IP Library › Granted Patent US 12,697,326
Granted Patent B2
US 12,697,326 · App. 18/667,886 · Granted Aug 4, 2026

Methods of treating hepatic encephalopathy

Inventor: William Forbes (Raleigh, NC)
Assignee: SALIX PHARMACEUTICALS, INC.
A61K31/437A61K31/08A61K31/395A61K31/4164A61K31/426A61K31/4439A61K31/606A61K31/7016A61K31/785A61K38/14A61K38/31A61K45/06
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,697,326
App. No.
18/667,886
Filed
May 17, 2024
Granted
Aug 4, 2026
Kind
B2
Art Unit
1627
USPC
514/13.5
Abstract

The application describes treatment of hepatic encephalopathy using gastrointestinal specific antibiotics. One example of a gastrointestinal specific antibiotic is rifaximin.

Claims (5)

1 . A method of decreasing lactulose use in a hepatic encephalopathy subject, the method comprising:

administering 550 mg rifaximin twice a day (BID) to the subject that is being treated with a baseline dosage of about 70 grams lactulose per day; and

tapering lactulose consumption to a dosage of about 20 grams per day.

2 . The method of claim 1 , wherein the administration of rifaximin initially results in the subject being treated with a dosage of lactulose that is increased from the baseline dosage.

3 . The method of claim 2 , wherein the subject is treated with the increased lactulose dosage for about 1 day to about 30 days.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Apr 8, 2025
From: BARCLAYS BANK PLC, AS COLLATERAL AGENT
To: SOLTA MEDICAL, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH IRELAND LIMITED (F/K/A/ VALEANT PHARMACEUTICALS IRELAND LIMITED); SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD; SANTARUS, INC.; MEDICIS PHARMACEUTICAL CORPORATION; HUMAX PHARMACEUTICAL S.A.; SOLTA MEDICAL IRELAND LIMITED; BAUSCH & LOMB MEXICO, S.A. DE C.V.; BAUSCH+LOMB OPS B.V.; BAUSCH HEALTH AMERICAS, INC.; BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH HOLDCO LIMITED; BAUSCH HEALTH MAGYARORSZAG KFT (A/K/A BAUSCH HEALTH HUNGARY LLC); BAUSCH HEALTH POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA (F/K/A VALEANT PHARMA POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA); BAUSCH HEALTH US, LLC; BAUSCH HEALTH, CANADA INC. / SANTE BAUSCH, CANADA INC.; ICN POLFA RZESZOW SPOLKA AKCYJNA (A/K/A ICN POLFA RZESZOW S.A.); ORAPHARMA, INC.; PRZEDSIEBIORSTWO FARMACEUTYCZNE JELFA SPOLKA AKCYJNA (A/K/A PRZEDSIEBIORSTWO FARMACEUTYCZNE JELFA S.A.); SOLTA MEDICAL DUTCH HOLDINGS B.V.; V-BAC HOLDING CORP.; VRX HOLDCO LLC; 1261229 B.C. LTD.; 1530065 B.C. LTD.
Reel/Frame 070778/0199 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Sep 3, 2024
From: BAUSCH HEALTH IRELAND LIMITED; SALIX PHARMACEUTICALS, INC.
To: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 068821/0550 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Sep 3, 2024
From: BAUSCH HEALTH IRELAND LIMITED; SALIX PHARMACEUTICALS, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 068821/0559 →
SECOND LIEN INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Sep 3, 2024
From: BAUSCH HEALTH IRELAND LIMITED; SALIX PHARMACEUTICALS, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 068821/0568 →
Continuity (13)
Continuation 18135823 · Apr 18, 2023
Continuation 18117899 · Mar 6, 2023
Continuation 17213678 · Mar 26, 2021
Continuation 16893651 · Jun 5, 2020
Continuation 16414018 · May 16, 2019
Continuation 15922010 · Mar 15, 2018
Continuation 15460704 · Mar 16, 2017
Continuation 14612697 · Feb 3, 2015
Continuation 13768617 · Feb 15, 2013
Continuation 13077373 · Mar 31, 2011
Continuation PCTUS2009059321 · Oct 2, 2009
Provisional Application 61102349 · Oct 2, 2008
Related Publication 20240299368A1 · Sep 12, 2024
References Cited (332)
US 4341785A · Marchi et al. · 1982 [cited by applicant]
US 4343785A · Schmolka · 1982 [cited by applicant]
US 4557866A · Cannata et al. · 1985 [cited by applicant]
US 5981474A · Manning et al. · 1999 [cited by applicant]
US 6562629B1 · Lin et al. · 2003 [cited by applicant]
US 7045620B2 · Viscomi et al. · 2006 [cited by applicant]
US 7612199B2 · Viscomi et al. · 2009 [cited by applicant]
US 7718608B2 · Lin et al. · 2010 [cited by applicant]
US 7902206B2 · Viscomi et al. · 2011 [cited by applicant]
US 7906542B2 · Viscomi et al. · 2011 [cited by applicant]
US 7915275B2 · Viscomi et al. · 2011 [cited by applicant]
US 7928115B2 · Forbes et al. · 2011 [cited by applicant]
US 8158644B2 · Viscomi et al. · 2012 [cited by applicant]
US 8158781B2 · Viscomi et al. · 2012 [cited by applicant]
US 8193196B2 · Viscomi et al. · 2012 [cited by applicant]
US 8518949B2 · Viscomi et al. · 2013 [cited by applicant]
US 8642573B2 · Forbes · 2014 [cited by examiner]
US 8741904B2 · Viscomi et al. · 2014 [cited by applicant]
US 8829017B2 · Forbes · 2014 [cited by examiner]
US 8835452B2 · Viscomi et al. · 2014 [cited by applicant]
US 8853231B2 · Viscomi et al. · 2014 [cited by applicant]
US 8946252B2 · Forbes · 2015 [cited by examiner]
US 8946573B2 · Bae · 2015 [cited by applicant]
US 8969398B2 · Forbes · 2015 [cited by examiner]
US 9271968B2 · Viscomi et al. · 2016 [cited by applicant]
US 9421195B2 · Forbes · 2016 [cited by examiner]
US 9629828B2 · Forbes · 2017 [cited by examiner]
US 9629829B2 · Forbes · 2017 [cited by examiner]
US 9855254B2 · Forbes · 2018 [cited by examiner]
US 9949958B2 · Forbes · 2018 [cited by examiner]
US 10314828B2 · Forbes · 2019 [cited by examiner]
US 10335397B2 · Forbes · 2019 [cited by examiner]
US 10709694B2 · Forbes · 2020 [cited by examiner]
US 11633384B2 · Forbes · 2023 [cited by examiner]
US 20020028764A1 · Grofte et al. · 2002 [cited by applicant]
US 20020032166A1 · Shefter et al. · 2002 [cited by applicant]
US 20040106590A1 · Eisenstein · 2004 [cited by applicant]
US 20040157840A1 · Cabana et al. · 2004 [cited by applicant]
