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Use of Natriuretic Peptide for Treating Heart Failure

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Use of Natriuretic Peptide for Treating Heart Failure (19) TZZ _Z _T (11) EP 2 510 942 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 38/22 (2006.01) A61P 9/04 (2006.01) 02.09.2015 Bulletin 2015/36 (21) Application number: 12156696.2 (22) Date of filing: 07.04.2006 (54) Use of natriuretic peptide for treating heart failure Verwendung eines natriuretischen Peptids zur Behandlung von Herzversagen Utilisation de peptide natriuretique pour le traitement d’une insuffisance cardiaque (84) Designated Contracting States: (56) References cited: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR • ELSNER DET AL: "Efficacyof prolonged infusion HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI of urodilatin [ANP-(95-126)] in patients with SK TR congestive heart failure", AMERICAN HEART JOURNAL, MOSBY- YEAR BOOK INC, US LNKD- (30) Priority: 08.04.2005 US 669751 P DOI:10.1016/0002-8703(95)90328-3, vol. 129, no. 07.04.2005 US 669786 P 4, 1 April 1995 (1995-04-01) , pages 766-773, 01.11.2005 US 732585 P XP004530285, ISSN: 0002-8703 • MITROVIC V ET AL: "Urodilatin induces cGMP- (43) Date of publication of application: mediated haemodynamic effects in patients with 17.10.2012 Bulletin 2012/42 decompensated congestive heart failure", EUROPEAN HEART JOURNAL; ESC CONGRESS (62) Document number(s) of the earlier application(s) in 2004;MUNICH, GERMANY; AUGUST28 20040801 accordance with Art. 76 EPC: OXFORD UNIVERSITY PRESS, GB, FR, vol. 25, 06749753.7 / 1 865 976 no. SUPPLEMENT S, 1 August 2004 (2004-08-01), page 452, XP008124232, ISSN: 0195-668X (73) Proprietor: Cardiorentis AG • MITROVIC ET AL: "Effects of the renal natriuretic 6300 Zug (CH) peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: A double- (72) Inventors: blind, placebo-controlled, ascending-dose trial", • Mitrovic, Veselin AMERICAN HEART JOURNAL, MOSBY- YEAR 61231 Bad Nauheim (DE) BOOK INC, US LNKD- DOI:10.1016/J.AHJ. • Lüss, Hartmut 2005.01.022, vol. 150, no. 6, 1 December 2005 30559 Hannover (DE) (2005-12-01), pages 1239.E1-1239.E8, • Forssmann, Wolf-Georg XP005199298, ISSN: 0002-8703 79692 Kleines Wiesental (DE) • Brookes L.: "SIRIUS II: Safety and Efficacy of an • Meyer, Markus Intravenous Placebo-Controlled Randomized 30625 Hannover (DE) Infusion of Ularitide in a Prospective Double- • Döhler, Klaus-Dieter blind Study in Patients With Symptomatic, 30657 Hannover (DE) Decompensated Chronic Heart Failure (Phase IIb)", , 10 October 2005 (2005-10-10), (74) Representative: Von Kreisler Selting Werner - XP002592743, Retrieved from the Internet: URL: Partnerschaft http://www.medscape.com/viewarticle/51 4120 von Patentanwälten und Rechtsanwälten mbB [retrieved on 2010-07-12] Deichmannhaus am Dom Bahnhofsvorplatz 1 50667 Köln (DE) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 510 942 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 510 942 B1 • PARIKH CHIRAG R ET AL: "Prevention of acute • MITROVIC VESELIN ET AL: "Haemodynamic and renal failure (ARF) following allogeneic clinical effects of ularitide in decompensated myeloablative hematopoietic cell transplantation heartfailure", EUROPEAN HEART JOURNAL, vol. (MHCT) using urodilatin and mannitol: A phase II 27, no. 23, December 2006 (2006-12), pages trial.", JOURNAL OF THE AMERICAN SOCIETY 2823-2832, XP002592745, ISSN: 0195-668X OF NEPHROLOGY, vol. 14, no. Abstracts Issue, • LUESS HARTMUT ET AL: "Renal effects of November 2003 (2003-11), page 355A, ularitide in patients with decompensated heart XP008124593, & MEETING OF THE AMERICAN failure", AMERICAN HEART JOURNAL, vol. 155, SOCIETY OF NEPHROLOGY RENAL WEEK; SAN no. 6, June 2008 (2008-06), XP002592746, ISSN: DIEGO, CA, USA; NOVEMBER 12-17, 2003 ISSN: 0002-8703 1046-6673 • VESELIN MITROVIC ET AL: "Role of guanylate • HUMMEL M ET AL: "Urodilatin: A new peptide cyclase modulators in decompensated heart with beneficial effects in the postoperative failure", HEART FAILURE REVIEWS, KLUWER therapy of cardiac transplant recipients", ACADEMIC PUBLISHERS, BO LNKD- DOI: CLINICAL INVESTIGATOR, SPRINGER 10.1007/S10741-009-9149-7, vol. 14, no. 4, 1 July INTERNATIONAL, BERLIN, DE, vol. 70, no. 8, 1 2009 (2009-07-01), pages 309-319, XP019748839, August 1992 (1992-08-01) , pages 674-682, ISSN: 1573-7322 XP008124241, ISSN: 0941-0198, DOI: 10.1007/BF00180284 [retrieved on 2004-11-29] • SACKNER-BERNSTEIN J D ET AL: "Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure", CIRCULATION 20050329 US LNKD- DOI: 10.1161/01.CIR.0000159340.93220.E4, vol. 111, no. 12, 29 March 2005 (2005-03-29), pages 1487-1491, XP002592744, ISSN: 0009-7322 2 EP 2 510 942 B1 Description BACKGROUND OF THE INVENTION 5 [0001] This application claims priority to U.S. provisional applications 