# US 12,215,174 B2 · Compositions of hydroxypropyl-β-cyclodextrin and methods of purifying the same

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- Number: US 12,215,174 B2
- Document ID: US12215174B2
- Status: Granted
- Kind: B2
- Application number: 18/633,063
- Filed: 2024-04-11
- Published: 2024-08-15
- Granted: 2025-02-04
- Earliest claimed: 2022-02-18
- Assignees: Beren Therapeutics P.B.C.
- Applicants: Beren Therapeutics P.B.C.
- Inventors: Steven Pfeiffer; Dustin McMinn; Gabor Benkovics
- Web page: https://patentgrep.com/patent/US12215174B2

## CPC

- C08B 37/0012: {Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof}
- C08L 5/16: Cyclodextrin; Derivatives thereof
- A61K 31/724: Cyclodextrins
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- 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)

## Abstract

The present disclosure relates to compositions comprising mixtures of hydroxypropyl-β-cyclodextrin, wherein the compositions may be isomerically purified. The disclosure also relates to methods of isomerically purifying a mixture of hydroxypropyl-β-cyclodextrins.

## Claims

### Claim 1

A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising: β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”); wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”), and wherein the mixture has an average degree of substitution of 6.02-7.98, and wherein the total amount of impurities are measured to be less than or equal to 0.05% by HPLC.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”).

### Claim 3 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with three hydroxypropyl groups (“DS-3”).

### Claim 4 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 0.05% by mass unsubstituted beta-cyclodextrin (“DS-0”) and less than 0.05% by mass β-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).

### Claim 5 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with eight hydroxypropyl groups (“DS-8”).

### Claim 6 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with nine hydroxypropyl groups (“DS-9”).

### Claim 7 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with ten hydroxypropyl groups (“DS-10”).

### Claim 8 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with eleven hydroxypropyl groups (“DS-11”).

### Claim 9 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with twelve hydroxypropyl groups (“DS-12”).

### Claim 10 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with thirteen hydroxypropyl groups (“DS-13”).

### Claim 11 (depends on 1)

The composition of claim 1, wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with fourteen hydroxypropyl groups (“DS-14”).

### Claim 12 (depends on 1)

The mixture of claim 1, wherein the composition has an HPLC-CAD mean retention time of about 10.1 minutes.

### Claim 13 (depends on 1)

The composition of claim 1, wherein the osmolality of the composition is about 635-695 mOs/kg; and/or wherein the true density of the composition is about 1.096-1.098 g/cm3.

### Claim 14 (depends on 1)

The composition of claim 1, wherein the composition further comprises no more than 10 ppb of propylene glycol as measured by HPLC.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the composition further comprises no more than 10 ppb propylene glycol as measured by gas chromatography.

### Claim 16 (depends on 1)

The composition of claim 1, wherein the composition further comprises no more than 10 ppb propylene glycol as measured by PG/EG-ratio of propylene glycol to ethylene glycol.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the composition further comprises no more than 1 ppm propylene oxide.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the composition further comprises between 0 and 10 ppm chloride.

### Claim 19 (depends on 1)

The composition of claim 1, wherein the composition has a conductivity between 0 and 8 μS/cm.

### Claim 20

A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising: β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”); wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”), and wherein the composition has an average degree of substitution of 6.02-7.98, and wherein the total amount of impurities are measured to be less than or equal to 0.05% by HPLC.

### Claim 21 (depends on 20)

The mixture further of claim 20, wherein the composition comprises less than 1% by mass β-cyclodextrin substituted with three hydroxypropyl groups (“DS-3”).

### Claim 22 (depends on 20)

The composition of claim 20, wherein the mixture further comprises less than 0.05% by mass unsubstituted beta-cyclodextrin (“DS-0”) and less than 0.05% by mass β-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).

### Claim 23

A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising: β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”); wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”), and wherein the mixture has an average degree of substitution of 6.02-7.98 and the mixture is determined by MALDI-TOF mass spectrometry.

### Claim 24 (depends on 23)

The composition of claim 23, wherein the percentage of DS-5 is determined by MALDI-TOF mass spectrometry.

### Claim 25 (depends on 23)

The composition of claim 23, wherein the composition is suitable for administration to a human patient in need thereof.

### Claim 26

A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising: β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”); wherein the mixture further less than 1% by mass β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”), and wherein the mixture has an average degree of substitution of 6.02-7.98 and the mixture is determined by MALDI-TOF mass spectrometry.

### Claim 27 (depends on 26)

The composition of claim 26, wherein the percentage of DS-4 is determined by MALDI-TOF mass spectrometry.

### Claim 28 (depends on 26)

The composition of claim 26, wherein the composition is suitable for administration to a human patient in need thereof.