US 20040229948A1 · Summar et al. · 2004 [cited by applicant]
US 20050142099A1 · Halow · 2005 [cited by applicant]
US 20050272754A1 · Viscomi et al. · 2005 [cited by applicant]
US 20060210592A1 · Kodsi · 2006 [cited by applicant]
US 20080075771A1 · Vaughn et al. · 2008 [cited by applicant]
US 20080119554A1 · Jalan et al. · 2008 [cited by applicant]
US 20080132530A1 · Viscomi et al. · 2008 [cited by applicant]
US 20080262012A1 · Viscomi et al. · 2008 [cited by applicant]
US 20090028940A1 · Jahagirdar et al. · 2009 [cited by applicant]
US 20090088423A1 · Sayada · 2009 [cited by applicant]
US 20090130201A1 · Viscomi et al. · 2009 [cited by applicant]
US 20090149453A1 · Sayada · 2009 [cited by applicant]
US 20100069421A1 · Bettenhausen · 2010 [cited by applicant]
US 20100136125A1 · Jacobus et al. · 2010 [cited by applicant]
US 20100174064A1 · Gushurst et al. · 2010 [cited by applicant]
US 20100204173A1 · Forbes · 2010 [cited by applicant]
US 20100239664A1 · Gushurst et al. · 2010 [cited by applicant]
US 20100317681A1 · Forbes · 2010 [cited by applicant]
US 20110035232A1 · Forbes et al. · 2011 [cited by applicant]
US 20110071103A1 · Forbes et al. · 2011 [cited by applicant]
US 20110243879A1 · Forbes · 2011 [cited by applicant]
US 20200061032A1 · Forbes et al. · 2020 [cited by applicant]
US 20200368213A1 · Forbes · 2020 [cited by applicant]
US 20230091701A1 · Forbes · 2023 [cited by applicant]
EP 0616808A1 · 1994 [cited by applicant]
EP 0858804A1 · 1998 [cited by applicant]
EP 0860166A1 · 1998 [cited by applicant]
EP 2011486A1 · 2009 [cited by applicant]
MX 2010009197A · 2010 [cited by applicant]
NZ 531622A · 2004 [cited by applicant]
WO WO2003047577A2 · 2003 [cited by applicant]
WO WO2005044823A2 · 2005 [cited by applicant]
WO WO2006102536A2 · 2006 [cited by applicant]
WO WO2007103448A2 · 2007 [cited by applicant]
WO WO2008016708A2 · 2008 [cited by applicant]
WO WO2008035109A1 · 2008 [cited by applicant]
WO 2009108814A1 · 2009 [cited by applicant]
WO WO2009108730A2 · 2009 [cited by applicant]
WO WO2010040020A1 · 2010 [cited by applicant]
WO 2011005388A1 · 2011 [cited by applicant]
Leevy et al., Hospitalizations During the Use of Rifaximin Versus Lactulose for the Treatment of Hepatic Encephalopathy, Dig Dis Sci (Jan. 24, 2007) 52:737-741. [cited by examiner]
A Multi Center, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy, Safety and Tolerability of Rifaximin 550 Mg BID for 6 Months in Preventing Hepatic Encephalopathy, updated on Feb. 28, 2006. [cited by examiner]
VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives, Rifaximin for Treatment of Chronic Hepatic Encephalopathy in Chronic Liver Disease, Criteria for Use, Nov. 2016, availabl… [cited by examiner]
Extended European Search Report issued in European Application No. 24155114.2, dated May 15, 2024, 5 pages. [cited by applicant]
Statement of Facts & Arguments filed in Opposition against European Patent No. 2350096, dated Aug. 6, 2020, 20 pages. [cited by applicant]
Bass, Nathan M., Emerging Therapies for the Management of Hepatic Encephalopathy, Seminars in Liver Disease, vol. 27, Supplement 2, Aug. 1, 2007, pp. 18-25. [cited by applicant]
DuPont, H. L. et al., “Rifaximin: In vitro and in vivo Antibacterial Activity—A Review,” Chemotherapy, 2005, 51(suppl 1): pp. 67-72. [cited by applicant]
Bass, N. et al., “Rifaximin is Effective in Maintaining Remission in Hepatic Encephalopathy: Results of a Large, Randomized, Placebo-Controlled Trial,” Apr. 25, 2009, p. S39. [cited by applicant]
Bass, Nathan M. et al., “ Rifaximin Treatment in Hepatic Encephalopathy,” The New England Journal of Medicine, Mar. 25, 2010, vol. 362, No. 12, pp. 1071-1081. [cited by applicant]
Opposition against European Patent No. 2350096, dated Aug. 31, 2020, 21 pages. [cited by applicant]
Salix Pharmaceuticals, Ltd. United States Securities and Exchange Commission Form 10-K/A for the fiscal year ended Dec. 31, 2007, 92 pages. [cited by applicant]
Opposition against European Patent No. 2350096, dated Sep. 9, 2020, 12 pages. [cited by applicant]
Opposition against European Patent No. 2350096, dated Sep. 7, 2020, 13 pages. [cited by applicant]
Statement of Facts & Arguments filed in Opposition against European Patent No. 2350096, dated Sep. 9, 2020, 20 pages. [cited by applicant]
Tapper, Elliot B. et al., “A Risk Score to Predict the Development of Hepatic Encephalopathy in a Population-Based Cohort of Patients with Cirrhosis,” Hepatology, 2018, vol. 68, No. 4, pp. 1498-1507. [cited by applicant]
Response to Article 94(3) Communication issued in European Patent Application No. 09818544.0, filed Jul. 11, 2013, 8 pages. [cited by applicant]
Response to Brief Communication issued in European Patent Application No. 09818544.0, filed Aug. 30, 2017, 6 pages. [cited by applicant]
Shen, Bo et al., “ Rifaximin for maintenance therapy in antibiotic-dependent pouchitis,” BMC Gastroenterology, 2008, 8:26, 7 pages. [cited by applicant]
Morgan, M. Y. et al., “The treatment of hepatic encephalopathy,” Metab. Brain Dis., 2007, 22:389-405. [cited by applicant]
Response to Article 94(3) Communication issued in European Patent Application No. 09818544.0, Dec. 12, 2016, 13 pages. [cited by applicant]
Salix Pharmaceuticals, Inc., Clinical Study Report RFHE3001, Apr. 13, 2009, 18 pages. [cited by applicant]
Williams, Roger et al., “ Rifaximin, a Nonabsorbed Oral Antibiotic, in the Treatment of Hepatic Encephalopathy: Antimicrobial Activity, Efficacy, and Safety,” Reviews in Gastroenterological Disorders, 2005, vol. 5, Supp… [cited by applicant]
Statement of Facts & Arguments filed in Opposition against European Patent No. 2350096, dated Sep. 11, 2020, 13 pages. [cited by applicant]
Opposition against European Patent No. 2350096, dated Sep. 11, 2020, 17 pages. [cited by applicant]
