`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________
`
`
`GLAXOSMITHKLINE CONSUMER HEALTHCARE HOLDINGS (US), LLC,
`Petitioner
`
`v.
`
`CIPLA LTD.,
`Patent Owner
`
`____________________
`
`Case No. IPR2020-00368
`U.S. Patent No. 8,163,723
`____________________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 8,163,723
`
`
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`C.
`
`TABLE OF CONTENTS
`
`Table of Authorities ............................................................................................... ii
`List of Exhibits ..................................................................................................... iii
`I.
`Introduction ................................................................................................. 1
`II.
`Identification of Challenge and Precise Relief Requested ............................ 1
`III.
`Priority Date ................................................................................................ 2
`IV. Level of Ordinary Skill ................................................................................ 2
`V.
`The Challenged Claims Are Unpatentable ................................................... 3
`A.
`Summary ........................................................................................... 3
`B.
`Ground 1: Obviousness over PDR 1999 in View of Segal ................ 3
`1.
`Independent Claim 1 ................................................................ 3
`2.
`Dependent Claim Limitations .................................................11
`Ground 2: Obviousness over Cramer in View of PDR 1999 ............26
`1.
`Independent Claim 1 ...............................................................26
`2.
`Dependent Claim Limitations .................................................35
`D. No Objective Indicia Demonstrating Nonobviousness ......................53
`1.
`No Unexpected Results over the Closest Prior Art ..................53
`2.
`No Long-Felt but Unmet Need ................................................55
`3.
`No Industry Praise ..................................................................56
`VI. Mandatory Notices ......................................................................................56
`A.
`Real Parties-in-Interest ......................................................................56
`B.
`Related Matters .................................................................................56
`C.
`Counsel and Service Information ......................................................57
`VII. The Grounds Are Not Redundant ................................................................57
`VIII. The Petition Should Not Be Denied under § 325(d) ....................................58
`IX. Conclusion ..................................................................................................58
`Certificate of Compliance with Word Count
`Certificate of Service
`
`
`- i -
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`TABLE OF AUTHORITIES
`Cases
`
`Amneal Pharm., LLC v. Supernus Pharm., Inc.,
`IPR2013-00368, Paper 8 (PTAB Dec. 17, 2013) .............................................. 52
`Eli Lilly & Co. v. Trs. of the Univ. of Pa.,
`IPR2016-00458, Paper 7 (PTAB July 14, 2016) .............................................. 52
`
`
`Statutes
`
`35 U.S.C. §§ 311-319 ............................................................................................. 1
`35 U.S.C. § 325(d) ................................................................................................ 56
`
`Regulations
`
`37 C.F.R. § 42.100 et seq. ....................................................................................... 1
`
`
`
`
`- ii -
`
`

`

`LIST OF EXHIBITS
`Exhibit
`No.
`Ex. 1001
`
`Exhibit Name
`
`’620 Patent
`
`Ex. 1002
`
`’723 Patent
`
`Ex. 1003
`
`’428 Patent
`
`Ex. 1004
`
`’585 Patent
`
`Ex. 1005
`
`’620 File History
`
`U.S. Patent No. 8,163,723
`Petition for Inter Partes Review
`
