Granted Patent
B2
US 12,465,599 · App. 19/097,314 · Granted Nov 11, 2025
Compositions for the treatment of hypertension
Assignee:
THE GEORGE INSTITUTE FOR GLOBAL HEALTH
A61K31/4422A61K31/277A61K31/382A61K31/40A61K31/4035A61K31/404A61K31/41A61K31/4178A61K31/4184A61K31/4418A61K31/495A61K31/517A61K31/549A61K31/554A61P9/12
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Provided herein are pharmaceutical compositions that are useful for the treatment of hypertension comprising an angiotensin II receptor blocker, a diuretic, and a calcium channel blocker.
Claims (24)
1 . A pharmaceutical composition comprising:
(a) telmisartan;
(b) indapamide; and
(c) amlodipine besylate,
wherein the dose of telmisartan is from about 8 mg to about 12 mg, the dose of indapamide is from about 0.5 mg to about 0.75 mg, and the dose of amlodipine besylate is from about EQ 1 mg base to about EQ 1.5 mg base or from about EQ 1.5 mg base to about EQ 2 mg base; and wherein the pharmaceutical composition is free of beta-blocker.
2 . The pharmaceutical composition of claim 1 , wherein the dose of indapamide is about 0.625 mg.
3 . The pharmaceutical composition of claim 1 , wherein the dose of the amlodipine besylate is from about EQ 1 mg base to about EQ 1.5 mg base.
4 . The pharmaceutical composition of claim 1 , wherein the dose of the amlodipine besylate is from about EQ 1.5 mg base to about EQ 2 mg base.
5 . The pharmaceutical composition of claim 1 , wherein the dose of telmisartan is about 10 mg.
6 . The pharmaceutical composition of claim 1 , wherein the dose of indapamide is about 0.625 mg, the dose of amlodipine besylate is from about EQ 1.5 mg base to about EQ 2 mg ase , and the dose of telmisartan is about 10 mg.
7 . A pharmaceutical composition comprising:
(a) telmisartan;
(b) indapamide; and
(c) amlodipine besylate,
wherein the dose of telmisartan is from about 16 mg to about 24 mg, the dose of indapamide is from about 1 mg to about 1.5 mg, and wherein a dose of the amlodipine besylate is from about EQ 2 m base to about EQ 3.75 mg base, from about EQ 2 mg base to about EQ 3 mg base, from about EQ 2.25 mg base to about EQ 2.75 mg base, or from about EQ 3.75 mg base to about EQ 6.25 mg base, and wherein the pharmaceutical composition is free of beta-blocker.
8 . The pharmaceutical composition of claim 7 , wherein the dose of the amlodipine besylate is from about EQ 2 mg base to about EQ 3.75 mg base.
9 . The pharmaceutical composition of claim 7 , wherein the dose of the amlodipine besylate is from about EQ 2 mg base to about EQ 3 mg base.
10 . The pharmaceutical composition of claim 7 , wherein the dose of the amlodipine besylate is from about EQ 2.25 mg base to about EQ 2.75 mg base.
11 . The pharmaceutical composition of claim 7 , wherein the dose of the amlodipine besylate is from about EQ 3.75 mg base to about EQ 6.25 mg base.
12 . The pharmaceutical composition of claim 7 , wherein the dose of indapamide is about 1.25 mg.
13 . The pharmaceutical composition of claim 7 , wherein the dose of telmisartan is about 20 mg.
14 . The pharmaceutical composition of claim 7 , wherein the dose of indapamide is about 1.25 mg, the dose of amlodipine besylate is from about EQ 2 mg base to about EQ 3.75 mg base, and the dose of telmisartan is about 20 mg.
15 . The pharmaceutical composition of claim 1 or 7 , wherein the pharmaceutical composition is suitable for oral administration.
16 . The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is in the form of pill, tablet, or capsule.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 12, 2025
From: RODGERS, ANTHONY; MACMAHON, STEPHEN
To: THE GEORGE INSTITUTE FOR GLOBAL HEALTH
Reel/Frame 071999/0062 →
Continuity (8)
Continuation
PCTIB2018000083
· Jan 23, 2018
Provisional Application
62450324
· Jan 25, 2017
References Cited (139)
US 20030199492A1
· Scott
· 2003
[cited by applicant]
US 20040198789A1
· Leonardi et al.
· 2004
[cited by applicant]
US 20050187262A1
· Grogan et al.
