# US 11,441,190 B2 · Compositions and methods for the diagnosis and treatment of ovarian cancers that are associated with reduced SMARCA4 gene expression or protein function

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- Number: US 11,441,190 B2
- Document ID: US11441190B2
- Status: Granted
- Kind: B2
- Application number: 16/237,692
- Filed: 2019-01-01
- Published: 2019-10-10
- Granted: 2022-09-13
- Earliest claimed: 2013-12-31
- Assignees: Memorial Sloan Kettering Cancer Center
- Applicants: Memorial Sloan Kettering Cancer Center
- Inventors: Douglas A. Levine; Michael F. Berger; Robert A Soslow; Petar Jelinic
- Web page: https://patentgrep.com/patent/US11441190B2

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/136: Screening for pharmacological compounds
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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)

## Abstract

Provided are compositions and methods for the identification and treatment of ovarian cancers, such as small cell ovarian cancers, in particular small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), which ovarian cancers are characterized by reduced SMARCA4 gene expression and/or protein function and, as a consequence, are sensitive to growth and/or survival inhibition by one or more compounds that restore SMARCA4 gene expression and/or protein function.

## Claims

### Claim 1

A method for treating ovarian cancer characterized by ovarian cancer cells having reduced or undetectable SMARCA4 protein levels and/or protein function in a subject in need thereof, the method comprising administering to the subject one or more EZH2 inhibitors, wherein the ovarian cancer cells are a small cell carcinoma of the ovary hypercalcemic type.

### Claim 2

A method for treating a patient previously diagnosed with ovarian cancer that is associated with ovarian cancer cells exhibiting reduced or undetectable SMARCA4 protein levels and/or protein function, the method comprising administering to the patient one or more EZH2 inhibitors, wherein the ovarian cancer is small cell carcinoma of the ovary hypercalcemic type.

### Claim 3

A method for diagnosing and treating small cell carcinoma of the ovary hypercalcemic type (SCCOHT) in a patient in need thereof, the method comprising:
(i) detecting in an ovarian tumor sample from the patient one or more loss-of-function mutations in a SMARCA4 gene;
(ii) diagnosing the patient with SCCOHT when the presence of the one or more loss-of-function mutations in a SMARCA4 gene is detected; and
(iii) administering to the patient an effective amount of one or more EZH2 inhibitors.