Mutschler et al, “Klinische Prufung,” in Mutschler Arzneimittelwirkungen Lehrbuch der Pharmakologie und Toxikologie, 2001, pp. 123-124. [cited by applicant]
Blei, Andres T. et al., “Hepatic Encephalopathy,” The American Journal of Gastroenterology, 2001, 96(7): 1968-1976. [cited by applicant]
Munoz, Santiago J., “Hepatic Encephalopathy,” Medical Clinics of North America, 2008, 92(4): 795-812. [cited by applicant]
Bass, N. et al., “The Protective Effect of Rifaximin (1100 mg daily) from Hepatic Encephalopathy Observed in a Double-Blind Placebo Controlled Study is Substantiated and Durable Over the Long Term,” AASLD Abstract 305, … [cited by applicant]
Forbes, William P. et al., “Rifaximin Reduces the Risk of Hospitalizations in Patients with Previous Episodes of Hepatic Encephalopathy: Results from a Phase 3 Placebo-Controlled Trial,” AGA Abstract 66, A-11-A-12. [cited by applicant]
Reply of patent proprietor to the Communication Notices of Opposition filed against European Patent No. 2350096, dated Mar. 31, 2021 43 pages. [cited by applicant]
Williams, D. L. et al., “Contribution of rpoB Mutations to Development of Rifamycin Cross-Resistance in Mycobacterium tuberculosis,” Antimicrobial Agents and Chemotherapy, 1998, 1853-1857. [cited by applicant]
Williams, R. “Review article: bacterial flora and pathogenesis in hepatic encephalopathy,” Alimentary Pharmacology & Therapeutics, 2006, 25 (Suppl. 1): 17-22. [cited by applicant]
Farrell, David J., “Rifaximin in the Treatment of Irritable Bowel Syndrome Is There Risk for Development of Antimicrobial Resistance?” J. Clin. Gastroenterol., 2013, 47(3): 205-211. [cited by applicant]
Rothstein, David M., “Rifamycins, Alone and in Combination,” Cold Spring Harb. Perspect. Med., 2016. [cited by applicant]
Wright, Gerard D. et al., “Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr,” Proc. Natl. Acad. Sci., 2008, 105(12): 4886-4891. [cited by applicant]
Summons to attend oral proceedings issued in European Patent No. 2350096, dated Jul. 5, 2021, 38 pages. [cited by applicant]
Opponent response filed Jul. 5, 2022 in European Patent No. 2350096 to the reply of the patent proprietor to the Notice of Opposition dated Mar. 31, 2021 and the preliminary opinion of the Opposition Division dated Sep.… [cited by applicant]
Opponent response filed Jul. 6, 2022 in European Patent No. 2350096 to preliminary opinion of the Opposition Division dated Jul. 7, 2021, 7 pages. [cited by applicant]
Opponent response filed Jul. 11, 2022 in European Patent No. 2350096 to preliminary opinion of the Opposition Division dated Jul. 7, 2021, 4 pages. [cited by applicant]
Opponent response filed Jul. 11, 2022 in European Patent No. 2350096 to preliminary opinion of the Opposition Division dated Jul. 7, 2021, 8 pages. [cited by applicant]
Lichtenstein, Gary R., “Rifaximin: Recent Advances in Gastroenterology and Hepatology,” Gastroenterology & Hepatology, 2007, 3(6): 474-483. [cited by applicant]
Opponent response filed Jul. 12, 2022 in European Patent No. 2350096 in reply to the submission of the patentee dated Mar. 31, 2021 and the preliminary opinion of the Opposition Division, 7 pages. [cited by applicant]
Opponent response filed Jul. 12, 2022 n European Patent No. 2350096 in reply to the Summons to attend oral proceedings dated Jul. 5, 2021 and of Sep. 27, 2021, 22 pages. [cited by applicant]
Shawcross, Debbie L. et al., “Rifaximin reduces the incidence of spontaneous bacterial peritonitis, variceal bleeding and all-cause admissions in patents on the liver transplant waiting list,” Aliment. Pharmacol. Ther.,… [cited by applicant]
Kang, S. H. et al., “Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy,” Aliment. Pharmacol. Ther., 2017, 46: 8… [cited by applicant]
Xie, Wei-Fen et al., “Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis,” Hepatology International, 2021, 15:155-165. [cited by applicant]
Flamm, Steven L. et al., “Rifaximin has the potential to prevent complications of cirrhosis,” Therapeutic Advances in Gastroenterology, 2018, 11: 1-10. [cited by applicant]
Mukherjee, Samiran et al., “Lactulose,” StatPearls NCBI Bookshelf, StatPearls Publishing, Treasure Island (FL), Jan. 2022, 6 pages. [cited by applicant]
Bass, Nathan M. et al., “Rifaximin Treatment is Beneficial for Mild Hepatic Encephalopathy,” presented at The Liver Meeting, Oct. 29-Nov. 2, 2024, Boston, MA. [cited by applicant]
Forbes, William P. et al., “Rifaximin is Safe and Well Tolerated for Long-term Maintenance of Remission from Overt hepatic Encephalopathy,” Clinical Gastroenterology and Hepatology, 2014, 12: 1390-1397. [cited by applicant]
Declaration from Prof. Dr. med. J. Labenz, filed in the opposition proceedings against European Patent No. 2350096, dated Jul. 7, 2022, 16 pages. [cited by applicant]
Written submission filed by opponent on Aug. 26, 2022 filed in the opposition proceedings against European Patent No. 2350096, 1 page. [cited by applicant]
Adachi et al., Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. Clin Infect Dis. Feb. 15, 2006;42(4):541-7. [cited by applicant]
Als-Nielsen et al., Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. BMJ. May 1, 2004;328(7447):1046, 6 pages. [cited by applicant]
Bacchi et al., Polymorphism-structure relationships of rifamexil, an antibiotic rifamycin derivative. Mol Pharmacol. Mar. 1995;47(3):611-23. [cited by applicant]
Bajaj, Minimal hepatic encephalopathy matters in daily life. World J Gastroenterol. Jun. 21, 2008;14(23):3609-15. [cited by applicant]
Baker et al., New Drugs Approved by the FDA New Dosage Forms and Indications Agents Pending FDA Approval Labeling Changes Related to Safety. Hospital Pharmacy. Jun. 2003;38(6):582-597. [cited by applicant]
