(12) United States Patent
`Acheampong et al.
`
`(10) Patent N0.:
`
`(45) Date of Patent:
`
`US 9,248,191 B2
`*Feb. 2, 2016
`
`US009248191B2
`
`METHODS OF PROVIDING THERAPEUTIC
`EFFECTS USING CYCLOSPORIN
`COMPONENTS
`
`Applicant: Allergan, Inc., Irvine, CA (US)
`
`Inventors: Andrew Acheampong, Irvine, CA (US);
`Diane D. Tang-Liu, Las Vegas, NV
`(US); James N. Chang, Newport Beach,
`CA (US); David F. Power, San
`Clemente, CA (US)
`
`Assignee: Allergan, Inc., Irvine, CA (US)
`
`Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. l54(b) by 0 days.
`
`This patent is subject to a terminal dis-
`claimer.
`
`14/222,478
`
`Mar. 21, 2014
`
`Prior Publication Data
`
`US 2014/0206626 A1
`
`Jul. 24, 2014
`
`Related U.S. Application Data
`
`Continuation of application No. 13/961,828, filed on
`Aug. 7, 2013, now Pat. No. 8,685,930, which is a
`continuation of application No. 11/897,177, filed on
`Aug. 28, 2007, now Pat. No. 8,618,064, and a
`continuation of application No. 10/927,857, filed on
`Aug. 27, 2004, now abandoned.
`
`Provisional application No. 60/503,137, filed on Sep.
`15, 2003.
`
`Int. Cl.
`A61K 38/13
`A61K 47/02
`A61K 9/00
`A61K 47/44
`A61K 9/107
`A61K 47/10
`A61K 47/22
`A61K 47/32
`U.S. Cl.
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`cpc ............. .. A61K 47/02 (2013.01); A61K 9/0048
`(2013.01); A61K 9/107 (2013.01); A61K38/13
`(2013.01); A61K47/10 (2013.01); A61K47/22
`(2013.01); A61K47/32 (2013.01); A61K47/44
`(2013.01)
`
`Field of Classification Search
`None
`
`See application file for complete search history.
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`3,278,447 A
`4,347,238 A
`4,388,229 A
`
`10/1966 McNicholas
`8/1982 Hollingsbee
`6/1983 Fu
`
`4,388,307
`4,614,736
`4,649,047
`4,764,503
`4,814,323
`4,839,342
`4,970,076
`4,990,337
`4,996,193
`5,011,681
`5,047,396
`5,051,402
`5,053,000
`5,075,104
`5,286,730
`5,286,731
`5,294,604
`5,296,158
`5,342,625
`5,364,632
`5,368,854
`5,411,952
`5,424,078
`5,441,732
`5,474,919
`5,474,979
`5,496,811
`5,504,068
`5,540,931
`5,543,393
`5,578,586
`
`>3>D>>D>3>>>3>D>>D>D>>D>D>D>>D>D>>D>D>>D>D>>D>D>D>D>
`
`6/ 1983 Cavanak
`9/ 1986 Delevallee et al.
`3/ 1987 Kaswan
`8/ 1988 Wenger
`3/1989 Andrieu et al.
`6/ 1989 Kaswan
`11/ 1990 Horrobin
`2/ 1991 Kurihara et al.
`2/1991 Hewitt et al.
`4/1991 Ciotti et al.
`9/1991 Orban et al.
`9/ 1991 Kurihara et al.
`10/1991 Booth et al.
`12/1991 Gressel et al.
`2/ 1994 Caufield et al.
`2/ 1994 Caufield et al.
`3/ 1994 Nussenblatt et al.
`3/ 1994 MacGilp et al.
`8/ 1994 Hauer et al.
`11/ 1994 Benita et al.
`11/ 1994 Rennick
`5/ 1995 Kaswan
`6/ 1995 Dziabo
`8/1995 Hoeg et al.
`12/1995 Chartrain et al.
`12/1995 Ding et al.
`3/ 1996 Aviv et al.
`4/ 1996 Komiya et al.
`7/ 1996 Hewitt et al.
`8/1996 Kim et al.
`11/1996 Glonek et al.
`
`(Continued)
`
`FOREIGN PATENT DOCUMENTS
`
`19810655
`0448856
`
`9/1999
`10/1991
`
`(Continued)
`
`OTHER PUBLICATIONS
`
`Abdulrazik, M. et al, Ocular Delivery of Cyclosporin A II. Effect of
`Submicron Emulsion’s Surface Charge on Ocular Distribution of
`Topical Cyclosporin A, S.T.P. Pharma Sciences, Dec. 2001, 427-432,
`11(6).
`
`(Continued)
`
`Primary Examiner — Marcela M Cordero Garcia
`
`(74) Attorney, Agent, or F1'rm—Laura L. Wine; Joel B.
`German; Debra D. Condino
`
`(57)
`
`ABSTRACT
`
`Methods of treating an eye of a human or animal include
`administering to an eye of a human or animal a composition
`in the form of an emulsion including water, a hydrophobic
`component and a cyclo sporin component in a therapeutically
`effective amount of less than 0.1% by weight of the compo-
`sition. The weight ratio of the cyclosporin component to the
`hydrophobic component is less than 0.8.
`
`27 Claims, No Drawings
`
`TEVA - EXHIBIT 1001
`
`TEVA - EXHIBIT 1001
`
`

`
`US 9,248,191 B2
`Page 2
`
`8/2
`6/2
`8/2
`1 1/2
`1/2
`1/2
`2/2
`2/2
`2/2
`4/2
`8/2
`8/2
`1 1/2
`1/2
`3/2
`3/2
`3/2
`3/2
`5/2
`6/2
`6/2
`6/2
`6/2
`7/2
`7/2
`8/2
`9/2
`1/2
`3/2
`1/2
`2/2
`4/2
`6/2
`2/2
`3/2
`6/2
`8/2
`5/2
`1 1/2
`1/2
`1 2/2
`1 0/2
`3/2
`
`>—->—>—->—>—GGGG>—-L:JI\.)>—>—$©O000O0O0\l\l\l\lUIUIDJDJDJDJDJDJDJDJDJDJL:JLoJLo-)LoJI\J[\JI\JI\JI\JI\JI\)I\)I\)>—->->-{J1
`
`Chang ................ .. A61K 9/0048
`Neuer et al.
