United States Patent
`(12)
`(10) Patent No.:
`US 9,220,698 B2
`
`Ault et a].
`(45) Date of Patent:
`*Dec. 29, 2015
`
`US009220698B2
`
`(75)
`
`(54) METHOD FOR DELIVERINGA
`PHARMACEUTICAL COMPOSITION TO
`PATIENT IN NEED THEREOF
`_
`.
`.
`Inventorsz BrlanAult,W11m1ngton,DE (US);
`Mark Sostek, Wilmington, DE (US);
`Everardus Orlemans, Chapel Hill, NC
`.
`-
`(US), John R. Plachetka, Chapel H111,
`NC (US)
`
`.
`( * ) Not1ce:
`
`.
`.
`(73) A551gnees: Pozen Inc., Chapel H111, NC (US);
`Horizon Pharma USA, Inc., Deerfield,
`IL (US)
`.
`.
`.
`.
`Subject. to any disclaimer, the term ofth15
`patent IS extended or adjusted under 35
`U.S.C. 154(b) by 553 days.
`.
`.
`.
`.
`.
`This patent IS subject to a terminal dls-
`Claimer.
`
`.
`(21) Appl'No“ 12/553’107
`.
`Flledi
`
`Sep- 3, 2009
`
`(22)
`
`(65)
`
`Prior Publication Data
`
`US 2010/0062064 A1
`
`Mar. 11, 2010
`
`(60)
`
`(51)
`
`(52)
`
`(58)
`
`(56)
`
`Related U.S. Application Data
`
`Provisional application No. 61/095,584, filed on Sep.
`9, 2008.
`
`Int. Cl.
`
`A61K 31/4439
`A61K 31/192
`U.S. Cl.
`
`(2006.01)
`(2006.01)
`
`CPC ........... A61K31/192 (2013.01); A61K 31/4439
`(2013.01)
`
`Field of Classification Search
`
`CPC ...................... A61K 31/4439; A61K 31/192
`See application file for complete search history.
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`4,198,390 A
`4,255,431 A
`4,344,929 A
`4,508,905 A
`4,554,276 A
`4,562,261 A
`4,619,934 A
`4,676,984 A
`4,704,278 A
`4,726,951 A
`4,738,974 A
`4,757,060 A
`4,758,579 A
`4,766,117 A
`4,786,505 A
`4,853,230 A
`4,865,847 A
`4,948,581 A
`4,965,065 A
`5,026,560 A
`5,035,899 A
`
`4/1980 Rider
`3/1981 Junggren et a1.
`8/1982 Bonsen et a1.
`4/1985 Junggren et a1.
`11/1985 LaMattina
`12/1985 Hirata et a1.
`10/1986 Sunshine et a1.
`6/1987 Wu et a1.
`11/1987 Wu et a1.
`2/1988 Panoz et a1.
`4/1988 Brandstrom
`7/1988 Lukacsko et a1.
`7/1988 Kohl et a1.
`8/1988 Crawford et a1.
`11/1988 Lovgren et a1.
`8/1989 Lovgren et a1.
`9/1989 Gosswein
`8/1990 Sawayanagi et a1.
`10/1990 Lukacsko et a1.
`6/1991 Makino et a1.
`7/1991 Saeki et a1.
`
`5,037,815 A
`,
`,
`28433;; 2
`5,093,132 A
`5,204,118 A
`5,260,333 A
`5,364,616 A
`2,2335%; 2
`,
`,
`5,417,980 A
`5,466,436 A
`5,514,663 A
`5,601,843 A
`5,631,022 A
`5,643,960 A
`5,667,802 A
`5,679,376 A
`5,686,105 A
`5,702,723 A
`5,714,504 A
`5,716,648 A
`5,750,531 A
`5,817,338 A
`5,817,340 A
`5,840,737 A
`5,900,424 A
`5,955,451 A
`6,013,281 A
`6,025,395 A
`6,093,734 A
`6,132,768 A
`6,132,771 A
`6,136,344 A
`6,160,020 A
`A
`6,162,816
`6,183,776 B1
`6,183,779 B1
`6,207,188 B1
`
`8/1991 Lukacsko et a1.
`anoz e a .
`$1331 lgukacslio ft al~
`3/1992 Makino et a1.
`4/1993 Goldman et a1.
`11/1993 Lukacsko et a1.
`11/ 1994 Singer et a1.
`1313321 gaWZI ettall
`zawa e a .
`5/1995 Goldman et a1.
`11/1995 Stables
`5/1996 Mandel
`2/1997 Gimet et a1.
`5/ 1997 Mandel et 31~
`7/1997 Breitneretal.
`9/1997 Grimberg
`10/1997 St
`t
`l.
`1 1/1997 KSYEEZIS
`12/1997 Griffin
`2/1998 Lindberg et a1.
`2/1998 Halskov etal.
`5/1998 Lee et a1.
`10/1998 Bergstrand et a1.
`10/1998 Roche et a1.
`11/1998 Phillips
`5/1999 Kallstrom etal.
`9/1999 Lichtenberger et a1.
`1/2000 Lundberg et a1.
`2/2000 Breitner et a1.
`7/2000 Garst et 31.
`10/2000 Sachs et al.
`10/2000 Depui et a1.
`10/2000 Depui et a1.
`12/2000 Ohannesian et al.
`12/2000 Bohlin et a1.
`2/2001 Depui et a1.
`2/2001 Ouali et a1.
`3/2001 Gustavsson et a1.
`
`(Continued)
`
`FOREIGN PATENT DOCUMENTS
`
`AU
`CA
`
`2006235929
`2139653
`
`11/2006
`7/2000
`
`(Continued)
`
`OTHER PUBLICATIONS
`
`Abelo et a1., “Pharmacodynamic modeling of reversible gastric acid
`pump inhibition in dog and man,” European Journal of Pharmaceu-
`tical Sciences, 14, pp. 339-346 (2001).