Baker et al., New Drugs Approved by the FDA New Dosage Forms and Indications Agents Pending FDA Approval Significant Labeling Changes Related to Safety. Hospital Pharmacy. Dec. 1, 2003;38(12):1163-1174. [cited by applicant]
Barrett et al., Benefits of the Antibiotic Rifaximin as Empiric Therapy in Patients with Irritable Bowel Syndrome. The American Journal of Gastroenterology. Sep. 2006;101(9):S479-S480. Abstract 1238. [cited by applicant]
Bass et al., Rifaximin is Effective in Maintaining Remission in Hepatic Encephalopathy: Results of a Large, Randomized, Placebo-Controlled Trial. Journal of Hepatology. Apr. 1, 2009;50:S39. Abstract 93. [cited by applicant]
Bass et al., Rifaximin treatment in hepatic encephalopathy. N Engl J Med. Mar. 25, 2010;362(12):1071-81. [cited by applicant]
Bass, A Meta-Analysis of Rifaximin for the Treatment of Hepatic Encephalopathy. Hepatology, AASLD Abstracts. Oct. 2005;406A, Abstract No. 533. [cited by applicant]
Bass, Emerging Therapies for the Management of Hepatic Encephalopathy. Semin Liver Dis. 2007;27(Suppl 2):18-25. [cited by applicant]
Bass. Review article: the current pharmacological therapies for hepatic encephalopathy. Aliment Pharmacol Ther. Feb. 2007;25 Suppl 1:23-31. [cited by applicant]
Bavin, Polymorphism in process development. Chemistry & Industry. Aug. 21, 1989;16:527-529. [cited by applicant]
Bolukbas et al., Child-Pugh classification dependent alterations in serum leptin levels among cirrhotic patients: a case controlled study. BMC Gastroenterol. Sep. 23, 2004;4:23. 6 pages. [cited by applicant]
Boulware. Travel medicine for the extreme traveler. Dis Mon. Aug. 2006;52(8):309-25. [cited by applicant]
Business Wire, Salix Pharmaceuticals Development Update; XIFAXAN® Trials Initiated in C. Difficile-Associated Diarrhea, Irritable Bowel Syndrome and Hepatic Encephalopathy. Press Release, 2 pages, Jan. 11, 2006. [cited by applicant]
BusinessWire, Rifaximin Demonstrates Highly Statistically Significant Results in Prevention of Hepatic Encephalopathy in Pivatol Phase 3 Study. Salix Pharmaceuticals, Inc. Press Release, Oct. 6, 2008, 3 pages. [cited by applicant]
Bustamante et al., Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. May 1999;30(5):890-5. [cited by applicant]
Byrn et al., Hydrates and Solvates. Solid-State Chemistry of Drugs. Second Edition. SSCI, Inc. West Lafayette, Indiana. Chapter 11, pp. 233-247, (1999). [cited by applicant]
Byrn et al., Pharmaceutical solids: a strategic approach to regulatory considerations. Pharm. Res. Jul. 1995;12(7):945-54. [cited by applicant]
Castelli et al., Epidemiology of travelers' diarrhea. J Travel Med. Dec. 2001;8(Suppl 2):S26-30. [cited by applicant]
Center for Drug Evaluation and Research, Application No. 21-361, Pharmacology Review(s). Trade Name: Lumenax, Generic Name: Rifaximin. 46 pages. Apr. 22, 2004. [cited by applicant]
Cheng et al., Update on Traveler's Diarrhea. Curr Infect Dis Rep. Feb. 2002;4(1):70-77. [cited by applicant]
ClinicalTrials.gov, NCT00098384. Rifaximin versus placebo in the prevention of travelers' diarrhea. Posted: Dec. 8, 2004, Updated: May 9, 2006, Accessed: Dec. 18, 2019. (6 pages). [cited by applicant]
ClinicalTrials.gov, NCT00269412, Randomized, Double Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Different Doses of Rifaximin Administered BID Either Two or Four Weeks in the Treatment of P… [cited by applicant]
ClinicalTrials.gov, NCT00292344. Rifaximin, loperamide and the combination to treat travelers' diarrhea. Posted: Feb. 15, 2006, Updated: Apr. 20, 2009, Accessed: Dec. 18, 2019. (6 pages). [cited by applicant]
ClinicalTrials.gov, NCT00298038, A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy, Safety and Tolerability of Rifaximin 550 Mg BID for 6 Months in Preventing Hepatic Encephalop… [cited by applicant]
Colecchia et al., Efficacy of long term cyclic administration of the poorly absorbed antibiotic Rifaximin in symptomatic, uncomplicated colonic diverticular disease. World J Gastroenterol. Jan. 14, 2007;13(2):264-9. [cited by applicant]
Crum et al., New issues in infectious diarrhea. Rev Gastroenterol Disord. 2005;5 Suppl 3:S16-25. [cited by applicant]
Cuoco et al., Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin. Minerva Gastroenterol Dietol. Mar. 2006;52(1):89-95. [cited by applicant]
Datta et al., Crystal structures of drugs: advances in determination, prediction and engineering. Nat Rev Drug Discov. Jan. 2004;3(1):42-57. [cited by applicant]
De Marco et al., Rifaximin in collateral treatment of portal-systemic encephalopathy: a preliminary report. Curr Ther Res. 1984;36:668-674. [cited by applicant]
De Melo et al., Rifaximin for the treatment of hepatic encephalopathy. Am J Health Syst Pharm. May 1, 2008;65(9):818-22. [cited by applicant]
Derbyshire, Securities and Exchange Commission, Form 8-K. Salix Pharmaceuticals, Ltd., 6 pages, Sep. 5, 2007. [cited by applicant]
Di Piazza et al., Rifaximine versus neomycin in the treatment of portosystemic encephalopathy. Ital J Gastroenterol. Sep.-Oct. 1991;23(7):403-7. [cited by applicant]
Dimick, Xifaxan®. Center for Drug Evaluation and Research, Application No. 22-554, Medical Reviews. 206 pages, Mar. 24, 2010. [cited by applicant]
Dupont et al., A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers' diarrhea. Ann Intern Med. May 17, 2005;142(10):805-12. [cited by applicant]
Dupont et al., Influence of rifaximin treatment on the susceptibility of intestinal Gram-negative flora and enterococci. Clin Microbiol Infect. Nov. 2004;10(11):1009-11. [cited by applicant]
Dupont et al., Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial. Clin Infect Dis. Dec. 1, 2001;33(11):1807-15. [cited by applicant]
Dupont et al., Treatment of travelers' diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone. Clin Gastroenterol Hepatol. Apr. 2007;5(4):451-6. [cited by applicant]