`Fischer et al.
`Garst
`Patel et a1.
`Cavanak et a1.
`Floc’h et al.
`Richter et al.
`Olbrich et al.
`Kawashin1a
`Petszulat et a1.
`Meinzer et al.
`Richter et al.
`Kang et al.
`Ueno
`Stergiopoulos et al.
`Muller
`Cavanak et a1.
`Or et al.
`Or et al.
`Benita et al.
`Or et a1.
`Or et al.
`Ambuhl et al.
`Hauer et al.
`Yang et al.
`Fricker et al.
`Bakhit et al.
`Acheampong
`Chang
`Tien et al.
`"ien et al.
`Chang et al.
`Graham et al.
`Chang et al.
`Graham et al.
`Graham et a1.
`Tien et al.
`Morgan et al.
`Schiffman
`Morgan et al.
`Chang et al.
`Chang et al.
`
`*
`
`D>?>3>D>>D>D>D>D>D>D>D>D>D>D>D>D>>D>>D>>D>>D>>D>>D>>D>>D>>D>>D>>D>D>D>D>UZ1
`
`» »
`
`G©®©®©®©®©®$®©®$®©$©$QGGGQGGGQGGGQGGG
`
`I\—)I\JI\—)I\JI\JI\JI\JI\JI\JI\.>I\JI\JI\.>I\JI\JI\JI\JI\JI\JI\.>I\JI\.>I\JI\.>l\JI\—)l\JI\—>I\JI\—)I\JI\—)I\JI\—)I\JI\—)I\J
`
`9,101,574
`1/0003589
`1/0014665
`1/0036449
`2/0012680
`2/0013272
`2/0016290
`2/0016292
`2/0025927
`2/0045601
`2/0107183
`2/0119190
`2/0165134
`3/0021816
`3/0044452
`3/0055028
`3/0059470
`3/0060402
`3/0087813
`3/0104992
`3/0108626
`3/0109425
`3/0109426
`3/0133984
`3/0143250
`3/0147954
`3/0166517
`5/0014691
`5/0059583
`7/0015691
`7/0027072
`7/0087962
`7/0149447
`8/0039378
`8/0070834
`8/0146497
`8/0207495
`9/0131307
`2010/0279951
`2011/0009339
`2011/0294744
`2012/0270805
`2013/0059796
`
`FOREIGN PATENT DOCUMENTS
`
`0471293
`0480690
`0547229
`0760237
`2222770 A
`0558906 A
`8901772 A1
`9318752 A1
`1995-031211
`00-00179
`01-32142
`01-41671
`02-09667
`02-49603
`03-030834
`03-053405
`
`2/1992
`4/1992
`1/1993
`3/1997
`3/1990
`3/1993
`3/1989
`9/1993
`11/1995
`1/2000
`5/2001
`6/2001
`2/2002
`6/2002
`4/2003
`7/2003
`
`OTHER PUBLICATIONS
`
`Acheampong, Andrew et al, Cyclosporine Distribution into the Con-
`junctiva, Cornea, Lacrimal Gland and Systemic Blood Following
`Topical Dosing of Cyclosporine to Rabbit, Dog and Human eyes,
`1996, 179.
`Acheampong, Andrew et al, Cyclosporine Distribution Into the Con-
`junctiva, Cornea. Lacrimal Gland. and Systemic Blood Following
`Topical Dosing of Cyclosporine to Rabbit, Dog, and Human Eyes,
`Adv. Exp. Med. Biol, 1998, 1001-1004, 438.
`Acheampong, Andrew et al, Distribution of Cyclosporin a in Ocular
`Tissues After Topical Administration to Albino Rabbits and Beagle
`Dogs, Current Eye Research, 1999, 91-103, 18(2).
`
`514/20.5
`
`.
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`5,589,455
`5,591,971
`5,614,491
`5,639,724
`5,652,212
`5,719,123
`5,721,273
`5,739,105
`5,753,166
`5,766,629
`5,798,333
`5,807,820
`5,827,822
`5,827,862
`5,834,017
`5,843,452
`5,843,891
`5,858,401
`5,866,159
`5,891,846
`5,916,589
`5,929,030
`5,951,971
`5,962,014
`5,962,017
`5,962,019
`5,977,066
`5,981,479
`5,981,607
`5,998,365
`6,004,566
`6,007,840
`6,008,191
`6,008,192
`6,022,852
`6,024,978
`6,046,163
`6,057,289
`6,159,933
`6,197,335
`6,254,860
`6,254,885
`6,267,985
`6,284,268
`6,294,192
`6,306,825
`6,323,204
`6,346,511
`6,350,442
`6,413,547
`6,420,355
`6,468,968
`6,475,519
`6,486,124
`6,544,953
`6,555,526
`6,562,873
`6,569,463
`6,582,718
`6,656,460
`6,872,705
`6,984,628
`7,202,209
`7,276,476
`7,288,520
`7,297,679
`7,501,393
`8,211,855
`8,288,348
`8,618,064
`8,629,111
`8,633,162
`8,642,556
`8,648,048
`8,685,930
`
`gggg$gggggggggJ>D>J>J>J>J>i>J>D>D>D>D>J>D>D>D>D>D>D>D>D>D>D>D>D>D>D>D>D>D>D>D>D>i>D>i>i>D>i>
`
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32
`32*
`
`12/1996
`1/1997
`3/1997
`6/1997
`7/1997
`2/1998
`2/1998
`4/1998
`5/1998
`6/1998
`8/1998
`9/1998
`10/1998
`10/1998
`11/1998
`12/1998
`12/1998
`1/1999
`2/1999
`4/1999
`6/1999
`7/1999
`9/1999
`10/1999
`10/1999
`10/1999
`11/1999
`11/1999
`11/1999
`12/1999
`12/1999
`12/1999
`12/1999
`12/1999
`2/2000
`2/2000
`4/2000
`5/2000
`12/2000
`3/2001
`7/2001
`7/2001
`7/2001
`9/2001
`9/2001
`10/2001
`11/2001
`2/2002
`2/2002
`7/2002
`7/2002
`10/2002
`11/2002
`11/2002
`4/2003
`4/2003
`5/2003
`5/2003
`6/2003
`12/2003
`3/2005
`1/2006
`4/2007
`10/2007
`10/2007
`11/2007
`3/2009
`7/2012
`10/2012
`12/2013
`1/2014
`1/2014
`2/2014
`2/2014
`4/2014
`
`Woo
`Shahar et al.
`Walch et al.
`Cavanak
`Cavanak et al.
`Morley et al.
`Sallee et al.
`Kim et al.
`Dalton et al.
`Cho et al.
`Sherman
`Elias
`Floc’h et al.
`Yamamura
`Cho et al.
`Wiedmann et al.
`Sherman
`Bhalani et al.
`Hauer et al.
`Ishida et al.
`Hauer et al.
`Hamied et al.
`Kawashima et al.
`Hauer et al.
`Hauer et al.
`Cho et al.
`Cavanak
`Ko et al.
`Ding et al.
`Sherman
`Friedman et al.
`Hauer et al.
`Singh
`Al-Razzak et al.
`Klokkers et al.
`Hauer et al.
`Stuchlik et al.
`Mulye
`Sherman
`Sherman
`Garst
`Cho et al,
`Chen et al.
`Mishra et al.
`Patel et al.
`Cavanak
`Burke
`Singh et al.
`Garst
`Bennett et a1.
`Richter et al.
`Cavanak et al.
`Meinzer et al.
`Olbrich et al.
`Tsuzuki et al.
`Matsuo et al.
`Olejnik et al.
`Patel et al.
`Kawashima
`Benim et a1.
`Lyons
`Bakhit et al.
`Chang
`Chang et a1.
`Chang et al.
`Chang
`Tien et al.
`Chang et a1.
`Chang et al.
`Acheampong et al.
`Acheampong et al.
`Acheampong et al.
`Acheampong et al.
`Acheampong et al.
`Acheampong et al.
`
`

`
`US 9,248,191 B2
`Page 3
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Akpek, Esen Karamursel et al, A Randomized Trial of Topical
`Cyclosporin
`0.05% in
`Topical
`Steroid-Resistant Atopic
`Keratoconjunctivitis, Ophthalmology, 2004, 476-482, 111.
`Angelov, O. et al, Preclinical Safety Studies of Cyclosporine
`Ophthalmic Emulsion, Adv Exp Med Biol, 1998, 991-995, 438.
`Angelov, O. et al, Safety Assessment of Cyclosporine Ophthalmic
`Emulsion in Rabbits and Dogs, XIth Congress ofthe European Soci-
`ety ofOphthalmology, 1997, 25-28, 1-5, Soc. Ophtl1almolEur., HU.
`Ardizzone, Sandro et al, A Practical Guide to the Management of
`Distal Ulcerative Colitis, Drugs, 1998, 519-542, 55(4).
`Banic, Marko et al, Effect of Cyclosporine in a Murine Model of
`Experimental Colitis, Digestive Diseases and Sciences, Jun. 2002,
`1362-1368, 47(6).
`BF Goodrich, Carbopol 1342 ANew Polymer Which Functions Both
`As a Thickener and an Emulsifier TDS-73, Carbopol High Perfor-
`mance Polymers, 1987, 25 Pages.
`BF Goodrich, Carbopol, Pemulen and Noveon Polymers, 1995, 2
`Pages.
`BF Goodrich, Pemulen Polymeric Emulsifiers TDS-182, Mar. 1993,
`9 Pages.
`Bonini, S. et al,Vernal Keratoconjunctivitis, Eye, 2004, 345-351, 18.
`Brewster, Marcus et al, Enhanced Delivery of Ganciclovir to the
`Brain Through the Use of Redox Targeting, Antimicrobial Agents
`and Chemotherapy, Apr. 1994, 817-823, 38(4).
`Brewster, Marcus et al, Intravenous and Oral Pharmacokinetic Evalu-
`ation of a 2-Hydroxypropyl-[3-cyclodextrin-Based Formulation of
`Carbarnazepine in the Dog: Comparison with Commercially Avail-
`able Tablets and Suspensions, Journal of Pharmaceutical Sciences,
`Mar. 1997, 335-339, 86(3).
`Brewster, Marcus et al, Preparation, Characterization, andAnesthetic
`Properties of 2-Hydroxypropyl-[3-cyclodextrin Complexes of
`Pregnanolone and Pregnenolone in Rat and Mouse, Journal of Phar-
`maceutical Sciences, Oct. 1995, 1154-1159, 84(10).
`Brinkmeier, Thomas et al, Pyodermatitis-Pyostomatitis Vegetans: A
`Clinical Course of Two Decades with Response to Cyclosporine and
`Low-Dose Prednisolone, Acta Derm Venereol, 2001, 134-136., 81.
`Castillo, Jose M. Benitez Del et al, Influence ofTopical Cyclosporine
`A and Dissolvent on Corneal Epithelium Permeability of Fluores-
`cein, Documenta Ophthalmologica, 1995, 49-55, 91.
`Cheeks, Lisa et al, Influence ofVehicle andAnterior Chamber Protein
`Concentration on Cyclosporine Penetration Through the Isolated
`Rabbit Cornea, Current Eye Research, 1992, 641-649, 11(7).
`Database WPI Week 200044, Derwent Pub. Ltd., London, GB; An
`2000-492678 & JP2000/143542. 2000, 2 Pages.
`Ding, Shulin et al, Cyclosporine Ophthalmic O/W emulsion: Formu-
`lation and Emulsion Characterization, Pharm Res, 1997, 1 page, 14
`(11).
`Donnenfeld, Eric D., The Economics ofUsing Restasis, Ophthalrnol-
`ogy Management, Oct. 2003, 3 pages, US.
`Drosos, A. A. et al, Efficacy and Safety of Cyclosporine-A Therapy
`for Primary Sjogren’s Syndrome, Ter. Arkh., 1998, 77-80, 60(4).
`Drosos, A.A. et al, Cyclosporin a Therapy in Patients with Primary
`Sjogren’s Syndrome: Results at One Year, Scand J Rheumatology,
`1986, 246-249, 61.
`al, Pilocarpine Bioavailability From a
`Durrani, A.M.
`et
`Mucoadhesive I_ipo somal Ophthalmic Drug Delivery System, Inter-
`national Journal of Pharmaceutics, 1992. 409-415, 88.
`Eisen, Drore et al, Topical Cyclosporine for Oral Mucosal Disorders,
`JAmAcad Dermatol, Dec. 1990, 1259-1264, 23.
`Epstein, Joel et al, Topical Cyclo sporine in a Bioadhesive for Treat-
`ment of Oral Lichenoid Muscosal Reactions, Oral Surg Oral Med
`Oral Pathol Oral, 1996, 532-536, 82.
`Erdmarm,
`S.
`et
`al, Pemphigus Vulgaris Der Mund—Und
`Kehlkopfschleimlraut Pemphigus Vulgaris of the Oral Mucosa and
`the Larynx, H+G Zeitschrift Fuer Hautkrankheiten, 1997, 283-286,
`72(4).
`FDA Concludes Restasis (Cyclosporine) Not Effective for Dry Eye
`(Jun. 18, 1999). Accessed online at http://www.dJyeyeinfo.org/
`Restasis_Cyclosporine.htm on Aug. 14, 2009. 1 Page.
`
`Gaeta, G.M. et al, Cyclosporin Bioadhesive Gel in the Topical Treat-
`ment of Erosive Oral Lichen Planus,
`International Journal of
`Immunopathology and Pharmacology, 1994, 125-132, 7(2).
`Gipson, Ilene et al, Character of Ocular Surface Mucins and Their
`Alteration in Dry Eye Disease, The Ocular Surface, Apr. 2004, 131-
`148, 2(2).
`Gremse, David et al, Ulcerative Colitis in Children, Pediatr Drugs,
`2002, 807-815, 4(12).
`al, Topical Cyclosporin Treatment of
`Gunduz, Kaan
`et
`Keratoconjunctivitis Sicca in Secondary Sjogren’s Syndrome, Acta
`Ophthalmologica, 1994, 438-442, 72.
`http://web.archive.org/web/2001030625323/http://wwwsurfactant.
`co.kr/surfactants/pegester.html, 2001, 6 Pages, retrieved on Jul. 5,
`2008.
`Hunter, P.A. et al, Cyclosporin A Applied Topically to the Recipient
`Eye Inhibits Corneal Graft Rejection, Clin Exp Immunol, 1981,
`173-177, 45.
`Jurnaa, Muhannad et al, Physicochemical Properties and Hemolytic
`Effect of Different Lipid Emulsion Formulations Using a Mixture of
`Emulsifiers, Pharmaceutica Acta Helvetiae, 1999, 293-301, 73.
`Kanai, A. et al, The Effect on the Cornea of Alpha Cyclodextrin
`Vehicle for Eye Drops, Transplantation Proceedings, Feb. 1989,
`3150-3152, vol. 21.
`Kanpolat, Ayfer et al, Penetration of Cyclosporin a into the Rabbit
`Cornea and Aqueous Humor after Topical Drop and Collagen Shield
`Administration, Cornea/External Disease, Apr. 1994, 119-122,
`20(2).
`Kaur, Rabinder et al, Solid Dispersions of Drugs in Polyocyethylene
`40 Stearate: Dissolution Rates and PhysicoChemical Interactions,
`Journal of Pharmacy and Pharmacology, Dec. 1979, 48P
`Kuwano, Mitsuaki et al, Cyclosporine A Formulation Affects Its
`Ocular Distribution in Rabbits, Pharmaceutical Research, Jan. 2002,
`108-111,19(1).
`for
`Lambert Technologies Corp. Material Safety Data Sheet
`LUMULSET-V1 POE-40 MS KP, last revision Aug. 22, 2003. 3 pages.
`Leibovitz, Z. et al., Our Experience in Processing Maize (Corn) Germ
`Oil, Journal of the American Oil Chemists Society, Feb. 1983, 395-
`399, 80 (2), US.
`Lixin, Xie et al, Effect of Cyclo sporine a Delivery System in Corneal
`Transplantation, Chinese Medical Journal, 2002, 110-113, 115 (1),
`US.
`Lopatin, D.E., Chemical Compositions and Functions of Saliva, Aug.
`24,2001, 31 Pages.
`Lyons, R.T. et al, Influence of Three Emulsion Formulation Param-
`eters on the Ocular Bioavailability of Cyclosporine A in Albino
`Rabbits, AmAssoc Pharm Sci, 2000, 1 Page, 2(4).
`Pedersen, Anne Marie et al, Primary Sjogren’s Syndrome: Oral
`Aspects on Pathogenesis, Diagnostic Criteria, Clinical Features and
`Approaches for Therapy, Expert Opin Pharrna, 2001, 1415-1436,
`2(9).
`Phillips, Thomas et al, Cyclosporine Has a Direct Effect on the
`Differentiation of a Mucin-Secreting Cell Line, Journal of Cellular
`Physiology, 2000, 400-408, 184.