`
`(Continued)
`
`Primary Examiner 7 Gina Justice
`
`(74) Attorney, Agent, or Firm 7 Parker Highlander PLLC
`
`(57)
`
`ABSTRACT
`
`The present disclosure is directed to a method for delivering
`a pharmaceutical composition to a patient in need thereof,
`comprising: administering to said patient a pharmaceutical
`composition in unit dose form comprising naproxen, or phar-
`maceutically acceptable salt thereof, and esomeprazole, or
`pharmaceutically acceptable salt thereof.
`
`7 Claims, 9 Drawing Sheets
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 1
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 1
`
`

`

`US 9,220,698 B2
`
`Page 2
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`2010/0178334 A1
`2010/0330179 A1
`2012/0064156 A1
`
`7/2010 Johansson et a1.
`12/2010 Aultetal.
`3/2012 Plachetka
`
`6,231,888 B1
`6,287,600 B1
`6,365,184 B1*
`6,369,085 B1
`6,372,255 B1
`6,387,410 B1
`6,395,298 B1
`6,428,810 B1
`6,485,747 B1
`6,489,346 B1
`6,544,556 Bl
`6,599,529 Bl
`6,610,323 Bl
`6,613,354 B2
`6,632,451 B2
`6,641,838 B2
`6,645,988 B2
`6,673,819 B2
`6,685,964 B1
`6,699,885 B2
`6,713,089 B1
`6,749,867 B2
`6,780,882 B2
`6,787,164 B2
`6,797,283 B1
`6,869,615 B2
`6,875,872 B1
`6,926,907 B2*
`7,029,701 B2
`7,004,400 00
`7,399,772 B2
`7,411,070 B2
`7,488,497 B2
`7,745,466 B2
`7,785,626 B2
`7,846,914 B2
`8,206,741 B2
`
`.................. 424/472
`
`5/2001 Lerner et al.
`9/2001 0ualietal.
`4/2002 Depuietal.
`4/2002 Cotton etal.
`4/2002 Saslawski et al.
`5/2002 Woolfe etal.
`5/2002 Flanagan etal.
`8/2002 Bergstrand etal.
`11/2002 Flanagan etal.
`12/2002 Phillips
`4/2003 Chen etal.
`7/2003 Skinhojetal.
`8/2003 Lundberg etal.
`9/2003 Depuietal.
`10/2003 Penhasietal.
`11/2003 Father et a1.
`11/2003 Phillips
`1/2004 Bergman et al.
`2;2004 Bleluitlholomaeus et al.
`3 2004 P i
`ips
`3/2004 Bertelsen et al.
`6/2004 Robinson et al.
`8/2004 Phillips
`9/2004 Gelberetal.
`9/2004 Edgren et al.
`3/2005 Chen etal.
`4/2005 Lindberg etal.
`8/2005 Plachetka ..................... 424/472
`4/2006 Chen
`00000 0000000
`7/2008 Phillips
`8/2008 Cotton etal.
`2/2009 Depuietal.
`6/2010 Cotton etal.
`8/2010 Pettersson etal.
`12/2010 Petrus
`6/2012 Plachetka
`
`2002/0012676 A1
`2002/0042433 A1
`2002/0044962 A1
`2002/0045184 A1
`2002/0086029 A1
`2002/0090395 A1
`2003/0008903 A1
`2003/0113375 A1
`2003/0215527 A1
`2003/0232080 A1
`2004/0048896 A1
`2004/0121004 A1
`2004/0131676 A1
`2004/0171646 A1
`2005/0004171 A1
`2005/0042304 A1
`2005/0054682 A1
`2005/0147668 A1
`2005/0163847 A1
`2005/0227949 A1
`2005/0249806 A1
`2006/0165797 A1
`2006/0177504 A1
`2006/0178348 A1
`2006/0178349 A1
`2006/0287284 A1
`2007/0122470 A1
`2007/0154542 A1
`2007/0184078 A1
`2007/0237820 A1
`2007/0243251 A1
`2008/0031941 A1
`2008/0031950 A1
`2008/0103169 A1
`2009/0074863 A1
`2009/0075950 A1
`2010/0172983 A1
`
`1/2002 Lundberg etal.
`4/2002 Yelle etal.
`4/2002 Cherukurietal.
`4/2002 Chen
`7/2002 Lundberg etal.
`7/2002 Woolfe etal.
`1/2003 Barberich etal.
`6/2003 Lundberg etal.
`11/2003 Phillips
`12/2003 Patheretal.
`3/2004 Phillips
`6/2004 Taneja
`7/2004 Taneja
`9/2004 Phillips
`1/2005 Phillips
`2/2005 Phillips
`3/2005 Phillips
`7/2005 Bertelsen et 31.
`7/2005 Cheng etal.
`10/2005 Edalatpour
`11/2005 Proehletal.
`7/2006 Plachetka
`8/2006 Sundharadas
`8/2006 Plachetka
`8/2006 Plachetka
`12/2006 Schutze et a1.
`5/2007 Johansson et 31.
`7/2007 Tananbauin etal.
`8/2007 Chen
`10/2007 Cheng etal.
