I 1111111111111111 11111 lllll lllll 111111111111111 1111111111 111111111111111111
`US008168620B2
`
`c12) United States Patent
`Lulla et al.
`
`(IO) Patent No.:
`(45) Date of Patent:
`
`US 8,168,620 B2
`May 1, 2012
`
`(54) COMBINATION OF AZELASTINE AND
`STEROIDS
`
`(75)
`
`Inventors: Amar Lulla, Mumbai (IN); Geena
`Malhotra, Mumbai (IN)
`
`(73) Assignee: CIPLA Limited, Mumbai (IN)
`
`( *) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 987 days.
`
`(21) Appl. No.:
`
`10/518,016
`
`(22) PCT Filed:
`
`Jun. 13, 2003
`
`(86) PCT No.:
`
`PCT /GB03/02557
`
`§ 371 (c)(l),
`(2), ( 4) Date:
`
`Jul. 6, 2005
`
`(87) PCT Pub. No.: WO03/105856
`
`PCT Pub. Date: Dec. 24, 2003
`
`(65)
`
`Prior Publication Data
`
`US 2006/0025391 Al
`
`Feb.2,2006
`
`(30)
`
`Foreign Application Priority Data
`
`Jun. 14, 2002
`
`(GB) ................................... 0213739.6
`
`(51)
`
`Int. Cl.
`A0lN 45100
`(2006.01)
`A61K 31156
`(2006.01)
`A61K 31155
`(2006.01)
`A61K 31157
`(2006.01)
`A61K 31158
`(2006.01)
`A61K 9/00
`(2006.01)
`A61P 37108
`(2006.01)
`A61P 27114
`(2006.01)
`A61P 11106
`(2006.01)
`(52) U.S. Cl. ....................................................... 514/171
`( 58) Field of Classification Search . ... ... ... ... .. ... . 514/171
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`2,837,464 A
`6/1958 Nobile
`3,067,197 A
`12/1962 Agnello et al.
`3,312,590 A
`4/ 1967 Elks et al.
`3,506,694 A
`4/1970 Oxley
`3,557,162 A
`l/ 1971 Voorschoten et al.
`3,639,434 A
`2/1972 Oxley et al.
`3,755,302 A
`8/ 1973 Ercoli et al.
`3,828,080 A
`8/1974 May et al.
`3,856,828 A
`12/1974 Phillipps et al.
`6/ 197 5 Phillipps et al.
`3,891,631 A
`9/1976 Phillipps et al.
`3,981,894 A
`3,989,686 A
`11/1976 Phillipps et al.
`6/ 1978 Phillipps et al.
`4,093,721 A
`9/ 1978 Karnano et al.
`4,113,680 A
`2/1980 Edwards
`4,187,301 A
`2/1980 Edwards
`4,188,385 A
`4/ 1980 Alvarez
`4,198,403 A
`9/ 1980 Bodor et al.
`4,221,787 A
`
`4,261,984 A
`4,263,289 A
`4,267,173 A
`4,285,937 A
`4,310,466 A
`4,335,121 A
`4,377,575 A
`4,472,393 A
`4,607,028 A
`4,710,495 A
`4,861,765 A
`4,992,474 A
`4,994,439 A
`4,996,335 A
`5,063,222 A
`5,081,113 A
`5,164,194 A
`5,202,316 A
`5,232,919 A
`5,271,946 A
`5,362,721 A
`5,420,120 A
`5,608,093 A
`5,658,549 A
`5,658,919 A
`5,707,984 A
`5,837,699 A
`5,849,265 A
`5,889,015 A
`5,914,122 A
`
`Alvarez
`4/1981
`Edwards
`4/1981
`Draper
`5/1981
`Kalvoda
`8/1981
`Edwards
`1/1982
`Phillipps et al.
`6/1982
`Stache et al.
`3/1983
`Shapiro
`9/1984
`Schmidlin
`8/1986
`Bodor
`12/1987
`Mitsukuchi et al.
`8/1989
`Skidmore et al.
`2/1991
`Longenecker et al.
`2/1991
`Bodor
`2/1991
`Komoto eta!.
`11/1991
`Claussner et al.
`1/1992
`Hettche
`11/1992
`Claussner et al.
`4/1993
`Scheffler et al.
`8/1993
`Hettche
`12/1993
`Stache et al.
`11/1994
`Boltralik
`5/1995
`Stache et al.
`3/1997
`Akehurst et al.
`8/1997
`Ratnaraj et al.
`8/1997
`Tjoeng et al.
`1/1998
`Sequeira et al.
`11/1998
`Li-Bovet et al.
`12/1998
`Sequeira et al.
`3/1999
`Otterbeck et al.
`6/1999
`(Continued)
`
`AU
`
`FOREIGN PATENT DOCUMENTS
`2003244799 B2
`12/2003
`(Continued)
`
`OTHER PUBLICATIONS
`
`preservative. (n.d.) Dorland's Medical Dictionary for Health Con(cid:173)
`sumers. (2007). Retrieved Nov. 4, 2009 from http://medical-dictio(cid:173)
`nary.thefreedictionary.com/preservative. *
`preservative. (n.d.) The American Heritage® Medical Dictionary.
`(2007). Retrieved Nov. 4, 2009 from http://medical-dictionary.
`thefreedictionary.com/preservative. *
`preservative. (n.d.) Mosby' s Medical Dictionary, 8th edition. (2009).
