# US 10,369,155 B2 · Method for treating cancer

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

- Number: US 10,369,155 B2
- Document ID: US10369155B2
- Status: Granted
- Kind: B2
- Application number: 15/851,978
- Filed: 2017-12-22
- Published: 2018-05-17
- Granted: 2019-08-06
- Earliest claimed: 2014-10-16
- Assignees: Epizyme, Inc.
- Applicants: Epizyme, Inc.
- Inventors: Heike Keilhack
- Web page: https://patentgrep.com/patent/US10369155B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/45: having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
- A61K 31/453: containing a six-membered ring with oxygen as a ring hetero atom
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61K 31/5375: 1,4-Oxazines, e.g. morpholine
- 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 invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.

## Claims

### Claim 1

A method of inhibiting the ability of a cancer cell to induce immune dysfunction, comprising a step of contacting the cell with a therapeutically effective amount of an EZH2 inhibitor, wherein the cell (1) comprises aberrant, misregulated, or increased EZH2 activity; or (2) comprises a chromosomal translocation t(x; 18)(p11.2;q11.2) that causes a SS18-SSX fusion gene; or (3) has reduced function and/or expression of INI1.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cell comprises aberrant, misregulated, or increased EZH2 activity.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cell comprises a chromosomal translocation t(x; 18)(p11.2;q11.2), wherein the translocation causes a SS18-SSX fusion gene.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cell has reduced function or expression of INI1.

### Claim 5 (depends on 4)

The method of claim 4, wherein the cell has reduced function and expression of INI1.

### Claim 6 (depends on 1)

The method of claim 1, wherein the EZH2 inhibitor is Compound A, having the following formula:
or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The method of claim 1, wherein the EZH2 inhibitor is selected from the group consisting of
and pharmaceutically acceptable salts thereof.

### Claim 8 (depends on 1)

The method of claim 1, wherein the cancer cell is in a subject.

### Claim 9 (depends on 8)

The method of claim 8, wherein the subject is human.

### Claim 10 (depends on 1)

The method of claim 1, wherein the ability of the cancer cell to induce immune dysfunction is characterized by reduced expression of one or more of MHC, β2 microglobulin, Tumor Necrosis Factor (TNF) receptor, Low Molecular Mass Polypeptide 2 (LMP2), Low Molecular Mass Polypeptide 7 (LMP7), Transporter Associated with Antigen Processing (TAP), and TAP-associated glycoprotein (tapasin) in the cancer cell when compared to a non-cancerous cell.

### Claim 11 (depends on 10)

The method of claim 10, wherein the MHC is human leukocyte antigen (HLA), wherein the HLA is selected from the group consisting of HLA-A, HLA-B, HLA-C, HLDA-DM alpha, HLA-DM beta, HLA-DO alpha, HLA-DO beta 1, HLA-DP alpha 1, HLA-DP beta 1, HLA-DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA-DR beta 4, HLA-E, HLA-F, HLA-G, HLA-K, and HLA-L.

### Claim 12

A method of treating or alleviating symptoms of a disorder characterized by cancer-cell induced immune dysfunction in a subject comprising a step of administering to the subject a therapeutically effective amount of an EZH2 inhibitor; wherein the subject (1) comprises a chromosomal translocation t(x; 18) that causes a SS18-SSX fusion gene; or (2) has reduced function and/or expression of INTL.

### Claim 13 (depends on 12)

The method of claim 12, wherein the subject comprises aberrant, misregulated, or increased EZH2 activity.

### Claim 14 (depends on 12)

The method of claim 12, wherein the subject comprises a chromosomal translocation t(x; 18)(p11.2;q11.2), wherein the translocation causes a SS18-SSX fusion gene.

### Claim 15 (depends on 12)

The method of claim 12, wherein the subject has reduced function or expression of INI1.

### Claim 16 (depends on 15)

The method of claim 15, wherein the subject has reduced function and expression of INI1.

### Claim 17 (depends on 12)

The method of claim 12, wherein the EZH2 inhibitor is Compound A, having the following formula:
or a pharmaceutically acceptable salts thereof.

### Claim 18 (depends on 12)

The method of claim 12, wherein the EZH2 inhibitor is selected from the group consisting of
and pharmaceutically acceptable salts thereof.

### Claim 19 (depends on 12)

The method of claim 12, wherein the method further comprises administering a chemotherapeutic compound.

### Claim 20 (depends on 19)

The method of claim 19, wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor.