# US 12,109,194 B2 · Synergistic combination therapy for treating ALS > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,109,194 B2 - Document ID: US12109194B2 - Status: Granted - Kind: B2 - Application number: 17/684,279 - Filed: 2022-03-01 - Published: 2022-08-11 - Granted: 2024-10-08 - Earliest claimed: 2021-02-05 - Assignees: BioJiva LLC - Applicants: BioJiva LLC - Inventors: Peter Milner; Nadia Litterman; Mark Midei - Web page: https://patentgrep.com/patent/US12109194B2 ## CPC - A61K 31/4152: having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone - A61K 31/202: having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557) - A61K 31/232: having three or more double bonds, e.g. etretinate - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Disclosed are methods for inhibiting the progression of amyotrophic lateral sclerosis (ALS) in humans. The methods use a synergistic combination of 3-methyl-1-phenyl-2-pyrazoline-5-one and deuterated arachidonic acid or a prodrug thereof, such as 11,11-D2-linoleic acid or an ester thereof. ## Claims ### Claim 1 A method for reducing the rate of disease progression of ALS in a patient the method comprising administering to the patient a therapeutically effective amount of 3-methyl-1-phenyl-2-pyrazoline-5-one or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of a deuterated arachidonic acid or a prodrug thereof; wherein the rate of disease progression in the patient is less than the aggregate achieved by either drug; and wherein the deuterated arachidonic acid or a prodrug thereof is administered using a dosing regimen that includes a loading dose and a maintenance dose. ### Claim 2 A method for reducing the rate of loss of functionality in an ALS patient being treated with a therapeutically effective amount of a deuterated arachidonic acid or a prodrug thereof the method comprising further administering a therapeutically effective amount of 3-methyl-1-phenyl-2-pyrazoline-5-one or a pharmaceutically acceptable salt thereof; wherein the rate of loss of functionality in the patient is less than the aggregate achieved by either drug; and wherein the deuterated arachidonic acid or a prodrug thereof is administered using a dosing regimen that includes a loading dose and a maintenance dose. ### Claim 3 A method for reducing the rate of loss of functionality in an ALS patient being treated with a therapeutically effective amount of 3-methyl-1-phenyl-2-pyrazoline-5-one or a pharmaceutically acceptable salt thereof the method comprising further administering a therapeutically effective amount of a deuterated arachidonic acid or a prodrug thereof; wherein the rate of loss of functionality in the patient is less than the aggregate achieved by either drug; and wherein the deuterated arachidonic acid or a prodrug thereof is administered using a dosing regimen that includes a loading dose and a maintenance dose. ### Claim 4 (depends on 1) The method of claim 1, wherein said deuterated arachidonic acid prodrug is 11,11-D2-linoleic acid or an ester thereof. ### Claim 5 (depends on 4) The method of claim 4, wherein said ester is a C1-C6 alkyl ester. ### Claim 6 (depends on 1) The method of claim 1, wherein said deuterated arachidonic acid or a prodrug thereof is an ester of 7,7,10,10,13,13-D6-arachidonic acid. ### Claim 7 (depends on 6) The method of claim 6, wherein said ester is a C1-C6 alkyl ester. ### Claim 8 (depends on 1) The method of claim 1, wherein said deuterated arachidonic acid is 7,7,10,10,13,13-D6-arachidonic acid or a pharmaceutically acceptable salt thereof. ### Claim 9 (depends on 4) The method of claim 4, wherein 11,11-D2-linoleic acid ethyl ester is administered daily at a dose of about 5.5 to about 12 grams/day during the loading phase and then at a dose that is from about 30% to about 65% of the loading dose during the maintenance phase of the dosing regimen. ### Claim 10 (depends on 9) The method of claim 9, wherein 3-methyl-1-phenyl-2-pyrazoline-5-one or a pharmaceutically acceptable salt thereof is administered as an infusion, an injectable composition, an oral composition or in combination with said deuterated arachidonic acid or a prodrug thereof. ### Claim 11 (depends on 1) The method of claim 1, wherein said deuterated arachidonic acid or a prodrug thereof is 7,7,10,10,13,13-D6-arachidonic acid, a pharmaceutically acceptable salt thereof or an ester thereof. ### Claim 12 (depends on 11) The method of claim 11, wherein said deuterated arachidonic acid prodrug is 7,7,10,10,13,13-D6-arachidonic acid ethyl ester. ### Claim 13 (depends on 1) The method of claim 1, wherein 7,7,10,10,13,13-D6-arachidonic acid or ester thereof is administered daily at a dose of about 0.05 to about 5 grams/day during the loading phase and then at a dose that is from about 30% to about 70% of the loading dose during the maintenance phase of the dosing regimen. ### Claim 14 (depends on 13) The method of claim 13, wherein 7,7,10,10,13,13-D6-arachidonic acid or ester thereof is administered daily at a dose of about 0.5 to about 5 grams/day during the loading phase. ### Claim 15 (depends on 13) The method of claim 13, wherein 3-methyl-1-phenyl-2-pyrazoline-5-one or a pharmaceutically acceptable salt thereof is administered as an infusion, an injectable composition, an oral composition. ### Claim 16 (depends on 1) The method of claim 1, wherein 3-methyl-1-phenyl-2-pyrazoline-5-one or a pharmaceutically acceptable salt thereof is administered as an injectable composition or an oral composition. ### Claim 17 (depends on 1) The method of claim 1, wherein 3-methyl-1-phenyl-2-pyrazoline-5-one or a pharmaceutically acceptable salt thereof is administered as an oral composition in combination with deuterated arachidonic acid or a prodrug thereof. ### Claim 18 (depends on 1, 2, 3) The method of any one of claims 1, 2 or 3, wherein the method further comprises restricting the patient's consumption of excessive dietary polyunsaturated fatty acids during administration of said deuterated arachidonic acid.