`Retrieved Nov.
`4,
`2009
`from
`http://medical-dictionary.
`thefreedictionary.com/preservative. *
`Database Medline Online! US National Library of Medicine (NLM),
`Bethesda, MD, US: 2000 Portmann D et al: Acceptability of local
`treatment of allergic rhinitis with a combination of a corticoid
`(beclomethasone) and an antihistarninic (azelastine); vol. 121, No. 4,
`2000, pp. 273-279.
`
`(Continued)
`
`Primary Examiner -
`Johann Richter
`Assistant Examiner - Thor Nielsen
`(74) Attorney, Agent, or Firm - Conley Rose, P.C.; Rodney
`B. Carroll
`
`ABSTRACT
`(57)
`A pharmaceutical product or formulation, which comprises
`azelastine or a pharmaceutically acceptable salt, solvate or
`physiologically functional derivative thereof, and a steroid, or
`a pharmaceutically acceptable salt, solvate or physiologically
`functional derivative thereof, preferably the product or for(cid:173)
`mulation being in a form suitable for nasal or ocular admin(cid:173)
`istration.
`
`48 Claims, No Drawings
`
`

`

`US 8,168,620 B2
`Page 2
`
`............... 514/646
`
`....................... 424/45
`
`U.S. PATENT DOCUMENTS
`5,972,920 A
`10/1999 Seidel
`5,981,517 A
`11/1999 Bodor
`6,017,963 A *
`1/2000 Alfonso et al.
`6,057,307 A
`5/2000 Sequeira et al.
`10/2000 Yuen eta!.
`6,127,353 A
`6,136,294 A
`10/2000 Adjei et al.
`6,197,761 Bl
`3/2001 Biggadike et al.
`6,261,539 Bl
`7/2001 Adjei et al
`6,294,153 Bl*
`9/2001 Modi
`6,319,513 Bl
`11/2001 Dobrozsi
`6,330,938 Bl
`12/2001 Herve et al.
`6,391,340 Bl*
`5/2002 Malmqvist-Granlund
`et al.
`............................. 424/489
`5/2002 Straub et al.
`7/2002 Fassberg et al. ................ 424/45
`2/2003 Chauvin et al.
`3/2003 Biggadike et al
`.............. 514/603
`6/2003 Link et al.
`9/2004 Biggadike et al.
`7/2005 Cuenoud et al.
`9/2006 Biggadike et al.
`7/2007 Pieper et al.
`8/2010 Pairet et al.
`5/2002 Osbakken et al.
`6/2002 Kaplan et al.
`6/2002 Woolfe et al.
`8/2002 Stache et al.
`11/2002 Biggadike et al.
`11/2002 Biggadike
`11/2002 Biggadike
`1/2003 Meade eta!.
`4/2003 Biggadike et al.
`6/2003 Biggadike et al.
`7/2003 Biggadike et al.
`8/2003 Cuenoud et al.
`3/2004 Komoto et al.
`7/2004 Garrett et al.
`10/2004 Osbakken et al.
`11/2004 Weinrich et al.
`12/2004 Yanni et al.
`7/2005 Miyadai et al.
`9/2005 Jost-Price et al.
`5/2006 Dang et al.
`10/2006 Lane
`1/2007 Dang et al.
`11/2009 Myles et al.
`11/2009 Lulla et al.
`12/2009 Lulla et al.
`6/2010 Fuge et al.
`
`6,395,300 Bl
`6,416,743 Bl*
`6,525,228 B2
`6,537,983 Bl
`6,583,180 B2 *
`6,787,532 B2
`6,921,757 B2
`7,101,866 B2
`7,244,742 B2
`7,776,315 B2
`2002/0061281 Al
`2002/0076382 Al
`2002/0081266 Al
`2002/0103392 Al
`2002/0165211 Al
`2002/0173496 Al
`2002/0177581 Al
`2003/0018019 Al
`2003/0073676 Al
`2003/0109511 Al
`2003/0144257 Al
`2003/0158163 Al
`2004/0053904 Al
`2004/0136918 Al
`2004/0204399 Al
`2004/0235807 Al
`2004/0242638 Al
`2005/0163724 Al
`2005/0192261 Al
`2006/0110331 Al
`2006/0228306 Al
`2007 /0020330 Al
`2009/0286762 Al
`2009/0291143 Al
`2009/0318397 Al
`2010/0152147 Al
`
`BE
`DE
`DE
`DE
`DE
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`EP
`GB
`GB
`GB
`GB
`GB
`GB
`GB
`GB
`GB
`IL
`JP
`JP
`
`FOREIGN PATENT DOCUMENTS
`889563 A
`11/1981
`1059906
`6/1959
`19947234
`4/2001
`10152369 Al
`5/2002
`3836579 Al
`8/2009
`0004773
`10/1979
`0057401
`8/1982
`0179583
`4/1986
`0393658
`10/1990
`0416951
`3/1991
`* 6/1997
`0 780 127
`* 6/1997
`0780127
`1519731 Bl
`4/2009
`2072051 Al
`6/2009
`1191965
`5/1970
`1296458
`11/1972
`1384372
`2/1975
`1438940
`6/1976
`1517278
`7 /1978
`2079755
`1/1982
`2088877
`6/1982
`2140800
`12/1984
`2389530 A
`12/2003
`109656
`2/1998
`04208267
`7 /1992
`8291072
`11/1996
`
`JP
`JP
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`ZA
`
`8291073
`2002-053485
`8903390
`9015816
`9104252
`9214472
`9531964
`9619199
`9632151
`9701337
`9705136
`9715298
`9721721
`9721724
`9724365
`9740836
`9746243 Al
`9817676
`9834596
