Treatment of recurrent pericarditis by delivery of Anti-interleukin-1 receptor antibody

Abstract

The present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control.

Description

ATTORNEY DOCKET NO.: KPL-062WO1TREATMENT OF RECURRENT PERICARDITIS BY DELIVERY OF ANTIINTERLEUKIN-1 RECEPTOR ANTIBODYCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Application No. 63 / 755,981, filed February 7, 2025, U.S. Provisional Application No.63 / 761,351, filed February 21, 2025, U.S. Provisional Application No. 63 / 785,412, filed April 8, 2025, U.S. Provisional Application No. 63 / 810,394, filed May 22, 2025, and U.S. Provisional Application No. 63 / 883,451, filed September 17, 2025; the disclosure of each of which is hereby incorporated by reference in its entirety.INCORPORATION-BY-REFERENCE OF SEQUENCE LISTING

[0002] This application contains a sequence listing filed electronically in XML format. The present application hereby incorporates by reference the entire contents of the XML file named “KPL-062WOl_SL.xml”, which was created on February 5, 2026, and is 59,481 bytes in size.BACKGROUND

[0003] Recurrent pericarditis (RP) is a rare autoinflammatory disease which affects 20% to 30% of patients after an incident acute pericarditis event (Imazio 2014) and can be debilitating due to pain and limitations in physical function. RP is characterized by an initial acute pericarditis event followed by one or more subsequent acute recurrences after a symptom-free interval of 4-6 weeks (Adler 2015). Pericarditis recurrences increase rates of emergency room admissions and hospitalizations. In the United States, 5% of patients presenting to the emergency room with non-ischemic chest pain are diagnosed with pericarditis (Agarwal 2015).

[0004] Currently available treatments for pericarditis or recurrent pericarditis include medications to reduce the inflammation and swelling associated with pericarditis. Commonly used medications are steroids, such as colchicine. Colchicine can reduce the duration of pericarditis symptoms and decrease the risk that the condition will recur, but the medicationATTORNEY DOCKET NO.: KPL-062WO1is not safe for patients with pre-existing health conditions like liver or kidney disease or for patients taking certain medications and may cause side effects, including nausea and diarrhea, that can lead to discontinuation of treatment. Steroids are known to cause significant side effects, particularly with long-term use.SUMMARY OF THE INVENTION

[0005] The present invention provides, among other things, a convenient, more tolerable, and safer method for treating recurrent pericarditis (RP) based on an anti-ILlRl antibody using dosing regimens described herein. The present invention is, in part, based on a therapeutically effective dosing regimen resulting in (1) a statistically-significant drop on a Numerical Rating Scale (NRS) for assessment of pericarditis pain; (2) normalization of C-Reactive Protein level for assessment of pericarditis inflammation; (3) low recurrence rate; (4) rapid treatment response; and / or (5) rapid time to monotherapy (e.g., successful taper of background medications, concurrent therapies or standard of care).

[0006] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control.

[0007] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0008] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0009] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0010] In some embodiments, the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.ATTORNEY DOCKET NO.: KPL-062WO1

[0011] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0012] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0013] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0014] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0015] In some embodiments, a HCDR1, a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by Kabat numbering system. In some embodiments, a HCDR1, a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by ChothiaATTORNEY DOCKET NO.: KPL-062WO1numbering system. In some embodiments, a HCDR1, a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by IMGT numbering system.

[0016] In some embodiments, the one or more symptoms of recurrent pericarditis are assessed by a Numerical Rating Scale (NRS) for assessment of pericarditis pain. In some embodiments, the one or more symptoms of recurrent pericarditis are assessed by an echocardiogram (ECG). In some embodiments, the one or more symptoms of recurrent pericarditis are assessed by cardiac magnetic resonance imaging (MRI). In some embodiments, the one or more symptoms of recurrent pericarditis are assessed by a Quality of Life Questionnaire, or a portion thereof (e.g., SF-36 Health Survey, or Patient Global Impression of Pericarditis Symptom Severity (PGIPS)).

[0017] In some embodiments, the one or more symptoms of recurrent pericarditis comprise fever. In some embodiments, the one or more symptoms of recurrent pericarditis comprise pericardial rub. In some embodiments, the one or more symptoms of recurrent pericarditis comprise an elevated level of C-reactive protein (CRP). In some embodiments, the one or more symptoms of recurrent pericarditis comprise chest pain. In some embodiments, the one or more symptoms of recurrent pericarditis comprise shortness of breath. In some embodiments, the one or more symptoms of recurrent pericarditis comprise heart palpitations. In some embodiments, the one or more symptoms of recurrent pericarditis comprise swelling. In some embodiments, the one or more symptoms of recurrent pericarditis is fatigue. In some embodiments, the one or more symptoms of recurrent pericarditis is the inability to exercise.

[0018] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering subcutaneously to a patient an antiinterleukin-1 receptor type- 1 (IL1R1) antibody at a dose of 300 mg, wherein the anti-ILlRl antibody is administered once every two weeks or once every four weeks.

[0019] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering subcutaneously to a patient an antiinterleukin-1 receptor type- 1 (IL1R1) antibody at a dose of 300 mg, wherein the anti-ILlRl antibody is administered once every two weeks or once every four weeks, wherein the anti-IL1R1 antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, aATTORNEY DOCKET NO.: KPL-062WO1

[0020] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence comprising administering subcutaneously to a patient an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a dose of 300 mg, wherein the anti-ILlRl antibody is administered once every two weeks or once every four weeks.

[0021] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence comprising administering subcutaneously to a patient an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a dose of 300 mg, wherein the anti-ILlRl antibody is administered once every two weeks or once every four weeks, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0022] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering subcutaneously to a patient an antiinterleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks or once every four weeks.

[0023] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering subcutaneously to a patient an antiinterleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks or once every four weeks, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0024] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence comprising administering subcutaneously to a patient an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks or once every four weeks.

[0025] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence comprising administering subcutaneously to a patient an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks or once every four weeks, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, aATTORNEY DOCKET NO.: KPL-062WO1HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0026] In some embodiments, the patient has recurrence after a symptom-free interval. In some embodiments, the patient does not have a symptom-free interval.

[0027] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement.

[0028] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement, without a symptom-free interval.

[0029] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of is persisting signs and symptoms of pericarditis despite initial improvement, wherein the anti-IL1R1 antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0030] In one aspect, the present invention provides, among other things, a method of reducing symptoms or risk of recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose.

[0031] In one aspect, the present invention provides, among other things, a method of reducing symptoms or risk of recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type 1 (IL1R1) antibody at a therapeutically effective dose, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.ATTORNEY DOCKET NO.: KPL-062WO1

[0032] In one aspect, the present invention provides, among other things, a method of reducing symptoms or risk of recurrent pericarditis comprising administering subcutaneously to a patient an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg, wherein the anti-ILlRl antibody is administered once every two weeks or once every four weeks.

[0033] In one aspect, the present invention provides, among other things, a method of reducing symptoms or risk of recurrent pericarditis comprising administering subcutaneously to a patient an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg, wherein the anti-ILlRl antibody is administered once every two weeks or once every four weeks and the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0034] In one aspect, the present invention provides among other things, a method of reducing symptoms or risk of recurrent pericarditis comprising administering subcutaneously to a patient an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks or once every four weeks.

[0035] In one aspect, the present invention provides among other things, a method of reducing symptoms or risk of recurrent pericarditis comprising administering subcutaneously to a patient an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks or once every four weeks, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0036] In one aspect, the present invention provides, among other things, a method of reducing symptoms or risk of recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement.

[0037] In one aspect, the present invention provides, among other things, a method of reducing symptoms or risk of recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement,ATTORNEY DOCKET NO.: KPL-062WO1wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0038] In one aspect, the present invention provides, among other things, a method for the treatment of idiopathic recurrent pericarditis or reduction in risk of recurrence comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose.

[0039] In one aspect, the present invention provides, among other things, a method for the treatment of idiopathic recurrent pericarditis or reduction in risk of recurrence comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0040] In one aspect, the present invention provides, among other things, a method for the treatment of idiopathic recurrent pericarditis or reduction in risk of recurrence comprising administering subcutaneously to a patient an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a dose of 300 mg, wherein the anti-ILlRl antibody is administered once every two weeks or once every four weeks.

[0041] In one aspect, the present invention provides, among other things, a method for the treatment of idiopathic recurrent pericarditis or reduction in risk of recurrence comprising administering subcutaneously to a patient an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks or once every four weeks.

[0042] In one aspect, the present invention provides, among other things, a method for the treatment of idiopathic recurrent pericarditis or reduction in risk of recurrence comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement.

[0043] In one aspect, the present invention provides, among other things, a method for the treatment of idiopathic recurrent pericarditis or reduction in risk of recurrence comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS >ATTORNEY DOCKET NO.: KPL-062WO14 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0044] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence comprising administering to a patient, an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose.

[0045] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence comprising administering to a patient, an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0046] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence comprising administering to a patient, an anti-interleukin- 1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement.

[0047] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence comprising administering to a patient, an anti-interleukin- 1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0048] In some embodiments, the anti-ILlRl is administered at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control.ATTORNEY DOCKET NO.: KPL-062WO1

[0049] In some embodiments, the persisting signs and symptoms of pericarditis comprise one or more of: a) pericarditis pain; b) an elevated CRP level; c) pericardial rub; d) widespread ST segment elevation or PR segment depression according to ECG findings; e) pericardial effusion; f) pericardial inflammation; g) edema; h) evidence of pericarditis by late gadolinium enhancement; i) evidence of constriction; and j) fever, chest pain, shortness of breath, and / or heart palpitations.

[0050] In some embodiments, the persisting signs and symptoms of pericarditis do not include the combination of pericarditis pain NRS > 4 and CRP > 1.0 mg / dL.

[0051] In some embodiments, the initial improvement is an improvement of one or more signs or symptoms associated with an episode of acute pericarditis.

[0052] In some embodiments, the initial improvement comprises a reduction or improvement in one or more of: a) pericarditis pain; b) CRP; c) pericardial rub; d) widespread ST segment elevation or PR segment depression according to ECG findings; e) pericardial effusion; f) pericardial inflammation; g) edema; h) evidence of pericarditis by late gadolinium enhancement; i) evidence of constriction; and j) fever, chest pain, shortness of breath, and / or heart palpitations.

[0053] In some embodiments, pericarditis pain is measured by Numerical Rating Scale (NRS). In some embodiments, the initial improvement is indicated by a NRS of < 4. In some embodiments, the initial improvement is indicated by a NRS of < 3. In some embodiments, the initial improvement is indicated by a NRS of < 2.

[0054] In some embodiments, pericardial inflammation is assessed by cardiac MRI.

[0055] In some embodiments, edema is assessed by T2 short-tau inversion recovery (STIR) imaging.

[0056] In some embodiments, the evidence of pericarditis by late gadolinium enhancement is assessed by cardiac MRI.

[0057] In some embodiments, the initial improvement is indicated by CRP < 1.0 mg / dL.

[0058] In some embodiments, the period of persisting signs and symptoms of pericarditis is 1-10 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 2-10 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 4-10 weeks. In some embodiments, the period of persistingATTORNEY DOCKET NO.: KPL-062WO1signs and symptoms of pericarditis is 6-10 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 8-10 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 2-12 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 4-12 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 6-12 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 8-12 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 10-12 weeks.

[0059] In some embodiments, the period of persisting signs and symptoms of pericarditis is 2-8 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 2-6 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 2-4 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 4-6 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is 4-8 weeks.

[0060] In some embodiments, the period of persisting signs and symptoms of pericarditis is greater than 1 week. In some embodiments, the period of persisting signs and symptoms of pericarditis is greater than 2 weeks. In some embodiments, the period of persisting is signs and symptoms of pericarditis is greater than 4 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is greater than 6 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is greater than 8 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is greater than 10 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is greater than 12 weeks.

[0061] In some embodiments, the period of persisting signs and symptoms of pericarditis is less than 6 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is less than 5 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is less than 4 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is less than 3 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is less than 2 weeks. In some embodiments, the period of persisting signs and symptoms of pericarditis is less than 1 week.

[0062] In some embodiments, the one or more symptoms of recurrent pericarditis are assessed by a Numerical Rating Scale (NRS) for assessment of pericarditis pain. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, the one or more symptoms of recurrent pericarditis are assessed by an echocardiogram (ECG). In some embodiments, the one or more symptoms of pericarditis are assessed by cardiac magnetic resonance imaging (MRI). In some embodiments, the one or more symptoms of recurrent pericarditis are assessed by a Quality of Life Questionnaire, or a portion thereof (e.g., SF-36 Health Survey, or Patient Global Impression of Pericarditis Symptom Severity (PGIPS)).

[0063] In some embodiments, the one or more symptoms of recurrent pericarditis comprise fever. In some embodiments, the one or more symptoms of recurrent pericarditis comprise pericardial rub. In some embodiments, the one or more symptoms of recurrent pericarditis comprise an elevated level of C-reactive protein (CRP). In some embodiments, the one or more symptoms of recurrent pericarditis comprise chest pain. In some embodiments, the one or more symptoms of recurrent pericarditis comprise shortness of breath. In some embodiments, the one or more symptoms of recurrent pericarditis comprise heart palpitations. In some embodiments, the one or more symptoms of recurrent pericarditis comprise swelling. In some embodiments, the one or more symptoms of recurrent pericarditis is fatigue. In some embodiments, the one or more symptoms of recurrent pericarditis is the inability to exercise.

[0064] In some embodiments, the control is the patient prior to the administration of the anti-ILlRl antibody. In some embodiments, the control is a comparable recipient without the administration of the anti-ILlRl antibody. In some embodiments, the control is a comparable recipient administered a placebo. In some embodiments, the control is historical data.

[0065] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of greater than 10 mg.

[0066] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0067] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.ATTORNEY DOCKET NO.: KPL-062WO1

[0068] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0069] In some embodiments, the anti-ILlRl antibody comprises aHCDRl, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0070] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of greater than 10 mg, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0071] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of greater than 10 mg, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0072] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of greater than 10 mg, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0073] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of greater than 10 mg, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0074] In some embodiments, a HCDR1, a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by Kabat numbering system. In some embodiments, a HCDR1,ATTORNEY DOCKET NO.: KPL-062WO1a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by Chothia numbering system. In some embodiments, a HCDR1, a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by IMGT numbering system.

[0075] In some embodiments, the anti-ILlRl antibody is administered no more frequently than once every week.

[0076] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose no more frequently than once every week.

[0077] In some embodiments, the patient has received a previous treatment. In some embodiments, the previous treatment is an IL1 antagonist, an IL1R1 antagonist, an IL1 trap, NSAIDs, colchicine, corticosteroid, or a combination thereof. In some embodiments, the previous treatment is an IL1 antagonist. In some embodiments, the previous treatment is an IL1R1 antagonist. In some embodiments, the previous treatment is an IL1 trap. In some embodiments, the previous treatment is NSAIDs. In some embodiments, the previous treatment is colchicine. In some embodiments, the previous treatment is corticosteroid. In some embodiments, the previous treatment is rilonacept or anakinra. In some embodiments, the previous treatment is rilonacept. In some embodiments, the previous treatment is anakinra.

[0078] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0079] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0080] In some embodiments, the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0081] In some embodiments, the anti-ILlRl antibody comprises aHCDRl, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.ATTORNEY DOCKET NO.: KPL-062WO1

[0082] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose no more frequently than once every week, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0083] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose no more frequently than once every week, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0084] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose no more frequently than once every week, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0085] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose no more frequently than once every week, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0086] In some embodiments, a HCDR1, a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by Kabat numbering system. In some embodiments, a HCDR1, a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by Chothia numbering system. In some embodiments, a HCDR1, a HCDR2, a HCDR3, LCDR1, a LCDR2, and a LCDR3 are determined by IMGT numbering system.

[0087] In some embodiments, the therapeutically effective dose produces a median Cmax of at least 0.5 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 1.0 pg / mL. In some embodiments, the therapeuticallyATTORNEY DOCKET NO.: KPL-062WO1effective dose produces a median Cmax of at least 5 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 10 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 30 pg / mL.

[0088] In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 7 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 10 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 15 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 20 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 25 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 28 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 56 days.

[0089] In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 10 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 30 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 100 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 300 mg.

[0090] In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 10 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 30 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 100 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 150 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 188 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 225 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 263 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 300 mg.

[0091] In some embodiments, the anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg.ATTORNEY DOCKET NO.: KPL-062WO1

[0092] In some embodiments, the anti-ILlRl antibody is administered at a dose of 10 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 30 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 50 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 100 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 150 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 188 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 225 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 250 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 263 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 300 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 325 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 350 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 500 mg.

[0093] In some embodiments, the anti-ILlRl antibody is administered no more frequently than once every two weeks. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 3 weeks. In some embodiments, an anti-IL1R1 antibody is administered no more frequently than once every 4 weeks. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 5 weeks.

[0094] In some embodiments, the anti-ILlRl antibody is administered at a dose of 100 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 100 mg once every four weeks. In some embodiments, the anti-IL1R1 antibody is administered at a dose of 150 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 150 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 188 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 188 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 225 mg once every two weeks. In some embodiments, the anti-IL1R1 antibody is administered at a dose of 225 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 250 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 250 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 263 mg once every two weeks. In some embodiments, the anti-ILlRl antibody isATTORNEY DOCKET NO.: KPL-062WO1administered at a dose of 263 mg once every four weeks. In some embodiments, the anti-IL1R1 antibody is administered at a dose of 275 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 275 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 300 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered at a dose of 300 mg once every four weeks.

[0095] In some embodiments, the anti-ILlRl antibody is administered intravenously. In some embodiments, the anti-ILlRl antibody is administered subcutaneously.

[0096] In some embodiments, the patient has at least 1 day with pericarditis pain measurement >4 on NRS prior to the treatment.

[0097] In some embodiments, the patient has C-reactive protein (CRP) value >0.5 mg / dL prior to the treatment. In some embodiments, the patient has CRP value > 1.0 mg / dL prior to the treatment.

[0098] In some embodiments, the patient is an adult.

[0099] In some embodiments, the anti-ILlRl antibody is administered once every four weeks.

[0100] In some embodiments, the patient has at least a second pericarditis recurrence prior to the treatment. In some embodiments, the patient has at least a third pericarditis recurrence prior to the treatment. In some embodiments, the patient has a period of persisting pericarditis signs and symptoms despite initial improvement.

[0101] In some embodiments, the patient is receiving concomitant NSAIDs, colchicine, corticosteroid, or combinations thereof. In some embodiments, the patient is receiving concomitant NSAIDs. In some embodiments, the patient is receiving concomitant colchicine. In some embodiments, the patient is receiving corticosteroid.

[0102] In some embodiments, the NSAID is ibuprofen.

[0103] In some embodiments, the administration of the anti-ILlRl antibody results in a statistically-significant drop on a Numerical Rating Scale (NRS) for assessment of pericarditis pain.

[0104] In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 20% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 15% or less. In some embodiments, theATTORNEY DOCKET NO.: KPL-062WO1administration of the anti-ILlRl antibody results in a recurrence rate of 10% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 5% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 3% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 2% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 1% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 0%.

[0105] In some embodiments, the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 10 weeks. In some embodiments, the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 12 weeks. In some embodiments, the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 16 weeks. In some embodiments, the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 20 weeks. In some embodiments, the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 24 weeks. In some embodiments, the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 30 weeks. In some embodiments, the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 40 weeks. In some embodiments, the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 50 weeks.

[0106] In some embodiments, the median time-to-recurrence could not be determined due to a limited number of recurrence events.

[0107] In some embodiments, the limited number of recurrence events is less than 3. In some embodiments, the limited number of recurrence events is less than 1. In some embodiments, the limited number of recurrence events is substantially 0.

[0108] In some embodiments, the administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 60%. In some embodiments, the administration of the anti-IL1R1 antibody reduces a risk or recurrence by at least 70%. In some embodiments, the administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 80%. In some embodiments, the administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 90%. In some embodiments, the administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 95%. In some embodiments, theATTORNEY DOCKET NO.: KPL-062WO1administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 96%. In some embodiments, the administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 97%. In some embodiments, the administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 98%. In some embodiments, the administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 99%. In some embodiments, the administration of the anti-ILlRl antibody reduces a risk or recurrence by at least 100%.

