Granted Patent B2

US 12,599,576 · App. 19/264,750 · Granted Apr 14, 2026

Inventor: Herriot Tabuteau (New York, NY)

Assignee: ANTECIP BIOVENTURES II LLC

A61K31/137A61K9/2009A61K9/2013A61K9/2027A61K9/2054A61K9/2086A61K31/485

Abstract

Claims (20)

1 . A method of improving one or more behaviors associated with agitation in Alzheimer's disease in a CYP2D6 poor metabolizer comprising, selecting a human patient known to be a poor CYP2D6 metabolizer who is experiencing agitation in Alzheimer's disease, and administering, once daily in the morning for at least two weeks to the human patient, a dosage form containing 105 mg of bupropion hydrochloride and 45 mg of dextromethorphan hydrobromide, wherein the dextromethorphan C max of the human patient is 198% to 454% that of the dextromethorphan C max of extensive or ultra-extensive CYP2D6 metabolizers, wherein the one or more behaviors associated with agitation in Alzheimer's disease comprise incoherent babbling, inappropriate emotional response, demands for attention, threats, irritability, frustration, screaming, repetitive questions, mood swings, cursing, abusive language, physical outbursts, emotional distress, restlessness, shredding, sleeping disturbances, delusions, hallucinations, pacing, wandering, searching, rummaging, repetitive body motions, hoarding, shadowing, hitting, scratching, biting, combativeness, hyperactivity, kicking, or a combination thereof.

2 . The method of claim 1 , wherein the dextromethorphan C max of the human patient is about 300% that of the dextromethorphan C max of extensive or ultra-extensive CYP2D6 metabolizers.

3 . The method of claim 1 , wherein the dosage form is a bilayer tablet.

4 . The method of claim 1 , wherein the dosage form is orally administered.

5 . The method of claim 1 , wherein once-daily administration for 8 days avoids the human patient having an about 3-fold increase in the C max of dextromethorphan as compared to the C max of dextromethorphan that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.

6 . The method of claim 1 , wherein once-daily administration for 8 days avoids the human patient having an about 3.4-fold increase in the AUC 0-12 of dextromethorphan as compared to the AUC 0-12 of dextromethorphan that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.

7 . The method of claim 1 , wherein the dextromethorphan is in an immediate-release formulation.

8 . The method of claim 7 , wherein the bupropion is in an extended-release formulation.

9 . The method of claim 1 , wherein the dosage form further comprises carbomer homopolymer, colloidal silicon dioxide, crospovidone, glyceryl monocaprylocaprate, L-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, red iron oxide, sodium lauryl sulfate, stearic acid, talc, titanium dioxide, yellow iron oxide, or a combination thereof.

10 . The method of claim 1 , wherein twice-daily administration of the dosage form to the human patient for 8 days would result in the human patient having about same AUC 0-12 of bupropion as compared to the AUC 0-12 of bupropion that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.

11 . The method of claim 1 , wherein twice-daily administration of the dosage form to the human patient for 8 days would result in the human patient having about same C max of bupropion as compared to the C max of bupropion that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.

12 . A method of improving one or more behaviors associated with agitation in Alzheimer's disease in a CYP2D6 poor metabolizer comprising, selecting a human patient known to be a poor CYP2D6 metabolizer who is experiencing agitation in Alzheimer's disease, and administering, once daily in the morning for at least four weeks to the human patient, a dosage form containing 105 mg of bupropion hydrochloride and 45 mg of dextromethorphan hydrobromide, wherein the dextromethorphan C max of the human patient is 198% to 454% that of the dextromethorphan C max of extensive or ultra-extensive CYP2D6 metabolizers, wherein the one or more behaviors associated with agitation in Alzheimer's disease comprise incoherent babbling, inappropriate emotional response, demands for attention, threats, irritability, frustration, screaming, repetitive questions, mood swings, cursing, abusive language, physical outbursts, emotional distress, restlessness, shredding, sleeping disturbances, delusions, hallucinations, pacing, wandering, searching, rummaging, repetitive body motions, hoarding, shadowing, hitting, scratching, biting, combativeness, hyperactivity, kicking, or a combination thereof.

13 . The method of claim 12 , wherein the dextromethorphan C max of the human patient is about 300% that of the dextromethorphan C max of extensive or ultra-extensive CYP2D6 metabolizers.

14 . The method of claim 12 , wherein the dosage form is a bilayer tablet.

15 . The method of claim 12 , wherein the dosage form is orally administered.

16 . The method of claim 12 , wherein the dextromethorphan is in an immediate-release formulation.

17 . The method of claim 16 , wherein the bupropion is in an extended-release formulation.

18 . The method of claim 12 , wherein the dosage form further comprises carbomer homopolymer, colloidal silicon dioxide, crospovidone, glyceryl monocaprylocaprate, L-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, red iron oxide, sodium lauryl sulfate, stearic acid, talc, titanium dioxide, yellow iron oxide, or a combination thereof.

19 . The method of claim 12 , wherein twice-daily administration of the dosage form to the human patient for 8 days would result in the human patient having about same AUC 0-12 of bupropion as compared to the AUC 0-12 of bupropion that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.

20 . The method of claim 12 , wherein twice-daily administration of the dosage form to the human patient for 8 days would result in the human patient having about same C max of bupropion as compared to the C max of bupropion that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.

Assignments (1)

Continuity (7)

References Cited (400)