`9848839
`9901467
`9925359
`9932089
`0016814
`0033892
`0038811
`0048587
`0049993
`0066522
`0104118
`0120331
`0154481
`0154664
`0157025
`0162722
`0178736
`0178739
`0178741
`0178745
`0200199
`0200679
`0202565
`0207767
`0208243
`0212265
`0212266
`0213868
`0226723
`0236106
`02051422
`02053186
`02066422
`02070490
`02076933
`02085296
`02088167
`02100879
`03000241
`03013427
`03033000
`03035668
`03040691
`03042229
`03042230
`03048181
`03062259
`03064445
`03066033
`03066036
`03066656
`03072592
`03086399
`03105856 Al
`2004013156
`2004019955 Al
`2008012338 A2
`872389
`
`11/1996
`2/2002
`4/1989
`12/1990
`4/1991
`9/1992
`11/1995
`6/1996
`10/1996
`1/1997
`2/1997
`5/1997
`6/1997
`6/1997
`7 /1997
`11/1997
`12/1997
`4/1998
`8/1998
`11/1998
`1/1999
`5/1999
`7 /1999
`3/2000
`6/2000
`7/2000
`8/2000
`8/2000
`11/2000
`1/2001
`3/2001
`8/2001
`8/2001
`8/2001
`8/2001
`10/2001
`10/2001
`10/2001
`10/2001
`1/2002
`1/2002
`1/2002
`1/2002
`1/2002
`2/2002
`2/2002
`2/2002
`4/2002
`5/2002
`7/2002
`7/2002
`8/2002
`9/2002
`10/2002
`10/2002
`11/2002
`12/2002
`1/2003
`2/2003
`4/2003
`5/2003
`5/2003
`5/2003
`5/2003
`6/2003
`7/2003
`8/2003
`8/2003
`8/2003
`8/2003
`9/2003
`10/2003
`12/2003
`2/2004
`3/2004
`1/2008
`4/1987
`
`

`

`US 8,168,620 B2
`Page 3
`
`OTHER PUBLICATIONS
`Busse WW et al: "Corticosteroid-Sparing Effect of Azelastine in the
`Management of Bronchial Asthma"-American Journal of Respira(cid:173)
`tory and Critical Care Medicine, American Lung Association, new
`York, NW, vol. 153, No. 1, 1996, pp. 122-172, p. 127, col. 1, para(cid:173)
`graph 2.
`International Search Report under Section 17 UK Patent Office col(cid:173)
`lections, including GB, EP, WO & US patent specifications.
`Foreign communication from the priority application-International
`Search Report, PCT/GB03/02557, Sep. 17, 2003, 3 pages.
`Foreign communication from the priority application-International
`Preliminary Examination Report, PCT /GB03/02557, Aug. 26, 2004,
`6 pages.
`Foreign communication from a related counterpart application(cid:173)
`Examination Report, EP Application 03738280.1, Nov. 10, 2005, 4
`pages.
`Foreign communication from a related counterpart application(cid:173)
`Examination Report, EP Application 03738280.1, Jul. 18, 2007, 5
`pages.
`Applicants response to foreign communication-EP 03738280.1,
`May 22, 2006, 36 pages.
`Applicants response to foreign communication-EP 03738280.1,
`Jan. 18, 2008, 17 pages.
`May, Percy, et al., "May's Chemistry of Synthetic Drugs," Fifth
`Edition, 1964, pp. 12-17, Longmans.
`ABPI Compendium of Data Sheets and Sununaries of Product Char(cid:173)
`acteristics, 1999-2000, Cover page, p. 43 and Index p. 1882,
`Datapharm Publications Limited, London, Great Britain.
`Dykewicz, Mark S., et al., "Diagnosis and Management of Rhinitis:
`Complete Guidelines of the Joint Task Force on Practice Parameters
`in Allergy, Asthma and Immunology," Annals of Allergy, Asthma, &
`Immunology, vol. 81, November (Part II) 1998, pp. 478-518.
`Foreign communication from a related counterpart application(cid:173)
`Notice of Opposition, EP Application 03738280.1, Feb. 22, 2010, 22
`pages.
`Office Action dated Sep. 30, 2010, U.S. Appl. No. 12/508,388, filed
`Jul. 23, 2009, 22 pages.
`Office Action dated Sep. 30, 2010, U.S. Appl. No. 12/508,393, filed
`Jul. 23, 2009, 31 pages.
`Patent application entitled "Combination of azelastine and steroids,"
`by Amar Lulla, et al., filed Sep. 10, 2010 as U.S. Appl. No.
`12/879,515.
`Hodges, Norman, et al., "Antimicrobial Preservative Efficacy Test(cid:173)
`ing," Handbook of Microbiological Quality Control, Pharmaceuti(cid:173)
`cals and Medical Devices, 2000, p. 168 plus cover page and publi(cid:173)
`cation page, Rosamund M. Baird, et al., Editor, Taylor & Francis
`Publisher, USA and Canada.
`Herrero, Vanrell, R., "Preservatives in Ophthalmic Formulations: An
`Overview," Arch. Soc. Esp. Oftalmol, 2007, vol. 82., pp. 531-532.