DUPONT. Treatment of travelers' diarrhea. J Travel Med. Dec. 2001;8(Suppl 2):S31-3. [cited by applicant]
Durand et al., Assessment of the prognosis of cirrhosis: Child-Pugh versus MELD. J. Hepatol. 2005;42 Suppl(1):S100-7. [cited by applicant]
Ericsson. Rifaximin: a new approach to the treatment of travelers' diarrhea. Introduction. J Travel Med. Dec. 2001;8(Suppl 2):S25, S40. [cited by applicant]
European Medicines Agency. ICH Topic Q 6 A. Specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances. 1-32. (May 2000). [cited by applicant]
FDA Guideline. Guildine for submitting supporting documentation in drug applications for the manufacture of drug substances. Center for Drug Evaluation and Research. Feb. 1987. (47 pages). [cited by applicant]
Festi et al., Management of hepatic encephalopathy: focus on antibiotic therapy. Digestion. 2006;73 Suppl 1:94-101. [cited by applicant]
Festi et al., Rifaximin in the treatment of chronic hepatic encephalopathy; results of a multicenter study of efficacy and safety. Current Therapeutic Research. Nov. 1993;54(5):598-609. [cited by applicant]
Fiorucci et al., Inhibition of intestinal bacterial translocation with rifaximin modulates lamina propria monocytic cells reactivity and protects against inflammation in a rodent model of colitis. Digestion. 2002;66(4):… [cited by applicant]
Flamm et al., Rifaximin treatment for reduction of risk of overt hepatic encephalopathy recurrence. Therap Adv Gastroenterol. May 2011;4(3):199-206. [cited by applicant]
Garey et al., Rifamycin antibiotics for treatment of Clostridium difficile-associated diarrhea. Ann Pharmacother. Jun. 2008;42(6):827-35. [cited by applicant]
GenBank Accession No. AC025038, [cited by applicant]
GenBank Accession No. BAB47425, KIAA1796 protein, partial [ [cited by applicant]
GenBank Accession No. NM_001143774, [cited by applicant]
GenBank Accession No. NM_032439, [cited by applicant]
GenBank Accession No. NP_001137246, phytanoyl-CoA hydroxylase-interacting protein-like isoform 2 [ [cited by applicant]
GenBank Accession No. NP_115815, phytanoyl-CoA hydroxylase-interacting protein-like isoform 1 [ [cited by applicant]
GenBank Accession No. NT_030059, [cited by applicant]
GenBank Accession No. Q96FC7, RecName: Full=Phytanoyl-CoA hydroxylase-interacting protein-like. 10 pages, Sep. 12, 2018. [cited by applicant]
Gerard et al., Rifaximin: a nonabsorbable rifamycin antibiotic for use in nonsystemic gastrointestinal infections. Expert Rev Anti Infect Ther. Apr. 2005;3(2):201-11. [cited by applicant]
Ghoshal et al., Models for prediction of mortality from cirrhosis with special reference to artificial neural network: a critical review. Hepatol Int. Mar. 2008;2(1):31-8. [cited by applicant]
Giacomo et al., Rifaximin in the treatment of hepatic encephalopathy. Eur J Clin Res. 1993;4:57-66. [cited by applicant]
Gillis et al., Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs. Mar. 1995;49(3):467-84. [cited by applicant]
Gintant et al., Utility of hERG assays as surrogate markers of delayed cardiac repolarization and QT safety. Toxicol Pathol. 2006;34(1):81-90. [cited by applicant]
Gionchetti et al., Review—antibiotic treatment in inflammatory bowel disease: rifaximin, a new possible approach. Eur Rev Med Pharmacol Sci. Jan.-Feb. 1999;3(1):27-30. [cited by applicant]
Gionchetti et al., Rifaximin in patients with moderate or severe ulcerative colitis refractory to steroid-treatment: a double-blind, placebo-controlled trial. Dig Dis Sci. Jun. 1999;44(6):1220-1. [cited by applicant]
Gomi et al., In vitro antimicrobial susceptibility testing of bacterial enteropathogens causing traveler's diarrhea in four geographic regions. Antimicrob Agents Chemother. Jan. 2001;45(1):212-6. [cited by applicant]
Guillory. Generation of Polymorphs, Hydrates, Solvates, and Amorphous Solids. Drugs and the Pharmaceutical Sciences. 1999;95:183-226. [cited by applicant]
Halsey, Current and future treatment modalities for Clostridium difficile-associated disease. Am J Health Syst Pharm. Apr. 15, 2008;65(8):705-15. [cited by applicant]
Hartley et al., DNA cloning using in vitro site-specific recombination. Genome Res. Nov. 2000;10(11):1788-95. [cited by applicant]
Henney, Issued Related to Antimicrobial Resistance. Retrieved online at: http://www.fda.gov/NewsEvents/Testimony/ucm114917.htm. 10 pages. Sep. 20, 2000. [cited by applicant]
Huang et al., Rifaximin—a novel antimicrobial for enteric infections. J Infect. Feb. 2005;50(2):97-106. [cited by applicant]
Hufnagel et al., A putative sugar-binding transcriptional regulator in a novel gene locus in Enterococcus faecalis contributes to production of biofilm and prolonged bacteremia in mice. J Infect Dis. Feb. 1, 2004;189(3)… [cited by applicant]
Infante et al., Enteroaggregative [cited by applicant]
Chari et al., Brief report: treatment of hepatic failure with ex vivo pig-liver perfusion followed by liver transplantation. N Engl J Med. Jul. 28, 1994;331(4):234-7. [cited by applicant]
Ishii et al., A Case of Refractory Hepatic Encephalopathy Successfully Treated with Vancomycin Hydrochloride. Proceedings of the Symposium of the Japanese Society of Social Insurance Medicine. Oct. 1999, p. 106, Abstrac… [cited by applicant]
Jiang et al., Rifaximin versus nonabsorbable disaccharides in the management of hepatic encephalopathy: a meta-analysis. Eur J Gastroenterol Hepatol. Nov. 2008;20(11):1064-70. [cited by applicant]
Jiang et al., Rifaximin: in vitro and in vivo antibacterial activity—a review. Chemotherapy. 2005;51 Suppl 1:67-72. [cited by applicant]
Jozwiakowski, Alteration of the Sollid State of the Drug Substance: Polymorphs, Solvates, and Amorphous Forms. 3M Pharmaceuticals. St. Paul, Minnesota. Chapter 15, pp. 525-568, (2000). [cited by applicant]
