# US 12,216,128 B2 · Methods for guiding therapy decisions in seizure disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,216,128 B2 - Document ID: US12216128B2 - Status: Granted - Kind: B2 - Application number: 16/976,592 - Filed: 2019-04-12 - Published: 2021-05-13 - Granted: 2025-02-04 - Earliest claimed: 2018-04-12 - Assignees: Mayo Foundation for Medical Education and Research - Applicants: Mayo Foundation for Medical Education and Research - Inventors: Charles L. Howe; Benjamin D. Clarkson; Shailaja Kunda; Reghann G. LaFrance-Corey; Eric T. Payne - Web page: https://patentgrep.com/patent/US12216128B2 ## CPC - G01N 33/6869: {Interleukin} - A61K 38/2006: {IL-1} - A61P 25/08: Antiepileptics; Anticonvulsants - C12Q 1/6883: for diseases caused by alterations of genetic material - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/158: Expression markers - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract Materials and methods for identifying subjects as being likely or not likely to respond to an interleukin-1β receptor antagonist (IL-1RA) therapy for a seizure disorder, as well as materials and methods for treating subjects identified as being likely to respond to an IL-1RA therapy for a seizure disorder, are provided herein. ## Claims ### Claim 1 A method for treating a subject having a seizure disorder, said method comprising determining that the subject has decreased IL-1RA function as compared to the level of IL-1RA function in corresponding normal subjects who do not have the seizure disorder, and administering to the subject a treatment that attenuates IL-1R inflammatory signaling, wherein said treatment comprises one or more of anakinra, EBI-005, and MEDI-8968. ### Claim 2 (depends on 1) The method of claim 1, wherein the treatment comprises anakinra. ### Claim 3 (depends on 1) The method of claim 1, wherein the seizure disorder is FIRES, PASS, DIRA, or MRE. ### Claim 4 (depends on 1) The method of claim 1, wherein the subject is a human child. ### Claim 5 (depends on 1) The method of claim 1, wherein the determining comprises measuring IL-1RA activity in a biological sample from the subject, wherein the biological sample comprises serum, serum microvesicles, or CSF, and determining that the IL-1RA activity in the biological sample is decreased relative to a corresponding control level of IL-1RA activity. ### Claim 6 (depends on 1) The method of claim 1, wherein the determining comprises measuring an inflammatory response in primed and stimulated neutrophils, monocytes, or PBMCs isolated from the subject, and determining that the measured inflammatory response is higher than an inflammatory response for control primed and stimulated neutrophils, monocytes, or PBMCs from subjects who do not have the seizure disorder. ### Claim 7 (depends on 6) The method of claim 6, comprising determining that the measured inflammatory response is at least two standard deviations higher than the inflammatory response for control primed and stimulated neutrophils, monocytes, or PBMCs from subjects who do not have the seizure disorder. ### Claim 8 (depends on 6) The method of claim 6, wherein the inflammatory response comprises secretion of IL-1β, IL-1RA, IL-18, IL-33, IL-36, IL-37, or IL-38 from the neutrophils, monocytes, or PBMCs after stimulation. ### Claim 9 (depends on 6) The method of claim 6, comprising priming the neutrophils, monocytes, or PBMCs with LPS. ### Claim 10 (depends on 6) The method of claim 6, comprising stimulating the neutrophils, monocytes, or PBMCs with ATP. ### Claim 11 (depends on 1) The method of claim 1, wherein the determining comprises measuring the relative amounts of IL-1RA (protein) or IL1RN (mRNA) isoforms in a biological sample from the subject, and determining that the subject has a ratio of soluble IL-1RA: intracellular IL-1RA that is increased relative to a control ratio of soluble IL-1RA: intracellular IL-1RA. ### Claim 12 (depends on 11) The method of claim 11, wherein the control ratio of soluble IL-1RA: intracellular IL-1RA is the ratio of soluble IL-1RA: intracellular IL-1RA in control subjects not having the seizure disorder. ### Claim 13 A method for treating a subject having a seizure disorder, comprising identifying the subject as having a level of functional IL-1RA antagonism that is decreased below a predetermined threshold level of functional IL-1RA antagonism, and administering to the subject a treatment that attenuates IL-1R inflammatory signaling, wherein said treatment is selected from the group consisting of anakinra, EBI-005, and MEDI-8968. ### Claim 14 (depends on 13) The method of claim 13, wherein the treatment comprises anakinra. ### Claim 15 (depends on 13) The method of claim 13, wherein the seizure disorder is FIRES, PASS, DIRA, or MRE. ### Claim 16 (depends on 13) The method of claim 13, wherein the subject is a human child. ### Claim 17 (depends on 13) The method of claim 13, wherein the threshold level is 10% of the level of functional IL-1RA antagonism in corresponding control subjects who do not have the seizure disorder.