# US 8,785,387 B2 · Neuregulin based methods and compositions for treating cardiovascular disease > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,785,387 B2 - Document ID: US8785387B2 - Status: Granted - Kind: B2 - Application number: 12/879,023 - Filed: 2010-09-10 - Published: 2011-06-09 - Granted: 2014-07-22 - Earliest claimed: 2002-05-24 - Assignees: Zensun (Shanghai) Science & Technology, Co., Ltd. - Applicants: Mingdong Zhou - Inventors: Mingdong Zhou - Web page: https://patentgrep.com/patent/US8785387B2 ## CPC - A61K 38/1883: {Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor} - A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin - A61K 31/185: Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327) - A61K 31/355: Tocopherols, e.g. vitamin E - A61K 31/375: Ascorbic acid, i.e. vitamin C; Salts thereof - A61K 31/43: Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula [IMAGE cpc-sch-A61K-0952.gif], e.g. penicillins, penems - A61K 31/7088: Compounds having three or more nucleosides or nucleotides - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 38/2013: {IL-2} - A61K 38/212: {IFN-alpha} - A61K 38/556: {Angiotensin converting enzyme inhibitors} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors - A61P 7/10: Antioedematous agents; Diuretics - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/02: Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives - A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - A61P 9/06: Antiarrhythmics - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia - A61P 25/24: Antidepressants - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 31/04: Antibacterial agents - A61P 31/12: Antivirals - A61P 31/14: for RNA viruses - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 39/06: Free radical scavengers or antioxidants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 14/4756: {Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor} - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - 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 - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The present invention relates to compositions and methods for preventing, treating or delaying various cardiovascular diseases or disorders in mammals, particularly in humans. More particularly, the present invention provides for compositions and methods for preventing, treating or delaying various cardiovascular diseases or disorders using, inter alia, a neuregulin protein, or a functional fragment thereof, or a nucleic acid encoding a neuregulin protein, or a functional fragment thereof, or an agent that enhances production and/or function of said neuregulin. ## Claims ### Claim 1 A method for treating myocardial infarction or heart failure caused by myocardial infarction in a mammal, comprising administering to a mammal in need thereof a neuregulin 1 protein in an amount from about 10 U/kg to about 400 U/kg of body weight of the mammal once a day. ### Claim 2 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein carries out its anti-myocardial infarction activity via binding with ErbB2-ErbB4 receptors. ### Claim 3 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein is neuregulin α2 or neuregulin β2. ### Claim 4 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein comprises the amino acid sequence of SEQ ID NO:4. ### Claim 5 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein antagonizes the increase of left ventricular end-diastolic (LVEDD) and end-systolic diameters (LVESD) associated with the myocardial infarction. ### Claim 6 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein antagonizes the decrease of left ventricular EF associated with the myocardial infarction. ### Claim 7 (depends on 1) The method of claim 1, wherein the mammal is a human. ### Claim 8 (depends on 1) The method of claim 1, wherein the myocardial infarction has a clinical feature selected from the group consisting of left ventricular dilation, reduced systolic function and increased filling pressure. ### Claim 9 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein is administered with a pharmaceutically acceptable carrier or excipient. ### Claim 10 (depends on 1) The method of claim 1, further comprising administering a prophylactic or therapeutic agent for myocardial infarction. ### Claim 11 (depends on 10) The method of claim 10, wherein the neuregulin 1 protein is administered prior to, concurrently with, or subsequent to the administration of the prophylactic or therapeutic agent. ### Claim 12 (depends on 10) The method of claim 10, wherein the prophylactic or therapeutic agent is selected from the group