60/669,786, filed April 7; 2005, 60/669,751, filed April 8, 2005; and 60/732,585, filed November 1, 2005. BACKGROUND OF THE INVENTION 10 [0002] A family of related peptides has been discovered that works in concert to achieve salt and water homeostasis in the body. These peptides, termed natriuretic peptides for their role in moderating natriuresis and diuresis, have varying amino acid sequences and originate from different tissues within the body. This family of natriuretic peptides consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), Dendroaspis natri- uretic peptide (DNP), and urodilatin (URO, or ularitide). Their tissue-specific distribution is as follows: heart (ANP, BNP, 15 and DNP); brain (ANP, BNP, and CNP); endothelial cells (CNP); plasma (DNP); and kidney (URO). These peptides are constituents of a hormonal system that plays a critical role in maintaining an intricate balance of blood volume/pressure in the human body. For instance, urodilatin, a close analog of ANP secreted by kidney tubular cells, promotes excretion of sodium and water by acting directly on kidney cells in the collecting duct to inhibit sodium and water reabsorption. Like other natriuretic peptides, such as ANP and BNP, urodilatin has been studied for use in treating various conditions, 20 including renal failure or congestive heart failure (see, e.g., U.S. Patent Nos. 5,571,789 and 6,831,064; Kentsch et al., Eur. J. Clin. Invest. 1992, 22(10):662-669; Kentsch et al., Eur. J. Clin. Invest. 1995, 25(4):281-283; Elsner et al., Am. Heart J. 1995, 129(4):766-773; and Forssmann et al., Clinical Pharmacology and Therapeutics 1998, 64(3):322-330). [0003] MITROVIC V ET AL, Eur. Heart J., vol. 25, SUPPLEMENT S, 1 Aug, p. 452, refers to urodilatin infusions (7,5 or 15 or 30 ng/kg/min) to patients with decompensated congestive heart failure (DHF) over a time period of 24 hours. 25 [0004] Cardiovascular diseases are the leading causes of death in the United Sates, regardless of gender or ethnicity. Among these diseases, congestive heart failure (CHF) is highly prevalent. According to the American Heart Association, the number of hospital discharges and the number of deaths due to CHF both rose roughly 2.5-fold from 1979 to 1999. Currently, about 5 million Americans have been diagnosed with CHF, and about 550,000 new cases occur annually (American Heart Association 2001). This life-threatening condition is accompanied by great financial impact. Thus, there 30 exists a need for providing new and more effective methods for treating heart failure. [0005] Previous studies have shown that the administration of ularitide is effective in treating heart failure patients. The present inventors have discovered a new method for ularitide administration that is surprisingly effective for treating heart failure of varying causes, particularly acute decompensated heart failure. The method of this invention can also be used for treating heart conditions that generally relate to abnormal fluid accumulation in the heart, e.g., myocardial 35 edema. BRIEF SUMMARY OF THE INVENTION [0006] The present invention relates to a method for treating acute decompensated heart failure. The method comprises 40 the step of administering an effective amount of a natriuretic peptide, e.g., urodilatin, where such administration is continuous over a time period of at least 24 hours, preferably from 24 hours to 120 hours, and more preferably, from 24 hours to 48 hours, or at least 48 hours, such as from 48 hours to 60 hours, or, most preferably, from 48 hours to 72 hours. A preferred means for administering the natriuretic peptide is by intravenous administration. Other means of delivering the natriuretic peptide, such as by oral ingestion, are also available for the practice of this invention. For 45 intravenous administration, the method preferably does not include a bolus infusion of a natriuretic peptide, such that no potential impairment of kidney function will result. Kidney function can be impaired by heart failure and can result from impaired blood perfusion through the kidneys due to insufficient pumping action of the heart. For example, recom- binant BNP (Natrecor) is given to heart failure patients via a high dose intravenous bolus application followed by a lower dose intravenous infusion. Recent studies have shown that Natrecor application in heart failure may increase the risk 50 of worsening renal function (Sackner-Bernstein et al., Circulation 2005, 111:1487-1491). Impaired kidney function can be assessed and monitored by measuring serum creatinine or blood urea nitrogen (BUN), which are increased when kidney function is impaired or the kidneys are injured. Furthermore, glomerular filtration rate or calculated creatinine clearance rate are reduced when renal function is impaired.
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