KIT, COMPOSITION, AND COMBINATION THERAPY FOR FRAGILE X SYNDROME

• US 20190314309A1
• Filed: 04/12/2019
• Published: 10/17/2019
• Est. Priority Date: 04/13/2018
• Status: Active Grant

• Current Assignee: Healx Limited
• Original Assignee: Healx Limited
• Inventors: Brown, David
• Granted Patent: US 11,590,093 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

Described herein are kits, compositions, and combination therapies comprising sulindac for use in the treatment of fragile X syndrome (FXS).

Claims

1-3. -3. (canceled)

5-17. -17. (canceled)

18. A kit comprising:

(i) sulindac, or a pharmaceutically acceptable salt thereof; and

(ii) Compound A, or a pharmaceutically acceptable salt thereof, wherein Compound A is selected from the group consisting of;

minocycline, doxycycline, lovastatin, metformin, epigallocatechin gallate, lithium, tideglusib, lamotrigine, acamprosate, ganaxolone, basimglurant, mavoglurant, methylphenidate, L-carnitine, L-acetyl carnitine, zardaverine, ibudilast, metoprolol, penbutolol, fasudil, carbamazepine, midostaurin, sildenafil, tadalafil, gabapentin, stiripentol, ganaxolone, donepezil tetracyclines, cannabidiol, curcumin, simvastatin, atorvastatin, pravastatin, fluvastatin, rosuvastatin, pitavastatin, apigenin, telmisartan, medium and long chain fatty acids, indirubin, pregabalin, baclofen, arbaclofen, memantine, ethchlorvynol, fenobam, riluzole, crisaborole, S-rolipram, apremilast, cilomilast, roflumilast, dipyridamole, drotaverine, propentofylline, caffeine, papaverine, trapidil, flavoxate, amlexano X, pentoxifylline, propanolol, pindolol, acebutalol, bisoprolol, carvedilol, labetalol, metipranolol, oxprenalol, pindolol, tertatolol, timolol, topiramate, tianeptine, quercetin, disulfiram, imatinib, gefitinib, selumetinib, refametinib, fusidic acid, sertraline, lorazepam, phenobarbital, vardenafil, udenafil, avanafil, ruxolitinib, momelotinib, bortezomib, carfilzomib, carnosol, riluzole, luteolin, carnosic acid, resveratrol, methylphenidate, menadione, taurine, niacin, clorazepic acid, diazepam and other ‘

azepam’

class drugs, chlordiazepoxide, staurosporin, gaboxadol, progabide, tulrampator, ketamine, decanoic acid, piracetam, pramiracetam, dexmethylphenidate, oglemilast, levetiracetam and vigabatrin.

4. The kit of claim 18, wherein Compound A is selected from the group consisting of ibudilast, sertraline, quercetin, cannabidiol, minocycline, topiramate and metoprolol.

19-21. -21. (canceled)

22. A composition comprising:

(i) sulindac, or a pharmaceutically acceptable salt thereof; and

(ii) Compound A, or a pharmaceutically acceptable salt thereof, wherein Compound A is selected from the group consisting of;

minocycline, doxycycline, lovastatin, metformin, epigallocatechin gallate, lithium, tideglusib, lamotrigine, acamprosate, ganaxolone, basimglurant, mavoglurant, methylphenidate, L-carnitine, L-acetyl carnitine, zardaverine, ibudilast, metoprolol, penbutolol, fasudil, carbamazepine, midostaurin, sildenafil, tadalafil, gabapentin, stiripentol, donepezil, tetracyclines, cannabidiol, curcumin, simvastatin, atorvastatin, pravastatin, fluvastatin, rosuvastatin, pitavastatin, apigenin, telmisartan, medium and long chain fatty acids, indirubin, pregabalin, baclofen, arbaclofen, memantine, ethchlorvynol, fenobam, riluzole, crisaborole, S-rolipram, apremilast, cilomilast, roflumilast, dipyridamole, drotaverine, propentofylline, caffeine, papaverine, trapidil, flavoxate, amlexano X, pentoxifylline, propanolol, pindolol, acebutalol, bisoprolol, carvedilol, labetalol, metipranolol, oxprenalol, pindolol, tertatolol, timolol, topiramate, tianeptine, quercetin, disulfiram, imatinib, gefitinib, selumetinib, refametinib, fusidic acid, sertraline, lorazepam, phenobarbital, vardenafil, udenafil, avanafil, ruxolitinib, momelotinib, bortezomib, carfilzomib, carnosol, riluzole, luteolin, carnosic acid, resveratrol, methylphenidate, menadione, taurine, niacin, clorazepic acid, diazepam and other ‘

azepam’

class drugs, chlordiazepoxide, staurosporin, gaboxadol, progabide, tulrampator, ketamine, decanoic acid, piracetam, pramiracetam, dexmethylphenidate, oglemilast, levetiracetam and vigabatrin.