· 2005
[cited by applicant]
US 20070191438A1
· Rohrer
· 2007
[cited by applicant]
US 20070293552A1
· Gorczynski
· 2007
[cited by applicant]
US 20080096866A1
· Woo et al.
· 2008
[cited by applicant]
US 20120115854A1
· Shetty et al.
· 2012
[cited by applicant]
US 20200030296A1
· Rodgers et al.
· 2020
[cited by applicant]
US 20230125076A1
· Rodgers et al.
· 2023
[cited by applicant]
CA 3107616A1
· 2020
[cited by applicant]
CN 101450211A
· 2009
[cited by applicant]
CN 101618215A
· 2010
[cited by applicant]
CN 101966187A
· 2011
[cited by applicant]
CN 101966190A
· 2011
[cited by applicant]
CN 101966191A
· 2011
[cited by applicant]
CN 102225203A
· 2011
[cited by applicant]
CN 102327272B
· 2013
[cited by applicant]
CN 106074418A
· 2016
[cited by applicant]
CN 106310278A
· 2017
[cited by applicant]
EP 1272220B1
· 2006
[cited by applicant]
EP 2001469A2
· 2008
[cited by applicant]
EP 2575808A1
· 2013
[cited by applicant]
KR 20090057538A
· 2009
[cited by applicant]
WO WO03097045A1
· 2003
[cited by applicant]
WO WO2007098390A2
· 2007
[cited by applicant]
WO WO2007109037A2
· 2007
[cited by applicant]
WO WO2007146900A2
· 2007
[cited by applicant]
WO WO2009026517A2
· 2009
[cited by applicant]
WO WO2010127099A2
· 2010
[cited by applicant]
WO WO2011137734A1
· 2011
[cited by applicant]
WO WO2011149438A1
· 2011
[cited by applicant]
WO WO2014114627A1
· 2014
[cited by applicant]
WO WO2017054787A1
· 2017
[cited by applicant]
WO WO2018091967A1
· 2018
[cited by applicant]
WO WO2018138578A1
· 2018
[cited by applicant]
WO WO2020021341A1
· 2020
[cited by applicant]
Amlodipine Besylate Tablets. Greenstone Brand. NDS 19-787/S-042 (14 pgs) (2007).
[cited by applicant]
Andren et al. Enalapril with either a “very low” or “low” dose of hydrochlorothiazide is equally effective in essential hypertension: a double-blind trial in 100 hypertensive patients. J Hypertension I(suppl2):384-386 (…
[cited by applicant]
Anonymous. Assessment Report for Exforge HCT. European Medicines Agency. Evaluation of Medicines for Humane Use. Retrieved from the Internet: URL: https://www.ema.europa.eu/en/documents/assessment-report/exforge-hct-epa…
[cited by applicant]
Anonymous. Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial. ClinicalTrials.gov (Mar. 4, 2016). pp. 1-7. Retrieved from the Internet URL: https://clinicaltrials.gov/ct2/show/record/NCT02699645?v…
[cited by applicant]
Australian Institute of Health and Welfare 2017. Medicines for cardiovascular disease. Cat. No. CVD 80. Canberra: AIHW box 4 (36 pgs.) (2017).
[cited by applicant]
Beall et al. Could patents interfere with the development of a cardiovascular polypill? J Transl Med 14:242 (2016).
[cited by applicant]
Berge, Stephen M. et al. Pharmaceutical Salts. Journal of Pharmaceutical Sciences 66(1):1-19 (1977).
[cited by applicant]
Bisoprolol/hydrochlorothiazide (Rx). Medscape Drugs & Diseases. Available at https://reference.medscape.com/drug/ziac-bisoprolol-hydrochlorothiazide-999421 (retrieved Dec. 18, 2020).
[cited by applicant]
Chou. Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method. Cancer Res 70(2):440-446 (2010).
[cited by applicant]
Chrysant, Steven G. Single-pill triple-combination therapy: an alternative to multiple-drug treatment of hypertension. Postgrad Med 123(6):21-31 (2011).
[cited by applicant]
ClinicalTrials.gov Identifier: NCT02278471. The SCCS Polypill Pilot Trial, Record created Oct. 28, 2014. pp. 1-9. [retrieved on Jul. 9, 2024] Available at URL: https://clinicaltrials.gov/study/NCT02278471.