`
`Exhibit
`U.S. Patent No. 8,168,620 (issued May 1,
`2012)
`U.S. Patent No. 8,163,723 (issued April 24,
`2012)
`U.S. Patent No. 9,259,428 (issued Feb. 16,
`2016)
`U.S. Patent No. 9,901,585 (issued Feb. 27,
`2018)
`Excerpts from the prosecution file wrapper of
`the ’620 Patent:
`(A) Amendments and Response to Office
`Action Dated January 23, 2009 (July 23,
`2009) (“July 2009 ’620 Amendment”)
`(pages 1-20);
`(B) Declaration under 37 C.F.R. § 1.132 by
`Geena Malhotra (July 3, 2009) (“July 2009
`Malhotra Declaration”), with Exhibits A-C
`(pages 21-44);
`(C) Final Office Action (April 28, 2010)
`(“April 2010 ’620 Final Office Action”)
`(pages 45-65);
`(D) Amendments and Response to Final Office
`Action Dated April 28, 2010 (Sept. 24,
`2010) (“September 2010
`’620 Amendment”) (pages 66-87);
`(E) Declaration under 37 C.F.R. § 1.132 by
`Geena Malhotra (Sept. 23, 2010)
`(“September 2010 Malhotra Declaration”),
`with Exhibits A-D (pages 88-117);
`(F) Office Action (Feb. 16, 2011)
`(“February 2011 ’620 Office Action”)
`(pages 118-134);
`(G) Amendments and Response to Office
`Action Dated February 16, 2011 (Aug. 16,
`
`- iii -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1006
`
`’723 File History
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`Exhibit
`2011) (“August 2011 ’620 Amendment”)
`(pages 135-164);
`(H) Declaration under 37 C.F.R. § 1.132 by
`Nikhil Chopra (Dec. 8, 2011)
`(“December 2011 Chopra Declaration”),
`with Exhibit A (pages 165-173);
`(I) Declaration under 37 C.F.R. § 1.132 by
`Geena Malhotra (Aug. 12, 2011)
`(“August 2011 Malhotra Declaration”),
`with Exhibits A-C (pages 174-196);
`(J) Declaration under 37 C.F.R. § 1.132 by
`Joachim Maus (Aug. 16, 2011)
`(“August 2011 Maus Declaration”), with
`Exhibits A-H (pages 197-297);
`(K) Declaration under 37 C.F.R. § 1.132 by
`Sujeet Rajan (Aug. 16, 2011)
`(“August 2011 Rajan Declaration”), with
`Exhibit A (pages 298-318);
`(L) Notice of Allowance and Fees Due (Oct. 3,
`2011) with Notice of Allowability
`(“’620 Notice of Allowance”) (pages 319-
`327)
`(M) Notice of Allowance and Fees Due
`(Jan. 30, 2012) with Supplemental Notice
`of Allowability (“’620 Supplemental Notice
`of Allowance”) (pages 328-342)
`Excerpts from the prosecution file wrapper of
`the ’723 Patent:
`(A) Interview Summary (Nov. 23, 2011)
`(“November 2011 ’723 Interview
`Summary”) (pages 1-3);
`(B) Preliminary Amendment (Dec. 12, 2011)
`(“December 2011 ’723 Preliminary
`Amendment”) (pages 4-14);
`(C) Notice of Allowance and Fees Due
`(Jan. 26, 2012) (“’723 Notice of
`Allowance”) (pages 15-23)
`
`- iv -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1007
`
`’428 File History
`
`Ex. 1008
`
`’585 File History
`
`Ex. 1009
`
`Phillipps
`
`Ex. 1010
`
`PDR 1999
`
`Ex. 1011
`
`Cramer
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`Exhibit
`Excerpts from the prosecution file wrapper of
`the ’428 Patent:
`(A) Office Action (May 7, 2015) (“May 2015
`’428 Office Action”) (pages 1-8);
`(B) Interview Summary (May 7, 2015)
`(“May 2015 ’428 Interview Summary”)
`(pages 9-10);
`(C) Amendments and Response to Office
`Action Dated May 7, 2015 (Aug. 7, 2015)
`(“August 2015 ’428 Amendment”)
`(pages 11-22);
`(D) Supplemental Response to Office Action
`Dated May 7, 2015 (Oct. 14, 2015)
`(“October 2015 ’428 Supplemental
`Response”) (pages 23-32);
`(E) Notice of Allowance and Fees Due
`(Nov. 18, 2015) (“’428 Notice of
`Allowance”) (pages 33-41)
`Excerpts from the prosecution file wrapper of
`the ’585 Patent:
`(A) Office Action (Feb. 1, 2017)
`(“February 2017 ’585 Office Action”)
`(pages 1-9);
`(B) Response to Office Action Dated
`February 1, 2017 (Aug. 1, 2017)
`(“August 2017 ’585 Response”) (pages 10-
`29);
`(C) Notice of Allowance and Fees Due
`(Oct. 31, 2017) (“’585 Notice of
`Allowance”) (pages 30-42)
`U.S. Patent No. 4,335,121 (issued June 15,
`1982)
`“Flonase” and “Astelin,” in the Physicians’
`Desk Reference (1999) at 1122-1124 and 3191-
`3192
`European Patent Application Publication No.