Khankari et al., Pharmaceutical hydrates. Thermochimica Acta. 1995;248:61-79. [cited by applicant]
Kircheis et al., Critical flicker frequency for quantification of low-grade hepatic encephalopathy. Hepatology. Feb. 2002;35(2):357-66. [cited by applicant]
Koo et al., Current and future developments in travelers' diarrhea therapy. Expert Rev Anti Infect Ther. Jun. 2006;4(3):417-27. [cited by applicant]
Koo et al., The role of rifaximin in the treatment and chemoprophylaxis of travelers' diarrhea. Ther Clin Risk Manag. 2009;5:841-8. [cited by applicant]
Lauritano et al., Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. Jul. 1, 2005;22(1):31-5. [cited by applicant]
Lawrence et al., Rifaximin for the treatment of hepatic encephalopathy. Pharmacotherapy. Aug. 2008;28(8):1019-32. [cited by applicant]
Leevy et al., Hospitalizations during the use of rifaximin versus lactulose for the treatment of hepatic encephalopathy. Dig Dis Sci. Mar. 2007;52(3):737-41. [cited by applicant]
Lewis et al., The neurology of liver failure. QJM. Sep. 2003;96(9):623-33. [cited by applicant]
Liu et al., Hepatic encephalopathy (II). Chin J Gastroenterol. 2003;8(1):61-62. [cited by applicant]
Loguercio et al., Cyclic treatment of chronic hepatic encephalopathy with rifaximin. Results of a double-blind clinical study. Minerva Gastroenterol Dietol. Mar. 2003;49(1):53-62. Abstract Only. [cited by applicant]
Ma et al., Rifaximin is a gut-specific human pregnane X receptor activator. J Pharmacol Exp Ther. Jul. 2007;322(1):391-8. [cited by applicant]
Maclayton et al., Rifaximin for treatment of hepatic encephalopathy. Ann Pharmacother. Jan. 2009;43(1):77-84. [cited by applicant]
Malamud et al., Treatment of gastrointestinal infections. Curr Opin Gastroenterol. Jan. 2000;16(1):51-55. [cited by applicant]
Mas et al., Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. Jan. 2003;38(1):51-8. [cited by applicant]
Massa eta l., Treatment of hepatic encephalopathy with rifaximin: double blind, double dummy study versus lactulose. Eur J Clin Res. 1993;4:7-18. [cited by applicant]
Miglio et al., Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial. Curr Med Res Opin. 1997;13(10):593-601. [cited by applicant]
Miglioli et al., Effects of daily oral administration of rifaximin and neomycin on faecal aerobic flora in rats. Pharmacol Res. Nov. 2001;44(5):373-5. [cited by applicant]
Morgan et al., The treatment of hepatic encephalopathy. Metab Brain Dis. Dec. 2007;22(3-4):389-405. [cited by applicant]
Nagase et al., Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. Apr. 27, 2001;8(2):85-95. [cited by applicant]
Neff et al., Analysis of hospitalizations comparing rifaximin versus lactulose in the management of hepatic encephalopathy. Transplant Proc. Dec. 2006;38(10):3552-5. [cited by applicant]
Neff et al., Systematic Review of the Economic Burden of Overt Hepatic Encephalopathy and Pharmacoeconomic Impact of Rifaximin. Pharmacoeconomics. Jul. 2018;36(7):809-822. [cited by applicant]
Newman et al., Form Selection of Pharmaceutical Compounds. Handbook of Pharmaceutical Analysis. Lena Ohannesian (Ed.), Marcel Dekker, Inc., New York. Chapter 1, 61 pages, (2002). [cited by applicant]
Ninni, Il trattamento con rifamicina SV negli epatopazienti non peggiora lo stato di sofferenza preesistente e fa rilevare concentrazioni ematiche piu elevate. Chemotherapia. Jan. 1, 1963;7:567-568. [cited by applicant]
Ojetti et al., Rifaximin pharmacology and clinical implications. Expert Opin Drug Metab Toxicol. Jun. 2009;5(6):675-82. [cited by applicant]
Package Insert for the commercial product Xifaxan tablets from Physicians Desk Reference (PDR), (retrieved Jan. 2010), http://www.pdrel.com/View/Common/PrintReady. [cited by applicant]
Paik et al., Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study. Yonsei Med J. Jun. 2005;46(3):399-407. [cited by applicant]
Pakyz, Rifaximin: a new treatment for travelers' diarrhea. Ann Pharmacother. Feb. 2005;39(2):284-9. [cited by applicant]
Pawlowski et al., Diagnosis and treatment of acute or persistent diarrhea. Gastroenterology. May 2009;136(6):1874-86. [cited by applicant]
Pedretti et al., Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial. Ital J Gastroenterol. May 1991;23(4):175-8. [cited by applicant]
Pelizza et al., Polymorphism of rifampicin. Farmaco Sci. Jul. 1977;32(7):471-81. [cited by applicant]
Pigott, Foodborne illness. Emerg Med Clin North Am. May 2008;26(2):475-97. [cited by applicant]
Pimentel et al., The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. Ann Intern Med. Oct. 17, 2006;145(8):557-63. [cited by applicant]
Preidis et al., Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. Gastroenterology. May 2009;136(6):2015-31. [cited by applicant]
Prescribing Information for Rifaximin, Argentina, Date Unknown, but after Apr. 23, 1985, 1 page. [cited by applicant]
Prescribing Information for Rifaximin, Austria, Nov. 2005, 14 pages. [cited by applicant]
Prescribing Information for Rifaximin, Bulgaria, Jun. 2007, 5 pages. [cited by applicant]
Prescribing Information for Rifaximin, China, Oct. 2006, 6 pages. [cited by applicant]
Prescribing Information for Rifaximin, Czech Republic, Mar. 2008, 3 pages. [cited by applicant]
Prescribing Information for Rifaximin, Greece, 2001, 10 pages. [cited by applicant]
Prescribing Information for Rifaximin, Hungary, Apr. 2004, 8 pages. [cited by applicant]
Prescribing Information for Rifaximin, Italy, Apr. 23, 1985, 11 pages. [cited by applicant]
Prescribing Information for Rifaximin, Korea, Jan. 2006, 3 pages. [cited by applicant]
Prescribing Information for Rifaximin, Lebanon, Dec. 2002, 1 page. [cited by applicant]
Prescribing Information for Rifaximin, Mexico, Jul. 2007, 5 pages. [cited by applicant]
