding to amino acids P54 and T213 of SEQ ID NO: 1 or SEQ ID NO: 2 are modified.

3. The virus particle of claim 1 , further comprising an antigenically-modified glycoprotein B (gB), wherein the modification is in one of more of amino acids 47, 62, 85, 203, 303, 304, 305, 308, 328, 335, 419, 473, 594, or 640-670 of SEQ ID NO: 3 or amino acid 412 of SEQ ID NO: 4, or one or more amino acids corresponding to amino acids 47, 62, 85, 203, 303, 304, 305, 308, 328, 335, 419, 473, 594, or 640-670 of SEQ ID NO: 3 or amino acid 412 of SEQ ID NO: 4.

4. The virus particle of claim 1 , having a 438 mutation of SEQ ID NO: 1 or 2, or a mutation in a gD glycoprotein corresponding to a 438 mutation of SEQ ID NO: 1 or 2.

5. The virus particle of claim 1 , comprising a non-native ligand capable of binding a surface component of a target cell type.

6. The virus particle of claim 5 , wherein the target cell type is a cancer cell.

7. The virus particle of claim 5 , wherein the non-native ligand capable of binding a surface component of a target cell type is incorporated into a viral envelope glycoprotein of the virus particle.

8. The virus particle of claim 7 , wherein the viral envelope glycoprotein of the virus particle into which the ligand is incorporated is gD, gC, gB and/or gH.

9. The virus particle of claim 5 , wherein the surface component is one or more of EGFR, EGFRvIII, other oncogenic EGFR variants, HER2, CD133, CXCR4, carcinoembryonic antigen (CEA), CLC-3/annexin-2/MMP-2, human transferrin receptor, EpCAM, or c-Met.

10. The virus particle of claim 1 , wherein binding of at least one or more viral envelope glycoproteins to its natural receptor is eliminated.

11. The virus particle of claim 1 , wherein the genome comprises an exogenous expression cassette.

12. The virus particle of claim 11 , wherein the exogenous expression cassette encodes an agent that enhances tumor killing activity.

13. The virus particle of claim 1 , wherein the genome comprises a target sequence for one or more microRNAs.

14. A recombinant HSV genome encoding the virus particle of claim 1 .

15. A viral stock, comprising at least 10 5 pfus of a virus particle of claim 1 .

16. A pharmaceutical dosage form comprising at least 10 5 pfus of a virus particle of claim 1 , and a pharmaceutically-acceptable excipient.

17. The dosage form of claim 16 , formulated for parenteral delivery.

18. A method of treating a patient having a cancer, comprising administering to the patient an amount of the virus particle of claim 6 effective to treat a cancer patient.

19. The virus particle of claim 2 , wherein the modifications to SEQ ID NO: 1 or SEQ ID NO: 2 comprise P54Q and/or T213M.

20. A retargeted herpes simplex virus (HSV) particle, comprising a genome, a capsid, tegument, and an envelope comprising an antigenically-modified glycoprotein D (gD) protein, wherein the antigenically-modified gD protein comprises a P54Q and/or a T213M substitution in SEQ ID NO: 1 or SEQ ID NO: 2 and optionally one or more of amino acids 10-20, 75-79, 132, 140, 216, 222-224, and 262-279 of SEQ ID NO: 1 or SEQ ID NO: 2, or one or more amino acids corresponding to amino acids 10-20, 75-79, 132, 140, 216, 222-224, and 262-279 of SEQ ID NO: 1 or SEQ ID NO: 2, are modified in the gD glycoprotein of the virus particle, and

wherein the modifications:

reduce or eliminate neutralization of the retargeted virus particle by antibodies that recognize the gD glycoprotein, and

permit infection of a target cell by the retargeted virus particle.

21. The virus particle of claim 20 , further comprising an antigenically-modified glycoprotein B (gB), wherein the modification is in one of more of amino acids 47, 62, 85, 203, 303, 304, 305, 308, 328, 335, 419, 473, 594, or 640-670 of SEQ ID NO: 3, or amino acid 412 of SEQ ID NO: 4, or one or more amino acids corresponding to amino acids 47, 62, 85, 203, 303, 304, 305, 308, 328, 335, 419, 473, 594, or 640-670 of SEQ ID NO: 3, or amino acid 412 of SEQ ID NO: 4.

Assignments (5)
CONFIRMATORY LICENSE Recorded Oct 26, 2023
From: UNIVERSITY OF PENNSYLVANIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065365/0396 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2022
From: CAIRNS, TINA M.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 060785/0082 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2022
From: COHEN, GARY H.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 060785/0109 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2022
From: ATANASIU, DOINA
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 060785/0218 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 24, 2020
From: GLORIOSO, JOSEPH C., III; HALL, BONNIE LYNN; COHEN, JUSTUS B.; TUZMEN, CEREN
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 054459/0191 →
Continuity (2)
Provisional Application 62678737 · May 31, 2018
Related Publication 20210121513A1 · Apr 29, 2021
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