# US 10,245,266 B2 · 3-(4-((4-morpholinomethyl-benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione for the treatment of systemic lupus erythematosus

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- Number: US 10,245,266 B2
- Document ID: US10245266B2
- Status: Granted
- Kind: B2
- Application number: 15/312,450
- Filed: 2015-05-18
- Published: 2017-06-22
- Granted: 2019-04-02
- Earliest claimed: 2014-05-19
- Assignees: Celgene Corporation
- Applicants: Celgene Corporation
- Inventors: Peter H. Schafer; Lei Wu; Ying Ye
- Web page: https://patentgrep.com/patent/US10245266B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/5355: Non-condensed oxazines and containing further heterocyclic rings
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- G01N 33/6854: {Immunoglobulins}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2800/104: Lupus erythematosus [SLE]
- G01N 2800/24: Immunology or allergic disorders
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

Provided herein are methods of using compounds and compositions for treating, managing, and/or preventing systemic lupus erythematosus (SLE). Pharmaceutical compositions and dosing regimens for use in the methods are also provided herein.

## Claims

### Claim 1

A method for identifying a subject having systemic lupus erythematosus (SLE) who is likely to be responsive to a treatment with a compound of formula I
or a pharmaceutically acceptable salt, stereoisomer, tautomer or racemic mixture thereof, comprising:
(a) determining the level of a biomarker in a first sample from the subject, wherein the biomarker is selected from the group consisting of CRBN, IKZF1 (Ikaros), and IKZF3 (Aiolos); and
(b) comparing the level of the biomarker in the first sample to a reference level of the biomarker; wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the first sample is higher than the reference level of the biomarker.

### Claim 2 (depends on 1)

The method of claim 1, further comprising administering to the subject an effective amount of the compound.

### Claim 3 (depends on 1, 2)

The method of claim 1 or 2, wherein the reference is prepared by using a second sample obtained from a healthy subject not having SLE; and wherein the second sample is from the same source as the first sample.

### Claim 4 (depends on 1, 2)

The method of claim 1 or 2, wherein the biomarker is CRBN.

### Claim 5 (depends on 1, 2)

The method of claim 1 or 2, wherein the biomarker is IKZF1.

### Claim 6 (depends on 1, 2)

The method of claim 1 or 2, wherein the biomarker is IKZF3.

### Claim 7 (depends on 1, 2)

The method of claim 1 or 2, wherein the level of only one of the biomarkers is measured.

### Claim 8 (depends on 1, 2)

The method of claim 1 or 2, wherein the levels of two or more of the biomarkers are monitored simultaneously.

### Claim 9 (depends on 1, 2)

The method of claim 1 or 2, wherein the first sample is peripheral blood mononuclear cells (PBMC).

### Claim 10 (depends on 1, 2)

The method of claim 1 or 2, wherein the first sample is whole blood leukocyte.

### Claim 11 (depends on 10)

The method of claim 10, wherein the whole blood leukocyte is CD19+ B cells, CD3+ T cells, CD14+ monocytes, or granulocytes.

### Claim 12 (depends on 1, 2)

The method of claim 1 or 2, wherein the levels of one or more of the biomarkers are measured by determining the mRNA levels of the biomarkers.

### Claim 13 (depends on 1, 2)

The method of claim 1 or 2, wherein the levels of one or more of the biomarkers are measured by determining the cDNA levels of the biomarkers.

### Claim 14 (depends on 1, 2)

The method of claim 1 or 2, wherein the levels of one or more of the biomarkers are measured by determining the protein levels of the biomarkers.

### Claim 15 (depends on 1, 2)

The method of claim 1 or 2, wherein the compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione.

### Claim 16 (depends on 1, 2)

The method of claim 1 or 2, wherein the compound is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride.