# US 2025/0375441 A1 · Oncolytic therapy with a dual hdac3 and hdac8 targeting agent

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2025/0375441 A1
- Document ID: US20250375441A1
- Status: Published application
- Kind: A1
- Application number: 19/229,044
- Filed: 2025-06-05
- Published: 2025-12-11
- Earliest claimed: 2024-06-06
- Assignees: University of Florida Research Foundation, Inc.
- Applicants: University of Florida Research Foundation, Incorporated
- Inventors: Beth A. Rousseau; Sumita Bhaduri-Mclntosh; Michael Mclntosh; Guangrong Zheng; Yufeng Xiao
- Web page: https://patentgrep.com/patent/US20250375441A1

## CPC

- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
- A61K 31/662: Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61P 31/22: for herpes viruses
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure provides methods of treating or preventing a disease associated with a virus, methods of inhibiting cell proliferation or promoting apoptosis, methods of inducing a lytic phase of a virus, and methods of reactivating a virus by administering to a subject in need thereof a dual HDAC3 and HDAC8 targeting agent and an antiviral, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof.

## Claims

### Claim 1

A method of treating or preventing a disease associated with a virus in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of a dual HDAC3 and HDAC8 targeting agent, or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, further comprising administering to the subject in need thereof a therapeutically effective amount of an antiviral agent, or a pharmaceutically acceptable salt thereof and/or a therapeutically effective amount of an agent capable of sensitizing or potentiating induction of the lytic phase of the virus, or a pharmaceutically acceptable salt thereof.

### Claim at position 3

3-18. (canceled)

### Claim 19 (depends on 1)

The method of claim 1, wherein the dual HDAC3 and HDAC8 targeting agent is YX968, or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 2)

The method of claim 2, wherein the antiviral agent is ganciclovir, cidofovir, acyclovir, or foscarnet, or a pharmaceutically acceptable salt thereof.

### Claim 21

(canceled)

### Claim 22 (depends on 2)

The method of claim 2, wherein the additional agent capable of sensitizing or potentiating induction of the lytic phase of the virus is an EZH2 inhibitor.

### Claim 23 (depends on 22)

The method of claim 22, wherein the additional agent capable of sensitizing or potentiating induction of the lytic phase of the virus is tazemetostat.

### Claim 24 (depends on 1)

The method of claim 1, further comprising administering to the subject in need thereof a therapeutically effective amount of an additional agent capable of inducing the lytic phase of the virus, or a pharmaceutically acceptable salt thereof, wherein the additional agent capable of inducing the lytic phase of the virus is an HDAC inhibitor, a DNA methyltransferase inhibitor, a phorbol ester, a hypoxia-mimicking agent, or an immunoglobulin.

### Claim at position 10

25-26. (canceled)

### Claim 27 (depends on 24)

The method of claim 24, wherein the additional agent capable of inducing the lytic phase of the virus is sodium butyrate, valproic acid, romidepsin, MS-275, apicidin, oxamflatin, Scriptaid, panobinostat, or nanatinostat.

### Claim 28 (depends on 1)

The method of claim 1, wherein the virus is a herpesvirus.

### Claim 29

(canceled)

### Claim 30 (depends on 1)

The method of claim 1, wherein the virus is Epstein-Barr virus (EBV) or Kaposi's sarcoma-associated herpesvirus (KSHV).

### Claim at position 15

31-32. (canceled)

### Claim 33 (depends on 1)

The method of claim 1, wherein the disease is a proliferative disease selected from a lymphoproliferative disease, a cancer, chronic active EBV infection (CAEBV), and multiple sclerosis (MS).

### Claim 34

(canceled)

### Claim 35 (depends on 33)

The method of claim 33, wherein the lymphoproliferative disease is iatrogenic lymphoproliferative disorder, iatrogenic lymphoma, post-transplant lymphoproliferative disorder (PTLD), post-transplant lymphoma, Burkitt lymphoma, B-cell non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), CNS lymphoma, NK/T-cell lymphoma, T cell non-Hodgkin lymphoma, Hodgkin lymphoma, nasopharyngeal cell carcinoma, AIDS-related lymphoma, chronic active EBV infection (CAEBV), hemophagocytic lymphohistiocytosis, EBV-positive gastric carcinoma, or multicentric Castleman's disease.