`Johnson, Malcom, "Development of fluticasone propionate and com(cid:173)
`parison with other inhaled corticosteroids," J. Allergy Clin.
`Immunol., Apr. 1998, vol. 101, No. 4, Part 2, pp. S434-S439.
`Foreign communication from a related counterpart application(cid:173)
`CA2,489,427, Examination Report, Jun. 18, 2010, 3 pages.
`Foreign communication from a related counterpart application(cid:173)
`CA2,489,427, Examination Report, Mar. 24, 2011, 2 pages.
`Foreign communication from a related counterpart application(cid:173)
`Examination Report, EP Application 03738280.1, Nov. 10, 2005, 4
`pages.
`Foreign communication from a related counterpart application(cid:173)
`Examination Report, EP Application 03738280.1, Jul. 18, 2007, 5
`pages.
`Foreign communication from a related counterpart application(cid:173)
`Notice oflntentto Grant, EP Application 03738280.1, Oct. 23, 2008,
`6 pages.
`Foreign communication from a related counterpart application(cid:173)
`AU2003244799, Examination Report, Nov. 20, 2007, 2 pages.
`Foreign communication from a related counterpart application-KR
`10-2004-7020819, Examination Report, Aug. 26, 2010, 8 pages.
`Gennaro, Alfonso R., ed., et al., Remington: The Science and Practice
`of Pharmacy, 2000, 20th edition, vol. 1, pp. 785,830,831 plus cover
`page and publication page, Lippincott Williams & Wilkins.
`
`Gilbert, Peter, et al., "Preservation of pharmaceutical products,"
`Encyclopedia of Pharmaceutical Technology, 2002, 2nd edition, vol.
`3, p. 2278 plus cover page and publication page, Marcel Dekker, Inc.
`Office Action (Final) dated Feb. 18, 2011 (23 pages), U.S. Appl. No.
`12/508,388, filed Jul. 23, 2009.
`Office Action (Final) dated Feb. 24, 2011 (20 pages), U.S. Appl. No.
`12/508,393, filed Jul. 23, 2009.
`Reddy, Indra K., ed., Ocular Therapeutics and Drug Delivery: A
`Multi-Disciplinary Approach, 1996, pp. 382-385 plus cover page and
`publication page, Technomic Publishing Company, Inc.
`Foreign communication from a related counterpart application(cid:173)
`Summons to Attend Oral Proceedings, EP Application 03738280.1,
`Feb. 8, 2011, 1 page.
`Foreign communication from a related counterpart application(cid:173)
`Examination Report, RU 2005100781, Apr. 23, 2007, 6 pages.
`Foreign communication from a related counterpart application(cid:173)
`Examination Report, RU 2005100781, May 23, 2008, 3 pages.
`Pre-Grant Opposition, Indian Patent Application 2092/KOLNP/2007
`dated Jun. 8, 2007, 183 pages.
`McNeely, Wendy, et al., "Intranasal Azelastine A Review of its Effi(cid:173)
`cacy in the Management of Allergic Rhinitis," Drugs, 1998, vol. 56,
`No. 1, pp. 91-114.
`ABPI Data Sheet Compendium, 1995-96, cover page plus pp. 38-39,
`Datapharm Publications Limited, London, Great Britain.
`Aurora, Jack, "Nasal Delivery; Development of Nasal Delivery Sys(cid:173)
`tems: A Review," Drug Delivery Technology, vol. 2, No. 7, Oct. 2002,
`8 pages, http://www.drugdelivelytech.com/ME2/Segments/Publica(cid:173)
`tions: Article&id~9EB19EB2F29F462089CE081473F5F3CA.
`Block, John H., et al., "Inorganic Medicinal and Pharmaceutical
`Chemistry," 1986, cover, publication, and preface pages plus p. 100,
`Indian Edition, Varghese Publishing House, Bombay, India.
`Cipla Sixty-Ninth Annual Report 2004-2005, cover pages, informa(cid:173)
`tion page, plus pp. 3, 5, and 44.
`Drouin, Michel A., et al., "Adding Loratadine to Topical Nasal Ste(cid:173)
`roid Therapy Improves Moderately Severe Seasonal Allergic
`Rhinoconjunctivitis," Advances in Therapy, vol. 12, No. 6, Nov./Dec.
`1995, pp. 340-349, Health Communications Inc.
`Foreign communication from a related counterpart application(cid:173)
`Translation of Office Action, Israel Patent Application 165771, Jul.
`11, 2011, 3 pages.
`Hodges, N. A., et al., "Preservative Efficacy Tests in Formulated
`Nasal Products: Reproducibility and Factors Affecting Preservative
`Activity," J. Pharm. Pharmacol., 1996, vol. 48, pp. 1237-1242.
`Applicants response
`to
`foreign communication-KRl0-2004-
`7020819, Dec. 27, 2010, 18 pages.
`Prescribing Information for Asteproe®, Nov. 2010, 20 pages, Meda
`Pharmaceuticals Inc., Somerset, NJ, US.
`Prescribing Information for Rhinocort Aqua™, Dec. 2010, 3 2 pages,
`AstraZeneca LP, Wilmington, DE, US.
`Product Information, Nasonex®, Aug. 2001, 22 pages, Schering
`Corporation, Kenilworth, NJ, US.
