Granted Patent B2

US 11,103,559 · App. 16/845,229 · Granted Aug 31, 2021

Inventor: Steven Hoffman (Mahwah, NJ)

Assignee: Tyme, Inc.

A61K38/34A61K9/0019A61K9/0053A61K9/10A61K9/48A61K31/19A61K31/198A61K31/216A61K31/366A61K31/4166A61K31/436A61K31/55A61K31/787A61K38/12

Abstract

Claims (34)

1. A method of treating cervical cancer in a subject comprising administering an effective amount of a tyrosine hydroxylase inhibitor; a melanin promoter; a p450 3A4 promoter; and a leucine aminopeptidase inhibitor to the subject in need thereof, wherein:

the melanin promoter is methoxsalen or melanotan II;

the p450 3A4 promoter is 5, 5-diphenylhydantoin, valproic acid, or carbamazepine; and

the leucine aminopeptidase inhibitor is N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl]-L-leucine or rapamycin.

2. The method of claim 1 , further comprising administering a growth hormone inhibitor.

3. The method of claim 1 , wherein at least two of the promoters and inhibitors are administered simultaneously.

4. The method of claim 1 , wherein at least three of the promoters and inhibitors are administered simultaneously.

5. The method of claim 1 , wherein each of the promoters and inhibitors is administered simultaneously.

6. The method of claim 1 , wherein the promoters and inhibitors are administered orally, subcutaneously, intravenously, transdermally, vaginally, rectally or in any combination thereof.

7. The method of claim 6 , wherein the transdermal administration is done with oleic acid, 1-methyl-2-pyrrolidone, or dodecylnonaoxyethylene glycol monoether.

8. The method of claim 1 , wherein the promoters and inhibitors are administered during a cycle consisting of five to seven days of administering the promoters and inhibitors and one to two days of not administering the promoters and inhibitors.

9. The method of claim 8 , wherein the promoters and inhibitors are administered over the course of at least six of said cycles.

10. The method of claim 1 , wherein the tyrosine hydroxylase inhibitor is a tyrosine derivative.

11. The method of claim 10 , wherein the tyrosine derivative is one or more of methyl (2R)-2-amino-3-(2-chloro-4 hydroxyphenyl) propanoate, D-tyrosine ethyl ester hydrochloride, methyl (2R)-2-amino-3-(2,6-dichloro-3,4-dimethoxyphenyl) propanoate H-D-Tyr(TBU)-allyl ester HCl, methyl (2R)-2-amino-3-(3-chloro-4,5-dimethoxyphenyl) propanoate, methyl (2R)-2-amino-3-(2-chloro-3-hydroxy-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(4-[(2-chloro-6-fluorophenyl) methoxy] phenyl) propanoate, methyl (2R)-2-amino-3-(2-chloro-3,4-dimethoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-5-fluoro-4-hydroxyphenyl) propanoate, diethyl 2-(acetylamino)-2-(4-[(2-chloro-6-fluorobenzyl) oxy] benzyl malonate, methyl (2R)-2-amino-3-(3-chloro-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-4-hydroxy-5-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(2,6-dichloro-3-hydroxy-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-4-hydroxyphenyl) propanoate, H-DL-tyr-OMe HCl, H-3,5-diiodo-tyr-OMe HCl, H-D-3,5-diiodo-tyr-OME HCl, D-tyrosine methyl ester hydrochloride, (2R)-2-amino-3-(4-hydroxyphenyl) propionic acid, (2R)-2-amino-3-(4-hydroxyphenyl) methyl ester hydrochloride, methyl (2R)-2-amino-3-(4-hydroxyphenyl) propanoate hydrochloride, methyl (2R)-2-azanyl-3-(4-hydroxyphenyl) propanoate hydrochloride, 3-chloro-L-tyrosine, 3-nitro-L-tyrosine, 3-nitro-L-tyrosine ethyl ester hydrochloride, DL-m-tyrosine, DL-o-tyrosine, Boc-Tyr (3,5-I2)-OSu, Fmoc-tyr(3-NO 2 )-OH, and α-methyl-DL-tyrosine.

12. The method of claim 11 , wherein the tyrosine derivative is α-methyl-DL tyrosine.

13. The method of claim 11 , wherein 60 mg of the tyrosine derivative is administered orally and 0.25 mL of a 2 mg/mL suspension of the tyrosine derivative is administered subcutaneously.

14. The method of claim 1 , wherein the melanin promoter is methoxsalen.

15. The method of claim 14 , wherein 10 mg of the methoxsalen is administered orally and 0.25 mL of a 1 mg/mL suspension of the methoxsalen is administered subcutaneously.

16. The method of claim 1 , wherein the melanin promoter is melanotan II.

17. The method of claim 1 , wherein the p450 3A4 promoter is 5, 5-diphenylhydantoin.

18. The method of claim 17 , wherein 30 mg of the 5, 5-diphenylhydantoin is administered orally.

19. The method of claim 1 , wherein the p450 3A4 promoter is valproic acid or carbamazepine.

20. The method of claim 1 , wherein the leucine aminopeptidase inhibitor is N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl]-L-leucine.

21. The method of claim 20 , wherein 20 mg of the N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl]-L-leucine is administered orally.

22. The method of claim 1 , wherein the leucine aminopeptidase inhibitor is rapamycin.

23. The method of claim 20 , wherein the p450 3A4 promoter is 5,5-diphenylhydantoin.

24. The method of claim 23 , wherein the melanin promoter is melanotan II.

25. The method of claim 1 , further comprising administering an effective amount of D-leucine.

26. The method of claim 24 , wherein the tyrosine derivative is α-methyl-DL tyrosine.

27. The method of claim 1 , wherein the melanin promoter is melanotan II; the p450 3A4 promoter is 5, 5-diphenylhydantoin; and the tyrosine hydroxy lase inhibitor is α-methyl-DL tyrosine.

28. The method of claim 27 , wherein the leucine aminopeptidase inhibitor is N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl]-L-leucine.

29. The method of claim 27 , wherein the leucine aminopeptidase inhibitor is rapamycin.

30. The method of claim 1 , further comprising assessing progression of the cervical cancer in said subject.

31. The method of claim 2 , further comprising assessing progression of the cervical cancer in said subject.

Assignments (2)

Continuity (9)