`10/2007 Taneja
`2/2008 Pettersson
`2/2008 Sesha
`5/2008 Phillips
`3/2009 Taneja
`3/2009 Taneja
`7/2010 Plachetka
`
`FOREIGN PATENT DOCUMENTS
`
`BE
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`$3
`GB
`JP
`W0
`W0
`wo
`W0
`
`13
`W0
`W0
`W0
`W0
`W0
`WO
`
`W0
`W0
`W0
`W0
`W0
`W0
`W0
`W0
`
`$8
`W0
`W0
`W0
`W0
`wo
`W0
`
`$8
`W0
`W0
`W0
`W0
`wo
`WO
`
`$8
`WO
`WO
`W0
`W0
`WO
`W0
`W0
`
`lgggigfi
`0005129
`0124495
`0174726
`0320550
`0320551
`0166287
`0167958
`0244380
`0426479
`0550083
`1068867
`1726300
`1726301
`1020461
`$12,249,;
`2216413
`2005445894
`8503443
`9006925
`9116886
`9116895
`
`3113311
`9119712
`9311750
`9312817
`9407541
`9427988
`9501977
`
`9605177
`9605199
`9614839
`9622780
`9711701
`9725064
`9813073
`9822117
`
`3:31;?
`9900380
`9912524
`9929320
`9966919
`0001368
`0015195
`
`gggfigg
`0072838
`0078293
`0124777
`0166088
`0222108
`02066002
`
`208285223
`2004064815
`2005074536
`2005074930
`2006044202
`2007064274
`2007078874
`2008101060
`
`12/2334
`4/1981
`“1987
`4/1989
`6/1989
`6/1989
`8/1989
`1/1991
`1/1993
`2/1994
`3/1999
`9/2003
`11/2006
`11/2006
`7/2009
`Z1332
`10/1989
`60005
`8/1985
`6/1990
`11/1991
`11/1991
`
`151331
`”“991
`6/1993
`7/1993
`4/1994
`12/1994
`1/1995
`
`”996
`”996
`5/1996
`8/1996
`4/1997
`7/1997
`4/1998
`5/1998
`
`5133:
`“999
`3/1999
`6/1999
`12/1999
`1/2000
`3/2000
`
`$5888
`”/2000
`12/2000
`4/2001
`9/2001
`3/2002
`8/2002
`
`$88:
`”004
`”005
`80005
`40006
`6/2007
`7/2007
`8/2008
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 2
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 2
`
`

`

`US 9,220,698 B2
`
`Page 3
`
`(56)
`
`WO
`WO
`WO
`
`References Cited
`FOREIGN PATENT DOCUMENTS
`
`2009012393
`2009145905
`2010151697
`
`1/2009
`12/2009
`12/2010
`
`OTHER PUBLICATIONS
`
`Alexander, et al., “Pilot Evaluation of a Novel Combination Tablet
`(PN 400) Containing a Proton Pump Inhibitor and a Nonsteroidal
`Anti-Inflammatory Drug in Prevention of Upper Gastrointestinal
`Mucosal Injury,” American Journal of Gastroenterology, 100(9), p.
`S68, 135 (2005).
`Andersson, “Pharmacokinetics, metabolism and interactions of acid
`pump inhibitors,” Clin. Pharmacokinet. 31(1)9-28 (Jul. 1996).
`Anonymous: “A 12-month, phase 3, open-label, multi-center study to
`evaluate the long-term safety of PN 400” Internet article (Sep. 11,
`2007), XP00255347,
`retrieved from the internet, URL:http://
`clinicaltrials.gov/show/NCT00527904>.
`Anonymous: “PK Study to evaluate Esomeprazole plasma levels
`following the administration of PN 400” Internet article (Feb. 11,
`2008), XP002553435,
`retrieved from the internet: URL:http://
`clinicaltrials.gov/show/NCT00599404>.
`Anonymous: “Study evaluating the bioavailability of Naproxen 500
`mg in three formulations,” Internet article (May 11, 2008),
`XP002553436m retrieved from the internet: URL:http://clinicaltri-
`als.gov/show/NCT00665743>.
`Arthrotec Data sheet (Aug. 2009).
`Awtry, et al., “Aspirin,” Circulation 101:1206-1218 (2000).
`Ballinger, et al., “COX-2 Inhibitors vs. NSAIDs in Gastrointestinal
`Damage and Prevention,” Exp. Opin. Pharmacother. 2(1):31-40
`(2001).
`Barnett et al., “Effects of SCH 32651 on resting and stimulated acid
`secretion in guinea-pig isolated fundic mucosa,” Br. J. Pharmac., 83,
`pp. 75-82 (1984).
`Berardi et al., “Elevation of Gastric pH with Ranitidine does not
`affect the release characteristics of sustained release Ibuprofen tab-
`lets,” Biopharmaceutics & Drug Disposition, 9: pp. 337-347 (1988).
`Bergrnann et al., “Protection against aspirin-induced gastric lesions
`by lansoprazole:
`simultaneous
`evaluation of
`functional
`and
`morphologic responses,” Clin. Pharmcol. Ther., 52, pp. 413-416
`(Oct. 1992).
`Bianchi Porro et al., “Pantoprazole vs placebo in prevention of
`NSAID-induced ulcers,” Gastroenterology, 114(4), p. A74 (1998).
`Bianchi Porro, et al., “Prevention of gastroduodenal damage with
`omeprazole in patients receiving continuous NSAIDs treatment. A
`double blind placebo controlled study,” Ital.
`J. Gastroenterol.
`Hepatol., 30, pp. 43-47 (1998).
`Bianchi Porro, et al., “Why Are Non-Steroidal Anti-Inflammatory
`Drugs Important in Peptic Ulcers?” Aliment. Pharmacol. Therap, 1,
`pp. 5408-5478 (1987).
`Bigard English translationiBigard, et al. “Effet protecteur de
`l’omeprazole sur les lesions gastriques induites par une prise unique
`d’aspirine chez l’homme,” Gastroenterol. Clin. Biol., 12, pp. 770-771
`(1998).
`Bigard et a1 ., “Complete prevention by omeprazole ofaspirin induced
`gastric lesions in healthy subjects,” Gut, 29(5), p. A712, T49 (1988).
