# US 11,110,063 B2 · Storage stable sincalide formulations

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- Number: US 11,110,063 B2
- Document ID: US11110063B2
- Status: Granted
- Kind: B2
- Application number: 15/958,854
- Filed: 2018-04-20
- Published: 2019-02-28
- Granted: 2021-09-07
- Earliest claimed: 2017-08-25
- Assignees: Maia Pharmaceuticals, Inc.
- Applicants: MAIA Pharmaceuticals, Inc.
- Inventors: Srikanth Sundaram
- Web page: https://patentgrep.com/patent/US11110063B2

## CPC

- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- 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)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/1611: {Inorganic compounds}
- A61K 9/1617: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/1682: {Processes}
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are solid compositions that comprise sincalide and are storage stable and which lack a buffer, and optionally, also lack a surfactant/solubilizer, wherein such compositions are storage stable. Also disclosed herein are liquid compositions that comprise sincalide, wherein such compositions are storage stable, and may lack buffer and/or surfactant/solubilizer. Also provided are methods of making and administering the solid or liquid storage stable compositions to a patient in need of, e.g., for the treatment, prevention, and/or diagnosis of gall bladder- and/or pancreatic disorders; or other diagnostic imaging.

## Claims

### Claim 1

A solid composition comprising:
(i) from 2.5 to 10 mcg of sincalide;
(ii) from 1 to 4 mg of pentetic acid;
(iii) from 15 to 45 mg of arginine hydrochloride;
(iv) from 2 to 8 mg of L-methionine;
(v) from 7.5 to 30 mg of L-lysine hydrochloride;
(vi) from 0.02 to 1 mg of sodium metabisulfite; and
(vii) from 85 to 340 mg of mannitol,
wherein the solid composition comprises a pH of about 6.5 to about 7.5 when reconstituted in a pharmaceutically acceptable diluent,
wherein the solid composition does not contain a phosphate buffer,
wherein the solid composition does not contain a surfactant, a solubilizer, polysorbate 20, or polysorbate 80,
wherein the solid composition is formulated to be reconstituted in a pharmaceutically acceptable diluent for a quantity sufficient to 2.5 to 10 mL, and
wherein the solid composition maintains total impurities less than 5% after 15 months of storage at 25° C., 60% relative humidity or after 3 months of storage at 40° C., 75% relative humidity and optionally wherein the solid composition also maintains a sincalide level of at least 90% after 15 months of storage at 25° C., 60% relative humidity when tested by high-performance liquid chromatography.

### Claim 2 (depends on 1)

The solid composition of claim 1, wherein the solid composition does not contain a buffer having a pKa within one unit of the pH, and wherein the solid composition also does not contain a buffer selected from the group consisting of phosphoric acid, citric acid, citrate, sulfosalicylate, acetic acid, acetate, methyl boronic acid, boronate, disodium succinate hexahydrate, lactic acid, lactate, maleic acid, maleate, potassium chloride, benzoic acid, sodium benzoate, carbonic acid, carbonate, bicarbonate, boric acid, sodium borate, sodium chloride, succinic acid, succinate, tartaric acid, tartrate, tris-(hydroxymethyl)aminomethane, N-2-hydroxyethylpiperazine, N′-2-ethanesulfonic acid, CHAPS, and any combination thereof.

### Claim 3 (depends on 1)

The solid composition of claim 1, wherein the solid composition does not contain a polysorbate.

### Claim 4 (depends on 1)

The solid composition of claim 1, wherein the solid composition comprises:
(i) 5 mcg of sincalide;
(ii) 2 mg of pentetic acid;
(iii) 30 mg of arginine hydrochloride;
(iv) 4 mg of L-methionine;
(v) 15 mg of L-lysine hydrochloride;
(vi) 0.04 mg of sodium metabisulfite; and
(vii) 170 mg of mannitol.

### Claim 5 (depends on 4)

The solid composition of claim 4, wherein the solid composition does not contain a polysorbate.