`Present, D.H. et al, Cyclosporine and Other Immunosuppressive
`Agents: Current and Future Role in the Treatment of Inflammatory
`Bowel Disease, American Journal of Gastroenterology, 1993, 627-
`630, 88(5).
`Restasis® Product Information Sheet, Allergan, Inc., 2009, 5 Pages.
`Restasis® Increasing Tear Production, Retrieved on Aug. 14, 2009,
`http://www.restasisprofessional.com/_clinical/clinical_increasing.
`htrn 3 pages.
`Robinson, N. A. et al, Desquamative Gingivitis: A Sign of
`Mucocutaneous Disorders—a Review, Australian Dental Journal,
`2003, 205-211, 48(4).
`Rudinger, J., Characteristics of the Amino Acids as Components of a
`Peptide Hormone Sequence, Peptide Hormones. 1976, 1-7.
`Sall, Kenneth et al, Two Multicenter, Randomized Studies of the
`Efficacy and Safety of Cyclosporine Ophthalmic Emulsion in Mod-
`erate to Severe Dry Eye Disease, Ophthalmology, 2000, 631-639,
`107.
`Sandborn, William et al, A Placebo-Controlled Trial of Cyclosporine
`Enemas for Mildly to Moderately Active Left-Sided Ulcerative
`Colitis, Gastroenterology, 1994, 1429-1435, 106.
`
`

`
`US 9,248,191 B2
`Page 4
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Sandborn, William et al, Cyclosporine Enemas for Treatrnent-Resis-
`tant, Mildly to Moderately Active, Left-Sided Ulcerative Colitis,
`American Journal of Gastroenterology, 1993, 640-645, 88(5).
`Schwab, Matthias et al, Pharnracokinetic Considerations in the Treat-
`ment of Inflammatory Bowel Disease, Clin Pharm, 2001, 723-751,
`60(10).
`Secchi, Antonio et al, Topical Use of Cyclosporine in the Treatment
`ofVernal Keratoconjunctivitis, American Journal ofOphthalmology,
`Dec. 1990, 641-645, 110.
`Small, Dave et al, The Ocular Pharmacokinetics of Cyclosporine in
`Albino Rabbits and Beagle Dogs. Ocular Drug Delivery and Metabo-
`lisrn, 1999, 54.
`Small, David et al, Blood Concentrations of Cyclosporin a During
`Long-Term Treatment With Cyclosporin A ophthalmic Emulsions in
`Patients with Moderate to Severe Dry Eye Disease, Journal ofOcular
`Pharmacology and Therapeutics, 2002, 411-418, 18(5).
`Smilek, Dawn et al, A Single Amino Acid Change in a Myelin Basic
`Protein Peptide Confers the Capacity to Prevent Rather Than Induce
`Experimental Autoimmune Encephalomyelitis, Proc. Natl. Acad.
`Sci., Nov. 1991, 9633-9637, 88.
`Stephenson, Michelle, The Latest Uses of Restasis, Review of Oph-
`thalmology, Dec. 30, 2005, 7 Pages, US.
`Stevenson, Dara et al, Efficacy and Safety of Cyclosporin A
`ophthalmic Emulsion in the Treatment of Moderate-to-Severe Dry
`Eye Disease, Ophthalmology, 2000, 967-974, 107.
`Tesavibul, N. et al, Topical Cyclosporine A (C sA) for Ocular Surface
`Abnormalities
`in Graft Versus Host Disease Patients,
`Invest
`OphthalmolVis Sci, Feb. 1996, S1026, 37(3).
`The Online Medical Dictionary, Derivative, Analog, Analogue,
`Xerostomia, accessed Jul. 7, 2005 and Jul. 13, 2005, 6 Pages.
`The United States Pharmacopeia, USP XXII, Jan. 1990, 8 Pages, 22.
`Tibell, A. et al., Cyclosporin A in Fat Emulsion Carriers: Experimen-
`tal Studies on Pharmacokinetics and Tissue Distribution, Pharmacol-
`ogy & Toxicology, 1995, 115-121, 76, US.
`Tsubom, Kazuo et al, Use of Topical Cyclosporin a in a Primary
`Sjogren’s Syndrome Mouse Model, Invest Ophthalmol Vis Sci. Aug.
`1998, 1551-1559, 39(9).
`Van Der Reijden, Willy et al, Treatment of Oral Dryness Related
`Complaints (Xerostomia) in Sjogren’s Syndrome, Ann Rheum Dis,
`1999, 465-473, 58.
`Wiederholt, Michael et al, Pharmacokinetic ofTopical Cyclosporin A
`in the Rabbit Eye, Invest Ophtlralmol Vis Sci, 1986, 519-524, 27.
`Winter, T.A. et al, Cyclosporin A Retention Enemas in Refractory
`Distal Ulcerative Colitis and ’Pouchitis’, Scand J Gastroenterol,
`1993, 701-704, 28.
`Pending U.S. Appl . No. 13/961,828 and its entire prosecution history,
`filed Aug. 7, 2013.
`US. Appl. No. 90/009,944 and its entire prosecution history. filed
`Aug. 27, 2011.
`Albietz, Julie. Dry Eye: An Update on Clinical Diagnosis, Manage-
`ment and Promising New Treatments, Clin & Exp. Optometry, Apr.
`18, 2001, 84.
`Allergan Dry Eye Product Portfolio Fact Sheet (http://www.allergan.
`corn/assets/pdf/d1y_eye_product_portfolio_fact_sheet .pdf),
`4
`Pages, 2015.
`Allergan, Inc. 2001 Annual Report. Downloaded from http://agn.
`client.shareholder.corm’financials.cfm, last accessed Jan. 1. 2015, 54
`Pages.
`Allergan, Inc. 2002 Annual Report (http://agn.client.shareholder.
`com/financialscfm), 52 Pages, 2015.
`Allergan, Inc. 2003 Annual Report. Downloaded from http://agn.
