Therapy for kidney disease and/or heart failure

• US 9,616,107 B2
• Filed: 11/26/2014
• Issued: 04/11/2017
• Est. Priority Date: 02/25/2011
• Status: Active Grant

• Current Assignee: Capricor Therapeutics, Inc.
• Original Assignee: Capricor Therapeutics, Inc.
• Inventors: VanAntwerp, William P., Walsh, Andrew J. L., Manda, VenKatesh R., Burnes, John
• Primary Examiner(s): Shafer, Shulamith H
• Application Number:
  US14/555,016
• Publication Number:
  US 20150190473A1
• Time in Patent Office: 867 Days
• Field of Search: None
• CPC Class Codes: A61K 38/2242 Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61M 5/14228 with linear peristaltic action, i.e. comprising at least three pressurising members or a helical member
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

Medical systems and methods for treating kidney disease alone, heart failure alone, chronic kidney disease with concomitant heart failure, or cardiorenal syndrome are described. The systems and methods are based on delivery of a natriuretic peptide such as Vessel Dilator to a subject. Methods for increasing and maintaining peptide levels at a certain concentration include direct peptide delivery via either an external or implantable programmable pump.

Claims

1. A method, comprising the steps of:

continuously administering a natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, or with concomitant kidney disease and heart failure or cardiorenal syndrome using a drug provisioning component to chronically deliver a therapeutically effective amount of the natriuretic peptide to the subject at a rate which maintains a subject-specific mean steady state plasma concentration, and

maintaining the plasma concentration of the natriuretic peptide within a specified range,

wherein the specified range is pre-determined by administering a test dose of the natriuretic peptide to the subject so that the specified range is not greater than a plasma concentration of the natriuretic peptide reached in the subject during either a subcutaneous bolus at 18,000 ng/kg or a 1 hour intravenous infusion of the natriuretic peptide at 300 ng/(kg·

min) based on the subject'"'"'s body weight, and

wherein the drug provisioning component delivers the natriuretic peptide subcutaneously for multiple days.

2. The method of claim 1, wherein the natriuretic peptide is selected from any one of long-acting natriuretic peptide (LANP), kaliuretic peptide (KP), urodilatin (URO), atrial natriuretic peptide (ANP), vessel dilator (VD) and brain natriuretic peptide (BNP).

3. The method of claim 1, wherein the drug provisioning component is selected from an external or implantable drug delivery pump, an implanted or percutaneous vascular access port, a direct delivery catheter system, and a local drug-release device, and the drug provisioning component delivers the natriuretic peptide at a fixed, pulsed, continuous or variable rate.

4. The method of claim 1, wherein the specified range is not greater than a plasma concentration of the natriuretic peptide reached during either a subcutaneous bolus of the natriuretic peptide at 6000 ng/kg or a 1 hour intravenous infusion of the natriuretic peptide at 100 ng/kg·

min in the subject.

5. The method of claim 1, wherein the drug provisioning component subcutaneously delivers a therapeutically effective amount of the natriuretic peptide at a continuous rate (ng/kg of body weight) matching the area under the curve of a subcutaneous bolus at 6000 ng/kg of the subject.

6. The method of claim 1, further comprising the step of calculating a dosing schedule based on the subject'"'"'s body weight.

7. The method of claim 6, further comprising the step of adjusting the dosing schedule to meet pharmacokinetic variables calculated from one or more subject parameters, wherein the pharmacokinetic variables are selected from any one of area under the curve, clearance, volume of distribution, half-life, elimination rates, minimum inhibitory concentrations, route of administration, endogenous concentrations of the natriuretic peptides, diurnal variation, and rate of drug delivery.

8. A method for administering a natriuretic peptide to a subject suffering from kidney disease alone, heart failure alone, or with concomitant kidney disease and heart failure or cardiorenal syndrome, comprising:

continuously administering the natriuretic peptide to the subject using a drug provisioning component to maintain a subject-specific plasma level of the natriuretic peptide at a steady state concentration at a specified range, wherein

the specified range is pre-determined by administering a test dose of the natriuretic peptide to the subject and the specified range maintains a plasma level of the natriuretic peptide at a steady state concentration from about 0.5 to about 60 ng/mL and the drug provisioning component administers the natriuretic peptide subcutaneously for multiple days,

the natriuretic peptide is selected from any one of long-acting natriuretic peptide (LANP), kaliuretic peptide (KP), urodilatin (URO), atrial natriuretic peptide (ANP), vessel dilator (VD) and brain natriuretic peptide (BNP), and

the administration of the natriuretic peptide has one or more renal protective, cardiovascular protective or renal or cardiovascular protective effects.

9. The method of claim 8, wherein the one or more renal protective, cardiovascular protective or renal or cardiovascular protective effects includes one or more selected from the group consisting of lowering blood pressure;

lowering right atrial pressure;

slowing, preventing or reversing a change in the glomerular filtration rate of the subject;

increasing urine flow rate or sodium excretion rate;

lowering the presence of albumin in urine or lowering the presence of protein in urine;

reducing renal tissue damage; and

increasing renal cortical blood flow.

10. The method of claim 8, wherein the natriuretic peptide is vessel dilator (VD).

11. The method of claim 8, wherein kidney disease is selected from the group consisting of Stage 1 kidney disease, Stage 2 kidney disease, Stage 3 kidney disease, Stage 4kidney disease, Stage 5 kidney disease, and end-stage renal disease.

12. The method of claim 8, wherein cardiorenal syndrome (CRS) is selected from the group consisting of CRS Type I, CRS Type II, CRS Type III, CRS Type IV and CRS Type V.

13. The method of claim 8, wherein heart failure is selected from the group consisting of chronic heart failure, congestive heart failure, acute heart failure, decompensated heart failure, systolic heart failure, and diastolic heart failure.