### Claim 36

(canceled)

### Claim 37 (depends on 33)

The method of claim 33, wherein the cancer is:
a lymphoid malignancy selected from iatrogenic lymphoma, post-transplant lymphoma, Burkitt lymphoma, B-cell non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), central nervous system (CNS) lymphoma, NK/T-cell lymphoma, T cell non-Hodgkin lymphoma, Hodgkin's lymphoma, and a primary effusion lymphoma (PEL);
a non-lymphoid malignancy selected from EBV-positive gastric carcinoma and nasopharyngeal cell carcinoma;
a cancer associated with human immunodeficiency virus selected from oral hairy leukoplakia, central nervous system (CNS) lymphoma, or AIDS-related lymphoma; or
Kaposi's sarcoma.

### Claim at position 21

38-45. (canceled)

### Claim 46

A method of inhibiting cell proliferation or promoting apoptosis in a subject in need thereof, the method comprising administering to the subject in need thereof an effective amount of a dual HDAC3 and HDAC8 targeting agent, or a pharmaceutically acceptable salt thereof.

### Claim 47

A method of inducing a lytic phase of a virus in a subject in need thereof, the method comprising administering to the subject in need thereof an effective amount of a dual HDAC3 and HDAC8 targeting agent, or a pharmaceutically acceptable salt thereof.

### Claim at position 24

48-73. (canceled)

### Claim 74 (depends on 1)

The method of claim 1, further comprising administering to the subject in need thereof one or more additional pharmaceutical agents and/or radiation.

### Claim 75 (depends on 74)

The method of claim 74, wherein the one or more additional pharmaceutical agents are chemotherapeutic agents and/or PARP inhibitors.

### Claim at position 27

76-77. (canceled)

### Claim 78 (depends on 1)

The method of claim 1, wherein:
the subject in need thereof has been administered an immunosuppressive or immunomodulatory agent selected from corticosteroids (e.g., prednisone (Deltasone, Orasone), budesonide (Entocort EC), prednisolone (Millipred)), Janus kinase inhibitors (e.g., tofacitinib (Xeljanz)), calcineurin inhibitors (e.g., cyclosporine (Neoral, Sandimmune, SangCya), tacrolimus (Astagraf XL, Envarsus XR, Prograf)), mTOR inhibitors (e.g., sirolimus (Rapamune), everolimus (Afinitor, Zortress), inosine monophosphate dehydrogenase (IMDH) inhibitors (e.g., azathioprine (Azasan, Imuran), leflunomide (Arava), mycophenolate (CellCept, Myfortic), biologics (e.g., antibody, monoclonal antibody) (e.g., abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), ixekizumab (Taltz), natalizumab (Tysabri), rituximab (Rituxan), secukinumab (Cosentyx), tocilizumab (Actemra), ustekinumab (Stelara), vedolizumab (Entyvio), basiliximab (Simulect), daclizumab (Zinbryta)), and antimetabolites (e.g., methotrexate); and/or
the subject in need thereof has been administered one or more of T cell suppressive therapy and anti-TNF alpha therapy, wherein the T cell suppressive therapy is antithymocyte globulin or recombinant antithymocyte globulin therapy.

### Claim at position 29

79-89. (canceled)

### Claim 90 (depends on 1)

The method of claim 1, wherein the subject in need thereof comprises one or more of EBV-positive cancer cells, EBV-positive pre-cancerous cells, KSHV-positive cancer cells, and KSHV-positive pre-cancerous cells.

### Claim 91 (depends on 90)

The method of claim 90, wherein the EBV or KSHV is in a latent lytic state or abortive lytic state.

### Claim at position 32

92-112. (canceled)