Crystal forms of amino lipids

Patent metadata

Field	Value
Publication number	US-2022073449-A1
Application number	US-202117525352-A
Country	US
Kind code	A1
Filing date	Nov 12, 2021
Priority date	Mar 15, 2017
Publication date	Mar 10, 2022
Grant date	—

Abstract

Provided herein are novel solid forms of each of four compounds: (1) heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate (“Compound 1”), (2) heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate (“Compound 2”), (3) heptadecan-9-yl 8-((2-hydroxyethyl)(8-(nonyloxy)-8-oxooctyl)amino)octanoate (“Compound 3”), and (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (“MC3”), and related compositions and methods.

First claim

1 . A salt or cocrystal of heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate (“Compound 1”), heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate (“Compound 2”), or heptadecan-9-yl 8-((2-hydroxyethyl)(8-(nonyloxy)-8-oxooctyl)amino)octanoate (“Compound 3”), the salt or cocrystal of Compound 1, 2, or 3 having a melting point of about 50° C. or greater.

2 . A salt or cocrystal of heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate (“Compound 1”) and a compound selected from the group consisting of 4-hydroxybenzoic acid, oxalic acid, trimellitic acid, orotic acid, trimesic acid, and sulfuric acid.

3 . The salt or cocrystal of claim 2 , wherein the compound is 4-hydroxybenzoic acid.

4 . The salt or cocrystal of claim 2 , wherein the compound is oxalic acid.

5 . The salt or cocrystal of any one of the preceding claims, wherein the stoichiometry of Compound 1 and the compound is within the range of from about 1:0.2 to 1:5 or from about 1:0.5 to 1:2.

6 . The salt or cocrystal of any one of the preceding claims, wherein the stoichiometry of Compound 1 and the compound is about 1:1.

7 . The salt or cocrystal of any one of the preceding claims, being an anhydrate, a solvate, or a hydrate.

8 . The salt or cocrystal of any one of the preceding claims, which is 4-hydroxybenzoate of Compound 1, having an X-ray powder diffraction pattern obtained using Cu Kα radiation, comprising two, three, or more characteristic peaks expressed in degrees 2-theta (+/−0.2) selected from the group consisting of 4.5, 6.8, 9.1, and 11.4.

9 . The salt or cocrystal of claim 8 , wherein the salt or cocrystal exhibits an X-ray powder diffraction pattern obtained using Cu Kα radiation, having two, three, four, or more characteristic peaks expressed in degrees 2-theta (+/−0.2) selected from the group consisting of 4.5, 6.8, 9.1, 11.4, and 13.7.

10 . The salt or cocrystal of claim 8 , wherein the salt or cocrystal exhibits an X-ray powder diffraction pattern obtained using Cu Kα radiation, having characteristic peaks expressed in degrees 2-theta (+/−0.2) at 4.5, 6.8, 9.1, 11.4, 13.7, 18.3, 20.1, and 20.6.

11 . The salt or cocrystal of claim 8 , wherein the salt or cocrystal exhibits an X-ray powder diffraction pattern obtained using Cu Kα radiation, having at least eight characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 4.5, 6.8, 9.1, 11.4, 13.7, 16.0, 18.3, 20.1, and 20.6.

12 . The salt or cocrystal of claim 8 , wherein the salt or cocrystal exhibits an X-ray powder diffraction pattern obtained using Cu Kα radiation, having at least nine characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 4.5, 6.8, 9.1, 11.4, 13.7, 16.0, 16.6, 18.3, 20.1, and 20.6.

13 . The salt or cocrystal of claim 8 , wherein the salt or cocrystal exhibits an X-ray powder diffraction pattern obtained using Cu Kα radiation, having at least ten characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 4.5, 6.8, 9.1, 11.4, 13.7, 16.0, 16.6, 18.3, 20.1, 20.6, and 21.5.

14 . The salt or cocrystal of any one of the preceding claims, wherein the salt or cocrystal exhibits an X-ray powder diffraction pattern obtained using Cu Kα radiation, having peaks with 2-theta values substantially in accordance with FIG. 1 .

15 . The salt or cocrystal of any one of the preceding claims, wherein the salt or cocrystal exhibits an X-ray powder diffraction pattern obtained using Cu Kα radiation, having peaks with 2-theta values substantially in accordance with the table below.

Peak
Pos. [°2Th.]

1
4.6

2
6.8

3
9.1

4
11.4

5
13.7

6
16.0

7
16.6

8
18.3

9
20.1

10
20.6

11
21.5

12
23.8

16 . The salt or cocrystal of any one of the preceding claims, wherein the salt or cocrystal exhibits a differential scanning calorimetry thermogram showing a primary endotherm expressed in units of ° C. at a temperature of 103+/−2° C.

17 . The salt or cocrystal of claim 16 , wherein the salt or cocrystal exhibits a differential scanning calorimetry thermogram showing a second primary endotherm expressed in units of ° C. at a temperature of 68+/−2° C.

18 . The salt or cocrystal of any one of the preceding claims, wherein the salt or cocrystal exhibits a differential scanning calorimetry thermogram substantially in accordance with the DSC profile shown in FIG. 3 .

19 . The salt or cocrystal of any one of the preceding claims, wherein said salt or cocrystal is substantially free of impurities.

20 . The salt or cocrystal of any one of the preceding claims, wherein said salt or cocrystal is a crystalline solid substantially free of other crystalline forms of the salt or cocrystal.

21 . The salt or cocrystal of claim 20 , wherein said other crystalline forms of the salt or cocrystal comprises Polymorph B of 4-hydroxybenzoate of Compound 1.

22 . A salt or cocrystal of heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate (“Compound 2”) and a compound selected from the group consisting of trimesic acid, (−)-2,3-dibenzoyl-L-tartaric acid, 4-acetamido benzoic acid, (+)-L-tartaric acid, and methanesulfonic acid.

23 . The salt or cocrystal of claim 22 , wherein the stoichiometry of Compound 2 and the compound is within the range of from about 1:0.2 mol/mol to 1:5 mol/mol or from about 1:0.5 mol/mol to 1:2 mol/mol.

24 . The salt or cocrystal of claim 22 , wherein the stoichiometry of Compound 2 and the compound is about 1:1 mol/mol.

25 . The salt or cocrystal of any one of claims 22 - 24 , being an anhydrate, a solvate or a hydrate.

Assignees

• Modernatx Inc

Inventors

• Almarsson Orn
• Cheung Eugene

Classifications

• C07C229/24 Primary

  having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid · CPC title

• C07C65/03

  monocyclic and having all hydroxy or O-metal groups bound to the ring · CPC title

• C07C229/12 Primary

  to carbon atoms of acyclic carbon skeletons · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C229/16

  to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids · CPC title