### Claim 6

A solid composition comprising:
(a) 2.5 to 10 mcg of sincalide,
(b) 1 to 4 mg pentetic acid,
(c) 15 to 45 mg arginine hydrochloride,
(d) 2 to 8 mg methionine,
(e) 7.5 to 30 mg lysine hydrochloride,
(f) 0.02 to 1 mg sodium metabisulfite, and
(g) 85 to 340 mg mannitol,
wherein the solid composition comprises a pH from 6.5 to 7.5 when reconstituted in a pharmaceutically acceptable diluent,
wherein the solid composition does not contain a phosphate buffer,
wherein the solid composition does not contain a surfactant, a solubilizer, polysorbate 20, or polysorbate 80,
wherein the solid composition does not contain a buffer having a pKa within one unit of the pH, and
wherein the solid composition maintains total impurities of less than 5% after 15 months of storage at 25° C., 60% relative humidity or after 3 months of storage at 40° C., 75% relative humidity and optionally wherein the solid composition also maintains a sincalide level of at least 90% after 15 months of storage at 25° C., 60% relative humidity when tested by high-performance liquid chromatography.

### Claim 7 (depends on 1)

The solid composition of claim 1, wherein the solid composition is a lyophilized powder.

### Claim 8 (depends on 1)

A method for the treatment and/or diagnosis of gall bladder and/or pancreatic disorders, or other diagnostic imaging of a patient in need thereof comprising administering a therapeutically or diagnostically effective amount of the solid composition of claim 1 in reconstituted form to the patient.

### Claim 9 (depends on 1)

A method of making the solid composition of claim 1, the method comprising:
(1) mixing:
(i) sincalide,
(ii) pentetic acid,
(iii) arginine hydrochloride,
(iv) L-methionine,
(v) L-lysine hydrochloride,
(vi) sodium metabisulfite,
(vii) mannitol,
(viii) a pH adjuster, and
(ix) water to form a mixture having a pH of about 6.5 to about 7.5, and
(2) lyophilizing the pH-adjusted mixture.

### Claim 10 (depends on 6)

The solid composition of claim 6, wherein the solid composition is a lyophilized powder.

### Claim 11 (depends on 10)

The solid composition of claim 10, wherein the solid composition maintains total impurities of less than 4% and/or a sincalide level of at least 90% after 15 months of storage at 25° C., 60% relative humidity when tested by high-performance liquid chromatography.

### Claim 12 (depends on 10)

The solid composition of claim 10, wherein the solid composition maintains total impurities of less than 3% and/or a sincalide level of at least 90% after 15 months of storage at 25° C., 60% relative humidity when tested by high-performance liquid chromatography.

### Claim 13 (depends on 1)

A vial comprising the solid composition of claim 1.

### Claim 14 (depends on 13)

A kit comprising the vial of claim 13 and a fluid portion.

### Claim 15 (depends on 4)

The solid composition of claim 4, wherein the solid composition does not contain a buffer having a pKa within one unit of the pH, and wherein the solid composition also does not contain a buffer selected from the group consisting of phosphoric acid, citric acid, citrate, sulfosalicylate, acetic acid, acetate, methyl boronic acid, boronate, disodium succinate hexahydrate, lactic acid, lactate, maleic acid, maleate, potassium chloride, benzoic acid, sodium benzoate, carbonic acid, carbonate, bicarbonate, boric acid, sodium borate, sodium chloride, succinic acid, succinate, tartaric acid, tartrate, tris-(hydroxymethyl)aminomethane, N-2-hydroxyethylpiperazine, N′-2-ethanesulfonic acid, CHAPS, and any combination thereof.

### Claim 16 (depends on 6)

The solid composition of claim 6, wherein the solid composition also does not contain a buffer selected from the group consisting of phosphoric acid, citric acid, citrate, sulfosalicylate, acetic acid, acetate, methyl boronic acid, boronate, disodium succinate hexahydrate, lactic acid, lactate, maleic acid, maleate, potassium chloride, benzoic acid, sodium benzoate, carbonic acid, carbonate, bicarbonate, boric acid, sodium borate, sodium chloride, succinic acid, succinate, tartaric acid, tartrate, tris-(hydroxymethyl)aminomethane, N-2-hydroxyethylpiperazine, N′-2-ethanesulfonic acid, CHAPS, and any combination thereof.

### Claim 17 (depends on 1)

The solid composition of claim 1, wherein the solid composition maintains total impurities of less than 5% and a sincalide level of at least 90% for at least 18 months when stored at 25° C., 60% relative humidity.

### Claim 18 (depends on 4)

The solid composition of claim 4, wherein the solid composition maintains total impurities of less than 5% and a sincalide level of at least 90% for at least 18 months when stored at 25° C., 60% relative humidity.

### Claim 19 (depends on 6)

The solid composition of claim 6, wherein the solid composition maintains total impurities of less than 5% and a sincalide level of at least 90% for at least 18 months when stored at 25° C., 60% relative humidity.