Prescribing Information for Rifaximin, Poland, Apr. 2006, 9 pages. [cited by applicant]
Prescribing Information for Rifaximin, Portugal Date Unknown, but after Apr. 23, 1985, 7 pages. [cited by applicant]
Prescribing Information for Rifaximin, Romania, Nov. 2005, 4 pages. [cited by applicant]
Prescribing Information for Rifaximin, Russia, Date Unknown, but after Apr. 23, 1985, 7 pages. [cited by applicant]
Prescribing Information for Rifaximin, Slovakia, Sep. 2003, 7 pages. [cited by applicant]
Prescribing Information for Rifaximin, Spain, Date Unknown, but after Apr. 23, 1985, 5 pages. [cited by applicant]
Prescribing Information for Rifaximin, Tunisia, Mar. 2004, 2 pages. [cited by applicant]
Prescribing Information for Rifaximin, Turkey, Sep. 2007, 8 pages. [cited by applicant]
Prescribing Information for Rifaximin, United States, Jan. 2007, 18 pages. [cited by applicant]
Prescribing Information for Rifaximin, United States, Mar. 2010, 2 pages. [cited by applicant]
Prescribing Information for Rifaximin, United States, May 2004, 13 pages. [cited by applicant]
Prescribing Information for Rifaximin, Venezeula Sep. 2008, 2 pages. [cited by applicant]
Puxeddu et al., Rifaximin in the treatment of chronic hepatic encephalopathy, Current Medical Research and Opinion. 1995;13(5):274-81. [cited by applicant]
Rifaximin Tablet Label, Xifaxan@ (rifaximin) Tablets. Jul. 2006, 16 pages. [cited by applicant]
Riggio et al., Hepatic encephalopathy therapy: An overview. World J Gastrointest Pharmacol Ther. Apr. 6, 2010;1(2):54-63. [cited by applicant]
Riggio et al., Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled study. J Hepatol. May 2005;42(5):674-9. [cited by applicant]
Romero-Gómez et al., Value of the critical flicker frequency in patients with minimal hepatic encephalopathy. Hepatology. Apr. 2007;45(4):879-85. [cited by applicant]
Romero-Gómez, Critical flicker frequency: it is time to break down barriers surrounding minimal hepatic encephalopathy. J Hepatol. Jul. 2007;47(1):10-1. [cited by applicant]
Ruiz et al., In vitro antimicrobial activity of rifaximin against enteropathogens causing traveler's diarrhea. Diagn Microbiol Infect Dis. Dec. 2007;59(4):473-5. [cited by applicant]
Saab et al., MELD fails to measure quality of life in liver transplant candidates. Liver Transpl. Feb. 2005;11(2):218-23. [cited by applicant]
Salix Pharmaceuticals, Ltd. presentation for the Banc of America Conference2005. (45 pages). [cited by applicant]
[cited by applicant]
Sama et al., Clinical effects of rifaximin in patientswith hepatic encephalopathy intolerant or nonresponsive to previous lactulose treatment: An open-label, pilot study. Curr Ther Res Clin Exp. 2004 Sept;65(5):413-22. [cited by applicant]
Scarpellini et al., High dosage rifaximin for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. Apr. 1, 2007;25(7):781-6. [cited by applicant]
Scarpignato et al., Experimental and clinical pharmacology of rifaximin, a gastrointestinal selective antibiotic. Digestion. 2006;73 Suppl 1:13-27. [cited by applicant]
Scarpignato et al., Prevention and treatment of traveler's diarrhea: a clinical pharmacological approach. Chemotherapy. 1995;41 Suppl 1:48-81. [cited by applicant]
Scarpignato et al., Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy. 2005;51 Suppl 1:36-66. [cited by applicant]
Sharma et al., Critical flicker frequency: diagnostic tool for minimal hepatic encephalopathy. J Hepatol. Jul. 2007;47(1):67-73. [cited by applicant]
Simpson et al., Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. EMBO Rep. Sep. 2000;1(3):287-92. [cited by applicant]
Steffen et al., Therapy of Travelers' Diarrhea With Rifaximin on VariousGastroenterol. 2003;98(5):1073-8. [cited by applicant]
Steffen, Rifaximin: a nonabsorbed antimicrobial as a new tool for treatment of travelers' diarrhea. J Travel Med. Dec. 2001;8(Suppl 2):S34-9. [cited by applicant]
Su et al., Utility of the Nonabsorbed (<0.4%) Antibiotic Rifaximin in Gastroenterology and Hepatology. Gastroenterol Hepatol (N Y). Mar. 2006;2(3):186-197. [cited by applicant]
Taylor et al., A randomized, double-blind, multicenter study of rifaximin compared with placebo and with ciprofloxacin in the treatment of travelers' diarrhea. Am J Trop Med Hyg. Jun. 2006;74(6):1060-6. [cited by applicant]
Taylor et al., Systemic pharmacokinetics of rifaximin in volunteers with shigellosis. Antimicrob Agents Chemother. Mar. 2008;52(3):1179-81. [cited by applicant]
Transcript of Salix Pharmaceuticals, Ltd. presentation for the Banc of America Conference 2005. Jul. 28, 2005. (14 pages). [cited by applicant]
Trinh et al., Diarrheal Diseases in the elderly.Clin Geriatr Med. 2007;23(4):833-56. [cited by applicant]
Vignali et al., TIPS with expanded polytetrafluoroethylene-covered stent: results of an Italian multicenter study. AJR Am J Roentgenol. Aug. 2005;185(2):472-80. [cited by applicant]
Vilstrup et al., Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by AASLD and EASL. The American Association for Study of Liver Diseases. 74 pages, (2014). [cited by applicant]
Vippagunta et al., Crystalline solids. Adv Drug Deliv Rev. May 16, 2001;48(1):3-26. [cited by applicant]
Viscomi Declaration under 37 C.F.R. 1.132 filed in U.S. Appl. No. 10/728,090, Dated Jan. 10, 2006 (12 pages). [cited by applicant]
Wiemann et al., Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. Mar. 2001;11(3):422-35. [cited by applicant]
Williams et al., Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol. Feb. 2000;12(2):2… [cited by applicant]
Williams et al., Rifaximin, a nonabsorbed oral antibiotic, in the treatment of hepatic encephalopathy: antimicrobial activity, efficacy, and safety. Rev Gastroenterol Disord. 2005;5 Suppl 1:S10-8. [cited by applicant]
