IP Library Granted Patent US 10,471,063
Granted Patent B2
US 10,471,063 · App. 15/614,440 · Granted Nov 12, 2019

Drug combination of PDE3/PDE4 inhibitor and muscarinic receptor antagonist

Inventors: Michael J. A. Walker (Vancouver, CA); Mario Cazzola (Naples, IT); Luigino Calzetta (Rome, IT)
Assignee: Verona Pharma PLC
A61K31/519A61K9/008A61K9/0075A61K9/0078A61K9/0095A61K9/4858A61K31/137A61K31/167A61K31/40A61K31/44A61K31/46A61K45/06A61M15/009A61M2202/064
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Quick Facts
Patent No.
US 10,471,063
App. No.
15/614,440
Granted
Nov 12, 2019
Kind
B2
Abstract

The invention provides a composition which comprises (a) a PDE3/PDE4 inhibitor which is 9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (b) a muscarinic receptor antagonist.

Claims (13)

1. A nebulizer inhaler, a dry powder inhaler or a metered dose inhaler comprising:

(i) a composition which comprises (a) a therapeutically effective amount of a PDE3/PDE4 inhibitor which is 9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof, and (b) a therapeutically effective amount of a muscarinic receptor antagonist which is selected from the group consisting of atropine, methylatropine, homatropine, hyoscyamine, hyoscine, glycopyrrolate, ipratropium, oxitropium, clidinium and mepenzolate; and

(ii) one or more pharmaceutically acceptable carriers, diluents, or excipients.

2. A nebulizer inhaler, a dry powder inhaler or a metered dose inhaler composition according to claim 1 , in which the PDE3/PDE4 inhibitor (a) is 9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one.

3. A nebulizer inhaler, a dry powder inhaler or a metered dose inhaler composition according to claim 1 or 2 , in which the muscarinic receptor antagonist (b) is atropine, hyoscine, glycopyrrolate, ipratropium or oxitropium.

4. A nebulizer inhaler, a dry powder inhaler or a metered dose inhaler composition according to claim 1 , in which the muscarinic receptor antagonist (b) is atropine or glycopyrrolate.

5. A nebulizer inhaler, a dry powder inhaler or a metered dose inhaler composition according to claim 1 , wherein the composition is a fixed combination.

6. A method of treating a disease or condition which is based on acute or chronic obstruction of bronchi or vessels in the respiratory tract, in a subject in need thereof, which method comprises administering by inhalation to said subject (a) a therapeutically effective amount of a PDE3/PDE4 inhibitor which is 9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof, and (b) a therapeutically effective amount of a muscarinic receptor antagonist which is selected from the group consisting of atropine, methylatropine, homatropine, hyoscyamine, hyoscine, glycopyrrolate, ipratropium, oxitropium, clidinium and mepenzolate.

7. A method according to claim 6 , wherein the muscarinic receptor antagonist is selected from the group consisting of atropine, hyoscine, and glycopyrrolate.

8. A method according to claim 6 , wherein the disease or condition is asthma or chronic obstructive pulmonary disease (COPD).

9. A method according to claim 6 , wherein said subject is a human.

10. A method of treating a disease or condition in a subject in need thereof, which method comprises administering by inhalation to said subject (a) a therapeutically effective amount of a PDE3/PDE4 inhibitor which is 9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof simultaneously, separately or sequentially in combination with (b) a therapeutically effective amount of a muscarinic receptor antagonist which is selected from the group consisting of atropine, methylatropine, homatropine, hyoscyamine, hyoscine, glycopyrrolate, ipratropium, oxitropium, clidinium and mepenzolate,

wherein the disease or condition is selected from the group consisting of asthma, allergic asthma, bronchitis, emphysema, bronchiectasis, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), steroid resistant asthma, severe asthma and pediatric asthma.

Assignments (6)
RELEASE OF SECURITY INTEREST Recorded Oct 7, 2025
From: OAKTREE FUND ADMINISTRATION, LLC
To: VERONA PHARMA PLC
Reel/Frame 072495/0271 →
RELEASE OF SECURITY INTEREST IN PATENTS AT R/F 067387/0799 Recorded Mar 25, 2025
From: OAKTREE FUND ADMINISTRATION, LLC, AS AGENT
To: VERONA PHARMA PLC
Reel/Frame 070618/0561 →
SECURITY INTEREST Recorded May 13, 2024
From: VERONA PHARMA PLC
To: OAKTREE FUND ADMINISTRATION, LLC
Reel/Frame 067387/0708 →
SECURITY INTEREST Recorded May 13, 2024
From: VERONA PHARMA PLC
To: OAKTREE FUND ADMINISTRATION, LLC
Reel/Frame 067387/0799 →
CORRECTIVE ASSIGNMENT TO CORRECT THE TYPOGRAPHICAL ERROR IN THE DOC DATE FOR ASSIGNOR MICHAEL J. A. WALKER PREVIOUSLY RECORDED ON REEL 043287 FRAME 0813. ASSIGNOR(S) HEREBY CONFIRMS THE EXECUTION DATE TO BE AS FOLLOWS: MICHAEL J. A. WALKER DOC DATE IS 01/20/2014.. Recorded May 29, 2018
From: WALKER, MICHAEL J. A.; CAZZOLA, MARIO; CALZETTA, LUIGINO
To: VERONA PHARMA PLC
Reel/Frame 046166/0737 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2017
From: WALKER, MICHAEL J. A.; CAZZOLA, MARIO; CALZETTA, LUIGINO
To: VERONA PHARMA PLC
Reel/Frame 043287/0813 →
Continuity (3)
Continuation 14771109
Provisional Application 61799177 · Mar 15, 2013
Related Publication 20170266190A1 · Sep 21, 2017
Cited By (3)
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