`Bigard et al., “Effet protecteur de l’omeprazole sur les lesions
`gatriques induites par une prise unique d’aspirine chez l’homme,”
`Gastroenterol. Clin. Biol., 12, pp. 770-771 (1998).
`Bombardier et al., “Comparison of upper gastrointestinal toxicity of
`rofecoxib and naproxen in patients with rheumatoid arthritis,” N.
`Engl. J. Med., 343, pp. 1520-1528 (2000).
`Brown et al., “Prevention of the gastrointestinal adverse effects of
`nonsteroidal anti-inflammatory drugs,” Pract. Drug Safety, 21, pp.
`503-512 (1999).
`Brown, et al., “Asprin- and Indomethacin-Induced Ulcers and Their
`Antagonism by Antihistamines,” Euro. J. Pharm., 51, pp. 275-283
`(1978).
`Byrn et al., “Pharmaceutical solids: A strategic approach to regula-
`tory considerations,” Pharm. Res., 12(7), pp. 945-954 (1995).
`
`Carrasco-Portugal, et al., “Bioavailability of a Formulation Contain-
`ing a Diclofenac-Ranitidine Combination,” Proc. West. Pharmacol.
`800., 45, pp. 8-10 (2002).
`Chan et al., “Eradication of H. pylori versus maintenance acid sup-
`pression to prevent recurrent ulcer hemorrhage in high risk NSAID
`users: A prospective randomized study,” Gastroenterology, 114, p.
`A87, G0356 (1998).
`Chan, et al., “Clopidogrel versus Aspirin and Esomeprazole to pre-
`vent recurrent ulcer bleeding,” New Eng. J. Med. 352, pp. 238-244
`(2005).
`Chandrarnouli et al., J. Pharmaceutical Pain and Symptom Control,
`pp. 27-40 (2000).
`Chang et al., “Polymetharcrylates,” Handbook of Pharmaceutical
`Excipients, Fifth Edition, Ed. RaymondC. Rowe, Paul J. Sheskey and
`Sian C. Owen, London: Pharmaceutical Press, pp. 553-560 (2006).
`Cullen et al., “Primary gastroduodenal prophylaxis with omeprazole
`for
`non-steroidal
`anti-inflammatory
`drug
`users,” Aliment.
`Pharmacol. Ther., 12, pp. 135-140 (1998).
`Daj ani, Esam Z., “Perspective on the Gastric Antisecretory Effects of
`Misoprostol in Man,” Prostaglandins, 33, pp. 68-77 (1987).
`Daneshmend et al., “Abolition by omeprazole of aspirin-induced
`gastric mucosal injury in man,” Gut, 31, pp. 514-517 (1990).
`Daneshmend et al., “Use of microbleeding and an ultrathin
`endoscope to assess gastric mucosal protection by Famotidine,” Gas-
`troenterology, 97, pp. 944-949 (1989).
`Dent et al., “Why proton pump inhibition should heal and protect
`against nonsteroidal anti-inflammatory drug ulcers,” Am. J. Med.,
`104, pp. 528-558 (1998).
`Ehsanullah et a1, “Prevention of gastroduodenal damage induced by
`non-steroidal anti-inflammatory drugs: controlled trial ofranitidine,”
`BMJ, 297, pp. 1017-1021 (Oct. 1988).
`Ekstrom et al., “Prevention of peptic ulcer and dyspeptic symptoms
`with omeprazole in patients receiving continuous non-steroidal anti-
`inflammatory drug therapy,” Scand. J. Gastroenterol., 31, pp. 753-
`758 (1996).
`Ene et al., “A study of the inhibitory effects of SCH 28080 on gastric
`secretion in man,” Br. J. Pharmac., 76, pp. 389-391 (1982).
`Erlandsson et al., “Resolution of the enantiomers of omeprazole and
`some
`of
`its
`analogues
`by
`liquid
`chromatography on
`a
`trisphenycarbamoylcellulo se-based
`stationary
`phase,”
`J.
`Chromatog., 532, pp. 305-319 (1990).
`Feldman et al., “Effect on antacid on absorption on enteric-coated
`aspirin,” JAMA, 227(6), pp. 660-661 (1974).
`Florence et al., “Novel oral drug formulations their potential in
`modulating adverse effects,” Drug Safety, 10(3), pp. 233-266 (1994).
`Frank, et al., “Reduction of Indomethacin Induced Gastrduodenal
`Mucosal Injury and Gastro -intestinal Symptoms with Cimetidine in
`Normal Subjects,” J. Rheum., 16, pp. 1249-1252 (1989).
`Gengo, et al., “Prevalence of Platelet Nonresponsiveness to Aspirin
`in Patients Treated for Secondary Stroke Prophylaxis and in Patients
`With Recurrent Ischemic Events,” J. Clin. Pharmacol., 48, pp. 335-
`343 (2008).
`Goldstein et al., “116 A single tablet multilayer formulation of
`enteric-coated
`naproxen
`coupled with
`non-enteric-coated
`omeprazole is associated with a significantly reduced incidence of
`gastric ulcers vs. enteric-coated naproxen: A prospective, random-
`ized, double-blind study,” Gastroenterology, Elsevier, Philadelphia,
`PA, 134(4), p. A-19 (Apr. 1, 2008).
`Improves Upper
`Goldstein,
`et
`al.,
`“PN400
`Significantly
`Gastrointestinal Tolerability Compared with Enteric-Coated
`Naproxen Alone in Patients Requiring Chronic NSAID Therapy:
`Results from Two Prospective, Randomized, Controlled Trials,”
`Pozen Inc. sponsored study, 74th Annual Scientific Meeting of the
`American College of Gastroenterology, San Diego, CA (Oct. 27,
`2009).