[0109] In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.3. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.2. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.1. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.05. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.04. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.03. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.02. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.01. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.005.

[0110] In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 6 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 5 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 4 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 3 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 2 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 1 or less.[oni] In some embodiments, the NRS score of 2 or less is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 2 or less is achieved within 2 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 2 or less is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 2ATTORNEY DOCKET NO.: KPL-062WO1or less is achieved within 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 2 or less is achieved within 4 days from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 2 or less is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 2 or less is achieved within 2 days from the first administration of the anti-ILlRl antibody.

[0112] In some embodiments, the median time to achieve an NRS score of 2 or less is 7 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 2 or less is 6 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 2 or less is 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 2 or less is 4 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 2 or less is 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 2 or less is 2 days from the first administration of the anti-ILlRl antibody.

[0113] In some embodiments, the NRS score is maintained at 2 or less for more than 1 week. In some embodiments, the NRS score is maintained at 2 or less for more than 2 weeks. In some embodiments, the NRS score is maintained at 2 or less for more than 3 weeks. In some embodiments, the NRS score is maintained at 2 or less for more than 1 month. In some embodiments, the NRS score is maintained at 2 or less for more than 2 months. In some embodiments, the NRS score is maintained at 2 or less for more than 3 months. In some embodiments, the NRS score is maintained at 2 or less for more than 4 months. In some embodiments, the NRS score is maintained at 2 or less for more than 5 months. In some embodiments, the NRS score is maintained at 2 or less for more than 6 months. In some embodiments, the NRS score is maintained at 2 or less for more than 8 months. In some embodiments, the NRS score is maintained at 2 or less for or more than 1 year.

[0114] In some embodiments, the NRS score of 1 or less is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 1 or less is achieved within 2 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 1 or less is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 1ATTORNEY DOCKET NO.: KPL-062WO1or less is achieved within 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 1 or less is achieved within 4 days from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 1 or less is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, the NRS score of 1 or less is achieved within 2 days from the first administration of the anti-ILlRl antibody.

[0115] In some embodiments, the median time to achieve an NRS score of 1 or less is 7 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 1 or less is 6 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 1 or less is 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 1 or less is 4 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 1 or less is 1 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve an NRS score of 1 or less is 2 days from the first administration of the anti-ILlRl antibody.

[0116] In some embodiments, the NRS score is maintained at 1 or less for more than 1 week. In some embodiments, the NRS score is maintained at 1 or less for more than 2 weeks. In some embodiments, the NRS score is maintained at 1 or less for more than 3 weeks. In some embodiments, the NRS score is maintained at 1 or less for more than 1 month. In some embodiments, the NRS score is maintained at 1 or less for more than 2 months. In some embodiments, the NRS score is maintained at 1 or less for more than 3 months. In some embodiments, the NRS score is maintained at 1 or less for more than 4 months. In some embodiments, the NRS score is maintained at 1 or less for more than 5 months. In some embodiments, the NRS score is maintained at 1 or less for more than 6 months. In some embodiments, the NRS score is maintained at 1 or less for more than 8 months. In some embodiments, the NRS score is maintained at 1 or less for or more than 1 year.

[0117] In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 2.0 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 1.5 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 1.0 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP valueATTORNEY DOCKET NO.: KPL-062WO1of < 0.8 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.6 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.5 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.4 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.3 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.2 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.1 mg / dL.

[0118] In some embodiments, a reduced CRP value of < 0.5 mg / dL is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, a reduced CRP value of < 0.5 mg / dL is achieved within 2 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, a reduced CRP value of < 0.5 mg / dL is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, a reduced CRP value of < 0.5 mg / dL is achieved within 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, a reduced CRP value of < 0.5 mg / dL is achieved within 4 days from the first administration of the anti-ILlRl antibody. In some embodiments, a reduced CRP value of < 0.5 mg / dL is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, a reduced CRP value of < 0.5 mg / dL is achieved within 2 days from the first administration of the anti-IL1R1 antibody.

[0119] In some embodiments, the median time to achieve a reduced CRP value of < 0.5 mg / dL is within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve a reduced CRP value of < 0.5 mg / dL is within 2 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve a reduced CRP value of < 0.5 mg / dL is within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve a reduced CRP value of < 0.5 mg / dL is within 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve a reduced CRP value of < 0.5 mg / dL is within 4 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the median time to achieve a reduced CRP value of < 0.5 mg / dL is within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, the median time to achieve a reduced CRP value of < 0.5 mg / dL is within 2 days from the first administration of the anti-ILlRl antibody.ATTORNEY DOCKET NO.: KPL-062WO1

[0120] In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 1 week. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 2 weeks. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 3 weeks. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 1 month. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 2 months. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 3 months. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 4 months. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 5 months. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 6 months. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 8 months. In some embodiments, the CRP value < 0.5 mg / dL is maintained for longer than 1 year.

[0121] In some embodiments, the median time to a treatment response is 5 days or less from the first administration of the anti-ILlRl antibody.

[0122] In some embodiments, the % of subjects achieving a treatment response is 60%. In some embodiments, the % of subjects achieving a treatment response is 65%. In some embodiments, the % of subjects achieving a treatment response is 70%. In some embodiments, the % of subjects achieving a treatment response is 75%. In some embodiments, the % of subjects achieving a treatment response is 80%. In some embodiments, the % of subjects achieving a treatment response is 85%. In some embodiments, the % of subjects achieving a treatment response is 90%. In some embodiments, the % of subjects achieving a treatment response is 95%. In some embodiments, the % of subjects achieving a treatment response is 98%.

[0123] In some embodiments, the treatment response is NRS score of 2 or less and the CRP value < 0.5 mg / dL. In some embodiments, the treatment response is NRS score of 1 or less and the CRP value < 0.5 mg / dL. In some embodiments, the treatment response is NRS score of 2 or less and the CRP value < 0.1 mg / dL. In some embodiments, the treatment response is NRS score of 1 or less and the CRP value < 0.1 mg / dL. In some embodiments, the treatment response is NRS score of 1 or less and the CRP value < 0.1 mg / dL.

[0124] In some embodiments, the median time to anti-ILlRl antibody monotherapy is 4 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 6 weeks or less. In some embodiments, the median time to anti-ILlRlATTORNEY DOCKET NO.: KPL-062WO1antibody monotherapy is 7 weeks or less. In some embodiments, the median time to anti-IL1R1 antibody monotherapy is 7.5 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 8 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 10 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 12 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 14 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 16 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 18 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 20 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 22 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 24 weeks or less.

[0125] In some embodiments, the administration of the anti-ILlRl antibody results in decreased pericardiac effusion compared to a control.

[0126] In some embodiments, the control is a baseline pericardiac effusion level measured in the patient prior to the treatment. In some embodiments, the control is a pericardiac effusion level measured in a patient with comparable disease status but administered a placebo. In some embodiments, the control is a reference value indicative of pericardiac effusion in a subject with comparable disease status without treatment.

[0127] In some embodiments, the administration of the anti-ILlRl antibody results in absence of pericardiac effusion.

[0128] In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 2 weeks. In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 4 weeks. In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 1 month. In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 2 months. In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 3 months. In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 4 months. In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 5 months. In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 6 months. In some embodiments, the decreased or absence of pericardiac effusion isATTORNEY DOCKET NO.: KPL-062WO1maintained for longer than 8 months. In some embodiments, the decreased or absence of pericardiac effusion is maintained for longer than 1 year.

[0129] In some embodiments, the administration of the anti-ILlRl antibody results in a withdrawal, or a taper off, of a concurrent therapy or standard of care treatment in the patient. In some embodiments, the administration of the anti-ILlRl antibody results in a withdrawal of a concurrent therapy or standard of care treatment in the patient. In some embodiments, the administration of the anti-ILlRl antibody results in a taper off of a concurrent therapy or standard of care treatment in the patient.

[0130] In some embodiments, the concurrent therapy or standard of care treatment is NSAIDs. In some embodiments, the concurrent therapy or standard of care treatment is colchicine. In some embodiments, the concurrent therapy or standard of care treatment is corticosteroid.

[0131] In some embodiments, the administration of the anti-ILlRl antibody does not result in an adverse event. In some embodiments, the adverse event is injection-site reaction. In some embodiments, the adverse event is upper respiratory tract infection. In some embodiments, the adverse event is headache. In some embodiments, the adverse event is nausea. In some embodiments, the adverse event is vomiting. In some embodiments, the adverse event is diarrhea. In some embodiments, the adverse event is sinusitis. In some embodiments, the adverse event is arthralgia. In some embodiments, the adverse event is flulike symptoms. In some embodiments, the adverse event is abdominal pain. In some embodiments, the adverse event is pyrexia. In some embodiments, the adverse event is herpes. In some embodiments, the adverse event is transaminase elevation. In some embodiments, the adverse event is nasopharyngitis. In some embodiments, the adverse event is ischemic optic neuropathy. In some embodiments, the administration of the anti-ILlRl antibody does not result in a dose-limiting adverse events (AE). In some embodiments, the administration of the anti-ILlRl antibody does not result in a dose-related adverse events (AE). In some embodiments, the administration of the anti-ILlRl antibody does not result in a dose-limiting or dose-related adverse events (AE).

[0132] In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 85% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 90% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 92% identical to SEQ ID NO: 7. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, an anti-ILlRl antibody comprises a VH that is at least 93% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 94% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 95% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 96% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 97% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 98% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 99% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH of SEQ ID NO: 7.

[0133] In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 85% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 90% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 92% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 93% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 94% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 95% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 96% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 97% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 98% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 99% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL of SEQ ID NO: 8.

[0134] In some embodiments, the anti-ILlRl comprises a VH of SEQ ID NO: 7 and a VL of SEQ ID NO: 8.

[0135] In some embodiments, the anti-ILlRl antibody comprises an Fc region derived from IgGl. In some embodiments, the anti-ILlRl antibody comprises an Fc region derived from IgG2. In some embodiments, the anti-ILlRl antibody comprises an Fc region derived from IgG3. In some embodiments, the anti-ILlRl antibody comprises an Fc region derived from IgG4.ATTORNEY DOCKET NO.: KPL-062WO1

[0136] In some embodiments, an Fc region comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 93% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 9. In some embodiments, an Fc region comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 9. In some embodiments, the Fc region comprises an amino acid sequence of SEQ ID NO: 9.

[0137] In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 85% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 90% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 92% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 93% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 94% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 95% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 96% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 97% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 98% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 99% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain of SEQ ID NO: 10.

[0138] In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 85% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 90% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 92% identical toATTORNEY DOCKET NO.: KPL-062WO1SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 93% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 94% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 95% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 96% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 97% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 98% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 99% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain of SEQ ID NO: 11.

[0139] In some embodiments, the anti-ILlRl antibody comprises a heavy chain of SEQ ID NO: 10 and a light chain of SEQ ID NO: 11.BRIEF DESCRIPTION OF FIGURES

[0140] The drawings are for illustration purposes only not for limitation.

[0141] FIG. 1A is an exemplary graph showing observed concentrations of KPL-387 over time after a single administration of 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, or 600 mg of KPL-387 FIG. IB is an exemplary graph showing observed and predicted concentrations of KPL-387 overtime after a single administration of 300 mg of KPL-387. FIG. 1C and FIG. ID are exemplary box and whisker plots of observed PK parameters and NHP Pop PK-predicted values in the 300 mg cohort up to 70 days.

[0142] FIG. 2 is an exemplary graph showing observed concentrations of KPL-387 over time in healthy human participants after subcutaneous administration of 100 mg once every four weeks, 300 mg once every four weeks, and 300 mg once every two weeks.

[0143] FIG. 3 is an exemplary study schematic for Phase 2 (Part A) and Long-Term Extension (LTE; Part C).

[0144] FIG. 4 is an exemplary study schematic for Phase 3 (Part B) and Long-Term Extension (LTE; Part C).

[0145] FIG. 5 is an exemplary schematic for evaluation and clinical management of suspected pericarditis recurrence.ATTORNEY DOCKET NO.: KPL-062WO1

[0146] FIG. 6 is an exemplary graph showing the NRS scores and CRP levels for Subject X after administration of KPL-387.DEFINITIONS

[0147] In order for the present invention to be more readily understood, certain terms are first defined below. Additional definitions for the following terms and other terms are set forth throughout the specification. The publications and other reference materials referenced herein to describe the background of the invention and to provide additional detail regarding its practice are hereby incorporated by reference.

[0148] Any numerical values used in this application are meant to cover any variations within the standard deviation or normal fluctuations appreciated by one of ordinary skill in the relevant art.

[0149] Amino acid. As used herein, term “amino acid,” in its broadest sense, refers to any compound and / or substance that can be incorporated into a polypeptide chain. In some embodiments, an amino acid has the general structure H2N-C(H)(R)-COOH. In some embodiments, an amino acid is a naturally occurring amino acid. In some embodiments, an amino acid is a synthetic amino acid; in some embodiments, an amino acid is a d-amino acid; in some embodiments, an amino acid is an 1-amino acid. “Standard amino acid” refers to any of the twenty standard 1-amino acids commonly found in naturally occurring peptides.“Nonstandard amino acid” refers to any amino acid, other than the standard amino acids, regardless of whether it is prepared synthetically or obtained from a natural source. As used herein, “synthetic amino acid” encompasses chemically modified amino acids, including but not limited to salts, amino acid derivatives (such as amides), and / or substitutions. Amino acids, including carboxyl- and / or amino-terminal amino acids in peptides, can be modified by methylation, amidation, acetylation, protecting groups, and / or substitution with other chemical groups that can change the peptide’s circulating half-life without adversely affecting their activity. Amino acids may participate in a disulfide bond. Amino acids may comprise one or posttranslational modifications, such as association with one or more chemical entities (e.g., methyl groups, acetate groups, acetyl groups, phosphate groups, formyl moieties, isoprenoid groups, sulfate groups, polyethylene glycol moieties, lipid moieties, carbohydrate moieties, biotin moieties, etc. . The term “amino acid” is used interchangeably with “amino acid residue,” and may refer to a free amino acid and / or to anATTORNEY DOCKET NO.: KPL-062WO1amino acid residue of a peptide. It will be apparent from the context in which the term is used whether it refers to a free amino acid or a residue of a peptide.

[0150] Amelioration'. As used herein, the term "amelioration" is meant the prevention, reduction or palliation of a state, or improvement of the state of a subject.Amelioration includes, but does not require complete recovery or complete prevention of a disease condition. In some embodiments, amelioration includes increasing levels of relevant protein or its activity that is deficient in relevant disease tissues. In some embodiments, amelioration includes decreasing levels of relevant protein or its activity that is pathologically elevated in relevant disease tissues.

[0151] Delivery: As used herein, the term “delivery” encompasses both local and systemic delivery.

[0152] Equivalent dosing regimen: As used herein, the term “equivalent dosing regimen” or other grammatical equivalents refer to an alternative dosing regimen that delivers a substantially equivalent amount of a therapeutic agent (e.g., an antibody, a protein or small molecular compound drug) over a comparable dosing period or otherwise results in similar pharmacodynamic (PD) and / or pharmacokinetic (PK) response in vivo. As non-limiting examples, an equivalent dosing regimen of 100 mg once every 2 weeks can be 50 mg once a week, 200 mg once every four weeks, or 600 mg once every six weeks. In some embodiments, an equivalent dosing regimen may achieve a similar area under the curve (AUC), Caverage, Cmin, EC90 and / or Emax over a comparable dosing period.

[0153] Half-life: As used herein, the term “half-life” is the time required for a quantity such as nucleic acid or protein concentration or activity to fall to half of its value as measured at the beginning of a time period.

[0154] Improve, increase, or reduce: As used herein, the terms “improve,” “increase” or “reduce,” or grammatical equivalents, indicate values that are relative to a baseline measurement, such as a measurement in the same individual prior to initiation of the treatment described herein, or a measurement in a control subject (or multiple control subject) in the absence of the treatment described herein, e.g., a subject who is administered a placebo. A “control subject” is a subject with the same disease as the subject being treated, but who received no treatment, or who received placebo.

[0155] Substantial identity: The phrase "substantial identity" is used herein to refer to a comparison between amino acid or nucleic acid sequences. As will be appreciated by thoseATTORNEY DOCKET NO.: KPL-062WO1of ordinary skill in the art, two sequences are generally considered to be "substantially identical" if they contain identical residues in corresponding positions. As is well known in this art, amino acid or nucleic acid sequences may be compared using any of a variety of algorithms, including those available in commercial computer programs such as BLAS TN for nucleotide sequences and BLASTP, gapped BLAST, and PSI-BLAST for amino acid sequences. Exemplary such programs are described in Altschul, et al., Basic local alignment search tool, J Mol. Biol., 215(3): 403-410, 1990; Altschul, et al., Methods in Enzymology; Altschul etal., Nucleic Acids Res. 25:3389-3402, 1997; Baxevanis etal., Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, Wiley, 1998; and Misener, et al., (eds.), Bioinformatics Methods and Protocols (Methods in Molecular Biology, Vol. 132), Humana Press, 1999. In addition to identifying identical sequences, the programs mentioned above typically provide an indication of the degree of identity. In some embodiments, two sequences are considered to be substantially identical if at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more of their corresponding residues are identical over a relevant stretch of residues. In some embodiments, the relevant stretch is a complete sequence. In some embodiments, the relevant stretch is at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500 or more residues.

[0156] Patient: As used herein, the term “patient” refers to any organism to which a provided composition may be administered, e.g., for experimental, diagnostic, prophylactic, cosmetic, and / or therapeutic purposes. Typical patients include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and / or humans). In some embodiments, a patient is a human. A human includes pre- and post-natal forms.

[0157] Pharmaceutically acceptable: The term “pharmaceutically acceptable” as used herein, refers to substances that, within the scope of sound medical judgment, are suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0158] Recurrence: As used herein, the term “recurrence” is defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. Recurrence is often used interchangeably with “flare” and “relapse”. A pericarditis recurrence is usually indicated by any one or more of the following: an increase in the CRP level of >1 mg / dl in peripheral blood; or an increase in pain, determined in anATTORNEY DOCKET NO.: KPL-062WO1NRS scale of >4; or occurrence of pericardial effusion; a pericardial rub; or fever or any other symptomatic indication of the pericardial disease.

[0159] Initial Improvement: As used herein, the term “initial improvement” as used in connection with recurrent pericarditis patients refers to improvement of one or more signs or symptoms associated with an episode of acute pericarditis (also referred to as a flare) resulting from a treatment, including but not limited to reduction or improvement in one of more of: a) pericarditis pain; b) CRP; c) pericardial rub; d) widespread ST segment elevation or PR segment depression according to ECG findings; e) pericardial effusion; f) pericardial inflammation; g) edema; h) evidence of pericarditis by late gadolinium enhancement; i) evidence of constriction; and j) fever; chest pain; shortness of breath; and / or heart palpitations. In some embodiments, pericarditis pain is measured by NRS.

[0160] Subject'. As used herein, the term “subject” refers to a human or any nonhuman animal (e.g., mouse, rat, rabbit, dog, cat, cattle, swine, sheep, horse or primate). A human includes pre- and post-natal forms. In many embodiments, a subject is a human being. A subject can be a patient, which refers to a human presenting to a medical provider for diagnosis or treatment of a disease. The term “subject” is used herein interchangeably with “individual” or “patient.” A subject can be afflicted with or is susceptible to a disease or disorder but may or may not display symptoms of the disease or disorder.

[0161] Substantially. As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest. One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and / or proceed to completeness or achieve or avoid an absolute result. The term “substantially” is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.

[0162] Systemic distribution or delivery. As used herein, the terms “systemic distribution,” “systemic delivery,” or grammatical equivalent, refer to a delivery or distribution mechanism or approach that affect the entire body or an entire organism.Typically, systemic distribution or delivery is accomplished via body’s circulation system, e.g., blood stream. Compared to the definition of “local distribution or delivery.”ATTORNEY DOCKET NO.: KPL-062WO1

[0163] Target tissues'. As used herein, the term “target tissues” refers to any tissue that is affected by a disease or disorder to be treated. In some embodiments, target tissues include those tissues that display disease-associated pathology, symptom, or feature.

