# US 12,110,284 B2 · Fasoracetam crystalline forms

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- Number: US 12,110,284 B2
- Document ID: US12110284B2
- Status: Granted
- Kind: B2
- Application number: 18/060,098
- Filed: 2022-11-30
- Published: 2023-03-23
- Granted: 2024-10-08
- Earliest claimed: 2018-01-18
- Assignees: The Children's Hospital of Philadelphia
- Applicants: The Children's Hospital of Philadelphia
- Inventors: Tom Leyssens; Bram Harmsen
- Web page: https://patentgrep.com/patent/US12110284B2

## CPC

- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 207/28: 2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The disclosure is directed to crystalline forms and mixtures thereof of R-fasoracetam. Such crystalline forms include Form II monohydrate R-fasoracetam and the anhydrate form of R-fasoracetam. The disclosure further includes mixtures of the anhydrate form of R-fasoracetam together with one or more of Form I monohydrate R-fasoracetam and Form II monohydrate R-fasoracetam.

## Claims

### Claim 1

A mixture of fasoracetam monohydrate Form I, fasoracetam monohydrate Form II, and anhydrate fasoracetam, wherein:
the fasoracetam monohydrate Form I has an x-ray powder diffraction pattern comprising one or more peaks chosen from peaks at 7.2±0.2°2θ and 12.9±0.2°2θ;
the fasoracetam monohydrate Form II has an x-ray powder diffraction pattern comprising one or more peaks chosen from peaks at 5.7±0.2°2θ and 11.3±0.2°2θ; and
the anhydrate fasoracetam has an x-ray powder diffraction pattern comprising one or more peaks chosen from peaks at 8.9±0.2°2θ, 12.3±0.2°2θ, and 13.1±0.2°2θ.

### Claim 2

A mixture of anhydrate fasoracetam and fasoracetam monohydrate Form I or fasoracetam monohydrate Form II, wherein:
the fasoracetam monohydrate Form I has an x-ray powder diffraction pattern comprising one or more peaks chosen from peaks at 7.2±0.2°2θ and 12.9±0.2°2θ;
the fasoracetam monohydrate Form II has an x-ray powder diffraction pattern comprising one or more peaks chosen from peaks at 5.7±0.2°2θ and 11.3±0.2°2θ; and
the anhydrate fasoracetam has an x-ray powder diffraction pattern comprising one or more peaks chosen from peaks at 8.9±0.2°2θ, 12.3±0.2°2θ, and 13.1±0.2°2θ.

### Claim 3 (depends on 1)

The mixture of claim 1, prepared by melting and recrystallizing fasoracetam monohydrate Form I, optionally wherein the melting was done under partial vacuum.

### Claim 4

A mixture of fasoracetam monohydrate Form I, fasoracetam monohydrate Form II, and anhydrate fasoracetam, wherein the mixture has an x-ray powder diffraction pattern comprising one or more peaks chosen from peaks at 5.7±0.2°2θ, 7.2±0.2°2θ, and 12.9±0.2°2θ.

### Claim 5

A mixture of fasoracetam monohydrate Form I, fasoracetam monohydrate Form II, and anhydrate fasoracetam, wherein the mixture has an x-ray powder diffraction pattern comprising one or more peaks chosen from peaks at 5.7±0.2°2θ or 11.3±0.2°2θ or both, and 7.2±0.2°2θ, and one or more of the peaks chosen from peaks at 8.9±0.2°2θ, 12.3±0.2°2θ, and 13.1±0.2°2θ.

### Claim 6 (depends on 1)

The mixture of claim 1, having at least two melting events, optionally wherein the melting is measured by differential scanning calorimetry (DSC).

### Claim 7 (depends on 6)

The mixture of claim 6, wherein one onset melting temperature is at 93.5±3° C., optionally wherein the melting is measured by differential scanning calorimetry (DSC).

### Claim 8 (depends on 1)

A pharmaceutical composition comprising the mixture of claim 1 and one or more pharmaceutically acceptable excipients.

### Claim 9 (depends on 1)

A method treating a disease in a human selected from the group consisting of attention deficit hyperactivity disorder (ADHD), 22q11.2 deletion syndrome, anxiety, conduct disorder, and Tourette's syndrome, wherein the human has at least one copy number variation in a metabotropic glutamate receptor (mGluR) network gene, the method comprising administering to the subject an effective amount of the mixture of claim 1.

### Claim 10 (depends on 9)

The method of claim 9, wherein the mGluR network gene is selected from the group consisting of GRMS, GRM8, GRM7, GRM1, NEGR1, SGTB/NLN, USP24, CNTN4, CTNNA2, LARP7, MC4R, SNCA, and CA8.

### Claim 11 (depends on 2)

A pharmaceutical composition comprising the mixture of claim 2 and one or more pharmaceutically acceptable excipients.

### Claim 12 (depends on 2)

A method treating a disease in a human selected from the group consisting of attention deficit hyperactivity disorder (ADHD), 22q11.2 deletion syndrome, anxiety, conduct disorder, and Tourette's syndrome, wherein the human has at least one copy number variation in a metabotropic glutamate receptor (mGluR) network gene, the method comprising administering to the subject an effective amount of the mixture of claim 2.

### Claim 13 (depends on 12)

The method of claim 12, wherein the mGluR network gene is selected from the group consisting of GRMS, GRM8, GRM7, GRM1, NEGR1, SGTB/NLN, USP24, CNTN4, CTNNA2, LARP7, MC4R, SNCA, and CA8.