[cited by applicant]
ClinicalTrials.gov Identifier: NCT02699645. Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT), Record created Mar. 2, 2016. pp. 1-10. [retrieved on Jul. 9, 2024] Available at URL: https…
[cited by applicant]
ClinicalTrials.gov. Study to Evaluate the Efficacy and Safety of Telmisartan/Amlodipine/Rosuvastatin. [retrieved from internet on Nov. 11, 2019] URL:<https://clinicaltrials.gov/ct2/show/NCT03088254> First Posted Mar. 23…
[cited by applicant]
ClinicalTrials.gov. Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT). U.S. National Library of Medicine; (May 4, 2017) https://clinicaltrials.gov/ct2/history/NCT02699645?V 5=View#Study…
[cited by applicant]
Co-pending U.S. Appl. No. 19/073,585, inventors Rodgers; Anthony et al., filed Mar. 7, 2025.
[cited by applicant]
Crestor (rosuvastatin calcium) tablets drug label. Initial U.S. Approval: 2003. Reference ID: 3937746. May 2016.
[cited by applicant]
Diabetes Educational Services. Available at https://diabetesed.net/page/_files/ Antihypertensive-Meds-2012.pdf (3 pgs.) (2012).
[cited by applicant]
Dinicolantonio et al. Evidence-based diuretics: focus on chlorthalidone and indapamide . Future Cardiology 11:203-217 (2015).
[cited by applicant]
Drug Dosage. https://www.drugs.com/dosage/ (3 pgs.) (Accessed Apr. 2018).
[cited by applicant]
Emc+ Compendium. Latest Medicine Updates. https://www.medicines.org.uk/emc (2 pgs.) (Accessed Apr. 2018).
[cited by applicant]
Ershova A.K., Use of statins in patients with arterial hypertension. Russian Medical Journal 18(22):1389-1392 (2010) (English translation).
[cited by applicant]
Fishbane et al. Iron deficiency in non-dialysis chronic kidney disease. Kidney Int 75:752-754 (2009).
[cited by applicant]
Fletcher et al. Efficacy of drug therapy in the secondary prevention of cardiovascular disease and stroke. Am J Cardiol. 99(6C):1E-35E (2007).
[cited by applicant]
Glezer et al. Comparative analysis of the effectiveness of diuretic in the treatment of arterial hypertension in women. The results of the Athena study. Problems of Women's Health 2(4):5-16 (2009).
[cited by applicant]
Higaki, Jitsuo et al. Effect of Hydrochlorothiazide in Addition to Telmisartan/amlodipine Combination for Treating Hypertensive Patients Uncontrolled with Telmisartan/amlodipine: a Randomized, Double-blind Study. Hypert…
[cited by applicant]
Huffman et al. Low-Dose Combination Blood Pressure Pharmacotherapy to Improve Treatment Effectiveness, Safety and Efficiency. JAMA 320(6):552-554 (2018).
[cited by applicant]
Huo et al. Effect of Simvastatin on Ankle Brachial Index in Middle and Old Age Patients with Hypertension. China Pharmacy 24(40):3795-3796 (2013) (English Abstract).
[cited by applicant]
Jadhav, Uday et al. Blood Pressure Control with a Single-pill Combination of Indapamide Sustained-release and Amlodipine in Patients with Hypertension: The EFFICIENT study. PloS one 9(4):e92955, 1-6 (2014).
[cited by applicant]
Kenward et al. An improved approximation to the precision of fixed effects from restricted maximum likelihood. Computational Statistics & Data Analysis 53(7): 2583-2595 (2009).
[cited by applicant]
Kenward et al. The use of baseline covariates in crossover studies. Biostatistics 11(1):1-17 (2010).
[cited by applicant]
Kharkevich. Pharmacology 3rd ed. Revised and supplemented, -M: Medicine p. 34 (1987).
[cited by applicant]
Kirichenko. The angiotensin II receptor antagonist candesartan in the arsenal of the therapist. Consilium Medicum 18:76-80 (2016).
[cited by applicant]
Krosnyuk et al. Pharmaceutical technology: Technology of dosage forms: textbook. for stud. higher. study institutions 2nd ed. stereo- M.: Publishing Center “Academia”. p. 6 (2006).
[cited by applicant]
Kuriyama et al. Renoprotective effect of triple therapy with low-dose angiotensis receptor blocker, low-dose diuretic and Ca-antagonist in hypertensive type-2 diabetic patients with overt nephropathy. Japanese Journal o…
[cited by applicant]
Law et al. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technology Assessment 7(31):1-105 (2003).
