# US 2025/0205373 A1 · Enriched and stable radioligand therapy formulations and pharmaceutical compositions comprising same

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- Number: US 2025/0205373 A1
- Document ID: US20250205373A1
- Status: Published application
- Kind: A1
- Application number: 18/968,695
- Filed: 2024-12-04
- Published: 2025-06-26
- Earliest claimed: 2023-12-05
- Applicants: Mariana Oncology Inc.
- Inventors: Julie CUPIDO; Alex SUTTON; Henry MOK; Bernard LAMBERT; Wei ZHANG
- Web page: https://patentgrep.com/patent/US20250205373A1

## CPC

- A61K 51/088: {conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10)}
- A61K 51/121: {Solutions, i.e. homogeneous liquid formulation}
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- 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
- A61K 51/083: {the peptide being octreotide or a somatostatin-receptor-binding peptide}
- A61P 35/00: Antineoplastic agents
- C07B 59/008: {Peptides; Proteins}
- A61K 2121/00: Preparations for use in therapy
- 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
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present disclosure relates to stable compositions comprising a radiolabeled compound, and related pharmaceutical compositions and methods of manufacture. Such compositions are useful in both the diagnostic imaging of and the treatment of diseases (e.g., cancer).

## Claims

### Claim 1

A method of making a stabilized composition of a radiolabeled compound, comprising:
a. eluting a mixture comprising the radiolabeled compound and a corresponding unlabeled compound through a chromatography column, thereby separating the radiolabeled compound from the unlabeled compound;
b. collecting an eluate containing the separated radiolabeled compound in a vessel containing a stabilizing solution to afford the stabilized composition of the radiolabeled compound.

### Claim at position 2

2-4. (canceled)

### Claim 5 (depends on 1)

The method of claim 1, wherein eluting the mixture comprising the radiolabeled compound and unlabeled compound through a chromatography column comprises the use of mobile phase solvents, wherein the mobile phase solvents are pharmaceutically acceptable.

### Claim 6

(canceled)

### Claim 7 (depends on 1)

The method of claim 1, wherein the molar ratio of radiolabeled compound to unlabeled compound, prior to separation, is in the range of about 1:5 to about 1:15000.

### Claim at position 6

8-15. (canceled)

### Claim 16 (depends on 1)

The method of claim 1, wherein the stabilizing solution comprises one or more components selected from the group consisting of L-methionine, a polysorbate, ascorbic acid or a pharmaceutically acceptable salt thereof, and acetic acid or a pharmaceutically acceptable salt thereof.

### Claim at position 8

17-18. (canceled)

### Claim 19 (depends on 16)

The method of claim 16, wherein the mass ratio of ascorbic acid or a pharmaceutically acceptable salt thereof to polysorbate in the stabilizing solution is from 50:1 to 150:1.

### Claim 20 (depends on 16)

The method of claim 16, wherein the ascorbic acid or a pharmaceutically acceptable salt thereof is present in the stabilizing solution in an amount of ≤100 mg/mL.

### Claim 21 (depends on 16)

The method of claim 16, wherein the polysorbate is present in the stabilizing solution in an amount of ≤1 mg/mL.

### Claim at position 12

22-42. (canceled)

### Claim 43 (depends on 1)

The method of claim 1, wherein the radiolabeled compound comprises: (i) a peptide comprising a chelator, and (ii) a radioisotope.

### Claim at position 14

44-50. (canceled)

### Claim 51 (depends on 1)

The method of claim 1, wherein the stabilized composition has a specific molar activity in the range of 60-19500 μCi per nmol compound.

### Claim 52 (depends on 1)

The method of claim 1, wherein the stabilized composition has a specific molar activity in the range of 15-19 mCi per nmol compound.

### Claim at position 17

53-57. (canceled)

### Claim 58 (depends on 43)

The method of claim 43, wherein the mixture comprising the radiolabeled compound and unlabeled compound is prepared by combining the radioisotope and a reagent solution comprising the peptide.

### Claim at position 19

59-64. (canceled)

### Claim 65 (depends on 58)

The method of claim 58, wherein the reagent solution further comprises a reaction buffer.

### Claim 66 (depends on 65)

The method of claim 65, wherein the reaction buffer comprises a stabilizer comprising ascorbic acid or a pharmaceutically acceptable salt thereof.

### Claim at position 22

67-69. (canceled)

### Claim 70 (depends on 58)

The method of claim 58, wherein the reagent solution further comprises ethanol.

### Claim 71

(canceled)

### Claim 72 (depends on 58)

The method of claim 58, wherein the reagent solution does not comprise a polysorbate.