`Safety Data Sheet, SDS No. 110556, Jul.4, 2008, Vl4, FlonaseNasal
`Spray, 5 pages, GlaxoSmithKline.
`Safety Data Sheet, SDS No. 110536, Jun. 23, 2008, Vl3, Beconase
`Hayfever Allergy Spray, 5 pages, GlaxoSmithKline.
`Wiseman, Lynda R., et al., "Intranasal Fluticasone Propionate: A
`Reappraisal of its Pharmacology and Clinical Efficacy in the Treat(cid:173)
`ment of Rhinitis," Drugs, 1997, vol. 53, No. 5, pp. 885-907, Adis
`International Limited.
`World Review 2001: The Pharmaceutical Market, vol. 1 Interna(cid:173)
`tional, Ims Health, 2001, cover, preface, and copyright pages plus pp.
`4-42 and 5-1 through 5-11, IMS A.G.
`Opposition to EP 1518731, Aug. 8, 2011, 19 pages.
`Berge, Stephen M., et al., "Pharmaceutical Salts," Journal of Phar(cid:173)
`maceutical Sciences, vol. 66, No. 1, Jan. 1977, pp. 1-19.
`Avicel® RC/CL, Microcrystalline Cellulose and Carboxymethylcel(cid:173)
`lulose Sodium, NF Dispersible Cellulose, BP, Specifications and
`Analytical Methods, RC-16 Updated Oct. 1995 (Feb. 1999), 6 pages,
`FMC BioPolymer.
`Baena-Cagnani, Carlos E., "Safety and Tolerability of Treatments for
`Allergic Rhinitis in Children," Drug Safety 2004, vol. 27, No. 12, pp.
`883-898, ADIS Data Information BV.
`
`

`

`US 8,168,620 B2
`Page 4
`
`Galant, Stanley P., et al., "Clinical Prescribing of Allergic Rhinitis
`Medication in the Preschool and Young School-Age Child, What are
`the Options?," BioDrugs2001, vol. 15, No. 7, pp. 453-463, ADIS
`International Ltd.
`Wang, De-Yun, "Treatment of Allergic Rhinitis: HI-Antihistamines
`and Intranasal Steroids," Current Drug Targets-Inflammation &
`Allergy, 2002, vol. I, pp. 215-220, Bentham Science Publishers Ltd.
`Meltzer, Eli 0., "Allergic rhinitis: Managing the pediatric spectrum,"
`Allergy and Asthma Proceedings, Jan.-Feb. 2006, vol. 27, No. 1, pp.
`2-8, Oceanside Publications, Inc., USA.
`Ratner, Paul H., et al., "Combination therapy with azelastine hydro(cid:173)
`chloride nasal spray and fluticasone propionate nasal spray in the
`treatment of patients with seasonal allergic rhinitis," Annals of
`Allergy, Asthma & Immunology, Jan. 2008, vol. 100, Cover page,
`publishing page, pp. 74-81.
`Ratner, Paul H., et al., "A Comparison of the Efficacy ofFluticasone
`Propionate Aqueous Nasal Spray and Loratadine, Alone and in Com(cid:173)
`bination, for the Treatment of Seasonal Allergic Rhinitis," The Jour(cid:173)
`nal of Family Practice, Aug. 1998, vol. 47, No. 2, pp. 118-125,
`Appleton & Lange.
`Nielsen, Lars P., "Comparison oflntranasal Corticosteroids and Anti(cid:173)
`histamines in Allergic Rhinitis, A Review of Randomized, Controlled
`Trials," Am. J. Respir Med. 2003, vol. 2, No. 1, Cover page, publish(cid:173)
`ing page, pp. 55-65., ADIS International Limited.
`Nielsen, Lars Peter, et al., "Intranasal Corticosteroids for Allergic
`Rhinitis, Superior Relief?," Drugs 2001, vol. 61, No. 11, pp. 1563-
`1579, ADIS International Ltd.
`Di Lorenzo, G., et al., "Randomized Placebo-controlled Trial Com(cid:173)
`paring fluticasone aqueous nasal spray in mono-therapy, fluticasone
`plus cetirizine, fluticasone plus montelukast and cetirizine plus
`montelukast for seasonal allergic rhinitis," Clin. Exp. Allergy, 2004,
`vol. 34, pp. 259-267, Blackwell Publishing Ltd.
`Akerlund, Anders, et al., "Clinical trial design, nasal allergen chal(cid:173)
`lenge models, and considerations of relevance to pediatrics, nasal
`polyposis, and different classes of medication," J. Allergy Clin.
`Immunol., Mar. 2005, vol. ll5, No. 3, pp. S460-S482.
`Howarth, P.H., "A comparison of the anti-inflammatory properties of
`intranasal corticosteroids and antihistamines in allergic rhinitis,"
`Allergy 2000, vol. 62, pp. 6-ll, Munksgaard 2000.
`Salib Rarni Jean, et al., "Safety and Tolerability Profiles oflntranasal
`Antihistamines and Intranasal Corticosteroids in the Treatment of
`Allergic Rhinitis," Drug Safety 2003, vol. 26, No. 12, Cover page,
`publication page, pp. 863-893, ADIS Data Information BV.
`Simpson, Richard J., "Budesonide and terfenadine, separately and in
`combination, in the treatment of hay fever," Annals of Allergy, Dec.
`1994, vol. 73, Cover page, publication page, pp. 497-502.