[cited by applicant]
Law et al. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 326(7404):1427 (2003).
[cited by applicant]
Lee et al. A Randomized, Multicenter, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and the Tolerability of a Triple Combination of Amlodipine/Losartan/Rosuvastatin in Patients With Comorbid Essential …
[cited by applicant]
Liu et al. Should baseline be a covariate or dependent variable in analyses of change from baseline in clinical trials? Stat Med 28(20):2509-2530 (2009).
[cited by applicant]
Lozol® Indapamide Tablets. Aventis Pharmaceuticals Inc. (8 pgs.) (2005).
[cited by applicant]
Mahmud et al. Low-dose quadruple antihypertensive combination: more efficacious than individual agents—a preliminary report. Hypertension 49:272-275 (2007).
[cited by applicant]
Maladkar, Manish et al. Triple Drug Combination of Telmisartan, Amlodipine and Hydrochlorothiazide in the Treatment of Essential Hypertension. Open Journal of Internal Medicine vol. 2,2: pp. 67-71 (2012).
[cited by applicant]
Mallion et al. ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension. J Hum Hypertens 13:657-664 (1…
[cited by applicant]
Mashkovsky M.D. Medicines: In 2 vols. V. 1.—M.: New Wave Publishing House LLC, 540:11 (2021).
[cited by applicant]
Micardis (Telmisartan) Tablets. Boehringer Ingelheim. NDA 20-850/S-022/S-023 (12 pgs.) (2009).
[cited by applicant]
Morozova et al. Clinical and economic aspects of the use of statins in patients with arterial hypertension with lipid metabolism disorders. Quality Clinical Practice 3:66-70 (2008).
[cited by applicant]
Neutel et al. Comparison of Monotherapy with Irbesartan 150 mg or Amlodipine 5 mg for Treatment of Mild-to-Moderate Hypertension. J Renin-Angiotensin_Aldosteone System 6(2):84-89 (2005).
[cited by applicant]
Nickenig. Should Angiotensin II Receptor Blockers and Statins Be Combined? Circulation 10:1013-1020 (2004).
[cited by applicant]
O'Brien et al. Ambulatory Blood Pressure Measurement. What Is the International Consensus? Hypertension 62(6):988-994 (2013).
[cited by applicant]
Ohira et al. Comparisons of Increasing Calcium Channel Blocker dose and Adding Thiazide Diuretic in Hypertensive Patients Given Medium-dose Angiotensin II Receptor Blocker and Amlodipine. Dokkyo Journal of Medical Scien…
[cited by applicant]
PCT/IB2017/001524 International Search Report and Written Opinion dated Apr. 17, 2018.
[cited by applicant]
PCT/IB2018/000083 International Search Report and Written Opinion dated Apr. 24, 2018.
[cited by applicant]
PCT/IB2019/000923 International Search Report and Written Opinion dated Dec. 2, 2019.
[cited by applicant]
Pinto et al. Lessons from rat models of hypertension: from Goldblatt to genetic engineering. Cardiovascular Res 39(1):77-88 (1998).
[cited by applicant]
Preiss, David. et al. Lipids, lipid modifying agents and cardiovascular risk: a review of the evidence. Clinical Endocrinology 70(6):815-828 (2009).
[cited by applicant]
Rizos, Christos V. et al. Telmisartan: a multifaceted antihypertension drug. Current Medical Research and Opinion 32(8):1397-1398 (2016).
[cited by applicant]
RxList. https://www.rxlist.com (5 pgs.) (Accessed Apr. 2018).
[cited by applicant]
Salam et al. TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension (TRIUMPH): Study protocol. Am Heart J. 167(2):127-132 (2014).
[cited by applicant]
Sharma. Dr. Reddy's launches combo drug for hypertension. Available at https://www.businesstoday.in/industry/pharma/story/dr-reddys-launches-combo-drug-for-hypertension-135017-2014-01- 10 (2014).
[cited by applicant]
Shilov. III-generation calcium channel blockers in the treatment of arterial hypertension. Systemic hypertension 3:38-42 (2013).
[cited by applicant]
Skoularigis et al. Low dose hydrochlorothiazide (12.5 to 25 mg daily) as monotherapy in black patients with mild to moderate hypertension. Assessment by ambulatory blood pressure monitoring. Am J Hypertens 8(10 Pt 1):10…
[cited by applicant]
Smith, David H.G. et al. Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies. Blood Pressure Monitoring 8(3):111-117 (2003).
