# US 11,998,535 B2 · Methods of treatment of tuberous sclerosis complex > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,998,535 B2 - Document ID: US11998535B2 - Status: Granted - Kind: B2 - Application number: 18/315,723 - Filed: 2023-05-11 - Published: 2023-09-07 - Granted: 2024-06-04 - Earliest claimed: 2020-06-05 - Assignees: Noema Pharma AG - Applicants: Noema Pharma AG - Inventors: George Garibaldi - Web page: https://patentgrep.com/patent/US11998535B2 ## CPC - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/4858: {Organic compounds} - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/08: Antiepileptics; Anticonvulsants - 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 - A61P 35/00: Antineoplastic agents - 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 Provided herein are methods of treating tuberous sclerosis complex in a subject in need thereof by administering to the subject compositions comprising an mGlu5 negative allosteric modulator (NAM), having the structure of Formula I: ## Claims ### Claim 1 A method of treating a medical condition associated with tuberous sclerosis complex (TSC), comprising administering to a subject in need thereof a composition comprising a therapeutically effective amount of a pharmaceutically acceptable salt of a compound of Formula I, wherein the compound of Formula I has the structure: and wherein the pharmaceutically acceptable salt comprises a crystalline anhydrate form (Form A) of a monosulfate salt of the compound of Formula I, wherein the crystalline anhydrate form (Form A) is characterized by at least three peaks selected from the following X-ray powder diffraction peaks obtained with a CuKα radiation at 2θ (2 Theta): 9.8±0.2°, 13.4±0.2°, 14.2±0.2°, 18.1±0.2°, 18.9±0.2°, 19.6±0.2°, 22.6±0.2°, 22.9±0.2°, 25.7±0.2°, 27.1±0.2°, and 29.9±0.2°. ### Claim 2 (depends on 1) The method of claim 1, wherein the pharmaceutically acceptable salt comprises a crystalline anhydrate form (Form A) of a monosulfate salt of the compound of Formula I, wherein the crystalline anhydrate form (Form A) is characterized by the following X-ray powder diffraction peaks obtained with a CuKα radiation at 2θ (2 Theta): 9.8±0.2°, 13.4±0.2°, 14.2±0.2°, 18.1±0.2°, 18.9±0.2°, 19.6±0.2°, 22.6±0.2°, 22.9±0.2°, 25.7±0.2°, 27.1±0.2°, and 29.9±0.2°. ### Claim 3 (depends on 1) The method of claim 1, wherein the pharmaceutically acceptable salt comprises a crystalline anhydrate form (Form A) of a monosulfate salt of the compound of Formula I, wherein the crystalline anhydrate form (Form A) has a median particle size (Dv50) of less than or equal to about 100 μm. ### Claim 4 (depends on 1) The method of claim 1, wherein the pharmaceutically acceptable salt comprises a crystalline anhydrate form (Form A) of a monosulfate salt of the compound of Formula I, wherein the crystalline anhydrate form (Form A) and has a Tm of about 180-190° C. by differential scanning calorimetry analysis. ### Claim 5 (depends on 1) The method of claim 1, wherein the pharmaceutically acceptable salt is 90% by weight or more of the crystalline anhydrate form (Form A) based on the total weight of the salt present in the composition. ### Claim 6 (depends on 1) The method of claim 1, wherein the pharmaceutically acceptable salt is 95% by weight or more of the crystalline anhydrate form (Form A) based on the total weight of the salt present in the composition. ### Claim 7 (depends on 1) The method of claim 1, wherein the pharmaceutically acceptable salt is 99% by weight or more of the crystalline anhydrate form (Form A) based on the total weight of the salt present in the composition. ### Claim 8 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by assessing improvement based on the Sheehan Disability Scale (SDS). ### Claim 9 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by assessing improvement based on the Sheehan Disability Scale (SDS), where the subject shows a change from baseline. ### Claim 10 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by assessing improvement based on the Caregiver Global Impression of Change (CGIC) score. ### Claim 11 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by assessing improvement based on the Caregiver Global Impression of Change (CGIC) score, where the subject shows a change from baseline. ### Claim 12 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by an increase in the number of seizure free days within a four week period. ### Claim 13 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by a greater than or equal to 25% reduction in seizures from baseline within a four week period. ### Claim 14 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by a greater than or equal to 50% reduction in seizures from baseline within a four week period. ### Claim 15 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by a greater than or equal to 75% reduction in seizures from baseline within a four week period. ### Claim 16 (depends on 1) The method of claim 1, wherein therapeutic efficacy of the treatment is determined by a 100% reduction in seizures from baseline within a four week period. ### Claim 17 (depends on 1) The method of claim 1, wherein the therapeutic effect of the treatment is determined by a reduction of seizure occurrence or frequency. ### Claim 18 (depends on 1) The method of claim 1, wherein the therapeutic effect of the treatment is determined by reduction of the size of a tumor or suppression of tumor growth in the brain, eyes, heart, kidney, skin, or lungs. ### Claim 19 (depends on 1) The method of claim 1, wherein the therapeutic effect of the treatment is determined by improvement of cognitive function.