# US 12,760,007 B2 · Salt and crystal forms of GLP-1R agonists and uses thereof

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- Number: US 12,760,007 B2
- Document ID: US12760007B2
- Status: Granted
- Kind: B2
- Application number: 17/927,502
- Filed: 2021-05-26
- Published: 2023-06-29
- Granted: 2026-10-13
- Earliest claimed: 2020-05-27
- Assignees: Qilu Regor Therapeutics Inc.
- Applicants: Qilu Regor Therapeutics Inc.
- Inventors: Meng Jiang; Beibei Chen; Xudong Wei; Wenge Zhong
- Web page: https://patentgrep.com/patent/US12760007B2

## CPC

- C07D 405/14: containing three or more hetero rings
- C07C 55/22: Tricarboxylic acids
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

Various salt forms of Compound I and Compound II represented by the following structural formulae, and their corresponding pharmaceutical compositions, are disclosed. (I), (II) Particular single crystalline forms of 1:1 Compound I tris salt, 1:1 Compound II tris salt, and 1:1 Compound II citrate salt are characterized by a variety of properties and physical measurements. Methods of preparing specific crystalline forms are also disclosed. The present disclosure also provides methods of treating type 2 diabetes mellitus, pre-diabetes, obesity, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and cardiovascular disease in a subject.

## Claims

### Claim 1

A tris salt of Compound I, wherein Compound I is represented by the following structural formula:
wherein the molar ratio between Compound I and tris(hydroxymethyl)aminomethane is 1:1.

### Claim 2 (depends on 1)

The tris salt of claim 1, wherein the tris salt is a monohydrate.

### Claim 3 (depends on 1)

The tris salt of claim 1, wherein the tris salt is in a single crystalline form, Form A, characterized by an X-ray powder diffraction pattern which comprises at least three peaks selected from 17.5°, 20.1°, 20.7°, 21.1°, and 22.6°±0.2 in 2θ.

### Claim 4 (depends on 3)

The tris salt of claim 3, wherein the tris salt is in a single crystalline form, Form A, characterized by a differential scanning calorimeter (DSC) peak phase transition temperature of 173±3° C.

### Claim 5 (depends on 4)

The tris salt of claim 4, wherein at least 90% by weight of the tris salt is in single crystalline Form A.

### Claim 6 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1, and a pharmaceutically acceptable carrier.

### Claim 7 (depends on 1)

A method of treating cardiometabolic and associated diseases, the method comprising administering to a subject in need of such treatment a therapeutically effective amount of a salt of claim 1, or a pharmaceutical composition thereof, wherein the disease is type 1 diabetes (TID), type 2 diabetes mellitus (T2DM), hyperglycemia, kidney disease, obesity, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cardiovascular disease, hypertension, Parkinson's Disease, and Alzheimer's Disease.

### Claim 8 (depends on 2)

The tris salt of claim 2, wherein the tris salt is in a single crystalline form, Form A, characterized by an X-ray powder diffraction pattern which comprises peaks at 17.5°, 20.1°, 20.7°, 21.1°, and 22.6°±0.2 in 2θ.

### Claim 9 (depends on 2)

The tris salt of claim 2, wherein the tris salt is in a single crystalline form, Form A, characterized by an X-ray powder diffraction pattern which comprises peaks at 4.1°, 14.8°, 17.5°, 18.8°, 20.1°, 20.7°, 21.1°, and 22.6°±0.2 in 2θ.

### Claim 10 (depends on 2)

The tris salt of claim 2, wherein the tris salt is in a single crystalline form, Form A, characterized by an X-ray powder diffraction pattern which comprises peaks at 4.1°, 8.1°, 12.8°, 14.8°, 16.3°, 17.5°, 18.8°, 19.3°, 20.1°, 20.7°, 21.1°, 22.6°, 25.1°, and 25.8°±0.2 in 2θ.

### Claim 11 (depends on 1)

The tris salt of claim 1, wherein the tris salt is unsolvated.

### Claim 12 (depends on 7)

The method of claim 7, wherein the disease is type 2 diabetes mellitus.

### Claim 13 (depends on 7)

The method of claim 7, wherein the disease is obesity.

### Claim 14 (depends on 7)

The method of claim 7, wherein the disease is Alzheimer's Disease.

### Claim 15 (depends on 7)

The method of claim 7, wherein the disease is Parkinson's Disease.

### Claim 16 (depends on 7)

The method of claim 7, wherein the disease is hyperglycemia.

### Claim 17 (depends on 7)

The method of claim 7, wherein the disease is nonalcoholic fatty liver disease.

### Claim 18 (depends on 7)

The method of claim 7, wherein the disease is non-alcoholic steatohepatitis.

### Claim 19 (depends on 7)

The method of claim 7, wherein the disease is type 1 diabetes.

### Claim 20 (depends on 7)

The method of claim 7, wherein the disease is cardiovascular disease.

### Claim 21 (depends on 7)

The method of claim 7, wherein the disease is hypertension.

### Claim 22 (depends on 7)

The method of claim 7, wherein the disease is kidney disease.