[0164] Therapeutically effective amount'. As used herein, the term “therapeutically effective amount” of a therapeutic agent means an amount that is sufficient, when administered to a subject suffering from or susceptible to a disease, disorder, and / or condition, to treat, diagnose, prevent, and / or delay the onset of the symptom(s) of the disease, disorder, and / or condition. It will be appreciated by those of ordinary skill in the art that a therapeutically effective amount is typically administered via a dosing regimen comprising at least one unit dose.

[0165] Treating'. As used herein, the term “treat,” “treatment,” or “treating” refers to any method used to partially or completely alleviate, ameliorate, relieve, inhibit, prevent, delay onset of, reduce severity of and / or reduce the incidence or recurrence, or the risk thereof, of one or more signs, symptoms or features of a particular disease, disorder, and / or condition. Treatment may be administered to a subject who does not exhibit signs of a disease and / or exhibits only early signs of the disease for the purpose of decreasing the risk of developing pathology associated with the disease.DETAILED DESCRIPTION

[0166] The present invention provides, among other things, a convenient, more tolerable and safer method for treating recurrent pericarditis (RP) based on an anti-ILlRl antibody using dosing regimens described herein.Pericarditis and Recurrent Pericarditis

[0167] Pericarditis is swelling and irritation of the pericardium, the thin saclike membrane surrounding the heart. Pericarditis often causes chest pain and sometimes other symptoms. The sharp chest pain associated with pericarditis occurs when the irritated layers of the pericardium rub against each other. Signs and symptoms of pericarditis may include some or all of the following: sharp, piercing chest pain over the center or left side of the chest, which is generally more intense when breathing in or reclining; shortness of breath when reclining; heart palpitations; low-grade fever; an overall sense of weakness, fatigue or feeling sick; cough; and abdominal or leg swelling.ATTORNEY DOCKET NO.: KPL-062WO1

[0168] Pericarditis accounts for 5% of emergency department visits for chest pain in the absence of myocardial infarction (Khandaker et al, Mayo Clin Proc. 2010; 85:572-593). In 80% of cases in developed countries, the cause of pericarditis is either post viral or "idiopathic," in that it cannot be attributed to a specific condition (Imazio et al, Circulation.2010; 121:916-928; Zayas et al, Am J Cardiol. 1995; 75:378-382). Diagnosis is based on the presence of typical chest pain (improved by sitting up and leaning forward) along with fever, pericardial friction rub, electrocardiographic (ECG) changes, pericardial effusion, or elevated markers of inflammation (white blood cell [WBC] count, C-reactive protein [CRP], or erythrocyte sedimentation rate [ESR]) (Imazio, Revista Espanola de Cardiologia. 2014;67(5):345-348). The European Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases define a pericarditis episode as the presence of at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rubs, new widespread ST-elevation or PR depression on ECG, and pericardial effusion (new or worsening).Elevations of markers of inflammation (i.e., CRP, ESR, and WBD) or evidence of pericardial inflammation by an imaging technique (e.g., magnetic resonance imaging [MRI]) are used as supportive findings (Adler et al, Eur Heart J. 2015 Nov 7; 36(42): 2921-64.

[0169] The cause of pericarditis is often hard to determine. In most cases, doctors are either unable to determine a cause (idiopathic) or suspect a viral infection. Although the underlying pathogenesis of idiopathic recurrent pericarditis (RIP) (sometimes used interchangeably with recurrent idiopathic pericarditis) remains unclear, immune-mediated mechanisms are believed to play a key role in the pathogenesis (Imazio et al, 2005;96(5):736-739). A growing body of evidence suggests that these immune responses consist of both pathogenic autoimmune and auto-inflammatory processes (Cantarini et al, Autoimmunity Reviews 2015; 14:90-97; Doria et al, Autoimmunity Reviews 2012; 12:22-30). The presence of pro-inflammatory cytokines in the pericardial fluid of RIP patients lends direct support to both an autoimmune and / or auto-inflammatory etiopathogenesis (Pankuwait et al, 2000).

[0170] Recurrent pericarditis (RP) is a rare autoinflammatory disease which affects 20% to 30% of patients after an incident acute pericarditis event (Imazio 2014) and can be debilitating due to pain and limitations in physical function. Typically, RP is characterized by an initial acute pericarditis event followed by one or more subsequent acute recurrences after a symptom-free interval, e.g. of 4-6 weeks (Adler 2015). In some cases, however, RP patients can have persisting signs and symptoms of pericarditis despite initial improvement of theATTORNEY DOCKET NO.: KPL-062WO1initial acute pericarditis event without a symptom-free interval. In some embodiments, a recurrent pericarditis is an incessant pericarditis.

[0171] In some embodiments, the initial improvement is an improvement of one or more signs and symptoms associated with an episode of acute pericarditis. In some embodiments, the initial improvement comprises a reduction or improvement in one or more of:a) pericarditis pain;b) CRP;c) pericardial rub;d) widespread ST segment elevation or PR segment depression according to ECG findings;e) pericardial effusion;f) pericardial inflammation;g) edema;h) evidence of pericarditis by late gadolinium enhancement;i) evidence of constriction; andj) fever, chest pain, shortness of breath, and / or heart palpitations.

[0172] Typically, “persisting signs and symptoms of pericarditis,” “persistent pericarditis signs and symptoms” or its grammatical equivalents include one or more of (1) pericarditis pain; (2) an elevated CRP level; (3) pericardial rub; (4) widespread ST segment elevation or PR segment depression according to ECG findings; (5) pericardial effusion; (6) pericardial inflammation; (7) edema; (8) evidence of pericarditis by late gadolinium enhancement; (9) evidence of constriction; and (10) fever, chest pain, shortness of breath, and / or heart palpitations.

[0173] Pericarditis recurrences increase rates of emergency room admissions and hospitalizations. In the United States, 5% of patients presenting to the emergency room with non-ischemic chest pain are diagnosed with pericarditis (Agarwal 2015).

[0174] Potentially life-threatening complications of recurrent pericarditis include cardiac tamponade and constrictive pericarditis. Recurrent pericarditis may also result in theATTORNEY DOCKET NO.: KPL-062WO1need for invasive surgery (z.e., peri car di ectomy) in patients who are refractive to conventional treatments. The estimated prevalence of RP in the United States is approximately 40,000 patients, of whom approximately 14,000 experience multiple recurrences, may be refractory or intolerant to current therapeutic options, require long-term administration of corticosteroids to control their disease, and have persistent underlying disease (Imazio M, Brucato A, Trinchero R, Shabetai R, Spodick D, Adler Y. Corticosteroid therapy for pericarditis: a double-edged sword. Nature Clinical Practice, 2008 March;5:3:l 18-119.; Imazio M, Spodick DH, Brucato A, Trinchero R, Adler Y.Controversial issues in the management of pericardial diseases. Circulation. 2010; 121:916-928.; Khandaker MH, Espinosa RE, Nishimura RA, Sinak LJ, Hayes SN, Melduni RM, Oh JK. Pericardial disease: diagnosis and management. Mayo Clin Proc. 2010;85:572-593.; Lazaros G, Imazio M, Brucato A, et al. Anakinra: an emerging option for refractory idiopathic recurrent pericarditis: a systematic review of published evidence. J Cardiovasc Med. 2016;17:256-262.; Brucato A, Brambilla G, Moreo A, Alberti A, Munforti C, Ghirardello A, et al. Long- term outcomes in difficult-to-treat patients with recurrent pericarditis. Am J Cardiol. 2006;98:267-271.). Recurrent pericarditis is a serious, chronic, flaring disease which can last for years. In patients with two or more recurrences, the median duration of disease is 3 years, with one-third of patients still suffering at 5 years and one-quarter still suffering at 8 years.

[0175] Therapeutic options for the management of pericarditis episodes include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and / or corticosteroids, in sequential order (Lilly SL. Treatment of Acute and Recurrent Idiopathic Pericarditis.Circulation. 2013;127:1723-1726). Aspirin and other NSAIDs are the first-line approach. Because high doses of NSAIDs are often required, consideration must be given to gastric protection therapy, as potential risks of therapy include stomach ulcers and gastrointestinal (GI) bleeding as well as renal and cardiovascular toxicity. Colchicine is commonly used with NSAIDs to hasten the response to NSAIDs and reduce the risk of subsequent pericarditis recurrences. However, its use may be associated with the risks of fatal overdosing, significant drug-drug interactions, and neuromuscular toxicity. In addition, appropriately 10% to 15% of patients experience significant GI side effects with colchicine, including GI intolerance or severe diarrhea, requiring treatment discontinuation (Imazio M, Adler Y, Charron P.Recurrent pericarditis: Modem approach in 2016. Curr Cardiol Rep. 2016;18(6):50).ATTORNEY DOCKET NO.: KPL-062WO1

[0176] Patients with recurrent pericarditis who are refractory or intolerant to current therapeutic management options or who require long-term administration of corticosteroids and / or colchicine to control their disease can be challenging to manage. Some refractory patients, as a last resort, are referred for the surgical procedure of percardiectomy, with variable outcomes. Multiple immunosuppressive medications have been tried on an exploratory basis without consistent benefit (Brucato A, Imazio M, Gattorno M, Lazaros G, Maestroni S, Carraro M, Finetti M et al. Effect of anakinra on recurrent pericarditis among patients with colchicine resistance and corticosteroid dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016 Nov 8;316(18): 1906-1912).

[0177] Interleukin-1 (IL-1) is a key cytokine that drives the pathophysiology of many inflammatory processes. It is implicated as a causative factor in various inflammatory human diseases. Although the pathogenic mechanism of auto-inflammatory disease is not completely understood, there is a growing body of evidence that IL-1 may be a primary driver of the symptomology and that targeting this cytokine may provide important benefits (Hoffman & Patel, Arthritis and Rheum. 2004 Feb; 50(2): 345-349). In fact, a study of once-daily anakinra (KINERET®), a recombinant form of the human IL-1 receptor antagonist (IL-1RA), showed promising effects in RIP patients when colchicine failed and corticosteroid dependence (or intolerance) developed, with C-reactive protein (CRP) normalization within a mean of 7.1 days in 21 consecutively treated patients (Brucato et al, JAMA. 2016 Nov 8; 316(18): 1906-1912; Lazaros et al, J Cardiovasc Med 2016; 17(4):256-62). However, anakinra is a once-daily injection and is known to cause injection site reaction among other adverse events.Patients

[0178] The method described herein is suitable for treating recurrent pericarditis patients that have (1) a second recurrence with an initial acute pericarditis episode having been followed by a symptom-free interval; or (2) at least one episode of acute pericarditis followed by a period of persisting signs and symptoms of pericarditis despite initial improvement. The patients in group (2) do not experience a symptom -free interval.

[0179] In some embodiments, prior to the treatment, a patient presents with signs and symptoms of acute pericarditis (Qualifying Pericarditis Episode) despite treatment with standard therapies. In some embodiments, the patient has received a previous treatment for recurrent pericarditis. Exemplary treatments include, without limitation, IL1 antagonists,ATTORNEY DOCKET NO.: KPL-062WO1IL1R1 antagonists, IL1 traps, NSAIDs, colchicine, corticosteroids, or a combination thereof. In some embodiments, the patient received a previous treatment of rilonacept or anakinra.

[0180] In some embodiments, a patient has a history, or current clinical diagnosis, of pericarditis that is consistent with the 2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler 2015), fulfilling at least 2 of the following 4 criteria: (1) Pericarditic chest pain; (2) Pericardial rub; (3) New widespread ST segment elevation or PR segment depression according to ECG findings; and (4) Pericardial effusion (new or worsening).

[0181] In some embodiments, a patient has a qualifying pericarditis episode prior to the treatment. In some embodiments, a qualifying pericarditis episode is at least 1 day with pericarditis pain measurement > 4 on the 11 -point NRS and at least 1 CRP level > 1 mg / dL from a sample drawn within 7 days before or after the qualifying NRS.

[0182] In some embodiments, a patient has at least 1 day with pericarditis pain measurement >4 on NRS prior to the treatment.

[0183] In some embodiments, a patient has a C-reactive protein (CRP) value > 0.5 mg / dL prior to the treatment.

[0184] In some embodiments, a patient has a CRP value > 1.0 mg / dL prior to the treatment.

[0185] In some embodiments, prior to the treatment, a patient has an initial acute pericarditis episode followed by one or more pericarditis recurrences after an interval. In some embodiments, the patient has at least a first pericarditis recurrence (i.e., at least the second pericarditis episode) after an initial acute pericarditis episode that was followed by a symptom-free interval. In some embodiments, the patient has at least a second pericarditis recurrence (i.e., at least the third pericarditis episode) after an initial acute pericarditis episode that was followed by a symptom -free interval. In some embodiments, the patient has at least a third pericarditis recurrence (i.e., at least the fourth pericarditis episode) after an initial acute pericarditis episode that was followed by a symptom-free interval. In some embodiments, prior to the treatment, a patient has an initial acute pericarditis episode followed by one or more flares without a symptom -free interval. In some embodiments, prior to the treatment, a patient has persisting signs and symptoms of pericarditis despite initial improvement, without a symptom -free interval.ATTORNEY DOCKET NO.: KPL-062WO1

[0186] In some embodiments, prior to the treatment, the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis signs and symptoms despite initial improvement.

[0187] In some embodiments, prior to the treatment, the patient has persistent pericarditis signs and symptoms despite initial improvement without a symptom free interval.

[0188] In some embodiments, the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement. As used herein, a patient with persisting signs and symptoms of pericarditis typically has one or more of (1) pericarditis pain; (2) an elevated CRP level; (3) pericardial rub; (4) widespread ST segment elevation or PR segment depression according to ECG findings; (5) pericardial effusion; (6) pericardial inflammation; (7) edema; (8) evidence of pericarditis by late gadolinium enhancement; (8) evidence of constriction; and (9) fever, chest pain, shortness of breath, and / or heart palpitations.

[0189] In some embodiments, the patient with persisting pericarditis signs and symptoms of pericarditis has pericarditis pain. In some embodiments, the patient with persisting pericarditis signs and symptoms of pericarditis has pericarditis pain as measured by a NRS score > 1. In some embodiments, the NRS score is > 2. In some embodiments, the NRS score is > 3. In some embodiments, the NRS score is > 4.

[0190] In some embodiments, the patient with persisting signs and symptoms of pericarditis has an elevated CRP level. In some embodiments, the elevated CRP level is > 1 mg / dL. In some embodiments, the elevated CRP level is > 0.5 mg / dL. In some embodiments, the elevated CRP level is > 0.6 mg / dL. In some embodiments, the elevated CRP level is > 0.7 mg / dL. In some embodiments, the elevated CRP level is > 0.8 mg / dL. In some embodiments, the elevated CRP level is > 0.9 mg / dL.

[0191] In some embodiments, the patient with persisting signs and symptoms of pericarditis does not have a combination of pericarditis pain as measured by a NRS score > 4 and an elevated CRP level > 1 mg / dL.

[0192] In some embodiments, the patient with persisting signs and symptoms of pericarditis has pericardial rub. In some embodiments, the patient with persisting signs and symptoms of pericarditis has widespread ST segment elevation or PR segment depressionATTORNEY DOCKET NO.: KPL-062WO1according to ECG findings. In some embodiments, the patient with persisting signs and symptoms of pericarditis has pericardial effusion. In some embodiments, the patient with persisting signs and symptoms of pericarditis has pericardial inflammation. In some embodiments, the patient with persisting signs and symptoms of pericarditis has edema. In some embodiments, the patient with persisting evidence of pericarditis has evidence of pericarditis by late gadolinium enhancement according to cardiac MRI.

[0193] In some embodiments, the patient with persisting signs and symptoms of pericarditis has evidence of constriction. In some embodiments, the evidence of constriction is according to ECG findings.

[0194] In some embodiments, the patient with persisting pericarditis signs and symptoms has fever, chest pain, shortness of breath, heart palpitations or a combination thereof. In some embodiments, the patient with persisting signs and symptoms of pericarditis has fever. In some embodiments, the patient with persisting signs and symptoms of pericarditis has chest pain. In some embodiments, the patient with persisting signs and symptoms of pericarditis has shortness of breath. In some embodiments, the patient with persisting signs and symptoms of pericarditis has heart palpitations.

[0195] In some embodiments of the methods described herein, the patient is a pediatric patient. In some embodiments, the pediatric patient is > 12 and < 18 years old. In some embodiments, the pediatric patient is > 6 and < 18 years old. In some embodiments, the pediatric patient is > 6 and < 12 years old. In some embodiments, the pediatric patient is < 6 years old. In some embodiments, the pediatric patient is < 18 years old.Anti-ILIRI Antibodies

[0196] The anti-interleukin-1 receptor type- 1 (IL1R1) antibodies provide an advantageous mechanism of action for antagonizing both IL-la and IL-ip signaling and are beneficial for treating recurrent pericarditis according to methods described in the present invention.

[0197] An anti-ILlRl antibody described herein is a promising candidate for the treatment of patients with RP based on 1) the IL- 1 -antagonistic properties and in vivo pharmacokinetics (PK), which may enable monthly dosing in humans, 2) the established and favorable safety profile, and 3) the more convenient dosing schedule and easier dose administration.ATTORNEY DOCKET NO.: KPL-062WO1

[0198] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-ILlRl antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control.Antibody

[0199] A traditional antibody, also known as an immunoglobulin, is a Y-shaped structuring consisting of four polypeptides, two heavy chains and two light chains. The light chain consists of one variable region (VL) and one constant region (CL). The heavy chain consists of one variable region (VH) and at least three constant regions (CHI, CH2, CH3). The two light and two heavy chains are joined by disulfide bonds in the Y-shaped structure, with the light chains bracketing the heavy chains at the mouth of the Y-shape and continuing through the variable region. The variable regions determine the binding specificity of the antibody. Each variable region contains three hypervariable regions known as complementarity determining regions (CDRs) flanked by four relatively conserved regions known as framework regions (FRs). The three CDRs, referred to as CDR1, CDR2, and CDR3, contribute to the antibody binding specificity. Naturally occurring antibodies have often been used as starting material for engineered antibodies, such as chimeric antibodies and humanized antibodies. As used herein, an antibody described herein include antigenbinding fragments, including but not limited to Fab, Fab’, (Fab’)2, Fv, single chain antibodies (e.g., scFv), single-domain antibodies (e.g., sdAbs, VHH, nanobodies), Fd (fragment antigenbinding domain), dAb (domain antibody), biFab (bivalent Fab), minibodies, diabodies, and any other antigen-binding fragments known in the art. Examples of antibodies that have been modified or engineered include chimeric antibodies, humanized antibodies, and multispecific antibodies (e.g., bispecific antibodies).

[0200] Different antibody numbering schemes have been developed for accurate identification and subsequent comparison of variable regions of different antibodies. The most commonly used numbering schemes include Kabat, Chothia, and IMGT.

[0201] The Kabat numbering scheme was one of the first systems used to identify CDRs and is based on the analysis of antibody sequences, particularly the immunoglobulin variable (V) regions. In this scheme, CDRs are defined based on sequence variability, with CDRs being those segments of the variable regions that show the highest variability across different antibodies. Typically, in the Kabat numbering system, LCDR1 spans residues 24-ATTORNEY DOCKET NO.: KPL-062WO134, LCDR2 spans residues 50-56, LCDR3 spans residues 89-97, HCDR1 spans residues 31- 35, HCDR2 spans residues 50-65, and HCDR3 spans residues 95-102.

[0202] The Chothia numbering system is based on a structural analysis of antibody sequences and structures. It assigns residue numbers based on the positions of the amino acids in the context of the three-dimensional structure of the antibody. CDRs in Chothia numbering system scheme are defined based on structural features, primarily the loop regions that are responsible for binding to antigens. Typically, in the Chothia numbering system, LCDR1 spans residues 24-34, LCDR2 spans residues 50-56, LCDR3 spans residues 89-97, HCDR1 spans residues 27-35, HCDR2 spans residues 52-56, and HCDR3 spans residues 95-102.