`Juniper, E F., et al., "Comparison of beclomethasone dipropionate
`aqueous nasal spray, astemizone, and the combination in the prophy(cid:173)
`lactic treatment of ragweed pollen-induced rhinoconjunctivitis,"
`Journal of Allergy and Clinical Immunology, Mar. 1989, vol. 83, No.
`3, Cover page, Publications page, pp. 627-633, American Academy
`of Allergy and Immunology, C.V. Mosby Co.
`Barnes, M. L., et al., "Effects of levocetirizine as add-on therapy to
`fluticasone in seasonal allergic rhinitis," Clinical and Experimental
`Allergy, Jan. 27, 2006, vol. 36, pp. 676-684, Blackwell Publishing
`Ltd.
`Applicants response to foreign communication-EP 03738280.1
`(EP Patent 1519731), Sep. 6, 2010, 15 pages.
`File history of Australian Patent Application No. AU2003 244799, 3 8
`pages.
`File history of Korean Patent Application No. 10-2004-7020819, 89
`pages.
`File history of Mexican Patent Application No. PA/a/2004/01266
`(now Patent No. 265349), 86 pages.
`File history of South African Patent Application No. 2005/0331 (now
`Patent No. 2005/0331), 18 pages.
`Applicants response to foreign communication----CA 2489427, Dec.
`20, 2010, 10 pages.
`Applicant Response to foreign communication EP Patent 1519731,
`Aug. 11, 2011, 252 pages.
`Maus Exhibit B, Aug. 2011.
`Nielsen, et al., "Intranasal corticosteroids for allergic rhinitis: supe(cid:173)
`rior relief?" Drugs, 2001, vol. 61, No. 11, pp. 1535-1691.
`
`Opponent's Rll6 Submission for EP1519731, 2011.
`CIPLA's response to Statement of Opposition for EP151973 l, 2011.
`Shenfield, "Fixed drug combinations: which ones can be recom(cid:173)
`mended?" Current Therapeutics, 1986, pp. 15-29.
`Opponent's Statement of Opposition for EP151973 l, 2011.
`Result of oral proceedings dated Oct. 12, 2011 of EP Patent No.
`1519731.
`Opponent's submission dated Oct. 6, 20 ll to EPPatentNo. 1519731.
`Patentee's submission dated Oct. 5, 2011 to EP Patent No. 1519731.
`Patentee's submission dated Sep. 29, 2011 regarding list ofattendees
`at oral proceedings on EP Patent No. 1519731.
`Opponent's submission dated Sep. 23, 2011 regarding list of attend(cid:173)
`ees at oral proceedings on EP Patent No. 1519731.
`Opponent's submission dated Sep. 23, 20ll regarding additional
`documents on EP Patent No. 1519731.
`Patentee's submission dated Sep. 19, 2011 on EP Patent No.
`1519731.
`Patentee's response of Sep. 6, 2010 ofEP Patent No. 1519731.
`Hampel, Frank C., et al., Double-blind, placebo-controlled study of
`azelastine and fluticasone in a single nasal spray delivery device,
`Annals of Allergy, Asthma & Immunology, Aug. 2010, vol. 105, pp.
`168-173.
`Biggadike, Keith, Letter to the Editor, "Fluticasone furoate/
`fluticasone propionate----different drugs with different properties,"
`The Clinical Respiratory Journal, 2011, pp. 183-184.
`Rapid response report: sununary with critical appraisal, fluticasone
`furoate versus fluticasone propionate for seasonal allergic rhinitis: a
`review of the clinical and cost-effectiveness, Jun. 13, 2011,
`Fluticasone Furoate for Seasonal Allergic Rhinitis.
`Office Action dated Sep. 9, 2011 of U.S. Appl. No. 12/508,388 filed
`Jul. 23, 2009.
`Office Action dated Sep. 15, 2011 of U.S. Appl. No. 12/508,393 filed
`Jul. 23, 2009.
`Search Report dated May 12, 2009 ofEP 09075101.
`Search Report dated May 12, 2009 ofEP 09075100.
`Mealy, N. E., et al., "Ciclesonide: treatment of allergic rhinitis
`antiallergy/antiasthmatic," Drugs of the Future, Prous Science, ES,
`vol. 26, No. ll, Nov. 2001, pp. 1033-1039.
`Office Action dated Jul. 11, 2011-20632 IL.
`Office Action dated Aug. 31, 2010 (6 pages), U.S. Appl. No.
`12/374,523 filed on Jan. 21, 2009.
`Applicants' response dated Oct. 6, 2010 (8 pages) in U.S. Appl. No.
`12/374,523 filed on Jan. 21, 2009.
`Office Action dated Nov. 30, 2010 (16 pages), U.S. Appl. No.
`12/374,523 filed on Jan. 21, 2009.
`Applicants' response dated Feb. 24, (2010) 20ll (8 pages) in U.S.
`Appl. No. 12/374,523 filed on Jan. 21, 2009.
`Office Action (Final) dated May 3, 20ll (8 pages), U.S. Appl. No.
`12/374,523 filed on Jan. 21, 2009.
`Applicants' response dated Jun. 22, 2011 (9 pages) in U.S. Appl. No.
`12/374,523 filed on Jan. 21, 2009.
`Notice of Non-responsive Amendment dated Jul. 6, 2011 (3 pages),
`U.S. Appl. No. 12/374,523 filed on Jan. 21, 2009.
`Applicants' response dated Sep. 6, 20ll (8 pages) in U.S. Appl. No.