`Goldstein, et al., “PN400 Significantly Reduces the Incidence of
`Gastric Ulcers Compared With Enteric -Coated Naproxen in Patients
`Requiring Chronic NSAID Therapy Regardless ofLow-Dose Aspirin
`Use: Results from Two Prospective, Randomized Controlled Trials,”
`Pozen Inc. sponsored study, ACIUARHP Mtg, (Oct. 16-21, 2009).
`Graham, et al., “Duodenal and Gastric Ulcer Prevention with
`Misopro stol in Arthritis Patients Taking NSAIDs,” Ann. Intern. Med.
`119(4):257-262 (Aug. 1993).
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 3
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 3
`
`

`

`US 9,220,698 B2
`Page 4
`
`(56)
`
`References Cited
`OTHER PUBLICATIONS
`
`Grosser et al., “Thromboxane Generation,” in Platelets, Alan
`Michelson ed., Elseiver Science, pp. 565-574 (2007).
`Gurbel et al., “Abstract 4267: PA32520 (Single-tablet of enteric
`coated aspirin 325 mg + immediate-release omeprazole 20 mg):
`Aspirin therapy combining greater thromboxane supression and
`lower upper gastrointestinal damage,”, Circulation, 118, p. S855
`(2008).
`Hart, et al., “Aspirin Dosage and Thromboxane Synthesis in Patients
`with Vascular Disease,” Pharmacotherapy 23 (5):579-584 (2003).
`Hassan-Alin et al., “T1651 lack of drug-drug interaction between
`esomeprazole and naproxen in healthy subjects,” Gastroenterology,
`124(4), Supp. 1, p. A541 (Apr. 2003).
`Hawkey et al., “Omeprazole compared with misoprostol for ulcers
`associated with nonsteroidal anti-inflammatory drugs,” N. Engl. J.
`Med., 338, pp. 727-734 (1998).
`Hawkey et al., “Progress in prophylaxis against nonsteroidal anti-
`inflammatory drug-associated ulcers and erosions,” Am. J. Med.,
`104, pp. 678-748 (1998).
`Office Action dated Apr. 22, 2004 issued for US. Pat. No. 6,926,907.
`Office Action dated Oct. 10, 2004 issued for US. Pat. No. 6,926,907.
`Notice of Allowance dated Mar. 29, 2005 issued for US. Pat. No.
`6,926,907.
`Office Action dated Mar. 30, 2009 issued for US. Pat. No. 8,206,741.
`Office Action dated Nov. 19, 2009 issued forU.S. Pat. No. 8,206,741 .
`Office Action dated Oct. 25, 2010 issued for US. Pat. No. 8,206,741 .
`Office Action dated Jun. 16,2011 issued for US. Pat. No. 8,206,741 .
`Interview Summary dated Nov. 15, 2011 issued for US. Pat. No.
`8,206,741.
`Interview Summary dated Mar. 7, 2012 issued for US. Pat. No.
`8,206,741.
`Interview Summary dated Apr. 19, 2012 issued for US. Pat. No.
`8,206,741.
`Notice of Allowance dated May 13, 2012 issued for US. Pat. No.
`8,206,741.
`IPER issued for WO 2010/029335, Mar. 2011.
`ISR issued for WO 2010/029335, Nov. 2009.
`Supplemental ISR issued for WO 2010/029335, Sep. 2010.
`Written Opinion issued for WO 2010/029335, Mar. 2011.
`U.S.App1.No. 13/475,446, filed May 18, 2012.
`Preliminary Amendment for US. Appl. No. 13/475,446, filed May
`18, 2012.
`Hawkey et al., “Prophylaxis of aspirin-induced gasf ric mucosal
`bleeding with ranitidine,” Aliment. Pharmacol. Therap., 2, pp. 245-
`252 (1988).
`Hawkey et al., Scandinavian J. Gastroenterology, pp. 124-127 (1996)
`Handbook of Pharmaceutical Excipients, 5th Edition (2006).
`Hawkey et al., Scandinavian J. Gastroenterology, pp. 170-173
`(1986).
`Hawkins & Hanks, J. Pain and Symptom Management, pp. 140-151
`(2000).
`Helander et al., “Structure and function of rat parietal cells during
`treatment with omeprazole, SCH 28080, SCH 32651, or ranitidine,”
`Scan. J. Gastroenterol., 25, pp. 799-809 (1990).
`Histamine H2 antagonist information on drugs.com website, down-
`loaded Feb. 20, 2012.
`Hogan et al., “Prescription of nonsteroidal anti-inflammatory drugs
`for elderly people in Alberta,” Can. Med. Assoc., 151(3), pp. 315-322
`(1994).
`Pharmacology
`“Clinical
`Howden,
`Pharmacokinet, 20(1), pp. 38-49 (1991).
`Ife et al., “Reversible inhibitors ofthe Gastric (H.sup.+/K.sup.+)iA
`Tpase. 3. 3-Substituted-4-(phenylamino)quinolines,” J. Med. Chem.,
`35, pp. 3413-3422 (1992).
`Jiranek, et al., “Misoprostol Reduces Gastroduodenal Injury From
`One Week of Aspirin: An Endoscopic Study,” Gastroenterology, 96,
`pp. 656-661 (1989).
`Katz et al., “Gastric acidity and acid breakthrough with twice-daily
`omeprazole or iansoprazole,” Aliment. Pharmacol. Ther., 14, pp.
`709-714 (2000).
`
`of Omeprazole,” Clin.
`
`Keeling et al., “SK&F 96067 is a reversible, lumenally acting inhibi-
`tor of the gastric (H.sup.+ +K.sup.+)iATPase,” Biochemical Phar-
`macology, 42(1), pp. 123-130 (1991).