[0203] The IMGT numbering scheme is based on an extensive analysis of the immunoglobulin sequences in the IMGT database, which includes human and other species' sequences. This scheme is a more recent development and is the most widely used in genomics and bioinformatics tools. It defines CDRs based on the concept of framework regions and focuses on the sequence alignment of antibodies. Typically, in the IMGT numbering system, LCDR1 spans residues 27-38, LCDR2 spans residues 56-65, LCDR3 spans residues 105-117, HCDR1 spans residues 27-38, HCDR2 spans residues 56-65, and HCDR3 spans residues 105-117.

[0204] Table 1 below shows a summary of typical CDR residue numbers by different numbering schemes.Table 1. Amino Acid Residues of CDRs by Different Numbering Schemes

[0205] CDR sequences of an antibody can be determined by a known method in the art, for example, at website: aligncdr.labshare.cn / aligncdr / abrsa.php.

[0206] In some embodiments, a LCDR1, a LCDR2, and a LCDR3 of an antibody comprise amino acid residues 24-34, 50-56, and 89-97, respectively, of a variable light chain (VL). In some embodiments, a HCDR1, a HCDR2, and a HCDR3 of an antibody comprise amino acid residues 31-35, 50-65, and 95-102, respectively, of a variable heavy chain (VH).

[0207] In some embodiments, a LCDR1, a LCDR2, and a LCDR3 of an antibody comprise amino acid residues 24-34, 50-56, and 89-97, respectively, of a variable light chainATTORNEY DOCKET NO.: KPL-062WO1(VL). In some embodiments, a HCDR1, a HCDR2, and a HCDR3 of an antibody comprise amino acid residues 27-35, 52-56, and 95-102, respectively, of a variable heavy chain (VH).

[0208] In some embodiments, a LCDR1, a LCDR2, and a LCDR3 of an antibody comprise amino acid residues 27-38, 56-65, and 105-117, respectively, of a variable light chain (VL). In some embodiments, a HCDR1, a HCDR2, and a HCDR3 of an antibody comprise amino acid residues 27-38, 56-65, and 105-117, respectively, of a variable heavy chain (VH).Exemplary Anti-ILIRI Antibody Sequences

[0209] In some embodiments, an anti-ILlRl antibody comprises a variable heavy chain (VH) of SEQ ID NO: 7.Anti-ILIRI Variable Heavy Chain (VH) Amino Acid Sequence:EVQLMQSGAEVKKPGESLKISCKGSGYSFSFHWIAWVRQMPGKGLEWMGIIHPGAS DTRYSPSFQGQVTISADNSNSATYLQWSSLKASDTAMYFCARQRELDYFDYWGQGT LVTVSS (SEQ ID NO: 7)

[0210] In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 85% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 90% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 92% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 93% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 94% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 95% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 96% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 97% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 98% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH that is at least 99% identical to SEQ ID NO: 7. In some embodiments, an anti-ILlRl antibody comprises a VH of SEQ ID NO: 7.

[0211] In some embodiments, an anti-ILlR antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the VH of SEQ ID NO: 7, as shown by underlining, respectively:ATTORNEY DOCKET NO.: KPL-062WO1EVQLMQSGAEVKKPGESLKISCKGSGYSFSFHWIAWVRQMPGKGLEWMGIIHPGA SDTRYSPSFOGQVTISADNSNSATYLQWSSLKASDTAMYFCARQRELDYFDYWGQ GTLVTVSS (SEQ ID NO: 7)

[0212] In some embodiments, an anti-ILlR antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the VH of SEQ ID NO: 7, as shown by underlining, respectively:EVOLMQSGAEVKKPGESLKISCKGSGYSFSFHWIAWVROMPGKGLEWMGIIHPGAS DTRYSPSFQGQVTISADNSNSATYLQWSSLKASDTAMYFCARQRELDYFDYWGQG TLVTVSS (SEQ ID NO: 7)

[0213] In some embodiments, an anti-ILlR antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the VH of SEQ ID NO: 7, as shown by underlining, respectively:EVQLMQSGAEVKKPGESLKISCKGSGYSFSFHWIAWVRQMPGKGLEWMGIIHPGA SDTRYSPSFQGQVTISADNSNSATYLQWSSLKASDTAMYFCARQRELDYFDYWGQ GTLVTVSS (SEQ ID NO: 7)

[0214] In some embodiments, an anti-ILlRl antibody comprises a variable light chain (VL) of SEQ ID NO: 8.Anti-ILlRl Variable Light Chain (VL) Amino Acid Sequence:EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQSFSGVP SRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPLTFGGGTKVEIK (SEQ ID NO: 8)

[0215] In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 85% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 90% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 92% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 93% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 94% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 95% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 96% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 97% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL that is at least 98% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises aATTORNEY DOCKET NO.: KPL-062WO1VL that is at least 99% identical to SEQ ID NO: 8. In some embodiments, an anti-ILlRl antibody comprises a VL of SEQ ID NO: 8.

[0216] In some embodiments, an anti-ILlR antibody comprises a LCDR1, a LCDR2, and a LCDR3 in the VL of SEQ ID NO: 8, as shown by underlining, respectively:EIVLTQSPDFQSVTPKEKVTITCRASOSIGSSLHWYQQKPDQSPKLLIKYASOSFSGV PSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPLTFGGGTKVEIK (SEQ ID NO: 8)

[0217] In some embodiments, an anti-ILlR antibody comprises a LCDR1, a LCDR2, and a LCDR3 in the VL of SEQ ID NO: 8, as shown by underlining, respectively:EIVLTQSPDFQSVTPKEKVTITCRASOSIGSSLHWYQQKPDQSPKLLIKYASOSFSGVP SRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPLTFGGGTKVEIK (SEQ ID NO: 8)Anti-ILlRl CDR Amino Acid Sequences

[0218] In some embodiments, an anti-ILlRl antibody comprises aHCDRl, a HCDR2, and a HCDR3 as shown in any one of Tables 2-4. In some embodiments, an anti-IL1R1 antibody comprises a LCDR1, a LCDR2, and a LCDR3 as shown in any one of Tables 2-4.

[0219] In some embodiments, an anti-ILlRl antibody comprises aHCDRl, a HCDR2, a HCDR3, a LCDR1, a LCDR2, and a LCDR3 as shown in any one of Tables 2-4. Table 2. CDR Sequence of Anti-ILlRl Antibody by Kabat NumberingTable 3. CDR Sequence of Anti-ILlRl Antibody by Chothia NumberingATTORNEY DOCKET NO.: KPL-062WO1Table 4. CDR Sequence of Anti-ILIRI Antibody by IMGT Numbering

[0220] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0221] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0222] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0223] In some embodiments, an anti-ILlRl antibody comprises aHCDRl, a HCDR2, and a HCDR3 comprising amino acid residues 31-35, 50-65, and 95-102, respectively, of SEQ ID NO: 7 according to Kabat numbering. In some embodiments, an anti-ILlRl antibody comprises aLCDRl, aLCDR2, and aLCDR3 comprising amino acid residues 24-34, 50-56, and 89-97, respectively, of SEQ ID NO: 8 according to Kabat numbering.

[0224] In some embodiments, an anti-ILlRl antibody comprises aHCDRl, a HCDR2, and a HCDR3 comprising amino acid residues 27-35, 52-56, and 95-102, respectively, of SEQ ID NO: 7 according to Chothia numbering. In some embodiments, an anti-ILlRl antibody comprises aLCDRl, aLCDR2, and aLCDR3 comprising amino acid residues 24-34, 50-56, and 89-97, respectively, of SEQ ID NO: 8 according to Chothia numbering.

[0225] In some embodiments, an anti-ILlRl antibody comprises aHCDRl, a HCDR2, and a HCDR3 comprising amino acid residues 27-38, 56-65, and 105-117, respectively, of SEQ ID NO: 7 according to IMGT numbering. In some embodiments, anATTORNEY DOCKET NO.: KPL-062WO1anti-ILlRl antibody comprises aLCDRl, aLCDR2, and aLCDR3 comprising amino acid residues 27-38, 56-65, and 105-117, respectively, of SEQ ID NO: 8 according to IMGT numbering.

[0226] In some embodiments, an anti-ILlRl antibody comprises aHCDRl, a HCDR2, and a HCDR3 amino acid sequences in SEQ ID NO: 7 as determined by any convention known in the art. In some embodiments, an anti-ILlRl antibody comprises a LCDR1, a LCDR2, and a LCDR3 amino acid sequences in SEQ ID NO: 8 as determined by any convention known in the art.

[0227] Additional anti-ILlRl antibodies are described in International Patent Publications WO 2010 / 052505, WO 2005 / 023872, and WO 2004 / 022718, incorporated herein by reference. In some embodiments, an anti-ILlRl antibody comprises a HCDR1, a HCDR2, a HCDR3, a LCDR1, a LCDR2, and a LCDR3 as shown in Table 5.Table 5. CDR Sequences of Exemplary Anti-ILlRl Antibodies.ATTORNEY DOCKET NO.: KPL-062WO1

[0228] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 22, a LCDR1 of SEQID NO: 23, a LCDR2 of SEQ ID NO: 24, and a LCDR3 of SEQ ID NO: 25.

[0229] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 26, a LCDR1 of SEQID NO: 23, a LCDR2 of SEQ ID NO: 24, and a LCDR3 of SEQ ID NO: 27.

[0230] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 28, a LCDR1 of SEQID NO: 45, a LCDR2 of SEQ ID NO: 24, and a LCDR3 of SEQ ID NO: 29.

[0231] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 30, a LCDR1 of SEQID NO: 31, a LCDR2 of SEQ ID NO: 32, and a LCDR3 of SEQ ID NO: 33.

[0232] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 30, a LCDR1 of SEQID NO: 31, a LCDR2 of SEQ ID NO: 32, and a LCDR3 of SEQ ID NO: 46.ATTORNEY DOCKET NO.: KPL-062WO1

[0233] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 34, a LCDR1 of SEQ ID NO: 31, a LCDR2 of SEQ ID NO: 32, and a LCDR3 of SEQ ID NO: 35.

[0234] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 47, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 36, a LCDR1 of SEQ ID NO: 31, a LCDR2 of SEQ ID NO: 32, and a LCDR3 of SEQ ID NO: 48.

[0235] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 37, a LCDR1 of SEQ ID NO: 31, a LCDR2 of SEQ ID NO: 32, and a LCDR3 of SEQ ID NO: 38.

[0236] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 39, a LCDR1 of SEQ ID NO: 31, a LCDR2 of SEQ ID NO: 32, and a LCDR3 of SEQ ID NO: 40.

[0237] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 41, a LCDR1 of SEQ ID NO: 31, a LCDR2 of SEQ ID NO: 32, and a LCDR3 of SEQ ID NO: 42.

[0238] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 20, a HCDR2 of SEQ ID NO: 21, a HCDR3 of SEQ ID NO: 41, a LCDR1 of SEQ ID NO: 31, a LCDR2 of SEQ ID NO: 32, and a LCDR3 of SEQ ID NO: 44.

[0239] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 49, a HCDR2 of SEQ ID NO: 50, a HCDR3 of SEQ ID NO: 51, a LCDR1 of SEQ ID NO: 52, a LCDR2 of SEQ ID NO: 53, and a LCDR3 of SEQ ID NO: 54.

[0240] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 55, a HCDR2 of SEQ ID NO: 56, a HCDR3 of SEQ ID NO: 57, a LCDR1 of SEQ ID NO: 58, a LCDR2 of SEQ ID NO: 59, and a LCDR3 of SEQ ID NO: 60.

[0241] In some embodiments, an anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 55, a HCDR2 of SEQ ID NO: 61, a HCDR3 of SEQ ID NO: 62, a LCDR1 of SEQ ID NO: 58, a LCDR2 of SEQ ID NO: 59, and a LCDR3 of SEQ ID NO: 60.

[0242] In some embodiments, an anti-ILlRl antibody comprises an Fc region comprising an amino acid sequence of SEQ ID NO: 9.ATTORNEY DOCKET NO.: KPL-062WO1Fc region of Anti-ILIRI Antibody:ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVA GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVY TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 9)

[0243] In some embodiments an Fc region comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 92% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 93% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 94% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 96% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 9. In some embodiments an Fc region comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 9.

[0244] In some embodiments, an anti-ILlRl antibody comprises a heavy chain of SEQ ID NO: 10.Anti-ILIRI Heavy Chain Amino Acid Sequence:EVQLMQSGAEVKKPGESLKISCKGSGYSFSFHWIAWVRQMPGKGLEWMGIIHPGAS DTRYSPSFQGQVTISADNSNSATYLQWSSLKASDTAMYFCARQRELDYFDYWGQGT LVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT FPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPC PAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNA KTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDATTORNEY DOCKET NO.: KPL-062WO1GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 10)

[0245] In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 85% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 90% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 92% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 93% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 94% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 95% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 96% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 97% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 98% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain that is at least 99% identical to SEQ ID NO: 10. In some embodiments, an anti-ILlRl antibody comprises a heavy chain of SEQ ID NO: 10.

[0246] In some embodiments, an anti-ILlRl antibody comprises a light chain of SEQ ID NO: 11.Anti-ILlRl Light Chain Amino Acid Sequence:EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQSFSGVP SRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPLTFGGGTKVEIKRTVAAPSVFIF PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 11)

[0247] In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 85% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 90% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 92% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 93% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 94% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 95% identical toATTORNEY DOCKET NO.: KPL-062WO1SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 96% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 97% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 98% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain that is at least 99% identical to SEQ ID NO: 11. In some embodiments, an anti-ILlRl antibody comprises a light chain of SEQ ID NO: 11.IL-1 a and IL-ip Binding Proteins

[0248] IL-la and IL-ip binding proteins also antagonize both IL-la and IL-1 [3 signaling and are beneficial for treating recurrent pericarditis according to methods described herein. Therefore, in the methods described herein, administration of an IL-la and IL-ip binding protein (e.g., a dual variable domain binding protein that binds IL-la and IL-ip) can be substituted for administration of an anti-ILlRl antibody.

[0249] Dual variable domain binding proteins that bind IL-la and IL-ip are described in U.S. Patent No. 9,303,085 and U.S. Patent Application Publication 2015 / 0203592, each of which are incorporated herein by reference. In some embodiments, a dual variable domain binding protein that binds IL-la and IL-ip comprises a light chain variable domain of SEQ ID NO: 63 and a heavy chain variable domain of SEQ ID NO: 64. A dual variable domain binding protein that binds IL-la and IL-ip can comprise a heavy chain of SEQ ID NO: 65 and a light chain of SEQ ID NO: 66. In an embodiment, a dual variable domain binding protein that binds IL-la and IL-ip is lutikizumab, which is also known as ABT-981.Table 6. Amino Acid Sequences of an Exemplary Dual Variable Domain Binding Protein that Binds IL-la and IL-ip.ATTORNEY DOCKET NO.: KPL-062WO1

[0250] The dual variable domain binding proteins described above can be administered at a therapeutically effective dose. The dual variable binding proteins described above can be administered subcutaneously. In embodiments, the therapeutically effective dose is 250-500 mg. In embodiments, the therapeutically effective dose is 275-500 mg. In embodiments, the therapeutically effective dose is 300-500 mg. In embodiments, the therapeutically effective dose is 325-500 mg. In embodiments, the therapeutically effective dose is 350-500 mg. In embodiments, the therapeutically effective dose is 375-500 mg. In embodiments, the therapeutically effective dose is 400-500 mg. In embodiments, the therapeutically effective dose is 425-500 mg. In embodiments, the therapeutically effective dose is 450-500 mg. In embodiments, the therapeutically effective dose is 475-500 mg.

[0251] In embodiments, the therapeutically effective dose is 250-400 mg. In embodiments, the therapeutically effective dose is 250-375 mg. In embodiments, the therapeutically effective dose is 250-350 mg. In embodiments, the therapeutically effective dose is 250 to 325 mg. In embodiments, the therapeutically effective dose is 250-300 mg. In embodiments, the therapeutically effective dose is 150-300 mg. In embodiments, the therapeutically effective dose is 188-300 mg. In embodiments, the therapeutically effective dose is 225-300 mg. In embodiments, the therapeutically effective dose is 263-300 mg. In embodiments, the therapeutically effective dose is 275-300 mg. In embodiments, the therapeutically effective dose is 250-275 mg.

[0252] In embodiments, the therapeutically effective dose is 300-500 mg. In embodiments, the therapeutically effective dose is 300-475 mg. In embodiments, theATTORNEY DOCKET NO.: KPL-062WO1therapeutically effective dose is 300-450 mg. In embodiments, the therapeutically effective dose is 300-425 mg. In embodiments, the therapeutically effective dose is 300-400 mg. In embodiments, the therapeutically effective dose is 300-375 mg. In embodiments, the therapeutically effective dose is 300-350 mg. In embodiments, the therapeutically effective dose is 300-325 mg.

[0253] In embodiments, the therapeutically effective dose is 188 mg. In embodiments, the therapeutically effective dose is 225 mg. In embodiments, the therapeutically effective dose is 250 mg. In embodiments, the therapeutically effective dose is 263 mg. In embodiments, the therapeutically effective dose is 275 mg. In embodiments, the therapeutically effective dose is 300 mg. In embodiments, the therapeutically effective dose is 325 mg. In embodiments, the therapeutically effective dose is 350 mg. In embodiments, the therapeutically effective dose is 375 mg. In embodiments, the therapeutically effective dose is 400 mg. In embodiments, the therapeutically effective dose is 425 mg. In embodiments, the therapeutically effective dose is 450 mg. In embodiments, the therapeutically effective dose is 475 mg. In embodiments, the therapeutically effective dose is 500 mg.

[0254] In embodiments, the binding protein is administered at any of the doses described above every week. For example, the binding protein can be administered at a dose of 300 mg every week. In embodiments, the binding protein is administered at any of the doses described above every two weeks. For example, the binding protein can be administered at a dose of 300 mg every two weeks.

[0255] In embodiments, the binding protein is administered every week for 16 weeks and every two weeks thereafter. For example, the binding protein can be administered at a dose of 300 mg every week for 16 weeks and at a dose of 300 mg every two weeks thereafter.

[0256] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis, comprising administering subcutaneously to a patient a dual variable domain binding protein that binds IL- la and IL-ip, e.g., lutikizumab, at a dose of 300 mg, wherein the dual variable domain binding protein is administered to the patient once every week or once every two weeks. In one embodiment, administration of a dual variable domain binding protein that binds IL-la and IL-ip, e.g., lutikizumab, reduces the risk of pericarditis recurrence.ATTORNEY DOCKET NO.: KPL-062WO1Dosing Regimens

[0257] The present invention provides, among other things, a more efficacious and safer dosing regimens for treating recurrent pericarditis using an anti-ILlRl antibody described herein. In some embodiments, a method comprises administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control. In some embodiments, a method comprises administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of greater than 10 mg. In some embodiments, a method comprises administering to a patient, an antiinterleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose no more frequently than once every week.Dose

[0258] In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 10 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 15 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 20 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 25 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 30 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 35 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 40 mg. In some embodiments, the anti-IL1R1 antibody is administered at a dose of greater than 45 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 50 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 55 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 60 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 65 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 70 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 75 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 80 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 85 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 90 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 95 mg. In some embodiments, the anti-ILlRl antibody is administeredATTORNEY DOCKET NO.: KPL-062WO1at a dose of greater than 100 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 110 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 120 mg. In some embodiments, the anti-IL1R1 antibody is administered at a dose of greater than 130 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 140 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 150 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 160 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 170 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 180 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 188 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 190 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 200 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 225 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 250 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 263 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 275 mg. In some embodiments, the anti-IL1R1 antibody is administered at a dose of greater than 300 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 400 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of greater than 500 mg.

[0259] In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 5 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 10 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 15 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 20 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 25 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 30 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 40 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 50 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 60 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 70 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 80 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 90 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of atATTORNEY DOCKET NO.: KPL-062WO1least 100 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 110 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 125 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 150 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 175 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 200 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 250 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 300 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 350 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 400 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of at least 500 mg.

