# US 12,110,345 B2 · Crystalline salt forms of Boc-D-Arg-DMT-Lys-(Boc)-Phe-NH2

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,110,345 B2
- Document ID: US12110345B2
- Status: Granted
- Kind: B2
- Application number: 18/231,483
- Filed: 2023-08-08
- Published: 2024-05-02
- Granted: 2024-10-08
- Earliest claimed: 2017-04-05
- Assignees: Stealth BioTherapeutics Inc.
- Applicants: Stealth BioTherapeutics Inc.
- Inventors: Scott M. Duncan
- Web page: https://patentgrep.com/patent/US12110345B2

## CPC

- C07K 5/1019: {with the first amino acid being basic}
- C30B 29/58: Macromolecular compounds
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C30B: SINGLE-CRYSTAL GROWTH (by using ultra-high pressure, e.g. for the formation of diamonds, B01J3/06); UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL (zone-refining of metals or alloys C22B); PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE (casting of metals, casting of other substances by the same processes or devices B22D; working of plastics B29; modifying the physical structure of metals or alloys C21D, C22F); SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE (for producing semiconductor devices or parts thereof H10); APPARATUS THEREFOR
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

Disclosed are various crystalline salt forms of Boc-D-Arg-DMT-Lys(Boc)-Phe-NH2.

## Claims

### Claim 1

A crystalline form of the freebase of Compound (I),
(Boc)-D-Arg-DMT-Lys(Boc)-Phe-NH2).

### Claim 2 (depends on 1)

The crystalline form of claim 1, wherein said crystalline form is characterized by an endothermic event in its thermogravimetry differential thermal analysis at an onset of about 168.5° C.

### Claim 3 (depends on 1)

The crystalline form of claim 1, wherein said crystalline form is characterized by an endothermic event in its thermogravimetry differential thermal analysis at a peak at about 175.9° C.

### Claim 4

A method of preparing a crystalline form of the freebase of Compound (I), the method comprising:
a) preparing a mixture comprising the freebase of Compound (I) and a solvent; and
b) crystallizing the freebase of Compound (I) from the mixture.

### Claim 5 (depends on 4)

The method of claim 4, wherein the solvent is selected from methanol, ethanol, or trifluoroethanol.

### Claim 6 (depends on 5)

The method of claim 5, wherein the solvent is methanol.

### Claim 7 (depends on 4)

The method of claim 4, wherein the mixture is a solution, and the step of crystallizing the freebase of Compound (I) from the mixture comprises adding an anti-solvent, thereby causing the freebase of Compound (I) to precipitate.

### Claim 8 (depends on 7)

The method of claim 7, wherein the ratio of the solvent to the anti-solvent in the solution is about 3:1 to about 1:3 v/v.

### Claim 9 (depends on 7)

The method of claim 7, wherein the ratio of the solvent to the anti-solvent in the solution is about 3:1 v/v.

### Claim 10 (depends on 7)

The method of claim 7, wherein the ratio of the solvent to the anti-solvent in the solution is about 1:3 v/v.

### Claim 11 (depends on 7)

The method of claim 7, wherein the antisolvent is added at about 5 to about 50° C.

### Claim 12 (depends on 7)

The method of claim 7, wherein the antisolvent is added at about 50° C.

### Claim 13 (depends on 7)

The method of claim 7, wherein the antisolvent is added at about 5° C.

### Claim 14 (depends on 7)

The method of claim 7, wherein the anti-solvent is selected from acetonitrile, ethyl acetate, tetrahydrofuran, acetone, methyl ethyl ketone, toluene, tert-butyl methyl ether, and heptane.

### Claim 15

A method of making Compound (II), the method comprising
(a) preparing a mixture of a crystalline form of the freebase of compound (I), a scavenger, and a solvent
(b) adding an acid to the mixture, thereby making compound (II)

### Claim 16 (depends on 15)

The method of claim 15, wherein
the scavenger is triisopropylsilane, the solvent is 2,2,2-trifluoroethanol and
the acid is hydrochloric acid.

### Claim 17 (depends on 16)

The method of claim 16, wherein the mixture is a slurry.

### Claim 18 (depends on 17)

The method of claim 17, further comprising isolating compound (II) from the mixture.