`Kephart et al., “Coprescribing of nonsteroidal anti-inflammatory
`drugs and cytoprotective and antiulcer drugs in Nova Scotia’s senior
`population,” Clin. Ther., 17, pp. 1159-1173 (1995).
`Kimmey et al., “Role of H2-receptor blockers in the prevention of
`gastric injury resulting from nonsteroidal anti-inflammatory agents,”
`Am. J. Med., 84, pp. 49-52 (1988).
`Kitchingman, et al., “Enhanced Gastric Mucosal Bleeding with
`Doses of Asprin Used for Prophylaxis and Its Reduction by
`Ranitidine,” Br. J. Clin. Pharmac., 28, pp. 581-585 (1989).
`Konturek et al., “Effects of omeprazole, a substituted benzimidazole,
`on gastrointestinal secretions, serum gastrin, and gastric mucosal
`blood flow in dogs,” Gastroenterology, 86(1), pp. 71-77 (1984).
`Lad et al., “Management of nonsteroidal anti-inflammatory drug-
`induced gastroduodenal disease by acid suppression,” Can.
`J.
`Gastroenterol., 13, pp. 135-142 (1999).
`Lanas, A., “Prevention of aspirin-induced gastroduodenal damage:
`H. pylori infection eradication versus proton pump inhibitors or
`both,” Digestive and Liver Disease, 36, pp. 655-657 (2004).
`Lanza, et al., “A Double-Blind Placebo-Controlled Comparison of
`the efficacy and Safety of 50, 100, and 200 ug ofMisoprostol QID in
`the Prevention of Ibuprofen-Induced Gastric and Duodenal Muco sal
`Lesions and Symptoms,” Am. J Gastroenterol., 84(6), pp. 633-636
`(1989).
`Lanza, et al., “Double-Blind, Placebo-Controlled Endoscopic Com-
`parison of the Mucosal Protective Effects of Misoprostol Versus
`Cimetidine on Tolmetin-Induced Mucosal Injury to the Stomach and
`Duodenum,” Gastroenterology, 95, pp. 289-294 (1988).
`Larsson et al., “Animal pharmadynamics of omeprazole. A survey of
`its pharmacological properties in vivo,” Scand J Gastroenterol
`Suppl., 108, pp. 23-35 (1985).
`Lee et al., “Omeprazole prevents indomethacin-induced gastric
`ulcers in rabbits,” Aliment. Pharmacol. Ther., 10, pp. 571 -576 (1996).
`Leese, et al., “Effects of Celecoxib, a Novel Cyclooxygenase-2
`Inhibitor, on Platelet Function in Healthy Adults: A Randomized,
`Controlled Trial,” J. Clin. Pharmacol., 40, pp. 124-132 (2000).
`Leonards et al., “Reduction or prevention of aspirin-induced occult
`gastrointestinal blood loss in man,” Clinical Pharmacology and
`Therapeutics, 10(4), pp. 571-575 (1969).
`Lichtenbergetr et al., “Nonsteroidal anti-inflammatory drug and
`phospholipid prodrugs: combination therapy with antisecretory
`agents in rats,” Gastroenterology, 111, pp. 990-995 (1996).
`Lin and Lu, “Role of pharmacokinetics and metabolism in drug
`discovery and development,” Pharmacological Reviews, 49(4), pp.
`403-449 (1997).
`Maggi et al., Int. J. Pharm., pp. 173-179 (1993).
`Mason et al., “Kinetics of aspirin, salicyclic acid, and salicyuric acid
`following oral administration of aspirin as a tablet and two buffered
`solutions,” J. Pharmaceutical Sciences, 70(3), pp. 262-265 (1981).
`Mattson et al., “Omeprazole provides protection against experimen-
`tally induced gastric mucosal lesions,” Eur. J. Pharmacol., 91, pp.
`111-114 (1983).
`McKeage et al., “Esomeprazole: a review of its use in the manage-
`ment of gastric acid-related diseases in adults,” Drugs, 68(11), pp.
`1571-1607 (2008).
`Miner et al., “Clinical trial: evaluation of gastric acid suppression
`with three doses of immediate-release esomeprazole in the fixed dose
`combination of PN400 (naproxen/esomeprazole magnesium) com-
`pared with naproxen 500 mg and enteric coated esomeprazole 20 mg:
`a randomized, open-label, phase 1 study in healthy volunteers,” Ali-
`mentary pharmacology and therapeutics, 32, pp. 414-424, table 1
`(2010).
`Miner et al., “T1969 gastric acid suppression with PN400, a single-
`tablet, multilayer, fixed-dose formulation combining an immediate-
`release esomeprazole layer and an enteric-coated naproxen core,”
`Gastroenterology, Elsevier, Philadelphia, PA, 136(5), p. A-611 (May
`1, 2009).
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 4
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 4
`
`

`

`US 9,220,698 B2
`
`Page 5
`
`(56)
`
`References Cited
`OTHER PUBLICATIONS
`
`
`
`“T1972 Pharmacokinetics of Naproxen and
`al.,
`et
`Miner
`Esomeprazole in PN400, a single-tablet, multilayer formulation of
`enteric-coated Naproxen
`coupled with
`immediate-release
`Esomeprazole,” Gastroenterology, Elsevier, Philadelphia, PA,
`136(5), p. A-612 (May 1, 2009).
`VIorgner et al., “Esomeprazole: prevention and treatment of NSAID-
`induced
`symptoms
`and
`ulcers,”
`Expert
`opinion
`on
`pharmacotherapeutics, 8(7), pp. 975-988 (2007).
`VIorris, et al., “Gastric Cyloprotection is Secondary to Increased
`VIucosal Fluid Secretion: A Study of Six Cytoprotective Agents in the
`Rat,” J. Clin. Gastroenterol., 27, Supp. 1, pp. 853-863 (1998).