`client.shareholderconflfinancials.cfm, last accessed Jan. 1. 2015, 52
`Pages.
`Allergan, Inc. 2004 Annual Report. Downloaded from http://agn.
`client.shareholder.corm’financials.cfm, last accessed Jan. 1. 2015, 16
`Pages.
`Allergan, Inc. 2006 Annual Report. Downloaded from http://agn.
`client.shareholder.corm’financials.cfm, last accessed Jan. 1. 2015, 18
`Pages.
`
`Allergan, Inc. 2005 Annual Report, Downloaded from http://agn.
`client.share1o der.com/ inancialscfm, last accessed Jan. 1, 2015, 35
`
`. 2009 Annual Report, Downloaded from http://agn.
`der.corn/ inancialscfm, last accessed Jan. 1, 2015, 18
`
`. 2010 Annual Report, Downloaded from http://agn.
`der.com/inancialscfm,
`last accessed Jan. 1, 2015,
`
`206 Pages.
`Allegran, Inc. 2011 Annual Report, Downloaded from http://agn.
`client.share1o der.com/inancialscfm,
`last accessed Jan. 1, 2015,
`
`. 2012 Annual Report, Downloaded from http://agn.
`der.corn/ inancialscfm, last accessed Jan. 1, 2015, 28
`
`. 2013 Annual Report, Downloaded from http://agn.
`10 der.corn/ inancialscfm, last accessed Jan. 1, 2015, 28
`
`American Academy of Ophthalmology Cornea/External Disease
`Panel. Preferred Practice Pattem Guidelines. Dry Eye Syndrome. San
`Francisco, CA: American Academy of Ophthalmology, 2013, 44
`Pages.
`Autry, Jill et al, Mix It Up: When to Call a Compounding Pharmacist,
`Review of Optometry, Jul. 15, 2012, 30-37, 149.
`Bausch and Lomb “Dry Eye Products,” downloaded from Bausch and
`Lomb Website http://wwwbausch.corrflour-products/dry-eye-prod-
`ucts/dry-eye-products, last accessed Apr. 14, 2015, 2 Pages.
`Certain Ophthalmic Combination Drugs Containing a Steroid and
`Anti-Infective(s) for Human Use; Drug Efficacy Study Implementa-
`tion; Amendment, Federal Register, 1982, 21296-21301, 47.
`Certain Steroid Preparations for Ophthalmic and/or Otic Use, Federal
`Register, 1976, 34340-34342, 41.
`Chanana, Gurmukh et al, Particle Size Reduction of Emulsions by
`Formulation Design-II: Effect of Oil and Surfactant Concentration,
`PDA Journal of Pharmaceutical Science and Technology, 1995,
`71-76, 49(2).
`Chidambaram, N. et al. Effect ofNonionic Surfactant on Transport of
`Surface-Active and Non-Surface-Active Model Drugs and Emulsion
`Stability in Triphasic Systems, AAPS Pharmasci, 2000, 1-11, 2(3).
`Chung, Hesson et al, Oil Components Modulate Physical Character-
`istics and Function of the Natural Oil Emulsions As Drug or Gene
`Delivery System, Journal of Controlled Release, 2001, 339-350, 71.
`Coles, William et al, Dynamics of Occular Surface pH, British Jour-
`nal ofOphthalrnology, 1984, 549-552, 68.
`1 Page, 2015
`CTFA Becomes the Personal Care Products Council,
`(http://wwwpersonalcarecouncil.org/ctfa-becomes-personal-care-
`products-council).
`Curriculum Vitae of Christopher N. Ta, Ph.D., 23 Pages. 2015.
`Curriculum Vitae of Erning Xia, Ph.D., 17 Pages, 2015.
`Curriculum Vitae of Harry C. Boghigian, 11 Pages, 2015.
`De Paiva, C.S. et al, Rationale for Anti-Inflammatory Therapy in Dry
`Eye Syndrome, Arq. Bras. Oftalmol., 2008, 89-95, 71.
`Declaration of Christopher N. Ta. Ph.D., 57 Pages, 2015.
`Declaration of Erning Xia, Ph.D., 197 Pages, 2015.
`Declaration of Harry C. Boghigian, 37 Pages. 2015.
`Drugs@FDA: FDA Approved Drug Products, Lacrisert, downloaded
`from the FDA website http://www.accessdata.fda.gov/scripts/cder/
`drugsatfda/index.cfm?fuseaction:Search.DrugDetails, last accessed
`Apr. 16, 2015, 2 Pages.
`Drugs@FDA: FDA Approved Drug Products, Restasis, downloaded
`from the FDA website http://www.accessdata.fda.gov/scripts/cder/
`ob/docs/temptn.cfm, last accessed Apr. 14, 2015, 2 Pages.
`Dry Eye Drop Symptom Relief Product information at Systane.com,
`Systane products, Systane ultra Lubricant Eye Drops, downloaded
`from Alcon website http://www.systane.cont’Dry-Eye-Drop-aspx,
`last visited Apr. 21, 2015, 2 Pages.
`Freeman, Jerre Minor, The Punctum Plug: Evaluation of a New
`Treatment for the Dry Eye, Transactions American Academy of Oph-
`thalmology and Otolaryngology, 1975. 874-879, 79.
`Gilbard, Jeffery, Dry Eye, Blepharitis and Chronic Eye Irritation:
`Divide and Conquer, J Ophthalmic Nurs. Technol., 1999, 109-115,
`18.
`
`

`
`US 9,248,191 B2
`Page 5
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Goto, Eiki et al, Low-Concentration Homogenized Castor Oil Eye
`Drops for Noninflamed Obstructive Meibomian Gland Dysfunction,
`Ophthalmology, 2002, 2030-2035, 109.
`Inatomi, Tsutomu et al, Expression of Secretory Mucin Genes by
`Human Conjunctival Epithelia, Invest Ophthalmol Vis Sci, 1996,
`1684-1692, 37.