consisting of an angiotensin I-converting enzyme inhibitor (ACEI), a calcium antagonist, a β-receptor antagonist, aspirin, atropine, nitroglycerin, scopolamine and a thrombolytic agent. ### Claim 13 (depends on 12) The method of claim 12, wherein the ACEI is selected from the group consisting of Captopril, Rampril, Lisinopril, Zofenopril and Trandolapril. ### Claim 14 (depends on 12) The method of claim 12, wherein the calcium antagonist is diltiazem. ### Claim 15 (depends on 12) The method of claim 12, wherein the β-receptor antagonist is selected from the group consisting of propranolol, metoprolol, atenolol and timolol. ### Claim 16 (depends on 12) The method of claim 12, wherein the thrombolytic agent is selected from the group consisting of streptokinase, t-PA and anistreplase. ### Claim 17 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein is administered in vivo. ### Claim 18 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein is administered for about 21 days or less than 21 days. ### Claim 19 (depends on 1) The method of claim 1, wherein the neuregulin 1 protein is administered for a period of between 3 days and 21 days. ### Claim 20 (depends on 3) The method of claim 3, wherein the neuregulin 1 protein is neuregulin α2. ### Claim 21 (depends on 3) The method of claim 3, wherein the neuregulin 1 protein is neuregulin β2. ### Claim 22 (depends on 8) The method of claim 8, wherein the myocardial infarction has the clinical feature of left ventricular dilation. ### Claim 23 (depends on 8) The method of claim 8, wherein the myocardial infarction has the clinical feature of reduced systolic function. ### Claim 24 (depends on 8) The method of claim 8, wherein the myocardial infarction has the clinical feature of increased filling pressure. ### Claim 25 (depends on 11) The method of claim 11, wherein the neuregulin 1 protein is administered prior to the administration of the prophylactic or therapeutic agent. ### Claim 26 (depends on 11) The method of claim 11, wherein the neuregulin 1 protein is administered concurrently with the administration of the prophylactic or therapeutic agent. ### Claim 27 (depends on 11) The method of claim 11, wherein the neuregulin 1 protein is administered subsequent to the administration of the prophylactic or therapeutic agent. ### Claim 28 (depends on 12) The method of claim 12, wherein the prophylactic or therapeutic agent is an angiotensin I-converting enzyme inhibitor (ACEI). ### Claim 29 (depends on 12) The method of claim 12, wherein the prophylactic or therapeutic agent is a calcium antagonist. ### Claim 30 (depends on 12) The method of claim 12, wherein the prophylactic or therapeutic agent is a β-receptor antagonist. ### Claim 31 (depends on 12) The method of claim 12, wherein the prophylactic or therapeutic agent is aspirin. ### Claim 32 (depends on 12) The method of claim 12, wherein the prophylactic or therapeutic agent is atropine. ### Claim 33 (depends on 12) The method of claim 12, wherein the prophylactic or therapeutic agent is nitroglycerin. ### Claim 34 (depends on 12) The method of claim 12, wherein the prophylactic or therapeutic agent is scopolamine. ### Claim 35 (depends on 12) The method of claim 12, wherein the prophylactic or therapeutic agent is a thrombolytic agent. ### Claim 36 (depends on 13) The method of claim 13, wherein the ACEI is Captopril. ### Claim 37 (depends on 13) The method of claim 13, wherein the ACEI is Rampril. ### Claim 38 (depends on 13) The method of claim 13, wherein the ACEI is Lisinopril. ### Claim 39 (depends on 13) The method of claim 13, wherein the ACEI is Zofenopril. ### Claim 40 (depends on 13) The method of claim 13, wherein the ACEI is Trandolapril. ### Claim 41 (depends on 15) The method of claim 15, wherein the β-receptor antagonist is propranolol. ### Claim 42 (depends on 15) The method of claim 15, wherein the β-receptor antagonist is metoprolol. ### Claim 43 (depends on 15) The method of claim 15, wherein the β-receptor antagonist is atenolol. ### Claim 44 (depends on 15) The method of claim 15, wherein the β-receptor antagonist is timolol. ### Claim 45 (depends on 16) The method of claim 16, wherein the thrombolytic agent is streptokinase. ### Claim 46 (depends on 16) The method of claim 16, wherein the thrombolytic agent is t-PA. ### Claim 47 (depends on 16) The method of claim 16, wherein the thrombolytic agent is anistreplase. ### Claim 48 (depends on 18) The method of claim 18, wherein the neuregulin 1 protein is administered for about 21 days. ### Claim 49 (depends on 18) The method of claim 18, wherein the neuregulin 1 protein is administered for less than 21 days.