`EP 0,780,127 A1 (published June 25, 1997)
`
`- v -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1012
`
`Segal
`
`Ex. 1013
`
`Hettche
`
`Ex. 1014
`
`PDR 2000
`
`Ex. 1015
`Ex. 1016
`
`Perrin
`N/A
`
`Ex. 1017
`
`Stellato
`
`Ex. 1018
`
`Johnson
`
`Ex. 1019
`
`Dykewicz
`
`Ex. 1020
`
`Falser
`
`Ex. 1021
`
`Berger
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`Exhibit
`International Patent Application Publication
`No. WO 98/48839 (published November 5,
`1998)
`U.S. Patent No. 5,164,194 (issued Nov. 17,
`1992)
`“Flonase” and “Astelin,” in the Physicians’
`Desk Reference (2000) at 1184-1186 and 3147-
`3148
`Excerpts from Perrin & Dempsey, Buffers for
`pH and Metal Ion Control, (1973)
`not used
`Stellato, et al., “An In Vitro Comparison of
`Commonly Used Topical Glucocorticoid
`Preparations,” Journal of Allergy and Clinical
`Immunology 104(3):623-629 (1999)
`Johnson, “Development of Fluticasone
`Propionate and Comparison with Other Inhaled
`Corticosteroids,” Journal of Allergy and
`Clinical Immunology, 101(4):S434-S439
`(1998)
`Dykewicz, 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 81(5):478-518 (1998)
`Falser, et al., “Comparative Efficacy and Safety
`of Azelastine and Levocabastine Nasal Sprays
`in Patients with Seasonal Allergic Rhinitis,”
`Arzneimittel Forschung 51(5):387-393 (2001)
`Berger, et al., “Double-Blind Trials of
`Azelastine Nasal Spray Monotherapy Versus
`Combination Therapy with Loratadine Tablets
`and Beclomethasone Nasal Spray in Patients
`with Seasonal Allergic Rhinitis,” Annals of
`Allergy, Asthma & Immunology 82(6):535-
`541(1999)
`
`- vi -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1022
`
`Cauwenberge
`
`Ex. 1023
`
`Spector
`
`Ex. 1024
`
`Bousquet
`
`Ex. 1025
`
`Kusters
`
`Ex. 1026
`
`Wihl
`
`Ex. 1027
`
`Lieberman
`
`Ex. 1028
`
`Harris
`
`Ex. 1029
`
`Nielsen 2003
`
`Ex. 1030
`
`Watts
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`Exhibit
`Cauwenberge, et al., “Consensus Statement on
`the Treatment of Allergic Rhinitis,” Allergy
`55(2):116-134 (2000)
`Spector, “Ideal Pharmacology for Allergic
`Rhinitis,” Journal of Allergy and Clinical
`Immunology 103(3):S386-S387 (1999)
`Bousquet, et al., “Management of Allergic
`Rhinitis and Its Impact on Asthma,” Journal of
`Allergy and Clinical Immunology 108(5):S147-
`S334 (2001)
`Kusters, et al., “Effects of Antihistamines on
`Leukotriene and Cytokine Release from
`Dispersed Nasal Polyp Cells,” Arzneimittel
`Forschung 52(2):97-102 (2002)
`Wihl, et al., “Effect of the Nonsedative H1-
`Receptor Antagonist Astemizole in Perennial
`Allergic and Nonallergic Rhinitis,” Journal of
`Allergy and Clinical Immunology 75(6):720-
`727 (1985)
`Lieberman, “Treatment Update: Nonallergic
`Rhinitis,” Allergy and Asthma Proceedings
`22(4):199-202 (2001)
`Harris, et al., “Intranasal Administration of
`Peptides: Nasal Deposition, Biological
`Response, and Absorption of Desmopressin,”
`Journal of Pharmaceutical Sciences
`75(11):1085-1088 (1986)
`Nielsen & Dahl, “Comparison of Intranasal
`Corticosteroids and Antihistamines in Allergic
`Rhinitis, A Review of Randomized, Controlled
`Trials,” American Journal of Respiratory
`Medicine 2(1):55-65 (2003)
`Watts, et al., “Modulation of Allergic
`Inflammation in the Nasal Mucosa of Allergic
`Rhinitis Sufferers with Topical Pharmaceutical
`Agents,” Frontiers in Pharmacology 10(294):1-
`22 (2019)
`
`- vii -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1031
`
`Juniper 1997
`
`Ex. 1032
`
`Handbook
`
`Ex. 1033
`
`Remington
`
`Ex. 1034
`
`Ratner 1998
`
`Ex. 1035
`
`Drouin
`
`Ex. 1036
`
`Simpson
`
`Ex. 1037
`
`Howarth
`
`Ex. 1038
`
`Brooks
`
`Ex. 1039
`
`Juniper 1989
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`Exhibit
`Juniper, “First-line Treatment of Seasonal
`(Ragweed) Rhinoconjunctivitis),” Canadian
`Medical Association Journal 156(8):1123-1131
`(1997)
`Excerpts from Kibbe, Handbook of
`Pharmaceutical Excipients (3rd ed. 2000)
`Excerpts from Remington’s Pharmaceutical
`Sciences (17th ed. 1985)