23. (canceled)

24. A method of treating fragile x syndrome in a subject in need thereof comprising administering to the subject simultaneously, separately or sequentially:

(i) sulindac, or a pharmaceutically acceptable salt thereof; and

(ii) Compound A, or a pharmaceutically acceptable salt thereof, wherein Compound A is selected from the group consisting of;

minocycline, doxycycline, lovastatin, metformin, epigallocatechin gallate, lithium, tideglusib, lamotrigine, acamprosate, ganaxolone, basimglurant, mavoglurant, methylphenidate, L-carnitine, L-acetyl carnitine, zardaverine, ibudilast, metoprolol, penbutolol, fasudil, carbamazepine, midostaurin, sildenafil, tadalafil, gabapentin, stiripentol, ganaxolone, donepezil, tetracyclines, cannabidiol, curcumin, simvastatin, atorvastatin, pravastatin, fluvastatin, rosuvastatin, pitavastatin, apigenin, telmisartan, medium and long chain fatty acids, indirubin, pregabalin, baclofen, arbaclofen, memantine, ethchlorvynol, fenobam, riluzole, crisaborole, S-rolipram, apremilast, cilomilast, roflumilast, dipyridamole, drotaverine, propentofylline, caffeine, papaverine, trapidil, flavoxate, amlexano X, pentoxifylline, propanolol, pindolol, acebutalol, bisoprolol, carvedilol, labetalol, metipranolol, oxprenalol, pindolol, tertatolol, timolol, topiramate, tianeptine, quercetin, disulfiram, imatinib, gefitinib, selumetinib, refametinib, fusidic acid, sertraline, lorazepam, phenobarbital, vardenafil, udenafil, avanafil, ruxolitinib, momelotinib, bortezomib, carfilzomib, carnosol, riluzole, luteolin, carnosic acid, resveratrol, methylphenidate, menadione, taurine, niacin, clorazepic acid, diazepam and other ‘

azepam’

class drugs, chlordiazepoxide, staurosporin, gaboxadol, progabide, tulrampator, ketamine, decanoic acid, piracetam, pramiracetam, dexmethylphenidate, oglemilast, levetiracetam and vigabatrin.

30. The method of claim 24, wherein Compound A is selected from the group consisting of minocycline, doxycycline, lovastatin, metformin, epigallocatechin gallate, quercetin, lithium, sertraline, topiramate, cannabidiol, tideglusib, lamotrigine, acamprosate, ganaxolone, basimglurant, mavoglurant, methylphenidate, L-carnitine, L-acetyl carnitine, zardaverine, ibudilast, metoprolol, penbutolol, fasudil, carbamazepine, midostaurin, gabapentin, stiripentol, fenobam and donepezil.

31. The method of claim 24, wherein Compound A is selected from the group consisting of minocycline, doxycycline, lovastatin, metformin, lithium, sertraline, topiramate, cannabidiol, zardaverine, ibudilast, fasudil, midostaurin, fenobam, metoprolol and donepezil.

32. The method of claim 24, wherein Compound A is selected from the group consisting of ibudilast, sertraline, quercetin, cannabidiol, minocycline, topiramate and metoprolol.

33. The method of claim 24, wherein Compound A is selected from the group consisting of ibudilast, sertraline, quercetin, cannabidiol, minocycline and topiramate.

34. The method of claim 24, wherein the subject exhibits signs of hyperactivity, social anxiety, memory loss, or disruptive behaviour.

35. The method of claim 24, wherein the subject is human.

36. The method of claim 24, wherein sulindac and Compound A are administered simultaneously in a single dose once per day.

37. The method of claim 36, wherein the single dose comprises 200 mg to 400 mg of sulindac.

38. The method of claim 24, wherein sulindac and Compound A are administered simultaneously in a single dose twice per day.

39. The method of claim 38, wherein the single dose comprises 150 mg to 200 mg of sulindac.

40. The method of claim 24, wherein sulindac and Compound A are administered orally.

41. The method of claim 24, wherein sulindac and Compound A are administered parenterally, transdermally, sublingually, rectally or by inhalation.

42. The method of claim 24, wherein the subject is human;

and sulindac and Compound A are administered simultaneously in a single dose once per day.

43. The method of claim 24, wherein the subject is human;

and sulindac and Compound A are administered simultaneously in a single dose twice per day.

44. The method of claim 24, wherein Compound A is selected from the group consisting of ibudilast, sertraline, quercetin, cannabidiol, minocycline and topiramate;

the subject is human; and

sulindac and Compound A are administered simultaneously in a single dose once per day.

45. The method of claim 24, wherein Compound A is selected from the group consisting of ibudilast, sertraline, quercetin, cannabidiol, minocycline and topiramate;

the subject is human; and

sulindac and Compound A are administered simultaneously in a single dose twice per day.

25-29. -29. (canceled)