IP Library Granted Patent US 9,700,558
Granted Patent B2
US 9,700,558 · App. 14/771,109 · Granted Jul 11, 2017

Drug combination of PDE3/PDE4 inhibitor and muscarinic receptor antagonist

Inventors: Michael J. A. Walker (Vancouver, CA); Mario Cazzola (Napoli, 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 9,700,558
App. No.
14/771,109
Granted
Jul 11, 2017
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 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, wherein the muscarinic receptor antagonist is atropine or glycopyrrolate.

2. A 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 ]soquinolin-4-one.

3. A composition according to claim 1 , in which the muscarinic receptor antagonist (b) is atropine.

4. A composition according to claim 1 , in which the muscarinic receptor antagonist (b) is glycopyrrolate.

5. A composition according to claim 1 , wherein the composition is a fixed combination.

6. A pharmaceutical composition comprising a composition as defined in claim 1 and one or more pharmaceutically acceptable carriers, diluents, or excipients.

7. A pharmaceutical composition according to claim 6 which is for administration by dry powder inhaler (DPI) or metered-dose inhaler (MDI).

8. 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 to said subject a therapeutically effective, non-toxic amount of a composition comprising (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, wherein the muscarinic receptor antagonist is atropine or glycopyrrolate.

9. A method according to claim 8 , wherein the disease or condition is asthma.

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

11. A method according to claim 8 , wherin said subject is a human.

12. 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 to said subject (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 simultaneously, separately or sequentially in combination with (b) a muscarinic receptor antagonist, wherein the muscarinic receptor antagonist is atropine or glycopyrrolate.

13. A method of treating a disease or condition which is based on acute or chronic obstruction of bronchi or vessels in the respiratory tract, which method comprises administering to said subject (b) a muscarinic receptor antagonist simultaneously in combination with (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[6,1a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof, wherein the muscarinic receptor antagonist is atropine or glycopyrrolate.

Assignments (7)
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 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 8, 2016
From: CAZZOLA, MARIO
To: VERONA PHARMA PLC
Reel/Frame 037688/0117 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 8, 2016
From: CALZETTA, LUIGINO
To: VERONA PHARMA PLC
Reel/Frame 037688/0148 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 8, 2016
From: WALKER, MICHAEL J. A.
To: VERONA PHARMA PLC
Reel/Frame 037688/0108 →
Continuity (2)
Provisional Application 61799177 · Mar 15, 2013
Related Publication 20160000790A1 · Jan 7, 2016