`Kunert, Kathleen et al, Analysis of Topical Cyclo sporine Treatment
`of Patients With Dry Eye Syndrome, Arch Ophthalmol, 2000, 1489-
`1496, 118.
`Lacrisert (hydroxypropyl cellulose ophthalmic insert) Approved
`Label, downloaded from the FDA website http://wwwaccessdata.
`fda.gov/drugsatfda_docs/label/2008/018771s0171bl.pdf,
`last
`accessed Apr. 14, 2015, 7 Pages.
`Learn more about Systane Gel Drops at Systane.com, Systane Prod-
`ucts, Systane Gel Drops, Downloaded From Alcon Website http://
`wwwsystane.com/Gel-Drops.aspx, last accessed Apr. 21, 2015.
`Lemp, Michael, Report of the National Eye Institute/Industry Work-
`shop on Clinical Trials in Dry Eyes, CLAO, 1995, 221-232, 21.
`Liu, Kevin et al, Synthetic Approaches to the 2010 New Drugs,
`Bioorganic & Medicinal Chemistry, 2012. 1155-1174. 20.
`Maissa, Cecile et al, Effect of Castor Oil Emulsion Eyedrops on Tear
`Film Composition and Stability, Contact Lens &Anterior Eye, 2010,
`76-82, 33.
`Mann, Elaine, Drugs Used in the Treatment of Dry Eye Syndrome,
`Anti-Inflarmnatory Drugs and Topical Anti-Allergy Drugs, Continu-
`ing Education & training, 2007, 30-40.
`Murphy. Rob et al, The Once and Future Treatment of Dry Eye,
`Review of Optometry Jan. 2000 Cover Focus, 2000, 6 Pages (http://
`legacy.revopto1n.corm'archive/Features/ro0200f6.htm).
`Napper, G. et al, Ocular Therapeutics, Clin & Exp Optometry, 2003,
`414-415, 86.
`Ophthalmic Drug Products for Over-The-Counter Human Use; Final
`Monograph, Federal Register, 1988, 7076-7093 (http://wwwfda.
`gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/
`Over-theCounterOTCDrugs/StatusofOTCRulemakings/
`ucm071941.htrn), 53.
`Orange Book: Approved Drug Products with Therapeutic Equiva-
`lence Evaluations, patent and exclusivity data for Restasis, down-
`loaded from FDA website http://wwwaccessdata.fda.gov/scripts/
`cder/ob/docs/patexclnew.cfin?Appl_No=050790&Product_
`No:001&table1=OB_Rx, last accessed Jan. 12, 2015.
`Personal Care Production Council (http://personalcarecouncil.org/)
`3 Pages, 2015.
`Pflugfelder, Stephen et al, The Diagnosis and Management of Dry
`Eye: A Twenty-Five-Year Review, Cornea, 2000, 644-649, 19(5).
`Restasis Approved Label, download from the Allergan Website
`(https://www.restasisprofessional.com/RestasisProfessional/
`FullPrescribinglnformation) 6 Pages, 2015.
`Rowe, E.L., Effect of Emulsifier Concentration and Type on the
`Particle Size Distribution of Emulsions, Journal of Pharmaceutical
`Science, 1965, 260-264, 54.
`Solomon, Abraham et al, Doxycycline Inhibition of Interleukin-1 in
`the Corneal Epithelium, OphthalmolVis Sci, 2000, 25544-2557, 41.
`Systane Lubricant Eye Drops Information at Systane.com, Systane
`Products, Systane Balance Lubricant Eye Drops, Download from
`Alcon Website http://www.systane.co1n/systane-Balance-Lubricant-
`Eye-Drops.aspx. last accessed Apr. 21, 2015.
`Systane Lubricant Eye Gel, Systane Lubricant Eye Gel, Downloaded
`from Alcon Website http,//www.systane.corrv'systane-Lubricant-
`Eye-Gel.aspx, last visited Apr. 21, 2015, 2 pages.
`Taban, Mehryar et al, Update on Punctal Plugs, Comp. Ophthal1nol-
`ogy Update, 2006, 205-2012, 7(5).
`Turner. Kathleen et al, Interleukin-6 Levels in the Conjunctival Epi-
`thelium of Patients with Dry Eye Disease Treated with Cyclosporine
`Ophthalmic Emulsion, Cornea, Jul. 2000, 492-496, 19(4).
`
`Yeh, Steven et al, Apoptosis of Ocular Surface Cells in Experimen-
`tally Induced Dry Eye, Invest Ophthalmol Vis, 20 3, 124-129, 44.
`US"TO Before the Patent Tria and Appeal Board, Apotex Corp.,
`Apotex,
`Inc. Petitioner v. Allergan,
`Inc. Patent Owner, Case
`IPR2015-0 278, Patent 8,633,162, pp. 1-43, Jatec Sep. 18,2015.
`US ’TO Before the Patent Tria and Appeal Board, Apotex Corp.,
`Apotex,
`Inc. Petitioner v. Allergan,
`Inc. Patent Owner, Case
`IPR2015-0 282, Patent 8,629,111, pp. 1-46, Jatec Sep. 17,2015.
`US ’TO Before the Patent Tria and Appeal Board, Apotex Corp.,
`Apotex,
`Inc. Petitioner v. Allergan,
`Inc. Patent Owner, Case
`IPR2015-0 283, Patent 8,685,930, pp. 1-46, ')atec Sep. 17,2015.
`US )TO Before the Patent Tria and Appeal Board, Apotex Corp,
`Apotex,
`Inc. Petitioner v. Allergan,
`Inc. Patent Owner, Case
`IPR2015-0 284, Patent 8,648,048, pp. 1-43, Datec Sep. 22, 2015.
`US ’TO Before the Patent Tria and Appeal Board, Apotex Corp.,
`Apotex,
`Inc. Petitioner v. Allergan,
`Inc. Patent Owner, Case
`IPR2015-0 286, Patent 8,642,556, pp. 1-47, Jatec Sep. 18,2015.