`VIorrison et al., “The optimal analgesic dose of rofecoxib: overview
`of six randomized controlled trials,” JADA, 131, pp. 1729-1737
`(2000).
`VIuller English translationiMuller, et al., “Untersuchungen zur
`Schutzwirkung
`von
`Lansoprazol
`auf
`die menschliche
`Vlagenschleimhaut gegenuber niedrig dosierter Acetylsalicylsaure,”
`Arzneimittel Forschung, 47, pp. 758-760 (1997).
`VIuller English translationiMuller, et al., “Verbesserung der
`gastroduodenalen Vertraglichkeit von Azetylsalizylsaure durch
`Ranitidin,” Arzneimittel-Forschung/Drug Res., 41(1), pp. 638-639
`(1991).
`VIuller, et al., “Untersuchungen zur Schutzwirkung von Lansoprazol
`auf die menschliche Magenschleimhaut gegenuber niedrig dosierter
`Acetylsalicylsaure,” Arzneimittel Forschung, 47, pp. 758-760
`(1997).
`VIuller, et al., “Verbesserung der gastroduodenalen Vertraglichkeit
`von Azetylsalizylsaure durch Ranitidin,” Arzneimittel-Forschung/
`Drug Res., 41(1), pp. 638-639 (1991).
`\Iaesdal, et al., Gastro-Duodenal Protection in an Era of Cyclo-
`Oxygenase-2-Selective Nonsteroidal Anti-Inflammatory Drugs,
`European Journal of Gastroenterology & Hepatology, 13(12), pp.
`1401-1406 (2001).
`\Iaprosyn EC Label, Roche (1999).
`\Iefesoglu, et al., “Interaction of Omeprazole with Enteric-Coated
`Salicylate Tablets,” International Journal of Clinical Pharmacology
`and Therapeutics, 36(10), pp. 549-553 (1998).
`\Ieuvonen et al., “Enhancement of drug absorption ofantacids,” Clin.
`Pharmacokinet., 27(2), pp. 120-128 (1994).
`Oddsson et al., “Endoscopic findings in the stomach and duodenum
`after treatment with enteric-coated and plain naproxen tablets in
`healthy subjects,” Scand. J. Gastroenterol., 25, pp. 231-234 (1990).
`Oddsson, et al., “Comparison between Ranitidine and Omeprazole
`for Protection against Gastroduodenal Damage Caused by
`Naproxen,” Scand. J. Gastroenterol., 27, pp. 1045-1048 (1992).
`Okabe et al., “Antisecretory effect of leminoprazole on histamine-
`stimulated gastric acid secretion in dogs: potent local effect,” Jpn. J.
`Pharmacol., 69, pp. 91-100 (1995).
`Okabe et al., “Pharmacological regulation of gastric acid secretion in
`the apical membrane of parietal cells; a new target for antisecretory
`drugs,” Journal ofPhysiology and Pharmacology, 52(4), pp. 639-656
`(2001).
`Office Communication issued in Egyptian Patent Application No.
`2121/2011, dated Apr. 13, 2013. (English summary ofArabic text).
`Panara et al., “Effects of the novel anti-inflammatory compounds,
`N-[2-(cyclohexyloxy)-4-nitrophenyl]
`methanesulphonamide
`(NS-398) and 5-methanesulphonamido-6-(2,4-difluorothio-phenyl)-
`1-inda none (L-745,337), on the cyclo-oxygenase activity of human
`blood prostaglandin endoperoxide synthases,” British Journal of
`Pharmacology, 116, pp. 2429-2434 (1995).
`Pang et al., “Modeling of intestinal drug absorption: roles of trans-
`porters and metabolic enzymes (for the Gillette review series)” Drug
`Metabolism and Disposition, 31(12), pp. 1507-1519 (2003).
`Patrono,
`et
`al.,
`“Low-Dose Aspirin for
`the Prevention of
`Atherothrombosis,” New Eng. J. Med., 353, pp. 2373-2383 (2005).
`Petersen, “Doubts are raised on the safety of 2 popular arthritis
`drugs,” NY Times, p. C1 (May 22, 2001).
`
`“Development of an Oral Formulation of
`al.,
`et
`Pilbrant
`Omeprazole,” Scand. J. Gastroenterol., 20, Supp. 108, pp. 113-120
`(1985).
`Pirmohamed et al., “Adverse drug reactions as cause of admission to
`hospital: prospective analysis of 18,820 patients,” Br. Med. J., 329,
`pp. 15-19 (2004).
`Porter S.C., “Coating of Pharmaceutical Dosage Forms,” in: A.
`Gennaro (Ed.), Remington: the Science and Practice of Pharmacy,
`19th ed., pp. 1650-1651(1995).
`Qureshi,
`et
`al.,
`“Pharmacokinetics of Two Enteric-Coated
`Ketoprofen Products in Humans with or Coadministration of
`Omeprazole and Comparison with Dissolution Findings,” Pharma-
`ceutical Research, 11(11), pp. 1669-1672 (1994).
`Raskin, et al., “Misoprostol Dosage in the Prevention ofNonsteroidal
`Anti-Inflammatory Drug-Induced Gastric and Duodenal Ulcers: A
`Comparison of Three Regimens,” Ann. Intern. Med., 123(5), pp.
`344-350 (Sep. 1995).
`Richardson et al., “Proton pump inhibitors, pharmacology and ratio-
`nale for use in gastrointestinal disorders,” Drugs, 56(3), pp. 307-335
`(1998).
`Robinson, et al., “Effects of Ranitidine Gastroduodenal Mucosal
`Damage Induced by Nonsteroidal Anti-inflammatory Drugs,” Dig.
`Dis. Sci, 34(3), pp. 424-428 (Mar. 1989).