Wolf, Encephalopathy, Hepatic. Emedicine. Retrieved online at: http://basic.shsmu.edu.cn/jpkc/pathology/6/gxnb/htm. 7 pages. May 20, 2014. [cited by applicant]
Xifaxan Prescribing Information datasheet. Retrieved online at: http://www.salix.com/assets/pdf/prescribe_info/xifaxanpi.pdf. 2 pages, Mar. 2008. [cited by applicant]
Yang et al., Rifaximin versus other antibiotics in the primary treatment and retreatment of bacterial overgrowth in IBS. Dig Dis Sci. Jan. 2008;53(1):169-74. [cited by applicant]
Yoo et al., Relationship of the model for End-Stage Liver Disease (MELD) scale to hepatic encephalopathy, as defined by electroencephalography and neuropsychometric testing, and ascites. American Journal of Gastroentero… [cited by applicant]
Zeneroli et al., Antibacterial activity of rifaximin reduces the levels of benzodiazepine-like compounds in patients with liver cirrhosis. Pharmacol Res. Jun. 1997;35(6):557-60. [cited by applicant]
Zeneroli et al., Management of hepatic encephalopathy: role of rifaximin. Chemotherapy. 2005;51 Suppl 1:90-5. [cited by applicant]
Zhao, Clinical Study on New Medicine Rifaximin. Hainan Medical Journal. 2005;16(5), 7 pages. Translation only. [cited by applicant]
Amendment from U.S. Appl. No. 12/478,638, U.S. Pat. No. 7,612,199, filed Sep. 3, 2009, 14 pages. [cited by applicant]
International Search Report for Application No. PCT/US2010/038742, dated Aug. 18, 2010. 2 pages. [cited by applicant]
Decision revoking European Patent No. 2350096, dated Nov. 4, 2022, 84 pages. [cited by applicant]
Notice of Appeal filed Dec. 28, 2022 against decision revoking European Patent No. 2350096 dated Nov. 4, 2022, 2 pages. [cited by applicant]
Statement of grounds of appeal filed Mar. 2, 2023 against decision revoking European Patent No. 2350096, 47 pages. [cited by applicant]
Main and auxiliary requests filed Mar. 2, 2023 in appeal against decision revoking European Patent No. 2350096, 4 pages. [cited by applicant]
Gines, Pere et al., “The Use of Rifaximin in Patients with Cirrhosis,” Hepatology,2021, 74(3): 1660-1673. [cited by applicant]
Bloom, Patricia P. et al., “Microbiome therapeutics for hepatic encephalopathy,” Journal of Hepatology, 2021, 75: 1452-1464. [cited by applicant]
Gluud, Christian et al., “Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials,” BMJ first online, published Mar. 30, 2004, doi:10.1136/bmj.38048.506134.EE, 6 pages. [cited by applicant]
Gerbes, Alexander L. et al., “Aktualisierte S2k-Leitlinie der Deutschen Gesellschaft fur Gastroenterologie, Verdauungs-und Stoffwechselkrankheiten (DGVS) Kromplikationen der Leberzirrhose,” Gastroenterol., 2019, 57: 611… [cited by applicant]
Jalan, Rajiv et al., “Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy,” Journal of Hepatology, 2020, 73: 1526-1547. [cited by applicant]
Clinical Practice Guidelines, “Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guidelines by the European Association for the Study of Liver Diseases,” Journal of Hepatology, 2014, 61: 642-659. [cited by applicant]
Prof. Dr. med. J. Labenz, Expert Opinion on the treatment of hepatic encephalopathy—evidence and controversies filed on Feb. 23, 2023 in the appeal against the decision revoking European Patent No. 2350096, 11 pages. [cited by applicant]
Amended main request and auxiliary requests filed Mar. 2, 2023 in appeal against decision revoking European Patent No. 2350096, 4 pages. [cited by applicant]
Opponent reply to grounds of appeal in European Patent No. 2350096, filed Jul. 7, 2023, 33 pages. [cited by applicant]
Opponent reply to grounds of appeal in European Patent No. 2350096, filed Jul. 12, 2023, 15 pages. [cited by applicant]
Opponent reply to grounds of appeal in European Patent No. 2350096, filed Jul. 13, 2023, 33 pages. [cited by applicant]
Opponent reply to patentee's grounds of appeal in European Patent No. 2350096, filed Jul. 14, 2023, 22 pages. [cited by applicant]
Opponent reply to patentee's grounds of appeal in European Patent No. 2350096, filed Jul. 19, 2023, 17 pages. [cited by applicant]
Opponent reply to patentee's grounds of appeal in European Patent No. 2350096, filed Jul. 19, 2023, 23 pages. [cited by applicant]
Gerard, Laura, “Rifaximin: a nonabsorbalbe rifamycin antibiotic for use in nonsystemic gastrointestinal infections,” Expert Review of Anti-infective Therapy, 2005, 3(2): 201-211. [cited by applicant]
PD Dr. med. Jorg Braun et al., Basislehrbuch Innere Medizin, “7.8.3 Hepatische Enzephalopathie und Leberkoma,” 2001, Urban & Fischer publishers, pp. 648-649. [cited by applicant]
Rote Liste 2006, “B.1.2.1.1. Lactulose,” Bundesverband der Pharmazeutischen Industrie e.V., pp. 50051-50052. [cited by applicant]
Patentee response to Communication of Jul. 19, 2023 enclosing opponent's letters, filed Jan. 23, 2024 in appeal against decision revoking European Patent No. 2350096, 20 pages. [cited by applicant]
Communication of the Board of Appeals dated Oct. 25, 2024, in appeal against decision revoking European Patent No. 2350096, 29 pages. [cited by applicant]
Office Action issued in European Patent Application No. 24155114.2, dated Mar. 13, 2025, 5 pages. [cited by applicant]
Extended European Search Report issued in European Patent Application No. 25177992.2, dated Sep. 17, 2025, 5 pages. [cited by applicant]
Preliminary Appeal Decision issued in Brazilian Patent Application No. PI0920465-2, dated Oct. 8, 2025, 9 pages. [cited by applicant]
Office Action issued in European Patent Application No. 24155114.2, dated Sep. 3, 2025, 6 pages. [cited by applicant]
Fred Poordad et al., “The Protective Effect of Rifaximin (1100 Mg Daily) From Hepatic Encephalopathy Observed in a Double-Bund Placebo Controlled Study is Substantiated and Durable Over the Long Term,” Hepatology, 2009,… [cited by applicant]