`In the United States District Court for the Eastern District of Texas
`
`Marshall Division, Allergan, Inc. (Plaintiff) v. Actavis, Inc., Watson
`Laboratories, Inc., and Actavis Pharma, Inc. (f/Ida Watson Pharma,
`Inc.) (defendants), CA. No. 2:14-cv-638-JRG-Lead Case Consoli-
`dated with 2:14-cv-188-JRG, Actavis, Inc., Waston Laboratories,
`Inc., and Actavis Pharma, Inc.’s Invalidity Contentions Pursuant to
`Local Patent Rules 3-3 and 3-8, pp. 1-74, dated Oct. 15,2014.
`Letter from Victor Ramsaywak of Apotex, Inc., Notice of Certifica-
`tion Under 21 USC Section 355(j)(2)(B)(ii) (Section 505(j)(2)(B(ii)
`of the Federal Food, Drug and Cosmetic Act( and 21 CFR Section
`314.95 dated Jul. 23, 2015, pp. 1-116.
`Letter from Shashank Upadhye, Counsel for InnoPharma, Inc., of
`Amin Talati & Upadhye, Notification of Certification of Invalidity,
`Unenforceability and/or Non-infringement
`for US. Pat. No.
`5,474,979;
`8,629,111; 8,633,162;
`8,642,556; 8,648,048;
`and
`8,685,930 Pursuant to Section 5050)(2)(13)(iv) of the Federal Food,
`Drug, and Cosmetic Act, dated Jul. 31, 2015, pp. 1-98.
`Letter from J.C. Rozendaal of Kellogg, Huber, Hansen, Todd, Evans
`& Figel, PLLC, Notice of ANDA No. 203880 Concerning
`Cyclosporine Ophthalmic Emulsion, 0.05% with Paragraph IV Cer-
`tification Concerning U.S. Pat. Nos. 8,629,111;
`8,633,162;
`8,642,556, 8,648,048; and 8,685,930 dated Jul. 22, 2015, pp. 1-40.
`Letter from Joseph M. Reisman, Counsel for Mylan Pharmaceuticals
`Inc., of Knobbe Martens, Cyclosporine Emulsion 0.05%, Route of
`Administration: Ophthalmic, U.S. Pat. No. 8,629,111; 8,633,162;
`8,642,556, 8,648,048; and 8,685,930, Notice of Paragraph IV Certi-
`fication, dated Jul. 20, 2015, pp. 1-226.
`Letter from Joseph Bonaccorsi, General Counsel, Akorn, Inc., Noti-
`fication of Certification for US. Pat. Nos. 8,629,111; 8,633,162;
`8,642,556,
`8,648,048;
`and
`8,685,930 Pursuant
`to Section
`5050)(2)(13)(iv) of the Federal Food, Drug, and Cosmetic Act—21
`USC Section 355(j)(2)(B)(iv) Akorn ANDA 204561, dated Jul. 10,
`2015, pp. 1-26.
`USPTO Before the Patent "rial and Appeal Board, Apotex, Inc.
`Petitioner v. Allergan, Inc. Patent Owner, Case IPR2015-01278,
`Patent 8,633,162, pp. 1-63, Dated Jun. 4, 2015.
`USPTO Before the Patent Trial and Appeal Board, Apotex, Inc.
`Petitioner v. Allergan, Inc. Patent Owner, Case IPR2015-01282,
`Patent 8,629,111, pp. 1-63, Dated Jun. 4, 2015.
`USPTO Before the Patent Trial and Appeal Board, Apotex, Inc.
`Petitioner v. Allergan, Inc. Patent Owner, Case IPR2015-01283,
`Patent 8,685,930, pp. 1-63, Dated Jun. 4, 2015.
`USPTO Before the Patent Trial and Appeal Board, Apotex, Inc.
`Petitioner v. Allergan, Inc. Patent Owner, Case IPR2015-01284,
`Patent 8,648,048, pp. 1-63, Dated Jun. 4, 2015.
`USPTO Before the Patent Trial and Appeal Board, Apotex, Inc.
`Petitioner v. Allergan, Inc. Patent Owner, Case IPR2015-01286,
`Patent 8,642,556, pp. 1-63, Dated Jun. 4, 2015.
`
`* cited by examiner
`
`

`
`US 9,248,191 B2
`
`1
`METHODS OF PROVIDING THERAPEUTIC
`EFFECTS USING CYCLOSPORIN
`COMPONENTS
`
`RELATED APPLICATION
`
`This application is a continuation of copending U.S. Appli-
`cation Serial No. 13/961828 filed Aug. 7, 2013, which is a
`continuation of U.S. application Ser. No. 11/897,177, filed
`Aug. 28, 2007, now issued as U.S. Pat. No. 8,618,064, which
`is a continuation of U.S. application Ser. No. 10/927,857,
`filed Aug. 27, 2004, now abandoned, which claims the benefit
`ofU.S. Provisional Application No. 60/503,137 filed Sep. 15,
`2003, wl1ich are incorporated in their entirety herein by ref-
`erence.
`
`BACKGROUND OF THE INVENTION
`
`The present invention relates to methods of providing
`desired therapeutic effects to humans or animals using com-
`positions including cyclosporin components. More particu-
`larly, the invention relates to methods including administer-
`ing to an eye of a human or animal a therapeutically effective
`amount of a cyclosporin component to provide a desired
`therapeutic effect, preferably a desired ophthalmic or ocular
`therapeutic effect.
`The use of cyclosporin-A and cyclosporinA derivatives to
`treat ophthalmic conditions has been the subject of various
`patents, for example Ding et al U.S. Pat. No. 5,474,979; Garst
`U.S. Pat. No. 6,254,860; and Garst U.S. Pat. No. 6,350,442,
`this disclosure of each of which is incorporated in its entirely
`herein by reference. In ad