`Ratner et al., “A Comparison of the Efficacy of
`Fluticasone Propionate Aqueous Nasal Spray
`and Loratadine, Alone and in Combination, for
`the Treatment of Seasonal Allergic Rhinitis,”
`The Journal of Family Practice 47(1):118-125
`(1998)
`Drouin, et al. “Adding Loratadine to Topical
`Nasal Steroid Therapy Improves Moderately
`Severe Seasonal Allergic Rhinoconjunctivitis,”
`Advances in Therapy 12(6):340-349 (1995)
`Simpson, “Budesonide and Terfenadine,
`Separately and in Combination, in the
`Treatment of Hay Fever,” Annals of Allergy
`73(6):497-502 (1994)
`Howarth, “A Comparison of the Anti-
`Inflammatory Properties of Intranasal
`Corticosteroids and Antihistamines in Allergic
`Rhinitis,” Allergy 62:6-11 (2000)
`Brooks, et al., “Spectrum of Seasonal Allergic
`Rhinitis Symptom Relief with Topical
`Corticoid and Oral Antihistamine Given Singly
`or in Combination,” American Journal of
`Rhinology 10(3):193-199 (1996)
`Juniper et al., “Comparison of Beclomethasone
`Dipropionate Aqueous Nasal Spray,
`Astemizole, and the Combination in the
`Prophylactic Treatment of Ragweed Pollen-
`Induced Rhinoconjunctivitis,” Journal of
`
`- viii -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1040
`
`Benincasa
`
`Ex. 1041
`
`Galant
`
`Ex. 1042
`
`Nielsen 2001
`
`Ex. 1043
`
`November 2017
`Carr Declaration
`
`Ex. 1044
`
`Nelson
`
`Ex. 1045
`
`Ratner 2008
`
`Ex. 1046 Cipla Response in
`Argentum IPR
`
`Ex. 1047
`
`Pipkorn
`
`Ex. 1048
`
`Salib
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`Exhibit
`Allergy and Clinical Immunology 83(3):627-
`633 (1989)
`Benincasa & Lloyd, “Evaluation of Fluticasone
`Propionate Aqueous Nasal Spray Taken Alone
`and in Combination with Cetirizine in the
`Prophylactic Treatment of Seasonal Allergic
`Rhinitis,” Drug Investigation, 8(4): 225-233
`(1994)
`Galant & Wilkinson, “Clinical Prescribing of
`Allergic Rhinitis Medication in the Preschool
`and Young School-Age Child,” Biodrugs
`15(7):453-463 (2001)
`Nielsen et al., “Intranasal Corticosteroids for
`Allergic Rhinitis,” Drugs 61(11):1563-1579
`(2001)
`Second Declaration of Warner Carr, M.D.,
`IPR2017-00807 (Ex. 2147) (Nov. 20, 2017)
`Nelson, “Mechanisms of Intranasal Steroids in
`the Management of Upper Respiratory Allergic
`Diseases,” Journal of Allergy and Clinical
`Immunology 104(4):S138-S143 (1999)
`Ratner et al., “Combination Therapy with
`Azelastine Hydrochloride Nasal Spray and
`Fluticasone Propionate Nasal Spray in the
`Treatment of Patients with Seasonal Allergic
`Rhinitis,” Annals of Allergy, Asthma &
`Immunology 100:74-81 (2008)
`Patent Owner Response, IPR2017-00807
`(Paper 21) (Nov. 20, 2017)
`Pipkorn et al., “Inhibition of Mediator Release
`in Allergic Rhinitis by Pretreatment with
`Topical Glucocorticosteroids,” New England
`Journal of Medicine 316(24):1506-1510 (1987)
`Salib & Howarth, “Safety and Tolerability
`Profiles of Intranasal Antihistamines and
`Intranasal Corticosteroids in the Treatment of
`
`- ix -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1049
`
`Backhouse
`
`Ex. 1050
`
`Ratner 1994
`
`Ex. 1051
`
`Cipla’s Post-Trial
`Sur-Reply Brief in
`Apotex Litigation
`
`Ex. 1052
`
`Leung
`
`Ex. 1053
`
`GlobalData
`
`Ex. 1054
`
`Ex. 1055
`
`Ex. 1056
`Ex. 1057
`
`Cipla Preliminary
`Response in
`Argentum IPR
`Institution
`Decision in
`Argentum IPR
`Flonase Ad
`N/A
`
`Ex. 1058
`
`Donovan
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`Exhibit
`Allergic Rhinitis,” Drug Safety 26(12):863-893
`(2003)
`Backhouse et al., “Treatment of Seasonal
`Allergic Rhinitis with Flunisolide and
`Terfenadine,” Journal of International Medical
`Research 14(1):35-41 (1986)
`Ratner et al., “A Double-Blind, Controlled
`Trial to Assess the Safety and Efficacy of
`Azelastine Nasal Spray in Seasonal Allergic
`Rhinitis,” Journal of Allergy and Clinical
`Immunology 94(5):818-825 (1994)
`Plaintiffs’ Post-Trial Sur-Reply Brief on
`Objective Indicia of Nonobviousness, Meda
`Pharmaceuticals Inc. v. Apotex Inc., No. 1:14-
`cv-01453-LPS (D.I. 163) (D. Del.)