`Roth, et al., “Cimetidine Therapy in Nonsteroidal Anti-inflammatory
`Drug Gastropathy: Double-blind Long-term Evaluation,” Arch.
`Intern. Med., 147, pp. 1798-1801 (1987).
`Rubinstein, “Gastrointestinal anatomy physiology and permeation
`pathways,” Enhancement in Drug Discovery, CRC Press, pp. 3-35
`(2007).
`Sangiah et al., “Effects of misoprostol and omeprazole on basal
`gastric pH and free acid content in horses,” Res. Vet. Sci., 47(3), pp.
`350-354 (1989).
`Savarino et al., “Effect of one-month treatment with nonsteroidal
`anti-inflammatory drugs (NSAIDs) on gastric pH of rheumatoid
`arthritis patients,” Digestive Diseases and Sciences, 43, pp. 459-463
`(1998).
`Scarpignato et al., Gastroenterology International; pp. 186-215
`(1999).
`Scheiman et al., “NSAID-induced peptic ulcer disease: a critical
`review ofpathogenesis and management,” Dig. Dis., 12, pp. 210-222
`(1994).
`aspirin-induced
`ameliorates
`“Omeprazole
`al.,
`et
`Scheiman
`gastroduondenal injury,” Digestive Diseases and Sciences, 39(1), pp.
`97-103 (1994).
`Scheiman, Seminars in Arthritis and Rheumatism, pp. 201-210
`(1992).
`Scott and Sundell, “Inhibition of H+K+ ATPase by SCH 28080 and
`SCH 32651,” European Journal of Pharmacology, 112, pp. 268-270
`(1985).
`Seitz et al., “Tablet coating,” in The theory and practice of industrial
`pharmacy, Lachman et al. eds., Lea and Febiger, pp. 346-373 (1986).
`Selway et al., “Potential hazards of long-term acid suppression,”
`Scand. J. Gastroenterol., 25, Supp. 178, pp. 85-92 (1990).
`Sharma et al., “Comparison of 24-hour intragastric pH using four
`liquid formulations of lansoprazole and omeprazole,” Am. J. Health-
`Syst. Pharm., 56, Supp. 4, pp. SIS-S21 (1999).
`Silverman, The Organic Chemistry of Drug Design and Drug Action,
`2nd Edition, Academic Press, pp. 102 & 527 (2004).
`Silverstein et al., “Gastrointestinal
`toxicity with celecoxib vs.
`nonsteroidal anti-inflammatory drugs for osteoarthritis and rheuma-
`toid arthritis; the CLASS study: A randomized controlled trial,”
`JAMA, 284, pp. 1247-1255 (2000).
`Silverstein, et al., “Misoprostol Reduces Serious Gastrointestinal
`Complications in Patients with Rheumatoid Arthritis Receiving
`Nonsteroidal Anti-Inflammatory Drugs,” Ann. Intern. Med., 123(4),
`pp. 241-249 (1995).
`Simon English translationisimon, et al., “Schutzwirkung von
`Omeprazol
`gegenuber
`niedrig
`dosierter Acetylsalicylsaure,”
`Arzneimittel Forschung, 45, pp. 701-703 (1995).
`Simon, et al., “Schutzwirkung von Omeprazol gegenuber niedrig
`dosierter Acetylsalicylsaure,” Arzneimittel Forschung, 45, pp. 701-
`703 (1995).
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 5
`
`MYLAN PHARMS. INC. EXHIBIT 1089 PAGE 5
`
`

`

`US 9,220,698 B2
`Page 6
`
`(56)
`
`References Cited
`OTHER PUBLICATIONS
`
`Sung, “Management ofnonsteroidal anti-imflammatory drug-related
`peptic ulcer bleeding,” Am. J. Med., 110(1A), pp. 298-328 (2001).
`Tronstad et al., “Gastroscopic findings after treatment with enteric-
`coated and plain naproxen tablets in healthy subjects,” Scand. J.
`Gastroenterol, 20, pp. 239-242 (1985).
`Vane, et al., “The future of NSAID therapy: selective COX-2 inhibi-
`tors,” IJCP, 54(1), pp. 7-9 (Jan/Feb. 2000).
`Vimovo Press Release (Oct. 16, 2009).
`von Unge et al., “Stereochemical assignment of the enantiomers of
`omeprazole from X-ray anaylysis of a fenchyloxymethyl derivative
`of (+)-(R)-omeprazole,” Tetrahedron, 8(12), pp. 1967-1970 (1997).
`Wagner et al., “Effects of nonsteroidal anti-inflammatory drugs on
`ulcerogenesis and gastric secretion in pylorus-ligated ligated rat,”
`Digestive Diseases and Sciences, vol. 40, pp. 134-140 (1995).
`Wakitani et al., “Profile of JTE-522 as a human cyclooxygenase-2
`inhibitor,” Jpn. J. Pharmacol., 78, pp. 365-371 (1998).
`Wallmark et al., “The relationship between gastric acid secretion and
`gastric H.sup.+, K.sup.+-ATPase activity,” J. Biol. Chem., 260(25),
`pp. 13681-13684 (1985).
`
`Warner, et al., “Nonsteroid drug selectivities for cyclo-oxygenase-l
`rather
`than cyclo-oxygenase-2
`are
`associated with human
`gastrointestinal toxicity: A full in vitro analysis,” Proc. Natl. Acad.
`Sci. USA, 96, pp. 7563-7568 (Jun. 1999).
`Weil et al., “Prophylactic aspirin and risk of peptic ulcer bleeding,”
`Br. Med. J., 310, pp. 827-830 (1995).
`Wolfe et al., “Gastrointestinal toxicity of nonsteroidal anti-inflam-
`matory drugs,” N. Engl