Claims for Patent: 12,516,025

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Summary for Patent: 12,516,025

Title:	Cabozantinib compositions and methods of use
Abstract:	The present invention relates to oral compositions comprising cabozantinib salts and at least one pharmaceutically acceptable excipient and methods of using the oral compositions to increase the oral bioavailability of the cabozantinib and reduce the adverse events associate with the oral administration of cabozantinib. The invention also relates to methods for preparing cabozantinib lauryl sulfate salts.
Inventor(s):	Fang-Yu Liu, K. C. Sung, Yu Zhang, Shang Wei Qin, John Duan, George Kraft
Assignee:	Handa Oncology LLC
Application Number:	US19/184,766
Patent Claims:	1. A method for treating a human subject in need of cabozantinib treatment comprising orally administering to the subject a daily dose of about 7.5 mg to about 80 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt wherein the administration is once a day and comprises administering one or more capsules wherein the contents of the one or more capsules comprise: (i) about 7.5 mg to about 80 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt; and (ii) about 50 wt % to about 90 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with a hydrophilic-lipophilic balance (HLB) value of about 10 or greater selected from the group consisting of wetting agents, emulsifying agents, solubilizing surfactants and combinations thereof; and wherein the once daily administration of the one or more capsules results in a Cmax coefficient of variation of less than 30%. 2. The method of claim 1 wherein the daily dose comprises about 10 mg to about 50 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate. 3. The method of claim 1 wherein the one or more polyoxyethylene pharmaceutical acceptable excipients with an HLB value of about 10 or greater is selected from the group consisting of polyoxyethylene castor oil, polyoxyethylene stearates, polyoxyethylene hydrogenated castor oil, poloxamer, polyoxyethylene alkyl ethers, polyoxyethylene-polyoxypropylene copolymer or combinations thereof. 4. The method of claim 1 wherein the administrating step comprises one capsule administered once a day and the contents of the capsule comprise: (i) about 10 mg to about 40 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt; and (ii) about 60 wt % to about 85 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with an HLB value of about 10 or greater wherein the polyoxyethylene pharmaceutical acceptable excipient is a polyoxyethylene stearate with an HLB value of 12 or greater. 5. The method of claim 1 wherein the contents of the one or more capsules further comprise at least one additional pharmaceutically acceptable excipient selected from the group consisting of stabilizers, fillers, viscosity enhancing agents, binders, disintegrants, lubricants, glidants, flavoring agents, and combinations thereof. 6. The method of claim 1 wherein the Cmax coefficient of variation is less than 25%. 7. A method for treating a human subject in need of cabozantinib treatment comprising orally administering to the subject a daily dose of about 7.5 mg to about 80 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt wherein the administration is once a day and comprises administering one or more capsules wherein the contents of the one or more capsules comprise: (i) about 7.5 mg to about 80 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt; and (ii) about 50 wt % to about 90 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with a hydrophilic-lipophilic balance (HLB) value of about 10 or greater selected from the group consisting of wetting agents, emulsifying agents, solubilizing surfactants and combinations thereof; and wherein the once daily administration of the one or more capsules results in an AUC0-72, AUC0-168 or AUC0-∞ coefficient of variation of less than 30%. 8. The method of claim 7 wherein the daily dose comprises about 10 mg to about 50 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate. 9. The method of claim 7 wherein the one or more polyoxyethylene pharmaceutical acceptable excipients with an HLB value of about 10 or greater is selected from the group consisting of polyoxyethylene castor oil, polyoxyethylene stearates, polyoxyethylene hydrogenated castor oil, poloxamer, polyoxyethylene alkyl ethers, polyoxyethylene-polyoxypropylene copolymer or combinations thereof. 10. The method of claim 7 wherein the administrating step comprises one capsule administered once a day and the contents of the capsule comprise: (i) about 10 mg to about 40 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt; and (ii) about 60 wt % to about 85 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with an HLB value of about 10 or greater wherein the polyoxyethylene pharmaceutical acceptable excipient is a polyoxyethylene stearate with an HLB value of 12 or greater. 11. The method of claim 7 wherein the contents of the one or more capsules further comprise at least one additional pharmaceutically acceptable excipient selected from the group consisting of stabilizers, fillers, viscosity enhancing agents, binders, disintegrants, lubricants, glidants, flavoring agents, and combinations thereof. 12. The method of claim 7 wherein the AUC0-72, AUC0-168 or AUC0-∞ coefficient of variation is less than 25%. 13. The method of claim 7 wherein the AUC0-72, AUC0-168 or AUC0-∞ is AUC0-72. 14. A method for treating a human subject in need of cabozantinib treatment comprising orally administering to the subject a daily dose of about 7.5 mg to about 80 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt wherein the administration is once a day and comprises administering one or more capsules wherein the contents of the one or more capsules comprise: (i) about 7.5 mg to about 80 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt; and (ii) about 50 wt % to about 90 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with a hydrophilic-lipophilic balance (HLB) an HLB value of about 10 or greater selected from the group consisting of wetting agents, emulsifying agents, solubilizing surfactants and combinations thereof; and wherein the once daily administration of the one or more capsules results in a Cmax and an AUC0-72, AUC0-168 or AUC0-∞ coefficient of variation of less than 30%. 15. The method of claim 14 wherein the daily dose comprises about 10 mg to about 50 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate. 16. The method of claim 14 wherein the one or more polyoxyethylene pharmaceutical acceptable excipients with an HLB value of about 10 or greater is selected from the group consisting of polyoxyethylene castor oil, polyoxyethylene stearates, polyoxyethylene hydrogenated castor oil, poloxamer, polyoxyethylene alkyl ethers, polyoxyethylene-polyoxypropylene copolymer or combinations thereof. 17. The method of claim 14 wherein the administrating step comprises one capsule administered once a day and the contents of the capsule comprise: (i) about 10 mg to about 40 mg of cabozantinib free base in the form of cabozantinib lauryl sulfate salt; and (ii) about 60 wt % to about 85 wt % of one or more polyoxyethylene pharmaceutical acceptable excipients with an HLB value of about 10 or greater wherein the polyoxyethylene pharmaceutical acceptable excipient is a polyoxyethylene stearate with an HLB value of 12 or greater. 18. The method of claim 14 wherein the contents of the one or more capsules further comprise at least one additional pharmaceutically acceptable excipient selected from the group consisting of stabilizers, fillers, viscosity enhancing agents, binders, disintegrants, lubricants, glidants, flavoring agents, and combinations thereof. 19. The method of claim 14 wherein the Cmax and the AUC0-72, AUC0-168 or AUC0-∞ coefficient of variation is less than 25%. 20. The method of claim 14 wherein the AUC0-72, AUC0-168 or AUC0-∞ is AUC0-72.