[0260] In some embodiments, the anti-ILlRl antibody is administered at a dose of between 10 mg and 1000 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 10 mg and 500 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 50 mg and 500 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 50 mg and 400 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 100 mg and 400 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 75 and 350 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 10 and 100 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 50 mg and 150 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 75 mg and 125 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 150 and 400 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 150 and 300 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 150 and 350 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of between 175 mg and 325 mg.

[0261] In some embodiments, the anti-ILlRl antibody is administered at a dose of 1 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 3 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 5 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 10 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 15 mg. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, the anti-ILlRl antibody is administered at a dose of 20 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 25 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 30 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 35 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 40 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 45 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 50 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 55 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 60 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 65 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 70 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 75 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 80 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 85 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 90 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 95 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 100 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 110 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 120 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 125 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 130 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 150 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 175 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 188 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 200 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 225 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 250 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 263 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 275 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 300 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 325 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 350 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 375 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 400 mg. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, the anti-ILlRl antibody is administered at a dose of 500 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 750 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 800 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 900 mg. In some embodiments, the anti-ILlRl antibody is administered at a dose of 1000 mg.Administration Interval

[0262] In some embodiments, an anti-interleukin-1 receptor type- 1 (IL1R1) antibody at a therapeutically effective dose at an administration interval sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis.

[0263] In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 5 days. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 7 days. In some embodiments, an anti-IL1R1 antibody is administered no more frequently than once every 10 days. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 15 days. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 28 days. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every week. In some embodiments, an anti-ILlRl antibody is administered no more frequently than every other week. In some embodiments, an anti-IL1R1 antibody is administered no more frequently than once every 3 weeks. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 4 weeks. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 5 weeks. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 6 weeks. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every 7 weeks. In some embodiments, an anti-IL1R1 antibody is administered no more frequently than once every 8 weeks. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every month. In some embodiments, an anti-ILlRl antibody is administered no more frequently than once every two months.

[0264] In some embodiments, an anti-ILlRl antibody is administered once every 5 days. In some embodiments, an anti-ILlRl antibody is administered once every 7 days. In some embodiments, an anti-ILlRl antibody is administered once every 10 days. In some embodiments, an anti-ILlRl antibody is administered once every 15 days. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, an anti-ILlRl antibody is administered once every 28 days. In some embodiments, an anti-ILlRl antibody is administered once every week. In some embodiments, an anti-ILlRl antibody is administered once every other week. In some embodiments, an anti-ILlRl antibody is administered once every 3 weeks. In some embodiments, an anti-ILlRl antibody is administered once every 4 weeks. In some embodiments, an anti-ILlRl antibody is administered once every 5 weeks. In some embodiments, an anti-ILlRl antibody is administered once every 6 weeks. In some embodiments, an anti-ILlRl antibody is administered once every 7 weeks. In some embodiments, an anti-ILlRl antibody is administered once every 8 weeks. In some embodiments, an anti-ILlRl antibody is administered once every month. In some embodiments, an anti-ILlRl antibody is administered once every two months.

[0265] In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 5 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 7 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 10 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 15 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 28 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every week. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every other week. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 3 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 4 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 5weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 6 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 7 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every 8 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once every month. In some embodiments, an anti-ILlRl antibody is administered at a dose of greater than 10 mg once two months.

[0266] In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every 5 days. In some embodiments, an anti-ILlRlATTORNEY DOCKET NO.: KPL-062WO1antibody is administered at a dose of between 30 mg and 500 mg once every 7 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every 10 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every 15 days. In some embodiments, an anti-IL1R1 antibody is administered at a dose of between 30 mg and 500 mg once every 28 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every week. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every other week. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every 3 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every 4 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every 5 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every 6 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every 7 weeks. In some embodiments, an anti-IL1R1 antibody is administered at a dose of between 30 mg and 500 mg once every 8 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once every month. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg once two months.

[0267] In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 5 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 7 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 10 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 15 days. In some embodiments, an anti-IL1R1 antibody is administered at a dose of between 100 mg and 300 mg once every 28 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every week. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every other week. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 3 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 4 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 5 weeks. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 6 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every 7 weeks. In some embodiments, an anti-IL1R1 antibody is administered at a dose of between 100 mg and 300 mg once every 8 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every month. In some embodiments, an anti-ILlRl antibody is administered at a dose of between 100 mg and 300 mg once every two months.

[0268] In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 5 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 7 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 10 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 15 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every week. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every other week. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 3 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 4 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 5 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 6 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 7 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every 8 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every month. In some embodiments, an anti-ILlRl antibody is administered at a dose of 100 mg once every two months.

[0269] In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 5 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 7 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 10 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 15 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 28 days. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every week. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every other week. In some embodiments, an anti-ILlRl antibody is administered at a dose ofATTORNEY DOCKET NO.: KPL-062WO1300 mg once every 3 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 4 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 5 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 6 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 7 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 8 weeks. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every month. In some embodiments, an anti-ILlRl antibody is administered at a dose of 300 mg once every 2 months.

[0270] In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 1 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 1.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 2 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 2.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 3 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 3.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 4 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 4.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 5.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 6 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 6.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 7 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 7.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 8 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 8.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 9 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 9.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 10 mg / kg.

[0271] In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 1 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibodyATTORNEY DOCKET NO.: KPL-062WO1is administered to the patient at a dose of 1.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 2 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 2.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 3 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 3.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 4 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 4.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 5.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 6 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 6.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 7 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 7.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 8 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 8.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 9 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 9.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 10 mg / kg once every two weeks.

[0272] In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 1 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 1.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 2 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 2.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 3 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 3.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to theATTORNEY DOCKET NO.: KPL-062WO1patient at a dose of 4 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 4.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 5.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 6 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 6.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 7 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 7.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 8 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 8.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 9 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 9.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the patient at a dose of 10 mg / kg once every four weeks.

[0273] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks, or an equivalent dosing regimen thereof.

[0274] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0275] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ IDATTORNEY DOCKET NO.: KPL-062WO1NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0276] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0277] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0278] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every four weeks, or an equivalent dosing regimen thereof.

[0279] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0280] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0281] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1ATTORNEY DOCKET NO.: KPL-062WO1receptor type-1 (IL1R1) antibody at a dose of 100 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0282] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0283] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every two weeks, or an equivalent dosing regimen thereof.

[0284] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0285] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0286] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.ATTORNEY DOCKET NO.: KPL-062WO1

[0287] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0288] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every four weeks, or an equivalent dosing regimen thereof.

[0289] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0290] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0291] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0292] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 150 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, aATTORNEY DOCKET NO.: KPL-062WO1HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0293] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every two weeks, or an equivalent dosing regimen thereof.

[0294] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0295] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0296] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0297] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0298] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1ATTORNEY DOCKET NO.: KPL-062WO1receptor type-1 (IL1R1) antibody at a dose of 225 mg once every four weeks, or an equivalent dosing regimen thereof.

[0299] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0300] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0301] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0302] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 225 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0303] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every two weeks, or an equivalent dosing regimen thereof.

[0304] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1ATTORNEY DOCKET NO.: KPL-062WO1receptor type-1 (IL1R1) antibody at a dose of 250 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0305] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0306] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0307] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0308] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every four weeks, or an equivalent dosing regimen thereof.

[0309] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.ATTORNEY DOCKET NO.: KPL-062WO1

[0310] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0311] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0312] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 250 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0313] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every two weeks, or an equivalent dosing regimen thereof.

[0314] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0315] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ IDATTORNEY DOCKET NO.: KPL-062WO1NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0316] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0317] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every two weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.

[0318] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every four weeks, or an equivalent dosing regimen thereof.

[0319] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0320] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

[0321] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1ATTORNEY DOCKET NO.: KPL-062WO1receptor type-1 (IL1R1) antibody at a dose of 300 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

[0322] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg once every four weeks, or an equivalent dosing regimen thereof, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.Pediatric

[0323] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 1 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 1.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 2 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 2.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 3 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 3.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 4 mg / kg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 4.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 5.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 6 mg / kg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 6.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 7 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 7.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 8 mg / kg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 8.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 9 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatricATTORNEY DOCKET NO.: KPL-062WO1patient at a dose of 9.5 mg / kg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 10 mg / kg.

[0324] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 1 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 1.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 2 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 2.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 3 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 3.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 4 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 4.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 5.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 6 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 6.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 7 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 7.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 8 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 8.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 9 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 9.5 mg / kg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 10 mg / kg once every two weeks.

[0325] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 1 mg / kg once every four weeks. In some embodiments, the anti-ILlRlATTORNEY DOCKET NO.: KPL-062WO1antibody is administered to the pediatric patient at a dose of 1.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 2 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 2.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 3 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 3.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 4 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 4.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 5.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 6 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 6.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 7 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 7.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 8 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 8.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 9 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 9.5 mg / kg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 10 mg / kg once every four weeks.

[0326] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 10 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 20 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 30 mg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 40 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 50ATTORNEY DOCKET NO.: KPL-062WO1mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 60 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 70 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 80 mg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 90 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 100 mg.

[0327] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 110 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 120 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 130 mg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 140 mg. In some embodiment, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 150 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 160 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 170 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 180 mg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 190 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 200 mg.

[0328] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 210 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 220 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 230 mg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 240 mg. In some embodiment, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 250 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 260 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 270 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 280 mg. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 290 mg. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 300 mg.ATTORNEY DOCKET NO.: KPL-062WO1

[0329] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 10 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 20 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 30 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 40 mg once every two weeks. In some embodiment, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 50 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 60 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 70 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 80 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 90 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 100 mg once every two weeks.

[0330] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 110 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 120 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 130 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 140 mg once every two weeks. In some embodiment, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 150 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 160 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 170 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 180 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 190 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 200 mg once every two weeks.

[0331] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 210 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 220 mg once every two weeks.ATTORNEY DOCKET NO.: KPL-062WO1In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 230 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 240 mg once every two weeks. In some embodiment, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 250 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 260 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 270 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 280 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 290 mg once every two weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 300 mg once every two weeks.

[0332] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 10 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 20 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 30 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 40 mg once every four weeks. In some embodiment, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 50 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 60 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 70 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 80 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 90 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 100 mg once every four weeks.

[0333] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 110 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 120 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 130 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 140 mg once every four weeks. In someATTORNEY DOCKET NO.: KPL-062WO1embodiment, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 150 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 160 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 170 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 180 mg once every four weeks. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 190 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 200 mg once every four weeks.

[0334] In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 210 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 220 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 230 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 240 mg once every four weeks. In some embodiment, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 250 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 260 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 270 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 280 mg once every four weeks. In some embodiments, the anti-IL1R1 antibody is administered to the pediatric patient at a dose of 290 mg once every four weeks. In some embodiments, the anti-ILlRl antibody is administered to the pediatric patient at a dose of 300 mg once every four weeks.Treatment Period

[0335] The present invention provides, among other things, a method comprising administering an anti-ILlRl antibody for a treatment period sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis.

[0336] In some embodiments, an anti-ILlRl antibody is administered for at least 4 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 5 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 6 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 8 weeks. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, an anti-ILlRl antibody is administered for at least 10 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 12 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 14 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 16 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 18 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 20 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 24 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 28 weeks. In some embodiments, an anti-ILlRl antibody is administered for at least 30 weeks.

[0337] In some embodiments, an anti-ILlRl antibody is administered for at least 1 month. In some embodiments, an anti-ILlRl antibody is administered for at least 2 months. In some embodiments, an anti-ILlRl antibody is administered for at least 3 months. In some embodiments, an anti-ILlRl antibody is administered for at least 4 months. In some embodiments, an anti-ILlRl antibody is administered for at least 6 months. In some embodiments, an anti-ILlRl antibody is administered for at least 8 months. In some embodiments, an anti-ILlRl antibody is administered for at least 10 months. In some embodiments, an anti-ILlRl antibody is administered for at least 12 months. In some embodiments, an anti-ILlRl antibody is administered for at least 14 months. In some embodiments, an anti-ILlRl antibody is administered for at least 16 months. In some embodiments, an anti-ILlRl antibody is administered for at least 20 months. In some embodiments, an anti-ILlRl antibody is administered for at least 24 months.Exemplary medical uses

[0338] In one aspect, there is provided an anti-interleukin-1 receptor type-1 (IL1R1) antibody for use in a method of treating recurrent pericarditis (e.g., idiopathic recurrent pericarditis) in a subject in need thereof.

[0339] In another aspect, there is provided an anti-interleukin-1 receptor type-1 (IL1R1) antibody for use in method of reducing the risk of a pericarditis recurrence in a subject in need thereof. For instance, the subject may have been previously diagnosed with or treated for recurrent pericarditis (e.g., idiopathic recurrent pericarditis).

[0340] In a further aspect, there is provided an anti-interleukin-1 receptor type-1 (IL1R1) antibody for use in method of reducing symptoms of recurrent pericarditis in a subject in need thereof.ATTORNEY DOCKET NO.: KPL-062WO1

[0341] In a further aspect, there is provided an anti-interleukin-1 receptor type-1 (IL1R1) antibody for use in a method of treating recurrent pericarditis or reducing the risk of a pericarditis recurrence in a subject in need thereof.

[0342] In a further aspect, there is provided an anti-interleukin-1 receptor type-1 (IL1R1) antibody for use in a method of reducing symptoms or risk of recurrent pericarditis in a subject in need thereof.

[0343] In a further aspect, there is provided an anti-interleukin-1 receptor type-1 (IL1R1) antibody for use in a method for treatment of idiopathic recurrent pericarditis or reduction in risk of recurrence in a subject in need thereof.

[0344] Such uses comprise administering a therapeutically effective amount of the anti-ILRl antibody (e.g., KPL-387) to the subject to treat the recurrent pericarditis or reduce the risk of recurrence. The therapeutically effective amount may be administered as a single dose or multiple doses and may comprise 50 mg to 400 mg of the anti-ILlRl antibody. For example, a single dose of 50 mg to 150 mg, or 150 mg to 300 mg, of the anti-ILlRl antibody may be administered to the subject. In some embodiments, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg may be administered in a single dose. For instance, two single doses of 150 mg may be administered in a single doctor’s visit to achieve a total dose of 300 mg per administration interval. A suitable administration interval may be once every two weeks or once every four weeks.

[0345] Typically, the anti-ILlRl antibody is administered for at least four weeks, e.g., for at least eight weeks, at least twelve weeks, at least 16 weeks, at least 20 weeks, or at least 24 weeks. For instance, a four-to-eight-week treatment period may reduce symptoms of recurrent pericarditis (e.g., symptoms of idiopathic recurrent pericarditis) such as C-reactive protein levels and / or pain (e.g., as determined by a numerical rating scale score) to normal or close to normal levels. Continued administration of the IL1R1 antibody for a period of 12 to 24 weeks may prevent recurrence of pericarditis (e.g., idiopathic recurrent pericarditis).

[0346] In an exemplary embodiment, a dose of 50-150 mg (e.g., a 100 mg dose) of the anti-ILlRl antibody is administered to the subject once every two weeks, e.g., for a period of at least four weeks (for instance, for up to 12 weeks or 24 weeks).ATTORNEY DOCKET NO.: KPL-062WO1

[0347] In another exemplary embodiment, a dose of 50-150 mg (e.g., a 100 mg dose) of the anti-ILlRl antibody is administered to the subject once every four weeks, e.g., for a period of at least eight weeks (for instance, for up to 12 weeks or 24 weeks).

[0348] In a further exemplary embodiment, a dose of 200-400 mg (e.g., a 300 mg dose) of the anti-ILlRl antibody is administered to the subject once every two weeks, e.g., for at least four weeks (for instance, for up to 12 weeks or 24 weeks).

[0349] In another exemplary embodiment, a dose of 200-400 mg (e.g., a 300 mg dose) of the anti-ILlRl antibody is administered to the subject once every four weeks, e.g., for at least eight weeks (for instance, for up to 12 weeks or 24 weeks).

[0350] The anti-ILlRl antibody (e.g., KPL-387) may be administered subcutaneously or intravenously. Typically, the anti-ILlRl antibody is administered subcutaneously, especially when repeated dosing over a longer period (e.g., 12-24 weeks) is required.

[0351] A suitable anti-ILlRl antibody for the medical uses described herein is KPL-387, or another IgG antibody (e.g., an IgG2 antibody) with the same or substantially the same complementarity determining regions (CDRs) as KPL-387 that competes with KPL-387 for binding of IL-1R1. The CDRs of the anti-ILlRl antibody may vary depending on the numbering system (e.g., Kabat, Chothia or IMGT) used to determine the CDRs.

[0352] For example, the anti-ILlRl antibody may comprise a heavy chain complementarity determining region (HCDR) 1 comprising an amino acid sequence of FHWIA (SEQ ID NO: 1), an HCDR2 of IIHPGASDTRYSPSFQG (SEQ ID NO: 2), and an HCDR3 of QRELDYFDY (SEQ ID NO: 3); and a light chain complementarity determining region (LCDR) 1 comprising an amino acid sequence of RASQSIGSSLH (SEQ ID NO: 4), an LCDR2 of YASQSFS (SEQ ID NO: 5), and an LCDR3 of HQSSSLPLT (SEQ ID NO: 6) as determined using Kabat.

[0353] Alternatively, the anti-ILlRl antibody may comprise an HCDR1 comprising an amino acid sequence of GYSFSFH (SEQ ID NO: 12), an HCDR2 of HPGASD (SEQ ID NO: 13), and an HCDR3 of QRELDYFDY (SEQ ID NO: 3); and an LCDR1 comprising an amino acid sequence of RASQSIGSSLH (SEQ ID NO: 4), an LCDR2 of YASQSFS (SEQ ID NO: 5), and an LCDR3 of HQSSSLPLT (SEQ ID NO: 6) as determined using Chothia.

[0354] Alternatively, the anti-ILlRl antibody may comprise an HCDR1 comprising an amino acid sequence of GYSFSFHW (SEQ ID NO: 14), an HCDR2 of IHPGASDT (SEQ ID NO: 15), and an HCDR3 of ARQRELD YFD Y (SEQ ID NO: 19); and an LCDR1 ofATTORNEY DOCKET NO.: KPL-062WO1QSIGSS (SEQ ID NO: 16), an LCDR2 of YAS (SEQ ID NO: 17), and an LCDR3 of HQSSSLPLT (SEQ ID NO: 6) as determined using IMGT.

[0355] The anti-ILlRl antibody may comprise an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least about 85% (e.g., at least 90%, 95%, or 99%) identical to, or identical to, the sequence of SEQ ID NO: 7 and an immunoglobulin light chain variable (VL) region comprising an amino acid sequence that is at least about 85% (e.g., at least 90%, 95%, or 99%) identical to, or identical to, the sequence of SEQ ID NO: 8.

[0356] For example, the anti-ILlRl antibody may comprise an immunoglobulin heavy chain variable (VH) region comprising an amino acid sequence that is at least about 97% (e.g., at least 98% or 99%) identical to the sequence of SEQ ID NO: 7 and an immunoglobulin light chain variable (VL) region comprising an amino acid sequence that is at least about 97% (e.g., at least 98% or 99%) identical to the sequence of SEQ ID NO: 8.

[0357] In some embodiments, the anti-ILlRl antibody comprises a VH region comprising the amino acid sequence of SEQ ID NO: 7 and a VL region comprising the amino acid sequence of SEQ ID NO: 8. The anti-ILlRl antibody may comprise an immunoglobulin heavy chain comprising an amino acid sequence that is at least about 85% (e.g., at least 90%, 95%, or 99%) identical to, or identical to, the sequence of SEQ ID NO: 10 and an immunoglobulin light chain comprising an amino acid sequence that is at least about 85% (e.g., at least 90%, 95%, or 99%) identical to, or identical to, the sequence of SEQ ID NO: 11.

[0358] For example, the anti-ILlRl antibody may comprise an immunoglobulin heavy chain comprising an amino acid sequence that is at least about 97% (e.g., at least 98% or 99%) identical to the sequence of SEQ ID NO: 10 and an immunoglobulin light chain comprising an amino acid sequence that is at least about 97% (e.g., at least 98% or 99%) identical to the sequence of SEQ ID NO: 11.

