# US 11,999,993 B2 · Use of biomarkers in identifying cancer patients that will be responsive to treatment with a PRMT5 inhibitor

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- Number: US 11,999,993 B2
- Document ID: US11999993B2
- Status: Granted
- Kind: B2
- Application number: 17/669,008
- Filed: 2022-02-10
- Published: 2022-06-30
- Granted: 2024-06-04
- Earliest claimed: 2017-02-27
- Assignees: Janssen Pharmaceutica NV
- Applicants: Janssen Pharmaceutica NV
- Inventors: Dirk Brehmer; Lijs Beke; Dana Suzanne Gaffney; Christopher H. Moy
- Web page: https://patentgrep.com/patent/US11999993B2

## CPC

- C12Q 1/48: involving transferase
- C12Q 1/6827: for detection of mutation or polymorphism
- C12Q 1/68: involving nucleic acids
- G01N 33/575: for cancer
- G16H 50/30: for calculating health indices; for individual health risk assessment
- 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
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
- 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
- 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)
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present disclosure describes methods of identifying a patient that is likely to be responsive to treatment with a protein arginine N-methyltransferase 5 (PRMT5) inhibitor. The methods include evaluating a biological sample from the patient for the presence of a spliceosome mutation or alteration, wherein the presence of the alteration indicates a higher likelihood for the patient to be responsive to treatment with the PRMT5 inhibitor than in the absence of the mutation or alteration.

## Claims

### Claim 1

A method of treating a non-small cell lung cancer (NSCLC) in a human patient, the method comprising:
administering a protein arginine N-methyltransferase 5 (PRMT5) inhibitor to the human patient, wherein the human patient has been determined to have a I696fs mutation in RBM10 wherein the PRMT5 inhibitor is
or a pharmaceutically acceptable salt thereof or a solvate thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the human patient has been determined to have the I696fs mutation in RBM10 by testing a biological sample from the human patient for the presence of the I696fs mutation in RBM10, and wherein the testing of the biological sample from the patient comprises:
isolating RNA from the biological sample;
synthesizing cDNA from the isolated RNA;
pre-amplifying the cDNA; and
amplifying the pre-amplified cDNA with a pair of primers that bind to and amplify the mutation.

### Claim 3 (depends on 1)

The method of claim 1, wherein the PRMT5 inhibitor is
or a pharmaceutically acceptable salt thereof or a solvate thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the PRMT5 inhibitor is
or a pharmaceutically acceptable salt thereof or a solvate thereof.

### Claim 5

A method of treating a human patient having a NSCLC with a protein arginine N-methyltransferase 5 (PRMT5) inhibitor, the method comprising:
testing a biological sample from the human patient having the NSCLC for the presence of a I696fs mutation in RBM10; and
administering the PRMT5 inhibitor to the human patient having the I696fs mutation, wherein the PRMT5 inhibitor is
or a pharmaceutically acceptable salt thereof or a solvate thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein the testing of the biological sample from the human patient comprises:
isolating RNA from the biological sample;
synthesizing cDNA from the isolated RNA;
pre-amplifying the cDNA; and
amplifying the pre-amplified cDNA with a pair of primers that bind to and amplify the mutation.

### Claim 7 (depends on 5)

The method of claim 5, wherein the PRMT5 inhibitor is
or a pharmaceutically acceptable salt thereof or a solvate thereof.

### Claim 8 (depends on 5)

The method of claim 5, wherein the PRMT5 inhibitor is
or a pharmaceutically acceptable salt thereof or a solvate thereof.