[cited by applicant]
Spinler et al. ACE inhibitors versus ARBs: comparison of practice guidelines and treatment selection considerations. Formulary 41:274-284 (2006).
[cited by applicant]
Sureja, Dipen et al. Development and Validation of HPTLC Method for Simultaneous Estimation of Telmisartan and Indapamide in Pharmaceutical Solid Dosage Form. Journal of Chemical and Pharmaceutical Research vol. 7,11: p…
[cited by applicant]
Tandon et al. Antihypertensive drug prescription patterns, rationality, and adherence to Joint National Committee-7 hypertension treatment guidelines among Indian postmenopausal women. J Mid-life Health 5(2):78--83 (201…
[cited by applicant]
Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT). Available at https://clinicaltrials.gov/ct2/show/record/NCT02699645 . First posted Mar. 4, 2016 (16 pgs).
[cited by applicant]
Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT). Available at https://clinicaltrials.gov/ct2/show/record/NCT02699645 . First posted Mar. 4, 2016 (Latest version Oct. 2, 2018) (9 pgs).
[cited by applicant]
U.S. Appl. No. 15/352,425 Office Action dated May 5, 2017.
[cited by applicant]
U.S. Appl. No. 15/352,425 Office Action dated Nov. 30, 2017.
[cited by applicant]
U.S. Appl. No. 15/919,923 Office Action dated Aug. 15, 2018.
[cited by applicant]
U.S. Appl. No. 15/919,923 Office Action dated Nov. 15, 2018.
[cited by applicant]
U.S. Appl. No. 16/393,774 Office Action dated Jan. 15, 2020.
[cited by applicant]
U.S. Appl. No. 16/523,230 Office Action dated Jan. 8, 2021.
[cited by applicant]
U.S. Appl. No. 16/523,230 Office Action dated Jun. 21, 2022.
[cited by applicant]
U.S. Appl. No. 16/523,230 Office Action dated Nov. 8, 2021.
[cited by applicant]
U.S. Appl. No. 17/014,358 Office Action dated Dec. 16, 2021.
[cited by applicant]
U.S. Appl. No. 17/932,982 Office Action dated Dec. 6, 2023.
[cited by applicant]
U.S. Appl. No. 18/446,268 Office Action dated Sep. 5, 2024.
[cited by applicant]
U.S. Appl. No. 19/073,585 Office Action dated Apr. 28, 2025.
[cited by applicant]
Vengerovsky, A.I. Pharmacological incompatibility. Bulletin of Siberian Medicine 3:49-56.
[cited by applicant]
Volpe, Massimo et al. Rationale for Triple Fixed-Dose Combination Therapy With an Angiotensin Ii Receptor Blocker, a Calcium Channel Blocker, and a Thiazide Diuretic. Vascular Health and Risk Management vol. 8: pp. 371-…
[cited by applicant]
Wald, David S. et al. Randomized Polypill Crossover Trial in People Aged 50 and Over. PLOS One 7(7):1-6 (2012).
[cited by applicant]
Wald et al. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med 122(3):290-300 (2009).
[cited by applicant]
Webster et al. Fixed Low-Dose Triple Combination Antihypertensive Medication vs Usual Care for Blood Pressure Control in Patients With Mild to Moderate Hypertension in Sri Lanka: A Randomized Clinical Trial. JAMA 320(6)…
[cited by applicant]
Webster. Protocol changes to the TRIUMPH study. Am Heart J 191:e1 (2017).
[cited by applicant]
Li, Shaobo et al. Chapter 3: Strategies for administering drugs against hypertension in combination. Beijing, China: People's Military Medical Press (Eds.) (pp. 84-86) (2013) (w/English Translation).
[cited by applicant]
Zhao, Shuiping et al. (Eds.). Insights on Guidelines for Prevention and Treatment of Dyslipidemia in Chinese Adults (2nd ed.), “(II) Clinical Application”). People's Military Medical Press p. 231 (Jul. 2015) (w/English …
[cited by applicant]
ClinicalTrials.gov Identifier: NCT02699645. Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT), Record created Jun. 26, 2016. pp. 1-4. [retrieved on Apr. 11, 2023] Available at URL:https…
[cited by applicant]
Cited By (2)