# US 11,304,938 B2 · Compositions and methods for treating chemotherapy resistant cancer

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

- Number: US 11,304,938 B2
- Document ID: US11304938B2
- Status: Granted
- Kind: B2
- Application number: 16/083,687
- Filed: 2017-03-10
- Published: 2021-05-13
- Granted: 2022-04-19
- Earliest claimed: 2016-03-11
- Assignees: The Brigham and Women's Hospital, Inc.
- Applicants: The Brigham and Women's Hospital, Inc.
- Inventors: Josephine Kahn; Siddhartha Jaiswal; Benjamin Ebert
- Web page: https://patentgrep.com/patent/US11304938B2

## CPC

- A61K 31/4436: containing a heterocyclic ring having sulfur as a ring hetero atom
- A61K 31/381: having five-membered rings
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 33/243: Platinum; Compounds thereof
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- 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 features methods for increasing sensitivity and/or reversing resistance to chemotherapy, methods for treating or preventing a cancer in a subject, methods for treating clonal hematopoiesis of indeterminate potential in a subject, and methods of identifying resistance or sensitivity to chemotherapy in a subject. In some embodiments, the methods contain the step of administering an agent that inhibits the expression or activity of a Protein phosphatase 1D (PPM1D) polypeptide or polynucleotide. The present invention also features compositions for increasing sensitivity and/or reversing resistance to chemotherapy.

## Claims

### Claim 1

A method of increasing sensitivity or reversing resistance of a blood or hematologic cancer cell to a chemotherapeutic agent or inhibiting proliferation of a blood or hematologic cancer cell, the method comprising contacting the blood or hematologic cancer cell which is or has become resistant to a chemotherapeutic agent with an effective amount of a Protein phosphatase 1D (PPM1D) inhibitor, thereby increasing sensitivity or reversing resistance of the blood or hematologic cancer cell to the chemotherapeutic agent, or inhibiting proliferation.

### Claim 2 (depends on 1)

The method of claim 1, wherein the blood or hematologic cancer cell is in a subject having a blood or hematologic cancer.

### Claim 3 (depends on 2)

The method of claim 2, wherein the method treats the blood or hematologic cancer in the subject.

### Claim 4 (depends on 1)

The method of claim 1, wherein the blood or hematologic cancer cell is in vivo or in vitro.

### Claim 5 (depends on 1)

The method of claim 1, wherein the PPM1D inhibitor is selected from the group consisting of GSK2830371, CCT007093, and analogs thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein the chemotherapeutic agent is a DNA damaging agent selected from the group consisting of Cytarabine, Doxorubicin, Cyclophosphamide, and Cisplatin.

### Claim 7 (depends on 1)

The method of claim 1, wherein the PPM1D inhibitor inhibits the activity of a PPM1D polypeptide comprising a truncation mutation and/or a gain-of-function mutation.

### Claim 8 (depends on 2)

The method of claim 2, wherein the blood or hematologic cancer cell is a hematologic cancer cell.

### Claim 9 (depends on 2)

The method of claim 2, wherein the blood or hematologic cancer cell is a therapy-related myeloid neoplasm.

### Claim 10 (depends on 2)

The method of claim 2, wherein the blood or hematologic cancer cell is derived from blood, bone marrow or a tumor sample.