# US 2018/0021331 A1 · Hdac1,2 inhibitors and methods of using the same

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- Number: US 2018/0021331 A1
- Document ID: US20180021331A1
- Status: Published application
- Kind: A1
- Application number: 15/541,012
- Filed: 2015-12-29
- Published: 2018-01-25
- Earliest claimed: 2014-12-30
- Assignees: University of Utah Research Foundation
- Applicants: University of Utah Research Foundation
- Inventors: Srividya BHASKARA
- Web page: https://patentgrep.com/patent/US20180021331A1

## CPC

- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- G01N 33/57505: of the blood, e.g. leukaemia
- G01N 33/57575: {involving oncogenic proteins}
- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- G01N 2333/47: Assays involving proteins of known structure or function as defined in the subgroups
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Disclosed herein are methods for treating a cancer and a method for sensitizing a cancer to a chemotherapeutic agent. Each method administers an agent that selectively inhibits HDAC1 and HDAC2 to a subject in need thereof. Also disclosed herein are methods for determining if a cancer is sensitive to an agent that selectively inhibits HDAC1 and HDAC2 and methods for monitoring the efficacy of a treatment for a cancer that includes administration of an agent that selectively inhibits HDAC1 and HDAC2.

## Claims

### Claim 1

A method of treating a cancer characterized by BCR-ABL expression or BBAP overexpression in a subject in need thereof, the method comprising administering to the subject an agent that selectively inhibits HDAC1 and HDAC2.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cancer is a B cell malignancy.

### Claim 3 (depends on 2)

The method of claim 2, wherein the B cell malignancy is diffuse large B cell lymphoma or early Pre-B cell derived acute lymphoblastic leukemia (Pre-B-ALL).

### Claim 4 (depends on 3)

The method of claim 3, wherein the diffuse large B cell lymphoma contains a gain-of-function mutation in Enhancer of Zeste Homologue 2 (EZH2), a gain-of-function mutation in a histone H3K27 methyltransferase, or a loss-of-function mutation in a H3K27 demethylase.

### Claim 5 (depends on 3)

The method of claim 3, wherein the Pre-B-ALL contains a chromosomal translocation and wherein the chromosomal translocation is t(9;22).

### Claim 6 (depends on 1)

The method of claim 1, wherein the cancer is further characterized as being dependent upon on a double-stranded break repair pathway.

### Claim 7 (depends on 6)

The method of claim 6, wherein the double-stranded break repair pathway includes one or more of the group consisting of FEN1, EPC2, BAF180, and DNA Ligase I.

### Claim 8 (depends on 1)

The method of claim 1, wherein the cancer is further characterized by increased H3K27me3.

### Claim 9 (depends on 1)

The method of claim 1, further comprising determining if the cancer is characterized by BCR-ABL expression or BBAP overexpression,
wherein determining comprises detecting a level of BCR-ABL, a level of BBAP, or a level of BCR-ABL and a level of BBAP in a sample obtained from the subject, and comparing the detected levels of BCR-ABL, BBAP, or BCR-ABL and BBAP to levels of BCR-ABL, BBAP, or BCR-ABL and BBAP in a control sample, wherein if the detected level of BCR-ABL is increased relative to the control level of BCR-ABL, the cancer is characterized by BCR-ABL expression, and wherein if the detected level of BBAP is increased relative to the control level of BBAP, the cancer is characterized by BBAP overexpression.

### Claim 10

(canceled)

### Claim 11

(canceled)

### Claim 12

(canceled)

### Claim 13 (depends on 1)

The method of claim 1, further comprising administering doxorubicin to the subject.

### Claim 14

A method of sensitizing a cancer characterized by BCR-ABL expression or BBAP overexpression to a chemotherapeutic agent in a subject in need thereof, the method comprising administering an agent that selectively inhibits HDAC1 and HDAC2 to the subject.

### Claim 15 (depends on 14)

The method of claim 14, wherein the cancer is a B cell malignancy.

### Claim 16 (depends on 15)

The method of claim 15, wherein the B cell malignancy is diffuse large B cell lymphoma or early Pre-B cell derived acute lymphoblastic leukemia (Pre-B-ALL).

### Claim 17 (depends on 16)

The method of claim 16, wherein the diffuse large B cell lymphoma contains a gain-of-function mutation in Enhancer of Zeste Homologue 2 (EZH2), a gain-of-function mutation in a histone H3K27 methyltransferase, or a loss-of-function mutation in a H3K27 demethylase.

### Claim 18 (depends on 16)

The method of claim 16, wherein the Pre-B-ALL contains a chromosomal translocation and wherein the chromosomal translocation is t(9;22).

### Claim 19 (depends on 14)

The method of claim 14, wherein the cancer is further characterized as being dependent upon on a double-stranded break repair pathway.

### Claim 20 (depends on 19)

The method of claim 19, wherein the double-stranded break repair pathway includes one or more of the group consisting of FEN1, EPC2, BAF180, and DNA Ligase I.

### Claim 21 (depends on 14)

The method of claim 14, wherein the cancer is further characterized by increased H3K27me3.

### Claim 22 (depends on 14)

The method of claim 14, further comprising determining if the cancer is characterized by BCR-ABL expression or BBAP overexpression,
wherein determining comprises detecting a level of BCR-ABL, a level of BBAP, or a level of BCR-ABL and a level of BBAP in a sample obtained from the subject, and comparing the detected levels of BCR-ABL, BBAP, or BCR-ABL and BBAP to levels of BCR-ABL, BBAP, or BCR-ABL and BBAP in a control sample, wherein if the detected level of BCR-ABL is increased relative to the control level of BCR-ABL, the cancer is characterized by BCR-ABL expression, and wherein if the detected level of BBAP is increased relative to the control level of BBAP, the cancer is characterized by BBAP overexpression.

### Claim at position 23

23-44. (canceled)