# US 10,117,869 B2 · PDE III inhibitors for treatment of asymptomatic heart failure

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,117,869 B2
- Document ID: US10117869B2
- Status: Granted
- Kind: B2
- Application number: 13/832,292
- Filed: 2013-03-15
- Published: 2013-08-08
- Granted: 2018-11-06
- Earliest claimed: 2004-03-25
- Assignees: Boehringer Ingelheim Vetmedica GmbH
- Applicants: Juergen Daemmgen; Olaf Joens; Rainer Kleemann; Christian Troetschel; Andrea Vollmar
- Inventors: Juergen Daemmgen; Olaf Joens; Rainer Kleemann; Christian Troetschel; Andrea Vollmar
- Web page: https://patentgrep.com/patent/US10117869B2

## CPC

- A61K 31/501: not condensed and containing further heterocyclic rings
- A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/4166: having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
- A61K 31/4412: having oxo groups directly attached to the heterocyclic ring
- A61K 31/4427: containing further heterocyclic ring systems
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Phosphodiesterase type III (PDE III) inhibitor or a “Ca2+-sensitizing agent” or a pharmaceutically acceptable derivative thereof is used in the preparation of a medication for the reduction of the heart size of a patient suffering from heart failure, and as a medication for the reverse remodeling of the heart of a patient with asymptomatic (occult) heart failure and their delayed onset of clinical symptoms.

## Claims

### Claim 1

An article of manufacture including:
packaging material; and
at least one pharmaceutical composition contained in the packaging material, the at least one pharmaceutical composition comprising:
a therapeutically effective amount of a phosphodiesterase type III (PDE III) inhibitor comprising pimobendan, wherein said therapeutically effective amount is effective to prolong time until onset of clinical symptoms of heart disease and/or to reduce heart size for a patient having ISACHC (International Small Animal Cardiac Health Council) Class I heart failure; and
a second active therapeutic agent consisting of at least three of benazepril, enalapril, spironolactone, and furosemide.

### Claim 2 (depends on 1)

The article according to claim 1, wherein the PDE III inhibitor further comprises at least one of milrinone, levosimendan, amrinone, enoximone, piroximone, and pharmaceutically acceptable salts thereof.

### Claim 3 (depends on 2)

The article according to claim 2, wherein the PDE III inhibitor further comprises levosimendan.

### Claim 4 (depends on 1)

The article according to claim 1 further comprising a label indicating that the at least one pharmaceutical composition can be used to prolong the time until onset of symptoms and to reduce heart size of a patient having ISACHC (International Small Animal Cardiac Health Council) Class I heart failure.

### Claim 5 (depends on 1)

The article according to claim 1, wherein the reduction of the heart size is expressed in the relative change of the vertebral heart size.

### Claim 6 (depends on 1)

The article according to claim 1, wherein the ISACHC (International Small Animal Cardiac Health Council) Class I heart failure is asymptomatic dilated cardiomyopathy (DCM).

### Claim 7 (depends on 1)

The article according to claim 1, wherein prolongation until onset of clinical symptoms relates to the time from diagnosing the changes of the heart until the beginning of clinical symptoms of ISACHC (International Small Animal Cardiac Health Council) Class II or Class III heart failure.

### Claim 8 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the second active therapeutic agent consists of:
benazepril, spironolactone, and furosemide; or
enalapril, spironolactone, and furosemide.

### Claim 9

A pharmaceutical composition comprising:
a therapeutically effective amount of a phosphodiesterase type III (PDE III) inhibitor comprising pimobendan, wherein said therapeutically effective amount is effective to prolong time until onset of clinical symptoms of heart disease and/or to reduce heart size for a patient having ISACHC (International Small Animal Cardiac Health Council) Class I heart failure; and
a second active therapeutic agent consisting of at least three of benazepril, enalapril, spironolactone, and furosemide;
wherein the pharmaceutical composition includes the PDE III inhibitor and the second active therapeutic agent within a single dosage unit.

### Claim 10 (depends on 9)

The pharmaceutical composition according to claim 9, wherein the PDE III inhibitor further comprises at least one of milrinone, levosimendan, amrinone, enoximone, piroximone, and pharmaceutically acceptable salts thereof.

### Claim 11 (depends on 10)

The pharmaceutical composition according to claim 10, wherein the PDE III inhibitor further comprises levosimendan.

### Claim 12 (depends on 9)

The pharmaceutical composition according to claim 9, wherein the ISACHC (International Small Animal Cardiac Health Council) Class I heart failure is asymptomatic dilated cardiomyopathy (DCM).

### Claim 13 (depends on 9)

The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is in the form of a liquid.

### Claim 14 (depends on 9)

The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is in the form of a tablet and one or both of the pimobendan and the second pharmaceutical active agent is enteric coated within the tablet.

### Claim 15 (depends on 9)

The pharmaceutical composition according to claim 9, wherein the second active therapeutic agent consists of:
benazepril, spironolactone, and furosemide; or
enalapril, spironolactone, and furosemide.