`12/374,523 filed on Jan. 21, 2009.
`Spector, Sheldon, "Ideal pharmacotherapy for allergic rhinitis," J
`Allergy Clin Immunol, vol. 103, No. 3, Part 2, pp. S386-S387, 1999.
`Duonase Data Sheet, "The complete rhinitis control," 6 pages, Cipla
`Limited, Mumbai, India, 2004.
`Product Specification Bulletin, Avicel® RC-591, Bulletin AVC591-
`SPEC-02/09.RS, 2 pages, FMC BioPolymer, Feb. 2009.
`Product Specification Bulletin, Avicel® CL-611, Bulletin AVC6ll(cid:173)
`SPEC-02/09.RS, 2 pages, FMC BioPolymer, Feb. 2009.
`File history of Brazilian Patent Application No. PI 0312128-3, 27
`pages, Apr. 2011.
`File history of Canadian Patent Application No. 2,489,427, 19 pages,
`Dec. 2010.
`File history of Polish Patent Application No. P-373001, 95 pages,
`May 2011.
`File history of Russian Patent Application No. RU 2361593 C2, 65
`pages, Apr. 2009.
`
`

`

`US 8,168,620 B2
`Page 5
`
`Salib, et al.; "Safety and Tolerability Profiles of Intranasal
`Anihistaminese and Intranasal Corticosteroids in the Treatment of
`Allergic Rhinitis;" Drug Safety; 2003; vol. 26, No. 12, pp. 829-911.
`Office Action dated Apr. 7, 2011 (3 pages) from counterpart applica(cid:173)
`tion, AU2009243420.
`Moreno-Vargas, et al., "Synthesis and gylcosidase inhibitory activi(cid:173)
`ties of 5-( l' ,4'-dideoxy-1' ,4'-imino-D-erythrosyl)-2-methyl-3-furoic
`acid
`(~5-[(3S,4R)-3,4-dihydroxypyrrolidin-2-yl]-2methylfuran-3-
`carboxylic acid) derivatives: new leads as selective alpha-L(cid:173)
`fucosidase and beta-galactosidase inhibitors," Helvetica Chimica
`Acta, vol. 86, pp. 1894-1913, 2003.
`Nathan, et al., "A once daily fluticasone proprionate aqueous nasal
`spray is an effective treatment for seasonal allergic rhinitis," Annals
`of Allergy, 1991, vol. 67, pp. 332-338.
`Nelson, Harold, S., et al., Fluticasone propionate-salmeterol combi(cid:173)
`nation provides more effective asthma control than low-dose inhaled
`corticosteroid plus montelukast, J. Allergy Clin. Immunol., vol. 106,
`No. 6, Dec. 2000, pp. 1088-1095.
`Ong, John T. H., et al., "Micellar solubilization oftimobesone acetate
`in aqueous and aqueous propylene glycol solutions of nonionic
`surfactants," Pharmaceutical Research, vol. 5, No. 11, 1988, pp.
`704-708.
`Ong, John T. H., et al., "Intrinsic potencies of novel thiol ester
`corticosteroids RS-85095 and RS-21314 as compared with
`clobetasol 17-propionate and fluocinonide," Arch Dermatol, vol.
`125, Dec. 1989, pp. 1662-1665.
`Onrust, et al., "Mometasone furoate, a review of its intranasal use in
`allergic rhinitis," Drugs, vol. 56, No. 4, Oct. 1998, pp. 725-745, vol.
`21.
`Phillips, G. H., et al., "Synthesis and structure activity relationships
`in a series of anti-inflammatory corticosteroid analogues, halomethyl
`androstane-l 7B-carbothioates and- l 7B-carboselenoates," Jour(cid:173)
`nal of Medicinal Chemistry, 1994, vol. 37, pp. 3717-3729.
`Product Information Flonase (Fluticasone proprionate) Nasal Spray
`50 mcg, 2004, pp. 1-13.
`Product Information Rhinocort Aqua (budesonide) Nasal Spray 32
`mcg, 2005, pp. 1-2.
`Sakagami, et al., "Mucoadhexive BDP microspheres for powder
`inhalation-their unique pharmacokinetic-pharmacodynamic pro(cid:173)
`files," Respiratory Drug Delivery, vol. VI, pp. 193-199, 1998.
`Sandham, et al., "Synthesis and biological properties of novel
`glucocorticoid androstene C-17 furoate esters," Bioorganic &
`Medicinal Chemistry, 2004, vol. 12, pp. 5213-5224.
`Scadding, et al., "Clinical and physiological effects of fluticasone
`propionate aqueous nasal spray in the treatment of perennial rhinitis,"
`Rhinology, 1991, Suppl. 11, pp. 37-43.
`Settipane, et al., "Triamcinolone acetonide aqueous nasal spray in
`patients with seasonal ragweed allergic rhinitis: a placebo-controlled,
`double-blind study," Clin. Ther., 1995, vol. 17, No. 2, pp. 252-263.
`Shapiro, et al., "17-esters and 17,21-diesters of 9-alpha, 11-beta(cid:173)
`dichlorocorticoids. Synthesis and anti-inflammatory activity," Ste(cid:173)
`roids, vol. 9, No. 2, pp. 143-156, 1967.
`Shapiro, et al., "Synthesis and structure-activity studies of
`corticosteroid 17-heterocyclic aromatic esters. 1. 9-alpha, 11-beta
`dichloro series," Journal of Medicinal Chemistry, vol. 30, No. 6, pp.