[0359] In a specific embodiment, the anti-ILlRl antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 10, and a light chain comprising the amino acid sequence of SEQ ID NO: 11.

[0360] In an exemplary embodiment, provided is an anti-interleukin-1 receptor type- 1 (IL1R1) antibody comprising a heavy chain comprising the amino acid sequence that is at least about 97% (e.g., at least 98% or 99%) identical, or identical, to the sequence of SEQ IDATTORNEY DOCKET NO.: KPL-062WO1NO: 10, and a light chain comprising the amino acid sequence that is at least about 97% (e.g., at least 98% or 99%) identical to, or identical to, the sequence of SEQ ID NO: 11 for use in a method of treating recurrent pericarditis (e.g., idiopathic recurrent pericarditis) in a subject in need thereof, wherein the anti-IL-lRl is administered to the subject (e.g., subcutaneously) at a single dose of 50-400 mg (e.g., a 100 mg dose, or 300 mg dose) once every two weeks or once every four weeks.

[0361] Administration of the anti-ILlRl antibody to the subject may improve, stabilize, prevent, or reduce one or more symptoms of recurrent pericarditis (e.g., idiopathic recurrent pericarditis) in the subject relative to a control subject. The control subject may be the subject prior to the administration of the anti-ILlRl antibody. Alternatively, the control subject may be a comparable recipient to which the anti-ILlRl antibody has not been administered (e.g., a comparable recipient who was administered a placebo).Pharmacokinetics and Pharmacodynamics

[0362] Evaluation of an anti-ILlRl antibody concentration-time profiles in serum of subjects with pericarditis may be evaluated directly by measuring systemic serum anti-ILlRl antibody concentration-time profiles. Typically, anti-ILlRl antibody pharmacokinetic and pharmacodynamic profiles are evaluated by sampling the blood of treated subjects periodically. The following standard abbreviations are used to represent the associated pharmacokinetic parameters.Cmax maximum concentrationtmax time to maximum concentrationAUCo-t area under the concentration-time curve (AUC) from time zero to the last measurable concentration, calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrationsAUCo- / AUC from time zero to infinity calculated using the formula:where Ct is the last measurable concentration and Az is the apparent terminal elimination rate constantATTORNEY DOCKET NO.: KPL-062WO1kz apparent terminal elimination rate constant, where Az is the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phaseti / 2 apparent terminal elimination half-life (whenever possible), whereti / 2 = natural log (ln)(2) / AzCL clearanceVd volume of distribution (IV doses only)Vd / F apparent volume of distribution (SC doses only)

[0363] Typically, actual blood sample collection times relative to the start of anti-IL1R1 antibody administration are used in PK analysis. For example, blood samples are typically collected, for example, within 15 or 30 minutes prior to anti-ILlRl antibody administration (pre-inj ection baseline or time 0) and at periodic intervals following administration, e.g., hours 1, 4, 8 or 12, or days 1 (24 hours), 2, 3, 4, 5, 6, 7, 10, 14, 17, 21, 24, 28, 31, 38, 45, 52, 60, 70 or 90 days, following administration. In some embodiments, the blood samples are collected prior to an administration timepoint.

[0364] Various methods may be used to measure anti-ILlRl antibody concentration in serum. As a non-limiting example, enzyme-linked immunosorbent assay (ELISA) methods are used.

[0365] Pharmacokinetic parameters may be evaluated at any stage during the treatment, for example, at day 1, day 2, day 3, day 4, day 5, day 6, week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12, week 13, week 14, week 15, week 16, week 17, week 18, week 19, week 20, week 21, week 22, week 23, week 24, or later. In some embodiments, pharmacokinetic parameters may be evaluated at month 1, month 2, month 3, month 4, month 5, month 6, month 7, month 8, month 9, month 10, month 11, month 12, month 13, month 14, month 15, month 16, month 17, month 18, month 19, month 20, month 21, month 22, month 23, month 24, or later during the treatment.

[0366] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering a patient, an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose that produces a medianATTORNEY DOCKET NO.: KPL-062WO1Cmax of at least 0.1 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 0.2 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 0.3 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 0.5 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 0.6 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 0.8 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 0.9 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 1.0 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 3 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 5 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 7 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 8 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 9 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 10 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 12 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 15 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 20 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 25 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 30 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 40 pg / mL. In some embodiments, the therapeutically effective dose produces a median Cmax of at least 50 pg / mL.

[0367] In one aspect, the present invention provides, among other things, a method of treating recurrent pericarditis comprising administering a patient, an anti-interleukin- 1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose that maintains mean serum concentration greater than EC90. Typically, EC90 is a concentration of an antiinterleukin-1 receptor type-1 (IL1R1) antibody that results in 90% of the maximal effective activity. In some embodiments, effective activity is inhibition of IL- 1 -stimulated IL-6 production in primary human cells. In some embodiments, administration of an anti-ILlRl antibody results in a decrease in IL-6 levels in the subject. In some embodiments,ATTORNEY DOCKET NO.: KPL-062WO1administration of an anti-ILlRl antibody results in the normalization of IL-6 levels in the subject.

[0368] In some embodiments, EC90 is at least 0.01 gg / mL. In some embodiments, EC90 is at least 0.02 gg / mL. In some embodiments, EC90 is at least 0.03 gg / mL. In some embodiments, EC90 is at least 0.04 gg / mL. In some embodiments, EC90 is at least 0.05 gg / mL. In some embodiments, EC90 is at least 0.06 gg / mL. In some embodiments, EC90 is at least 0.07 gg / mL. In some embodiments, EC90 is at least 0.08 gg / mL. In some embodiments, EC90 is at least 0.09 gg / mL. In some embodiments, EC90 is at least 0.1 gg / mL. In some embodiments, EC90 is at least 0.2 gg / mL. In some embodiments, EC90 is at least 0.3 gg / mL. In some embodiments, EC90 is at least 0.4 gg / mL. In some embodiments, EC90 is at least 0.5 gg / mL. In some embodiments, EC90 is at least 0.6 gg / mL. In some embodiments, EC90 is at least 0.7 gg / mL. In some embodiments, EC90 is at least 0.8 gg / mL. In some embodiments, EC90 is at least 0.9 gg / mL. In some embodiments, EC90 is at least 1.0 gg / mL. In some embodiments, EC90 is at least 1.5 gg / mL. In some embodiments, EC90 is at least 2.0 gg / mL. In some embodiments, EC90 is at least 2.5 gg / mL. In some embodiments, EC90 is at least 3 gg / mL. In some embodiments, EC90 is at least 4 gg / mL. In some embodiments, EC90 is at least 5 gg / mL. In some embodiments, EC90 is at least 6 gg / mL. In some embodiments, EC90 is at least 7 gg / mL. In some embodiments, EC90 is at least 8 gg / mL. In some embodiments, EC90 is at least 9 gg / mL. In some embodiments, EC90 is at least 10 gg / mL. In some embodiments, EC90 is at least 12 gg / mL. In some embodiments, EC90 is at least 15 gg / mL. In some embodiments, EC90 is at least 18 gg / mL. In some embodiments, EC90 is at least 20 gg / mL. In some embodiments, EC90 is at least 22 gg / mL. In some embodiments, EC90 is at least 25 gg / mL. In some embodiments, EC90 is at least 28 gg / mL. In some embodiments, EC90 is at least 30 gg / mL. In some embodiments, EC90 is at least 32 gg / mL. In some embodiments, EC90 is at least 35 gg / mL. In some embodiments, EC90 is at least 38 gg / mL. In some embodiments, EC90 is at least 40 gg / mL. In some embodiments, EC90 is at least 42 gg / mL. In some embodiments, EC90 is at least 45 gg / mL. In some embodiments, EC90 is at least 48 gg / mL. In some embodiments, EC90 is at least 50 gg / mL.

[0369] In some embodiments, EC90 is between 0.01 and 50 gg / mL. In some embodiments, EC90 is between 0.02 and 40 gg / mL. In some embodiments, EC90 is between 0.03 and 40 gg / mL. In some embodiments, EC90 is between 0.03 and 30 gg / mL. In some embodiments, EC90 is between 0.05 and 25 gg / mL. In some embodiments, EC90 is between 0.05 and 20 gg / mL. In some embodiments, EC90 is between 0.1 and 20 gg / mL. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, EC90 is between 0.1 and 15 pg / mL. In some embodiments, EC90 is between 0.1 and 10 pg / mL. In some embodiments, EC90 is between 0.3 and 10 pg / mL. In some embodiments, EC90 is between 0.4 and 8 pg / mL. In some embodiments, EC90 is between 0.5 and 5 pg / mL. In some embodiments, EC90 is between 0.1 and 5 pg / mL. In some embodiments, EC90 is between 0.1 and 3 pg / mL. In some embodiments, EC90 is between 0.3 and 3 pg / mL. In some embodiments, EC90 is between 0.5 and 1 pg / mL.

[0370] In some embodiments, EC90 is 0.01 pg / mL. In some embodiments, EC90 is 0.02 pg / mL. In some embodiments, EC90 is 0.03 pg / mL. In some embodiments, EC90 is 0.04 pg / mL. In some embodiments, EC90 is 0.05 pg / mL. In some embodiments, EC90 is 0.06 pg / mL. In some embodiments, EC90 is 0.07 pg / mL. In some embodiments, EC90 is 0.08 pg / mL. In some embodiments, EC90 is 0.09 pg / mL. In some embodiments, EC90 is 0.1 pg / mL. In some embodiments, EC90 is 0.2 pg / mL. In some embodiments, EC90 is 0.3 pg / mL. In some embodiments, EC90 is 0.4 pg / mL. In some embodiments, EC90 is 0.5 pg / mL. In some embodiments, EC90 is 0.6 pg / mL. In some embodiments, EC90 is 0.7 pg / mL. In some embodiments, EC90 is 0.8 pg / mL. In some embodiments, EC90 is 0.9 pg / mL. In some embodiments, EC90 is 1.0 pg / mL. In some embodiments, EC90 is 1.5 pg / mL. In some embodiments, EC90 is 2.0 pg / mL. In some embodiments, EC90 is 2.5 pg / mL. In some embodiments, EC90 is 3 pg / mL. In some embodiments, EC90 is 4 pg / mL. In some embodiments, EC90 is 5 pg / mL. In some embodiments, EC90 is 6 pg / mL. In some embodiments, EC90 is 7 pg / mL. In some embodiments, EC90 is 8 pg / mL. In some embodiments, EC90 is 9 pg / mL. In some embodiments, EC90 is 10 pg / mL. In some embodiments, EC90 is 12 pg / mL. In some embodiments, EC90 is 15 pg / mL. In some embodiments, EC90 is 18 pg / mL. In some embodiments, EC90 is 20 pg / mL. In some embodiments, EC90 is 22 pg / mL. In some embodiments, EC90 is 25 pg / mL. In some embodiments, EC90 is 28 pg / mL.. In some embodiments, EC90 is 30 pg / mL. In some embodiments, EC90 is 32 pg / mL. In some embodiments, EC90 is 35 pg / mL. In some embodiments, EC90 is 38 pg / mL. In some embodiments, EC90 is 40 pg / mL. In some embodiments, EC90 is 42 pg / mL. In some embodiments, EC90 is 45 pg / mL. In some embodiments, EC90 is 48 pg / mL. In some embodiments, EC90 is 50 pg / mL.

[0371] In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 3 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 5 days. In some embodiments, the therapeutically effective dose maintains mean serumATTORNEY DOCKET NO.: KPL-062WO1concentration greater than EC90 for at least 7 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 10 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 12 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 14 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 15 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 18 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 20 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 21 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 25 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 28 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 30 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 35 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 40 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 42 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 45 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 50 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 56 days. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 60 days.

[0372] In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 1 week. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 2 weeks. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 3 weeks. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 4 weeks. In some embodiments, the therapeutically effective dose maintains meanATTORNEY DOCKET NO.: KPL-062WO1serum concentration greater than EC90 for at least 5 weeks. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 6 weeks. In some embodiments, the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 7 weeks.Clinical Efficacy Metrics / EndpointsNumerical Rating Scale (NRS)

[0373] In some embodiments, the effectiveness of the treatment using an anti-ILlRl antibody is determined by assessment of pain in the subject, such as by determination of 0-10 point NRS score.

[0374] In some embodiments, the patient has at least 1 day with pericarditis pain measurement >10 on NRS prior to the treatment. In some embodiments, the patient has at least 1 day with pericarditis pain measurement >9 on NRS prior to the treatment. In some embodiments, the patient has at least 1 day with pericarditis pain measurement >8 on NRS prior to the treatment. In some embodiments, the patient has at least 1 day with pericarditis pain measurement >7 on NRS prior to the treatment. In some embodiments, the patient has at least 1 day with pericarditis pain measurement >6 on NRS prior to the treatment. In some embodiments, the patient has at least 1 day with pericarditis pain measurement >5 on NRS prior to the treatment. In some embodiments, the patient has at least 1 day with pericarditis pain measurement >4 on NRS prior to the treatment. In some embodiments, the patient has at least 1 day with pericarditis pain measurement >3 on NRS prior to the treatment. In some embodiments, the patient has at least 1 day with pericarditis pain measurement >2 on NRS prior to the treatment.

[0375] In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 8 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 7 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 6 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 5 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 4 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 3 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 2 or less. In some embodiments, the administration of the anti-ILlRl antibody results inATTORNEY DOCKET NO.: KPL-062WO1NRS score of 1 or less. In some embodiments, the administration of the anti-ILlRl antibody results in NRS score of 0.

[0376] In some embodiments, NRS score of 4 or less is achieved within 12 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 10 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 8 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 7 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 6 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 5 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 4 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 2 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, NRS score of 4 or less is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 7 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 2 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 4 or less is achieved within 1 day from the first administration of the anti-ILlRl antibody. In the foregoing embodiments, the NRS score is determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.

[0377] In some embodiments, NRS score of 2 or less is achieved within 12 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 10 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 8 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 7 weeks from the first administration of the anti-ILlRl antibody. InATTORNEY DOCKET NO.: KPL-062WO1some embodiments, NRS score of 2 or less is achieved within 6 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 5 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 4 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 2 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, NRS score of 2 or less is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 7 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 2 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 2 or less is achieved within 1 day from the first administration of the anti-ILlRl antibody. In the foregoing embodiments, the NRS score is determined while the patient continues to receive a therapeutic dose of anti-IL1R1 antibody at an administration interval and treatment period according to the invention.

[0378] In some embodiments, NRS score of 1 or less is achieved within 12 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 10 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 8 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 7 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 6 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 5 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 4 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 2 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, NRS score of 1 or less is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, NRS scoreATTORNEY DOCKET NO.: KPL-062WO1of 1 or less is achieved within 7 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 2 days from the first administration of the anti-ILlRl antibody. In some embodiments, NRS score of 1 or less is achieved within 1 day from the first administration of the anti-ILlRl antibody. In the foregoing embodiments, the NRS score is determined while the patient continues to receive a therapeutic dose of anti-IL1R1 antibody at an administration interval and treatment period according to the invention.

[0379] In some embodiments, the NRS score is maintained at 4 or less for longer than 1 week. In some embodiments, the NRS score is maintained at 4 or less for longer than 2 weeks. In some embodiments, the NRS score is maintained at 4 or less for longer than 3 weeks. In some embodiments, the NRS score is maintained at 4 or less for longer than 4 weeks. In some embodiments, the NRS score is maintained at 4 or less for longer than 5 weeks. In some embodiments, the NRS score is maintained at 4 or less for longer than 6 weeks. In some embodiments, the NRS score is maintained at 4 or less for longer than 8 weeks. In some embodiments, the NRS score is maintained at 4 or less for longer than 10 weeks. In some embodiments, the NRS score is maintained at 4 or less for longer than 12 weeks. In some embodiments, the NRS score is maintained at 4 or less for longer than 1 month. In some embodiments, the NRS score is maintained at 4 or less for longer than 2 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 3 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 4 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 5 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 6 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 7 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 8 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 9 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 10 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 11 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 12 months. In some embodiments, the NRS score is maintained at 4 or less for longer than 1 year. In some embodiments, the NRS score is maintained at 4 or less for the above-indicated periods while the patient receives anti-ILlRl antibody in absence of any concurrent therapy.ATTORNEY DOCKET NO.: KPL-062WO1In the foregoing embodiments, the NRS score is determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.

[0380] In some embodiments, the NRS score is maintained at 2 or less for longer than 1 week. In some embodiments, the NRS score is maintained at 2 or less for longer than 2 weeks. In some embodiments, the NRS score is maintained at 2 or less for longer than 3 weeks. In some embodiments, the NRS score is maintained at 2 or less for longer than 4 weeks. In some embodiments, the NRS score is maintained at 2 or less for longer than 5 weeks. In some embodiments, the NRS score is maintained at 2 or less for longer than 6 weeks. In some embodiments, the NRS score is maintained at 2 or less for longer than 8 weeks. In some embodiments, the NRS score is maintained at 2 or less for longer than 10 weeks. In some embodiments, the NRS score is maintained at 2 or less for longer than 12 weeks. In some embodiments, the NRS score is maintained at 2 or less for longer than 1 month. In some embodiments, the NRS score is maintained at 2 or less for longer than 2 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 3 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 4 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 5 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 6 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 7 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 8 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 9 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 10 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 11 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 12 months. In some embodiments, the NRS score is maintained at 2 or less for longer than 1 year. In some embodiments, the NRS score is maintained at 2 or less for the above-indicated periods while the patient receives anti-ILlRl antibody in absence of any concurrent therapy. In the foregoing embodiments, the NRS score is determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.

[0381] In some embodiments, the NRS score is maintained at 1 or less for longer than 1 week. In some embodiments, the NRS score is maintained at 1 or less for longer than 2 weeks. In some embodiments, the NRS score is maintained at 1 or less for longer than 3ATTORNEY DOCKET NO.: KPL-062WO1weeks. In some embodiments, the NRS score is maintained at 1 or less for longer than 4 weeks. In some embodiments, the NRS score is maintained at 1 or less for longer than 5 weeks. In some embodiments, the NRS score is maintained at 1 or less for longer than 6 weeks. In some embodiments, the NRS score is maintained at 1 or less for longer than 8 weeks. In some embodiments, the NRS score is maintained at 1 or less for longer than 10 weeks. In some embodiments, the NRS score is maintained at 1 or less for longer than 12 weeks. In some embodiments, the NRS score is maintained at 1 or less for longer than 1 month. In some embodiments, the NRS score is maintained at 1 or less for longer than 2 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 3 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 4 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 5 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 6 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 7 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 8 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 9 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 10 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 11 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 12 months. In some embodiments, the NRS score is maintained at 1 or less for longer than 1 year. In some embodiments, the NRS score is maintained at 1 or less for the above-indicated periods while the patient receives anti-ILlRl antibody in absence of any concurrent therapy. In the foregoing embodiments, the NRS score is determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.

[0382] In some embodiments, the patient remains pain free for the duration of the extension period of the study. In some embodiments, the NRS score is maintained at 2 or less for while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention. In some embodiments, the NRS score is maintained at 2 or less for while the patient continues to receive a therapeutic dose of anti-ILlRl antibody in absence of any concurrent therapy.ATTORNEY DOCKET NO.: KPL-062WO1C-Reactive Protein (CRP)

[0383] C-Reactive Protein (CRP) is a recognized indicator of inflammation in pericarditis and recurrent pericarditis. In some embodiments, the effectiveness of the treatment using an anti-ILlRl antibody is determined by measuring inflammation, such as measuring the CRP level in peripheral blood.

[0384] In some embodiments, the patient has C-reactive protein (CRP) value >0.2 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >0.5 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >0.8 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >1 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >2 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >3 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >4 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >5 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >6 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >8 mg / dL prior to the treatment. In some embodiments, the patient has C-reactive protein (CRP) value >10 mg / dL prior to the treatment.

