Claims for Patent: 12,622,921

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Summary for Patent: 12,622,921

Title:	Stable formulations comprising thiotepa
Abstract:	The present disclosure provides pharmaceutical compositions comprising thiotepa and one selected from PEG, such as PEG400 or PEG600, and DMSO, and optionally water or an aqueous saline solution and thiosulfate. The composition is free or substantially free of impurities. Also provided is a method for treating cancer in a subject, or myeloablation prior to bone marrow transplantation using the composition. A method for enhancing the stability of a thiotepa formulation is also contemplated.
Inventor(s):	Sharon Cunningham, Orlaith RYAN, Johannes Jan Platteeuw
Assignee:	Shorla Pharma Ltd
Application Number:	US17/897,839
Patent Claims:	1. A method for treating cancer or inducing myeloablation prior to bone marrow transplantation or controlling intracavitary effusions secondary to diffuse or localized, neoplastic diseases of various serosal cavities in a subject in need thereof comprising: administering to the subject a composition comprising thiotepa and a solvent, wherein the solvent is selected from the group consisting of dimethylsulfoxide (DMSO), polyethylene glycol 400 (PEG400), polyethylene glycol 600 (PEG600), dimethylacetamide (DMA), and N-methylpyrrolidone (NMP), and wherein the thiotepa is present in an amount between about 1 and about 100 mg/mL, wherein the composition is substantially free of an impurity, wherein the impurity is one or more selected from the group consisting of formic acid, acetic acid, formaldehyde, acetaldehyde, and peroxide, and wherein the cancer is selected from the group consisting of bladder cancer, malignant meningeal neoplasm, breast cancer, ovarian cancer, lymphoma, and leptomeningeal metastasis. 2. The method of claim 1, wherein the impurity is present in an amount selected from the group consisting of less than about 150 ppm, less than about 100 ppm, less than about 35 ppm, less than about 30 ppm, less than about 25 ppm, less than about 20 ppm, less than about 15 ppm, less than about 10 ppm, and less than about 5 ppm. 3. The method of claim 1, wherein the composition does not comprise water. 4. The method of claim 3, wherein the composition comprises one or more of: less than about 150 ppm formic acid; less than about 15 ppm acetic acid; less than about 15 ppm formaldehyde; less than about 15 ppm acetaldehyde; or less than about 35 ppm peroxide. 5. The method of claim 4, wherein the composition comprises: less than about 150 ppm formic acid; less than about 15 ppm acetic acid; less than about 15 ppm formaldehyde; less than about 15 ppm acetaldehyde; and less than about 35 ppm peroxide. 6. The method of claim 5, wherein the composition comprises thiotepa and PEG400. 7. The method of claim 5, wherein the composition comprises thiotepa and PEG600. 8. The method of claim 5, wherein the composition comprises thiotepa and DMSO. 9. The method of claim 1, wherein the composition further comprises water. 10. The method of claim 9, wherein the water is present in an amount selected from the group consisting of up to about 30%, up to about 25%, up to about 20%, up to about 15%, up to about 10%, and up to about 5%. 11. The method of claim 10, wherein the composition comprises one or more of: less than about 150 ppm formic acid; less than about 15 ppm acetic acid; less than about 15 ppm formaldehyde; less than about 15 ppm acetaldehyde; or less than about 35 ppm peroxide. 12. The method of claim 11, wherein the composition comprises: less than about 150 ppm formic acid; less than about 15 ppm acetic acid; less than about 15 ppm formaldehyde; less than about 15 ppm acetaldehyde; and less than about 35 ppm peroxide. 13. The method of claim 12, wherein the composition comprises thiotepa and PEG400. 14. The method of claim 12, wherein the composition comprises thiotepa and PEG600. 15. The method of claim 12, wherein the composition comprises thiotepa and DMSO. 16. The method of claim 9, wherein the water is an aqueous saline solution. 17. The method of claim 1, wherein the composition further comprises thiosulfate. 18. The method of claim 17, wherein the thiosulfate is present in an amount of about 0.01% to about 1.0%. 19. The method of claim 1, wherein the composition is administered via injection which is selected from the group consisting of subcutaneous injection, intramuscular injection, intravenous injection, infusion, intraperitoneal injection, intrapleural injection, intrapericardial injection, intracavitary injection, intrathecal injection, intra-arterial injection, intravesical injection, and intralesional injection. 20. The method of claim 1, comprising administering about 300 mg to about 700 mg thiotepa. 21. A method for enhancing the stability of a thiotepa formulation comprising: combining thiotepa, and a component selected from PEG and DMSO; and homogenizing the combination, wherein the concentration of thiotepa after the step of homogenizing is between about 1 and about 100 mg/mL, wherein the formulation is substantially free of an impurity, and wherein the impurity is one or more selected from the group consisting of formic acid, acetic acid, formaldehyde, acetaldehyde, and peroxide. 22. The method of claim 1, wherein the method reduces a risk of graft rejection, and wherein the cancer includes adenocarcinoma of the breast or ovary and superficial papillary carcinoma of the urinary bladder. 23. The method of claim 1, comprising administering about 20 mg to about 40 mg thiotepa.