`1068-1073, 1987.
`Shapiro, et al., "17 heteroaroyl esters of corticosteroids 2. 11 beta
`hydroxy series," Journal of Medicinal Chemistry, American Chemi(cid:173)
`cal Society, Washington, US, vol. 30, No. 9, 1987, pp. 1581-1588.
`Smith, et al., "In vitro glucocorticoid receptor binding and transcrip(cid:173)
`by
`topically
`active
`glucocorticoids,"
`tional
`actJv1atJon
`Arzneimettelforschung, 1998, 48(II)(9), pp. 956-959.
`Smith, N., et al., "Comparison of the electroosmotic flow profiles and
`selectivity
`of
`stationary
`phases
`used
`in
`capillary
`electrochromatography," Journal of Chromatography A., vol. 832,
`1999, pp. 41-54.
`Souness, et al., "Immunosuppressive and anti-inflammatory effects
`of cyclic AMP phosphodiesterase (PDE) type 4
`inhibitors,"
`Immunopharmacology, 2000, vol. 47, Nos. 2/3, pp. 127-162.
`Stempel, et al., "Treatment of allergic rhinitis: an evidence-based
`evaluation of nasal corticosteroids versus nonsedating antihista(cid:173)
`mines," Am. J. Man. Care, 1998, vol. 4, pp. 89-96.
`
`Study No. 03DMW062-"Pharmacokinetics of GW685698X and
`CCI 18781 (fluticasone propionate) when co-administered by the
`intratracheal or intravenous route to the anaesthetised white pig,"
`2004.
`Study No. B30947-"The Pharmacokinetics of GW685698X and
`CCI 18781
`following
`intratracheal co-administration
`to
`the
`anaesthetised white pig," 2003.
`Szefler, Stanley J., et al., Chapter 21, "Glucocorticoids in severe
`asthma: mechanisms of action and route of administration," Difficult
`Asthma, pp. 371-375, Martin Dunitz Ltd., Informa Health Care,
`1999.
`Togashi, et al., 9-fluoro-llB, 17, 21-trihyrdroxy-16a-methyl-l,4-
`pregnadiene-3,
`20-dione
`21-
`cyclohexanecarboxylate
`17-cyclopropanecarboxylate (ST126); Oyo Yakuri, 2002, vol. 63,
`No. 5/6, pp. 61-77.
`Undem, et al., "Neural integration and allergic disease," J. Allergy
`Clin. Immunol., 2000, vol. 106, No. 5, pp. S213-S220.
`The United States Pharmacopoeia, 23rd Ed., US Pharmacopoeia
`Convention, Inc., Rockville MD, 1995, pp. 1843-1844, "Physical
`Tests/(941) X-Ray Diffraction."
`Van As, et al., "Once daily flluticasone propionate is as effective for
`perennial allergic
`rhinitis as
`twice daily beclomethasone
`dipropionate," J. Allergy Clin. Immunol., 1993, vol. 91, No. 6, pp.
`1146-1154.
`Van Bavel, et al., "Ocular efficacy and clinician overall evaluation of
`intranasal fluticasone proprionate (FP) versus loratadine (LOR) in
`seasonal allergic rhinitis (SAR)," Annals of Allergy, Asthma, &
`Immunology, 1997, vol. 78, p. 128, Abstract Pl 01.
`Wenkert, et al., "Short syntheses offuran and catechol derivatives. A
`synthesis ofhydrourushioll ,2," Journal American Chemical Society,
`vol. 105, pp. 2021-2029, 1983.
`Westlund, et al., "Fluticasone propionate aqueous nasal spray 200 mg
`once daily provides relief of ocular symptoms associated with sea(cid:173)
`sonal allergic rhinitis," 57th Annual Meeting of the American Acad(cid:173)
`emy of Allergy, Asthma and Immunology, New Orleans LA, Mar.
`16-21, 2001, Abstract No. 522.
`Woodford, et al., "Activity and bioavailability of a new steroid
`(Timobesone acetate) in cream and ointment compared with Lidex
`and Dermovate creams and ointments and Betnovate cream," Int'!
`Journal of Pharmaceutics, 1985, vol. 26, pp. 145-155.
`Observations on patentability of the object of the patent application
`PV 2003-352 (Czech Republic), 2003.
`Notice of Opposition to the grant of patent on Patent Application No.
`762/2001 (140397) (Pakistan), 2010.
`CIPLA Annual Report Extract; 2010; (report shows that they
`launched an FF+azelastine product in 2010).
`Declaration of Geena Malhotra for EP151973 l dated Aug. 11, 2011.
`Declaration of Joachim Maus for EP151973 l dated Aug. 10, 2011.
`Vanrell, "Preservatives in ophthalmic formulations: an overview,"
`Arch. Soc. Esp. Oftalmol., 2007, vol. 82, pp. 531-532.
`Malhotra Exhibit A, Aug. 2011.
`"Azelastine," STN Registry No. 58581-89-8, STN Registry File,
`Retrieved Nov. 23, 2010, p. 1.
`"Fluticasone Furoate," STN Registry No. 397864-44-7, STN Regis(cid:173)
`try File, Retrieved Nov. 23, 2010, p. 1.
`Astepro ( azelastine HCI) Nasal Spray O .15%, Meda Pharmaceuticals
`Inc., 2009