[0385] In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 5.0 mg / dL. In some embodiments, administration of the anti-IL1R1 antibody results in a reduced CRP value of < 4.0 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 3.0 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 2.0 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 1.5 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 1.0 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.8 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.6 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.5 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.4 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.3 mg / dL. InATTORNEY DOCKET NO.: KPL-062WO1some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.2 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of < 0.1 mg / dL. In some embodiments, administration of the anti-ILlRl antibody results in a reduced CRP value of substantially 0.

[0386] In some embodiments, the CRP value < 0.5 mg / dL is achieved within 12 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 10 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 8 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 6 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 5 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 4 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 2 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 10 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 7 days from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 5 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 2 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 0.5 mg / dL is achieved within 1 day from the first administration of the anti-ILlRl antibody. In the foregoing embodiments, the CRP value is determined while the patient continues to receive a therapeutic dose of anti-IL1R1 antibody at an administration interval and treatment period according to the invention.

[0387] In some embodiments, the CRP value < 1.0 mg / dL is achieved within 12 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 10 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 8ATTORNEY DOCKET NO.: KPL-062WO1weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 6 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value <1.0 mg / dL is achieved within 5 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 4 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 2 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 10 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 7 days from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 5 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 2 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 1.0 mg / dL is achieved within 1 day from the first administration of the anti-ILlRl antibody. In the foregoing embodiments, the CRP value is determined while the patient continues to receive a therapeutic dose of anti-IL1R1 antibody at an administration interval and treatment period according to the invention.

[0388] In some embodiments, the CRP value < 2.0 mg / dL is achieved within 12 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 10 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 8 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 6 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value <2.0 mg / dL is achieved within 5 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 4 weeks from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 2 weeks from the first administration of the anti-ATTORNEY DOCKET NO.: KPL-062WO1IL1R1 antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 10 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 7 days from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 6 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 5 days from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 4 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 3 days from the first administration of the anti-ILlRl antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 2 days from the first administration of the anti-IL1R1 antibody. In some embodiments, the CRP value < 2.0 mg / dL is achieved within 1 day from the first administration of the anti-ILlRl antibody. In the foregoing embodiments, the CRP value is determined while the patient continues to receive a therapeutic dose of anti-IL1R1 antibody at an administration interval and treatment period according to the invention.

[0389] In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 2 weeks. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 3 weeks. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 4 weeks. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 5 weeks. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 6 weeks. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 8 weeks. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 10 weeks. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 12 weeks. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 1 month. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 2 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 3 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 4 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 5 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 6 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 7 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 8 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longerATTORNEY DOCKET NO.: KPL-062WO1than 9 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 10 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 11 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 12 months. In some embodiments, the CRP value is maintained at < 2.0 mg / dL for longer than 1 year. In some embodiments, the CRP level is maintained at < 2.0 mg / dL for the above-indicated periods while the patient receives anti-ILlRl antibody in absence of any concurrent therapy. In the foregoing embodiments, the CRP value is determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.

[0390] In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 2 weeks. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 3 weeks. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 4 weeks. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 5 weeks. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 6 weeks. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 8 weeks. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 10 weeks. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 12 weeks. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 1 month. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 2 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 3 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 4 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 5 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 6 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 7 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 8 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 9 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 10 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 11 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 12 months. In some embodiments, the CRP value is maintained at < 1.0 mg / dL for longer than 1 year. In some embodiments, the CRP level is maintained at < 1.0 mg / dL for the above-indicated periods while the patient receives anti-ILlRl antibody in absence of any concurrent therapy. In the foregoing embodiments, the CRP value isATTORNEY DOCKET NO.: KPL-062WO1determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.

[0391] In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 2 weeks. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 3 weeks. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 4 weeks. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 5 weeks. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 6 weeks. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 8 weeks. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 10 weeks. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 12 weeks. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 1 month. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 2 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 3 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 4 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 5 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 6 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 7 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 8 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 9 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 10 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 11 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 12 months. In some embodiments, the CRP value is maintained at < 0.5 mg / dL for longer than 1 year. In some embodiments, the CRP level is maintained at < 0.5 mg / dL for the above-indicated periods while the patient receives anti-ILlRl antibody in absence of any concurrent therapy. In the foregoing embodiments, the CRP value is determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.Recurrence Rate or Recurrence-Free Period

[0392] In some embodiments, the effectiveness of treatment with an anti-ILlRl antibody is determined by reduction of the risk of recurrence.ATTORNEY DOCKET NO.: KPL-062WO1

[0393] A recurrence-free period of survival typically means that the subject does not experience an episode or occurrence of one or more symptoms of pericarditis or a flare of inflammation during the period. A pericarditis recurrence or flare is usually indicated by any one or more of the following: an increase in the CRP level of >1 mg / dL in peripheral blood; or an increase in pain, determined in an NRS scale of >4; or occurrence of pericardial effusion (e.g., as determined by ECG or ECHO); a pericardial rub; or fever or any other symptomatic indication of the pericardial disease (e.g., as determined by PGIPS, PGA-PA, SF-36, EQ-5D-5L, or ISI).

[0394] In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 1% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 2% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 3% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 4% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 5% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 8% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 10% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 12% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 15% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 18% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 20% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 25% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 30% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 35% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 40% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 45% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of 50% or less. In some embodiments, the administration of the anti-ILlRl antibody results in a recurrence rate of substantially 0%.

[0395] In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 80 weeks. In some embodiments, administrationATTORNEY DOCKET NO.: KPL-062WO1of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 70 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 60 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 55 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 50 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 45 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 40 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 35 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 30 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 25 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 20 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 15 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 10 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 8 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 4 weeks. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 1 week. In the foregoing embodiments, the medium time-to-recurrence is determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.

[0396] In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 24 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 20 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 18 months. In some embodiments, administration of the anti-IL1R1 antibody results in a median time-to-recurrence of greater than 16 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 14 months. In some embodiments, administration of the anti-ATTORNEY DOCKET NO.: KPL-062WO1IL1R1 antibody results in a median time-to-recurrence of greater than 12 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 10 months. In some embodiments, administration of the anti-IL1R1 antibody results in a median time-to-recurrence of greater than 8 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 6 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 5 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 4 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 3 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 2 months. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 1 month.

[0397] In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 5 years. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 4 years. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 3 years. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 2 years. In some embodiments, administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 1 year. In the foregoing embodiments, the medium time-to-recurrence is determined while the patient continues to receive a therapeutic dose of anti-IL1R1 antibody at an administration interval and treatment period according to the invention.

[0398] In some embodiments, the median time-to-recurrence could not be determined due to a limited number of recurrence events. In some embodiments, the limited number of recurrence events is less than 3. In some embodiments, the limited number of recurrence events is less than 2. In some embodiments, the limited number of recurrence events is less than 1. In some embodiments, the limited number of recurrence events is substantially 0.

[0399] In some embodiments, the effectiveness of treatment with an anti-ILlRl antibody is determined by a hazard ratio for recurrence when comparing a treatment group to a placebo group. A low hazard ratio indicates a significantly reduced risk of pericarditis recurrence with the treatment group; meaning the treatment (with an anti-ILlRl) significantly lowers the chance of a pericarditis flare-up compared to placebo or control.ATTORNEY DOCKET NO.: KPL-062WO1

[0400] In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.5. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.4. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.3. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.2. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.1. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.05. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.04. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.03. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.02. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.01. In some embodiments, the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.005.

[0401] In some embodiments, the effectiveness of treatment with an anti-ILlRl antibody is determined by a recurrence-free period during or subsequent to the treatment. In some embodiments, a subject continues to receive a therapeutic dose of anti-ILlRl antibody at an administrative interval and treatment period in accordance with the invention during the recurrence-free period. In some embodiments, a subject may be gradually weaned off an anti-ILlRl antibody treatment during the recurrence-free period.

[0402] In some embodiments, the effectiveness of treatment with an anti-ILlRl antibody is determined by the time period of recurrence-free survival (for examples, Days to flare). In some embodiments, the recurrence-free survival period is at least 30 days, 40 days, 50 days, 60 days, 70 days, 80 days, or 90 days from the first administration of the anti-ILlRl antibody. In some embodiments, the recurrence-free survival period is at least 91 days, 92 days, 93 days, 94 days, 95 days, 96 days, 97 days, 98 days, 99 days, 100 days from the first administration of the anti-ILlRl antibody. In some embodiments, the recurrence-free survival period is at least 105 days, or at least 110 days, or at least 115 days, or at least 120 days, or at least 130 days, or at least 140 days, or at least 150 days. In some embodiments, the recurrence-free survival period is at least 200 days or more, while receiving anti-ILlRlATTORNEY DOCKET NO.: KPL-062WO1antibody at an administration interval (e.g., a weekly dose) and treatment period according to the invention.

[0403] In some embodiments, the recurrence-free survival period is at least 30 days, 40 days, 50 days, 60 days, 70 days, or at least 80 days from the withdrawal of a pain medicine, or NSAID, while receiving a therapeutically effective dose of the anti-ILlRl antibody according to the invention. In some embodiments, the recurrence-free survival period from the withdrawal of NSAID is at least 81 days, 82 days, 83 days, 84 days, 85 days, 86 days, 87 days, 88 days, 89 days, 90 days, 91 days, 92 days, 93 days, 94 days, 95 days, 96 days, 97 days, 98 days, 99 days, 100 days, 110 days, 120 days, 130 days, 140 days, 150 days, 160 days, 170 days, 180 days, 190 days or 200 days or more, while receiving anti-ILlRl antibody at an administration interval (e.g., a weekly dose) and treatment period according to the invention.

[0404] In some embodiments, the recurrence-free survival period is at least 50 days from the withdrawal of a corticosteroid, while receiving a therapeutically effective dose of the anti-ILlRl antibody according to the invention. In some embodiments the flare-free survival period from the withdrawal of NSAID is at least 55 days, 60 days, 65 days, 70 days, 75 days, 80 days, 85 days, 90 days, 95 days, 100 days, 110 days, 120 days, 130 days, 140 days, 150 days, 160 days, 170 days, 180 days, 190 days or 200 days or more, while receiving anti-ILlRl antibody at an administration interval (e.g., a weekly dose) and treatment period according to the invention.Median Time to Monotherapy

[0405] In some embodiments, administration of an anti-ILlRl antibody in successful taper of steroids and other concurrent therapies, while the subject continues to receive an anti-ILlRl antibody protein at an administration interval and treatment period according to the invention. In some embodiments the median time to anti-ILlRl antibody monotherapy refers to successful taper of background medications, concurrent therapies or standard of care.

[0406] In some embodiments, the median time to anti-ILlRl antibody monotherapy is 1 week or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 2 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 3 weeks or less. In some embodiments, the median time to anti-IL1R1 antibody monotherapy is 4 weeks or less. In some embodiments, the median time toATTORNEY DOCKET NO.: KPL-062WO1anti-ILlRl antibody monotherapy is 6 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 8 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 10 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 12 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 14 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 16 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 18 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 20 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 22 weeks or less. In some embodiments, the median time to anti-ILlRl antibody monotherapy is 24 weeks or less.

[0407] In some embodiments, administration of an anti-ILlRl antibody results in tapering off of background medications, concurrent therapies, or standard of care treatment (e.g., NSAID, colchicine, corticosteroids in any combination) while receiving an anti-ILlRl antibody monotherapy.

[0408] In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 1 week from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 2 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 3 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 4 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-IL1R1 antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 5 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 6 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 7 weeks from the first administration ofATTORNEY DOCKET NO.: KPL-062WO1the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 8 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 10 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-IL1R1 antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 12 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 14 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 16 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 18 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 20 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-IL1R1 antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 22 weeks from the first administration of the anti-ILlRl antibody. In some embodiments, administration of an anti-ILlRl antibody results in cessation of background medications, concurrent therapies, or standard of care treatment at 24 weeks from the first administration of the anti-ILlRl antibody. In the foregoing embodiments, the time to cessation of background medications, concurrent therapies, or standard of care treatment is determined while the patient continues to receive a therapeutic dose of anti-ILlRl antibody at an administration interval and treatment period according to the invention.

[0409] In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 2 weeks. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 4 weeks. In some embodiments, administration ofATTORNEY DOCKET NO.: KPL-062WO1an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 6 weeks. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 8 weeks. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 10 weeks. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 12 weeks. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 1 month. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 2 months. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 4 months. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 6 months. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 8 months. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 10 months. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 12 months. In some embodiments, administration of an anti-ILlRl antibody results in a successful cessation of background medications, concurrent therapies, or standard of care treatment for longer than 1 year. In the foregoing embodiments, the duration of successful cessation of background medications, concurrent therapies, or standard of care treatment is determined while the patient continues to receive a therapeutic dose of anti-IL1R1 antibody at an administration interval and treatment period according to the invention.

[0410] In some embodiments, the patient continues to receive an anti-ILlRl antibody at a therapeutic dose and administration interval in accordance to the invention. In someATTORNEY DOCKET NO.: KPL-062WO1embodiments, the subject continues to receive an anti-ILlRl antibody without any concurrent therapy.Short Form Health Survey (SF-36)

[0411] In some embodiments, the effectiveness of treatment with an anti-ILlRl antibody is determined by SF-36.

[0412] The Short Form Health Survey (SF-36) is a widely used tool to measure a person's overall health status and quality of life. It consists of 36 questions that assess eight different dimensions of health, which can help provide a comprehensive view of an individual's physical and mental well-being. The SF-36 scores are weighted sums of the questions in each dimension, and they from 0 - 100. The eight dimensions are:• Vitality• Physical functioning• Bodily pain• General health perceptions• Physical role functioning• Emotional role functioning• Social role functioning• Mental Health

[0413] In some embodiments, the administration of the anti-ILlRl antibody results in an improvement as compared to a control, as assessed by SF-36. In some embodiments, an improvement in the SF-36 is indicated by a higher score.

[0414] In some embodiments, the administration of the anti-ILlRl antibody results in an improvement in vitality as compared to a control. In some embodiments, the administration of the anti-ILlRl antibody results in an improvement in physical functioning as compared to a control. In some embodiments, the administration of the anti-ILlRl antibody results in an improvement in bodily pain as compared to a control. In some embodiments, the administration of the anti-ILlRl antibody results in an improvement in general health perceptions as compared to a control. In some embodiments, the administration of the anti-ILlRl antibody results in an improvement in physical roleATTORNEY DOCKET NO.: KPL-062WO1functioning as compared to a control. In some embodiments, the administration of the anti-IL1R1 antibody results in an improvement in emotional role functioning as compared to a control. In some embodiments, the administration of the anti-ILlRl antibody results in an improvement in social role functioning as compared to a control. In some embodiments, the administration of the anti-ILlRl antibody results in an improvement in mental health as compared to a control.Adverse Events

[0415] Adverse effects related to the treatment of pericarditis can include injectionsite reaction, upper respiratory tract infection, headache, nausea, vomiting, diarrhea, sinusitis, arthralgia, flu-like symptoms, abdominal pain, pyrexia, herpes, transaminase elevation, ischemic optic neuropathy and nasopharyngitis.

[0416] In some embodiments, administration of an anti-ILlRl antibody does not result in an adverse event in the patient. In some embodiments, the administration of the anti-IL1R1 antibody does not result in a dose-limiting adverse events (AE). In some embodiments, the administration of the anti-ILlRl antibody does not result in a dose-related adverse events (AE). In some embodiments, the administration of the anti-ILlRl antibody does not result in a dose-limiting or dose-related adverse events (AE). In some embodiments, administration of an anti-ILlRl antibody does not result in serious adverse events in the patient. In some embodiments, administration of an anti-ILlRl antibody does not result in one or more of injection-site reaction, worsening of rheumatoid arthritis, upper respiratory tract infection, headache, nausea, vomiting, diarrhea, sinusitis, ischemic optic neuropathy, arthralgia, flu-like symptoms, abdominal pain, pyrexia, herpes, transaminase elevation and nasopharyngitis.

[0417] In some embodiments, administration of an anti-ILlRl antibody does not result in an injection-site reaction. In some embodiments, administration of an anti-ILlRl antibody does not result in upper respiratory tract infection. In some embodiments, administration of an anti-ILlRl antibody does not result in headache. In some embodiments, administration of an anti-ILlRl antibody does not result in nausea. In some embodiments, administration of an anti-ILlRl antibody does not result in vomiting. In some embodiments, administration of an anti-ILlRl antibody does not result in diarrhea. In some embodiments, administration of an anti-ILlRl antibody does not result in sinusitis. In some embodiments, administration of an anti-ILlRl antibody does not result in arthralgia. In some embodiments,ATTORNEY DOCKET NO.: KPL-062WO1administration of an anti-ILlRl antibody does not result in flu-like symptoms. In some embodiments, administration of an anti-ILlRl antibody does not result in abdominal pain. In some embodiments, administration of an anti-ILlRl antibody does not result in pyrexia. In some embodiments, administration of an anti-ILlRl antibody does not result in herpes. In some embodiments, administration of an anti-ILlRl antibody does not result in transaminase elevation. In some embodiments, administration of an anti-ILlRl antibody does not result in X. In some embodiments, administration of an anti-ILlRl antibody does not result in nasopharyngitis. In some embodiments, administration of an anti-ILlRl antibody does not result in ischemic optic neuropathy.

[0418] In some embodiments, the various safety assessments include pharmacokinetic and pharmacodynamic monitoring, including but not limited to: physical examination, measurement of vital signs, monitoring adverse event (AE), monitoring chest X-ray and screening for signs of tuberculosis.Other Measurement

[0419] In some embodiments, administration of an anti-ILlRl antibody results in improved cardiac function, such as decreased or ameliorated pericardiac effusion, compared to a control. Pericardial effusion (also known as “fluid around the heart”) is an abnormal accumulation of fluid in the pericardial cavity that is indicative of inflammation, which leads to an increased intrapericardial pressure and can negatively affect heart function. Cardiac health parameters, particularly pericardiac effusion, may be evaluated by echocardiography (ECHO), cardiac magnetic resonance imaging (MRI), and / or CT scanning. In some embodiments, administration of an anti-ILlRl antibody results in a decrease, absence or amelioration of pericardiac effusion.

[0420] A control is a reference cardiac parameter such as a reference pericardiac effusion level measured in a patient with comparable disease status but without treatment. For example, a control may be a baseline cardiac function such as a baseline pericardiac effusion measured in the patient being treated prior to the treatment. A control may also be a reference cardiac parameter such as a reference pericardiac effusion level measured in a patient with comparable disease status but treated with a placebo. In some embodiments, a control may be a reference value or graph indicative of cardiac parameters such as pericardiac effusion in a patient with comparable disease status without treatment based on historical data. In some embodiments, a control may be a reference value or graph indicative of aATTORNEY DOCKET NO.: KPL-062WO1cardiac parameter such as pericardiac effusion in a subject with comparable disease status who receives a standard of care therapy, in absence of an anti-ILlRl antibody administration.

[0421] In some embodiments, administration of an anti-ILlRl antibody results in improvement of cardiac parameters as indicated by ECG measurements. A reduction in the ST elevation and / or reduction in the depression after administration of the in an anti-ILlRl antibody is considered an improvement in the cardiac parameter.

[0422] In some embodiments, administration of an anti-ILlRl antibody results in improvement of cardiac effusion as determined by echocardiography (ECHO).

[0423] In some embodiments, administration of an anti-ILlRl antibody results in improvement of cardiac parameters as determined by CT scanning.

[0424] In some embodiments, administration of an anti-ILlRl antibody results in improvement of cardiac parameters as determined by cardiac magnetic resonance imaging (MRI). In some embodiments the cardiac parameters as determined by cardiac magnetic resonance imaging include pericardial delayed hyperenhancement, pericardial effusion or pericardial effusion size, and combinations thereof.

[0425] In some embodiments, administration of an anti-ILlRl antibody results in improvement of QoL scores. Typically, QoL scores comprise one or more assessments selected from: Patient Global Impression of Pericarditis Severity (PGIPS); Physician Global Assessment of Pericarditis Activity (PGA-PA); 36-Item Short Form Health Survey (SF-36); 5-Level EuroQoL-5D (EQ-5D-5L) and Insomnia severity Index (ISI).

