# US 11,026,997 B2 · Treatment of inflammatory conditions by delivery of interleukin-1 receptor antagonist fusion protein

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- Number: US 11,026,997 B2
- Document ID: US11026997B2
- Status: Granted
- Kind: B2
- Application number: 16/143,391
- Filed: 2018-09-26
- Published: 2019-05-23
- Granted: 2021-06-08
- Earliest claimed: 2017-09-26
- Assignees: Regeneron Pharmaceuticals, Inc.
- Applicants: Regeneron Pharmaceuticals, Inc.
- Inventors: Eben Tessari; John Paolini
- Web page: https://patentgrep.com/patent/US11026997B2

## CPC

- A61K 38/2006: {IL-1}
- A61K 38/1709: {from mammals}
- A61K 38/1793: {for cytokines; for lymphokines; for interferons}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61K 47/6813: {the drug being a peptidic cytokine, e.g. an interleukin or interferon}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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 provides, among other things, methods of treating post-cardiac injury syndrome (PCIS) or pericarditis, comprising a step of administering to a subject in need of treatment an interleukin-1 receptor-Fc fusion protein at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce one or more signs and symptoms of pericarditis relative to a control.

## Claims

### Claim 1

A method of treating recurrent pericarditis comprising administering subcutaneously to a patient in need of treatment, a loading dose of an interleukin-1 receptor-Fc fusion protein at 320 mg, followed by a maintenance dose of the interleukin-1 receptor-Fc fusion protein at 160 mg once weekly, wherein the interleukin-1 receptor-Fc fusion protein is rilonacept.

### Claim 2 (depends on 1)

The method of claim 1, wherein the patient is 18 years or older.

### Claim 3 (depends on 1)

The method of claim 1, wherein the loading dose is delivered as two injections of 160 mg.

### Claim 4 (depends on 3)

The method of claim 3, wherein each of the two 160 mg doses is delivered as a volume of less than or equal to 2 mL.

### Claim 5 (depends on 1)

The method of claim 1, wherein the maintenance dose is delivered as a volume of less than or equal to 2 mL.

### Claim 6 (depends on 1)

The method of claim 1, wherein the maintenance dose is administered a week after the loading dose.

### Claim 7 (depends on 1)

The method of claim 1, wherein the patient in need of treatment has a recurrence of pericarditis with pericarditis pain measurement≥4 Numerical Rating Scale (NRS) and C-reactive protein (CRP) level≥1 mg/dL.

### Claim 8 (depends on 1)

The method of claim 1, wherein the patient in need of treatment is diagnosed with idiopathic pericarditis.

### Claim 9 (depends on 1)

The method of claim 1, wherein the administration of the interleukin-1 receptor-Fc fusion protein results in a treatment response defined by pericardial pain NRS≤2 and CRP≤0.5 mg/dL.

### Claim 10 (depends on 9)

The method of claim 9, wherein the NRS score is reduced to 2 or less within 7 days from the first administration of the interleukin-1 receptor-Fc fusion protein.

### Claim 11 (depends on 9)

The method of claim 9, wherein CRP level is reduced to <0.5 mg/dL within 7 days from the first administration of the interleukin-1 receptor-Fc fusion protein.

### Claim 12 (depends on 9)

The method of claim 9, wherein the NRS score is reduced to 2 or less within 7 days from the first administration of the interleukin-1 receptor-Fc fusion protein, and CRP level is reduced to <0.5 mg/dL within 7 days from the first administration of the interleukin-1 receptor-Fc fusion protein.

### Claim 13 (depends on 1)

The method of claim 1, wherein the administration of the interleukin-1 receptor-Fc fusion protein results in a withdrawal of concurrent therapy or standard of care treatment in the patient.

### Claim 14 (depends on 13)

The method of claim 13, wherein the concurrent therapy or standard of care treatment is NSAIDs, steroid, colchicine, corticosteroid, or combinations thereof.

### Claim 15 (depends on 14)

The method of claim 14, wherein the administration of the interleukin-1 receptor-Fc fusion protein results in withdrawal of corticosteroid treatment in the patient.

### Claim 16 (depends on 15)

The method of claim 15, wherein the withdrawal of the corticosteroid treatment in the patient is at about 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks or 9 weeks after the first administration.

### Claim 17 (depends on 1)

The method of claim 1, wherein the administration of the interleukin-1 receptor-Fc fusion protein results in reduced risk of pericarditis recurrence of less than 5%.

### Claim 18

A method of treating recurrent pericarditis comprising administering subcutaneously to a pediatric patient≥12 and <18 years old, in need of treatment a loading dose of an interleukin-1 receptor-Fc fusion protein at 4.4 mg/kg up to a maximum of 320 mg, followed by a maintenance dose of the interleukin-1 receptor-Fc fusion protein at 2.2 mg/kg, up to a maximum of 160 mg, once weekly, wherein the interleukin-1 receptor-Fc fusion protein is rilonacept.

### Claim 19 (depends on 18)

The method of claim 18, wherein the loading dose is delivered as one or two injections.

### Claim 20 (depends on 19)

The method of claim 19, wherein each injection is delivered as a volume of less than or equal to 2 mL.

### Claim 21 (depends on 18)

The method of claim 18, wherein the maintenance dose is delivered as a volume of less than or equal to 2 mL.

### Claim 22 (depends on 18)

The method of claim 18, wherein the maintenance dose is administered a week after the loading dose.

### Claim 23 (depends on 18)

The method of claim 18, wherein the pediatric patient in need of treatment has a recurrence of pericarditis with pericarditis pain measurement≥4 Numerical Rating Scale (NRS) and C-reactive protein (CRP) level≥1 mg/dL.

### Claim 24 (depends on 18)

The method of claim 18, wherein the pediatric patient in need of treatment is diagnosed with idiopathic pericarditis.

### Claim 25 (depends on 18)

The method of claim 18, wherein the administration of the interleukin-1 receptor-Fc fusion protein results in a treatment response defined by pericardial pain NRS≤2 and CRP≤0.5 mg/dL.

### Claim 26 (depends on 25)

The method of claim 25, wherein the NRS score is reduced to 2 or less within 7 days from the first administration of the interleukin-1 receptor-Fc fusion protein.

### Claim 27 (depends on 25)

The method of claim 25, wherein CRP level is reduced to <0.5 mg/dL within 7 days from the first administration of the interleukin-1 receptor-Fc fusion protein.

### Claim 28 (depends on 25)

The method of claim 25, wherein the NRS score is reduced to 2 or less within 7 days from the first administration of the interleukin-1 receptor-Fc fusion protein, and CRP level is reduced to <0.5 mg/dL within 7 days from the first administration of the interleukin-1 receptor-Fc fusion protein.

### Claim 29 (depends on 18)

The method of claim 18, wherein the administration of the interleukin-1 receptor-Fc fusion protein results in a withdrawal of concurrent therapy or standard of care treatment in the patient.

### Claim 30 (depends on 29)

The method of claim 29, wherein the concurrent therapy or standard of care treatment is NSAIDs, steroid, colchicine, corticosteroid, or combinations thereof.

### Claim 31 (depends on 30)

The method of claim 30, wherein the administration of the interleukin-1 receptor-Fc fusion protein results in withdrawal of corticosteroid treatment in the pediatric patient.

### Claim 32 (depends on 31)

The method of claim 31, wherein the withdrawal of the corticosteroid treatment in the pediatric patient is at about 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks or 9 weeks after the first administration.

### Claim 33 (depends on 18)

The method of claim 18, wherein the administration of the interleukin-1 receptor-Fc fusion protein results in reduced risk of pericarditis recurrence of less than 5%.