### Claim at position 26

73-77. (canceled)

### Claim 78

A pharmaceutical composition comprising a radiolabeled compound and a stabilizing solution,
wherein the stabilizing solution comprises ascorbic acid or a pharmaceutically acceptable salt thereof and a polysorbate, and one or more components selected from the group consisting of ethanol, L-methionine, selenomethionine, histidine, melatonin, acetic acid or a pharmaceutically acceptable salt thereof, benzyl alcohol, p-aminobenzoic acid or a pharmaceutically acceptable salt thereof, cysteamine, 5-amino-2-hydroxybenzoic acid or a pharmaceutically acceptable salt thereof, nicotinic acid or a pharmaceutically acceptable salt thereof, nicotinamide, cysteine, monothioglycerol, sodium bisulfite, sodium metabisulfite, gentisic acid, and inositol, and
wherein the mass ratio of ascorbic acid or a pharmaceutically acceptable salt thereof to polysorbate in the pharmaceutical composition is from 50:1 to 150:1.

### Claim at position 28

79-83. (canceled)

### Claim 84 (depends on 78)

The pharmaceutical composition of claim 78, wherein the ascorbic acid or a pharmaceutically acceptable salt thereof is present in the pharmaceutical composition in an amount of ≤100 mg/mL.

### Claim 85 (depends on 78)

The pharmaceutical composition of claim 78, wherein the polysorbate is present in the pharmaceutical composition in an amount of ≤1 mg/mL.

### Claim 86

(canceled)

### Claim 87 (depends on 78)

The pharmaceutical composition of claim 78, wherein the pharmaceutical composition comprises L-methionine.

### Claim 88 (depends on 78)

The pharmaceutical composition of claim 78, wherein the pharmaceutical composition comprises acetic acid or a pharmaceutically acceptable salt thereof.

### Claim 89

(canceled)

### Claim 90 (depends on 78)

The pharmaceutical composition of claim 78, wherein the pharmaceutical composition comprises ethanol.

### Claim at position 36

91-99. (canceled)

### Claim 100 (depends on 78)

The pharmaceutical composition of claim 78, wherein the radiolabeled compound comprises: (i) a peptide comprising a chelator, and (ii) a radioisotope.

### Claim at position 38

101-112. (canceled)

### Claim 113 (depends on 78)

The pharmaceutical composition of claim 78, wherein the pharmaceutical composition comprises sodium ascorbate in a concentration of about 40 mg/mL to about 60 mg/mL, L-methionine in a concentration of about 10 mg/mL to about 30 mg/mL, polyoxyethylene (20) sorbitan monolaurate in an amount of from about 0.01% (w/v) to about 0.1% (w/v), ethanol in an amount of from about 1% (v/v) to about 10% (v/v), and acetate in a concentration of about 0.01 M to about 0.1 M.

### Claim at position 40

114-122. (canceled)

### Claim 123 (depends on 78)

The pharmaceutical composition of claim 78, comprising a radiolabeled compound having a specific molar activity in the range of 60-19500 μCi per nmol.

### Claim 124

(canceled)

### Claim 125 (depends on 78)

The pharmaceutical composition of claim 78, wherein the radiolabeled peptide has a specific molar activity in the range of from 15-19 mCi per nmol peptide.

### Claim 126

(canceled)

### Claim 127 (depends on 1)

A pharmaceutical composition prepared using the method as defined in claim 1.

### Claim 128

A pharmaceutical composition comprising:
a radiolabeled compound comprising (i) a peptide comprising a chelator, and (ii) a radioisotope, wherein radioisotope is chelated with the chelator;
ascorbic acid or a pharmaceutically acceptable salt thereof; and
a polysorbate;
wherein the pharmaceutical composition has a radiochemical purity (RCP) of >90% after 72 hours at 2-8° C.

### Claim at position 47

129-140. (canceled)

### Claim 141 (depends on 78)

The pharmaceutical composition of claim 78, wherein the pharmaceutical composition comprises:
a radiolabeled compound comprising (i) a peptide comprising a DOTA chelator and (ii) a radioisotope which is 225Ac, wherein the 225Ac is chelated with the DOTA chelator;
sodium ascorbate, which is present in an amount of ≤100 mg/mL; and
polyoxyethylene (20) sorbitan monolaurate, which is present in an amount of ≤1 mg/mL;
wherein the pharmaceutical composition has an RCP>90% after 72 hours.

### Claim at position 49

142-143. (canceled)

### Claim 144 (depends on 78)

The pharmaceutical composition of claim 78, wherein the pharmaceutical composition comprises:
a radiolabeled compound comprising (i) a peptide comprising a DOTA chelator and (ii) a radioisotope which is 177Lu, wherein the 177Lu is chelated with the DOTA chelator;
sodium ascorbate, which is present in an amount of ≤100 mg/mL; and
polyoxyethylene (20) sorbitan monolaurate, which is present in an amount of ≤1 mg/mL;
wherein the pharmaceutical composition has an RCP>90% after 72 hours.

### Claim 145 (depends on 1)

A method of treating cancer in a subject in need thereof, comprising administering to the subject a stabilized composition prepared by the method as defined in claim 1.

### Claim at position 52

146-147. (canceled)

### Claim 148 (depends on 78)

A method of treating cancer in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 78.

### Claim at position 54

149-150. (canceled)

### Claim 151 (depends on 145)

The method of claim 145, wherein the cancer comprises a cell surface protein characterized by an expression of 1000-100,000 copies per cell.