[0426] In some embodiments, the effectiveness of treatment using an anti-ILlRl antibody is determined by Patient Global Impression of Pericarditis Severity (PGIPS), and / or Physician Global Assessment of Pericarditis Activity (PGA-PA). The PGIPS is a single-item patient reported outcome (PRO) measure that assesses the subject’s impression of overall severity of pericarditis symptoms at the time the questionnaire is administered, using a 7-point rating scale ranging from absent (no recurrent pericarditis symptoms) to very severe (recurrent pericarditis symptoms cannot be ignored). The PGA-PA is a single-item clinician-reported outcome measure that investigators use to rate their impression of the patient’s overall pericarditis disease activity at the time the assessment is completed, using a 7-point rating scale ranging from absent to very severe. In some embodiments, administration of an anti-ILlRl antibody results in an improved PGIPS and / or PGA-PA compared to a control.ATTORNEY DOCKET NO.: KPL-062WO1

[0427] In some embodiments, at least 50% of the subjects undergoing treatment with an anti-ILlRl antibody report an absence or minimal pericarditis symptoms as determined by PGIPS. In some embodiments, at least 75% of the subjects undergoing treatment with an anti-ILlRl antibody report an absence or minimal pericarditis symptoms as determined by PGIPS. In some embodiments, at least 80% of the subjects undergoing treatment with an anti-ILlRl antibody report an absence or minimal pericarditis symptoms as determined by PGIPS. In some embodiments, at least 90% of the subjects undergoing treatment with an anti-ILlRl antibody report an absence or minimal pericarditis symptoms as determined by PGIPS. In some embodiments, at least 95% of the subjects undergoing treatment with an anti-ILlRl antibody report an absence or minimal pericarditis symptoms as determined by PGIPS. In some embodiments, 97%, 98%, 99% or 100% of the subjects undergoing treatment with an anti-ILlRl antibody report an absence or minimal pericarditis symptoms as determined by PGIPS.

[0428] In some embodiments, at least 50% of the subjects receiving an anti-ILlRl antibody show an absence or minimal pericarditis symptoms as determined by PGA-PA. In some embodiments, at least 75% of the subjects undergoing treatment with an anti-ILlRl antibody show an absence or minimal pericarditis symptoms as determined by PGA-PA. In some embodiments, at least 80% of the subjects undergoing treatment with an anti-ILlRl antibody show an absence or minimal pericarditis symptoms as determined by PGA-PA. In some embodiments, at least 90% of the subjects undergoing treatment with an anti-ILlRl antibody show an absence or minimal pericarditis symptoms as determined by PGA-PA. In some embodiments, at least 95% of the subjects undergoing treatment with an anti-ILlRl antibody show an absence or minimal pericarditis symptoms as determined by PGA-PA. In some embodiments, 96%, 97%, 98%, 99% or 100% of the subjects undergoing treatment with an anti-ILlRl antibody show an absence or minimal pericarditis symptoms as determined by PGA-PA.

[0429] In some embodiments, the effectiveness of the treatment using an anti-ILlRl antibody is determined by a 5-Level EuroQoL-5D (EQ-5D-5L) (additional information in: www.euroqol.org). The EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in assessing a wide range of health conditions and treatments. The EQ-5D-5L includes a descriptive system and the EQ VAS. The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain / discomfort and anxiety / depression. The rating scale records the subject’sATTORNEY DOCKET NO.: KPL-062WO1self-rated health on a vertical Visual Analog Scale (VAS). The scores on these 5 dimensions can be presented as a health profile or can be converted to a single summary index number (utility) reflecting preferability compared to other health profiles(euroqol . org / eq-5 d-instruments).

[0430] In some embodiments, the EQ-5D-5L is collected in subjects >18 years or older.

[0431] In some embodiments, administration of an anti-ILlRl antibody results in an improved EQ-5D-5L. In some embodiments, at least 50% of the subjects receiving an anti-IL1R1 antibody show a clinically relevant improved EQ-5D-5L score. In some embodiments, at least 75% of the subjects undergoing treatment with an anti-ILlRl antibody show a clinically relevant improved EQ-5D-5L score. In some embodiments, at least 80% of the subjects undergoing treatment with an anti-ILlRl antibody show a clinically relevant improved EQ-5D-5L score. In some embodiments, at least 90% of the subjects undergoing treatment with an anti-ILlRl antibody show a clinically relevant improved EQ-5D-5L score. In some embodiments, at least 95% of the subjects undergoing treatment with an anti-ILlRl antibody show a clinically relevant improved EQ-5D-5L score. In some embodiments, 96%, 97%, 98%, 99% or 100% of the subjects undergoing treatment with an anti-ILlRl antibody a clinically relevant improved EQ-5D-5L score.

[0432] In some embodiments, a control for a QoL measurements indicated in the preceding sections, is a baseline QoL scores determined in the subject prior to the treatment. In some embodiments, a control is reference QoL scores in a subject with comparable disease status but treated with a placebo. In some embodiments, a control is a reference indicative of QoL scores in a subject with comparable disease status without treatment. In some embodiments, a control is indicative of the QoL when a subject having the disease receives a standard of care therapy, in absence of IL an anti-ILlRl antibody administration.

[0433] In some embodiments, administration of an anti-ILlRl antibody results in an improved Insomnia Severity Index (ISI). The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The usual recall period is the “last 2 weeks” and the dimensions evaluated are severity o...

Claims

ATTORNEY DOCKET NO.: KPL-062WO1CLAIMS1. A method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control.

2. The method of claim 1, wherein the one or more symptoms of recurrent pericarditis are assessed by a Numerical Rating Scale (NRS) for assessment of pericarditis pain, an echocardiogram (ECG), cardiac magnetic resonance imaging (MRI), or by Quality of Life Questionnaire.

3. The method of claim 1, wherein the one or more symptoms of recurrent pericarditis comprise fever, pericardial rub, an elevated level of C-reactive protein (CRP), chest pain, shortness of breath, heart palpitations, and swelling.

4. A method of treating recurrent pericarditis comprising administering subcutaneously to a patient an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 300 mg, wherein the anti-ILlRl antibody is administered once every two weeks or once every four weeks.

5. A method of treating recurrent pericarditis comprising administering subcutaneously to a patient an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of 100 mg once every two weeks or once every four weeks.

6. The method of any one of claims 1-5, wherein the patient has a recurrence after a symptom-free interval.

7. A method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting signs and symptoms of pericarditis despite initial improvement.

8. The method of claim 7, wherein the anti-ILlRl is administered at a therapeutically effective dose sufficient to improve, stabilize, prevent or reduce one or more symptoms of recurrent pericarditis relative to a control.ATTORNEY DOCKET NO.: KPL-062WO19. The method of any one of claims 7-8, wherein the persisting signs and symptoms of pericarditis comprise one or more of:a. pericarditis pain;b. an elevated CRP level;c. pericardial rub;d. widespread ST segment elevation or PR segment depression according to ECG findings;e. pericardial effusion;f. pericardial inflammation;g. edema;h. evidence of pericarditis by late gadolinium enhancement;i. evidence of constriction; andj. fever, chest pain, shortness of breath, and / or heart palpitations.

10. The method of any one of claims 7-9, wherein the persisting signs and symptoms do not include the combination of pericarditis pain NRS > 4 and CRP > 1.0 mg / dL.

11. The method of any one of claims 7-10, wherein the initial improvement is an improvement of one or more signs or symptoms associated with an episode of acute pericarditis.

12. The method of claim 11, wherein the initial improvement comprises a reduction or improvement in one or more of:a. pericarditis pain;b. CRP level;c. pericardial rub;d. widespread ST segment elevation or PR segment depression according to ECG findings;e. pericardial effusion;f. pericardial inflammation;g. edema;h. evidence of pericarditis by late gadolinium enhancement;i. evidence of constriction; andj. fever, chest pain, shortness of breath, and / or heart palpitations.ATTORNEY DOCKET NO.: KPL-062WO113. The method of any one of claims 9-12, wherein the pericarditis pain is measured by Numerical Rating Scale (NRS).

14. The method of claim 13, wherein the initial improvement is indicated by a NRS of < 4.

15. The method of any one of claims 9-14, wherein pericardial inflammation is assessed by cardiac MRI.

16. The method of any one of claims 9-15, wherein edema is assessed by T2 short-tau inversion recovery (STIR) imaging.

17. The method of any one of claims 9-16, wherein the evidence of pericarditis by late gadolinium enhancement is assessed by cardiac MRI.

18. The method of claim 12, wherein the initial improvement is indicated by CRP < 1.0 mg / dL.

19. The method of any one of claims 7-18, wherein the period of persisting signs and symptoms of pericarditis is less than 4 weeks.

20. The method of any one of claims 7-18, wherein the period of persisting signs and symptoms of pericarditis is 4-6 weeks.

21. The method of any one of claims 7-18, wherein the period of persisting signs and symptoms of pericarditis is greater than 6 weeks.

22. The method of any one of the preceding claims, wherein the control is the patient prior to the administration of the anti-ILlRl antibody, a comparable recipient without the administration of the anti-ILlRl antibody, a comparable recipient administered a placebo, or historical data.

23. A method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a dose of greater than 10 mg.ATTORNEY DOCKET NO.: KPL-062WO124. The method of any one of the preceding claims, wherein the anti-ILlRl antibody is administered no more frequently than once every week.

25. A method of treating recurrent pericarditis comprising administering to a patient, an anti-interleukin-1 receptor type-1 (IL1R1) antibody at a therapeutically effective dose no more frequently than once every week.

26. The method of any one of the preceding claims, wherein the patient has received a previous treatment.

27. The method of claim 26, wherein the previous treatment is an IL 1 antagonist, an IL1R1 antagonist, an IL1 trap, NSAIDs, colchicine, corticosteroid, or a combination thereof.

28. The method of claim 26 or 27, wherein the previous treatment is rilonacept or anakinra.

29. The method of any one of the preceding claims, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 1, a HCDR2 of SEQ ID NO: 2, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

30. The method of any one of the preceding claims, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 12, a HCDR2 of SEQ ID NO: 13, a HCDR3 of SEQ ID NO: 3, a LCDR1 of SEQ ID NO: 4, a LCDR2 of SEQ ID NO: 5, and a LCDR3 of SEQ ID NO: 6.

31. The method of any one of the preceding claims, wherein the anti-ILlRl antibody comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 15, a HCDR3 of SEQ ID NO: 19, a LCDR1 of SEQ ID NO: 16, a LCDR2 of SEQ ID NO: 17, and a LCDR3 of SEQ ID NO: 6.

32. The method of any one of the preceding claims, wherein the anti-ILlRl antibody comprises a HCDR1, a HCDR2, and a HCDR3 in the variable heavy chain (VH) of SEQ ID NO: 7 and a LCDR1, a LCDR2, and a LCDR3 of the variable light chain (VL) of SEQ ID NO: 8.ATTORNEY DOCKET NO.: KPL-062WO133. The method of any one of claims 1-3 or 6-32, wherein the therapeutically effective dose produces a median Cmax of at least 0.5 pg / mL.

34. The method of claim 33, wherein the therapeutically effective dose produces a median Cmax of at least 1 pg / mL, at least 5 pg / mL, at least 10 pg / mL, at least 30 pg / mL.

35. The method of any one of claims 1-3 or 6-34, wherein the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 7 days.

36. The method of claim 35, wherein the therapeutically effective dose maintains mean serum concentration greater than EC90 for at least 10 days, at least 15 days, at least 20 days, at least 25 days, or at least 30 days.

37. The method of claim 36, wherein the therapeutically effective dose maintains mean serum concentration greater than EC90 for 28 days.

38. The method of any one of claims 1-3 or 6-37, wherein the anti-ILlRl antibody is administered at a dose of greater than 10 mg.

39. The method of claim 38, wherein the anti-ILlRl antibody is administered at a dose of at least 30 mg.

40. The method of claim 39, wherein the anti-ILlRl antibody is administered at a dose of between 30 mg and 500 mg.

41. The method of claim 40, wherein the anti-ILlRl antibody is administered at a dose of 100 mg.

42. The method of claim 40, wherein the anti-ILlRl antibody is administered at a dose of 300 mg.

43. The method of any one of the preceding claims, wherein the anti-ILlRl antibody is administered no more frequently than once every two weeks.ATTORNEY DOCKET NO.: KPL-062WO144. The method of claim 43, wherein the anti-ILlRl antibody is administered once every two weeks.

45. The method of claim 43, wherein the anti-ILlRl antibody is administered once every three weeks.

46. The method of claim 43, wherein the anti-ILlRl antibody is administered once every four weeks.

47. The method of claim 41, wherein the anti-ILlRl antibody is administered at a dose of 100 mg once every two weeks.

48. The method of claim 41, wherein the anti-ILlRl antibody is administered at a dose of 100 mg once every four weeks.

49. The method of claim 42, wherein the anti-ILlRl antibody is administered at a dose of 300 mg once every two weeks.

50. The method of claim 42, wherein the anti-ILlRl antibody is administered at a dose of 300 mg once every four weeks.

51. The method of any one of claims 1-4 or 6-50, wherein the anti-ILlRl antibody is administered intravenously or subcutaneously.

52. The method of claim 51, wherein the anti-ILlRl antibody is administered subcutaneously.

53. The method of any one of the preceding claims, wherein the patient has at least 1 day with pericarditis pain measurement >4 on NRS prior to the treatment.

54. The method of any one of the preceding claims, wherein the patient has C-reactive protein (CRP) value >0.5 mg / dL prior to the treatment.ATTORNEY DOCKET NO.: KPL-062WO155. The method of claim 54, wherein the patient has CRP value > 1.0 mg / dL prior to the treatment.

56. The method of any one of the preceding claims, wherein the patient is an adult.

57. The method of any one of the preceding claims, wherein the patient is > 18 and < 81 years of age.

58. The method of any one of the preceding claims, wherein the patient has at least a second pericarditis recurrence prior to the treatment.

59. The method of any one of claims 1-6 or 8-58, wherein the patient has at least one episode of acute pericarditis with pericarditis pain NRS > 4 and CRP > 1.0 mg / dL followed by a period of persisting pericarditis signs and symptoms despite initial improvement.

60. The method of any one of the preceding claims, wherein the patient is receiving concomitant NS AIDs, colchicine, corticosteroid, or combinations thereof.

61. The method of claim 60, wherein the NSAID is ibuprofen.

62. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody results in a statistically-significant drop on a Numerical Rating Scale (NRS) for assessment of pericarditis pain.

63. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody results in a recurrence rate of 10% or less.

64. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody results in a median time-to-recurrence of greater than 50 weeks.

65. The method of claim 64, wherein the median time-to-recurrence could not be determined due to a limited number of recurrence events.

66. The method of claim 65, wherein the limited number of recurrence events is less than 3, less than 1, or substantially 0.ATTORNEY DOCKET NO.: KPL-062WO167. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody reduces a risk of recurrence by at least 90%.

68. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody as compared to the control results in a hazard ratio of less than 0.1.

69. The method of any one of claims 62-68, wherein the administration of the anti-ILlRl antibody results in NRS score of 2 or less.

70. The method of claim 69, wherein the NRS score of 2 or less is achieved within 3 weeks, within 2 weeks or within 1 week from the first administration of the anti-ILlRl antibody.

71. The method of claim 69 or 70, wherein the NRS score is maintained at 2 or less for longer than 1 week, longer than 2 weeks, longer than 3 weeks, longer than 1 month, longer than 2 months, longer than 3 months, longer than 4 months, longer than 5 months, longer than 6 months, longer than 8 months, or longer than 1 year.

72. The method of any one of claims 62-71, wherein the administration of the anti-ILlRl antibody results in NRS score of 1 or less.

73. The method of claim 72, wherein the NRS score of 1 or less is achieved within 3 weeks, within 2 weeks or within 1 week from the first administration of the anti-ILlRl antibody.

74. The method of claim 72 or 73, wherein the NRS score is maintained at 1 or less for longer than 1 week, longer than 2 weeks, longer than 3 weeks, longer than 1 month, longer than 2 months, longer than 3 months, longer than 4 months, longer than 5 months, longer than 6 months, longer than 8 months, or longer than 1 year.

75. The method of any one of the preceding claims, wherein administration of the anti-IL1R1 antibody results in a reduced CRP value of < 2.0 mg / dL, < 1.5 mg / dL, < 1.0 mg / dL, < 0.8 mg / dL, < 0.6 mg / dL, < 0.5 mg / dL, < 0.4 mg / dL, < 0.3 mg / dL, < 0.2 mg / dL, or < 0.1 mg / dL.ATTORNEY DOCKET NO.: KPL-062WO176. The method of claim 75, wherein the administration of the anti-ILlRl antibody results in CRP value < 0.5 mg / dL.

77. The method of claim 76, wherein the CRP value < 0.5 mg / dL is achieved within 3 weeks, within 2 weeks or within 1 week from the first administration of the anti-ILlRl antibody.

78. The method of any one of claims 75-77, wherein the CRP value < 0.5 mg / dL is maintained for longer than 1 week, longer than 2 weeks, longer than 3 weeks, longer than 1 month, longer than 2 months, longer than 3 months, longer than 4 months, longer than 5 months, longer than 6 months, longer than 8 months, or longer than 1 year.

79. The method of any one of the preceding claims, wherein the median time to a treatment response is 5 days or less from the first administration of the anti-ILlRl antibody.

80. The method of any one of the preceding claims, wherein the % of subjects achieving a treatment response is 90%.

81. The method of claim 79 or 80, wherein the treatment response is NRS score of 2 or less and the CRP value < 0.5 mg / dL.

82. The method of any one of the preceding claims, wherein the median time to anti-IL1R1 antibody monotherapy is 8 weeks or less.

83. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody results in decreased pericardiac effusion compared to a control.

84. The method of claim 83, wherein the control is a baseline pericardiac effusion level measured in the patient prior to the treatment, or a pericardiac effusion level measured in a patient with comparable disease status but treated with a placebo, or a reference value indicative of pericardiac effusion in a subject with comparable disease status without treatment.

85. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody results in absence of pericardiac effusion.ATTORNEY DOCKET NO.: KPL-062WO186. The method of any one of claims 83-85, wherein the decreased or absence of pericardiac effusion is maintained for more than 2 weeks, more than 4 weeks, more than 1 month, more than 2 months, more than 3 months more than 4 months, more than 5 months, more than 6 months, more than 8 months, or more than 1 year.

87. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody results in a withdrawal or weaning of a concurrent therapy or standard of care treatment in the patient.

88. The method of claim 87, wherein the concurrent therapy or standard of care treatment is NSAIDs, colchicine, corticosteroid or combinations thereof.

89. The method of any one of the preceding claims, wherein the administration of the anti-ILlRl antibody does not result in an adverse event,wherein the adverse event is injection-site reaction, upper respiratory tract infection, headache, nausea, vomiting, diarrhea, sinusitis, arthralgia, flu-like symptoms, abdominal pain, pyrexia, herpes, transaminase elevation, nasopharyngitis, ischemic optic neuropathy and combinations thereof.

90. The method of any one of the preceding claims, wherein the anti-ILlRl comprises a variable heavy chain (VH) that is at least 90% identical to SEQ ID NO: 7.

91. The method of claim 90, wherein the VH comprises an amino acid sequence of SEQ ID NO: 7.

92. The method of any one of the preceding claims, wherein the anti-ILlRl comprises a variable light chain (VL) that is at least 90% identical to SEQ ID NO: 8.

93. The method of claim 92, wherein the VL comprises an amino acid sequence of SEQ ID NO: 8.

94. The method of any one of the preceding claims, wherein the anti-ILlRl comprises a VH of SEQ ID NO: 7 and a VL of SEQ ID NO: 8.ATTORNEY DOCKET NO.: KPL-062WO195. The method of any one of the preceding claims, wherein the anti-ILlRl antibody comprises an Fc region derived from IgGl, IgG2, IgG3, or IgG4.

96. The method of claim 95, wherein the Fc region is derived from IgG2.

97. The method of claim 96, wherein the Fc region comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 9.

98. The method of claim 96, wherein the Fc region comprises an amino acid sequence of SEQ ID NO: 9.

99. The method of claim 98, wherein the anti-ILlRl antibody comprises a heavy chain of SEQ ID NO: 10 and a light chain of SEQ ID NO: 11.

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