`Leung, et al. “The Editors’ Choice: MP29-02:
`A Major Achievement in the Treatment of
`Allergic Rhinitis,” Journal of Allergy and
`Clinical Immunology 129(5):1216-1217 (2012)
`GlobalData, “Allergic Rhinitis - Global Drug
`Forecast and Market Analysis to 2024,” 1-281
`(Sept. 2015)
`Patent Owner Preliminary Response, IPR2017-
`00807 (Paper 7) (May 30, 2017)
`
`Institution Decision, IPR2017-00807
`(Paper 19) (Oct. 30, 2017)
`“Flonase,” in Special Advertising Section of
`Sports Illustrated 93(11) (Sept. 18, 2000)
`not used
`Declaration by Maureen Donovan, Ph.D. dated
`January 3, 2020 (submitted in IPR of
`’723 Patent)
`
`Ex. 1059
`–
`Ex. 1061
`
`N/A
`
`not used
`
`- x -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1062
`
`Schleimer
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`Exhibit
`Declaration by Robert Schleimer, Ph.D. dated
`December 22, 2019 (submitted in IPR of
`’723 Patent)
`
`N/A
`
`not used
`
`Ex. 1063
`–
`Ex. 1064
`
`Ex. 1065
`
`Ex. 1066
`Ex. 1067
`–
`Ex. 1069
`
`Ansel
`
`BPC
`
`N/A
`
`Ex. 1070
`
`Greenhill
`
`
`
`
`Excerpts from Ansel, et al., Pharmaceutical
`Dosage Forms and Drug Delivery Systems, ch.
`7 (6th ed. 1995)
`Excerpts from British Pharmaceutical Codex
`(1973)
`
`not used
`
`Declaration by Kelley Hayes Greenhill dated
`January 3, 2020 (submitted in IPR of
`’723 Patent)
`
`- xi -
`
`

`

`U.S. Patent No. 8,163,723
`Petition for Inter Partes Review
`
`
`INTRODUCTION
`Petitioner GlaxoSmithKline Consumer Healthcare Holdings (US) LLC
`
`I.
`
`(“Petitioner” or “GSK”) requests inter partes review (“IPR”) of all claims 1-28
`
`(“the challenged claims”) of U.S. Patent No. 8,163,723 (“’723 Patent”; Ex. 1002)
`
`assigned to Cipla Ltd. (“Patent Owner” or “Cipla”) under 35 U.S.C. §§ 311-319
`
`and 37 C.F.R. § 42.100 et seq. This Petition demonstrates that there is a
`
`reasonable likelihood that Petitioner will prevail in proving, by a preponderance of
`
`the evidence, that the challenged claims are unpatentable over the prior art.
`
`Petitioner certifies that the ’723 Patent is available for IPR and that Petitioner is
`
`not barred or estopped from requesting an IPR challenging the claims on the
`
`grounds identified in this Petition.
`
`II.
`
`IDENTIFICATION OF CHALLENGE AND PRECISE RELIEF
`REQUESTED
`The challenged claims are unpatentable and should be cancelled based on
`
`the following grounds:
`
`Ground
`1
`
`2
`
`Claim(s)
`1-28
`
`1-28
`
`
`
`
`Basis
`Obvious over PDR 1999 (Ex. 1010) in view of
`Segal (Ex. 1012)
`Obvious over Cramer (Ex. 1011) in view of
`PDR 1999 (Ex. 1010)
`
`- 1 -
`
`

`

`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`III. PRIORITY DATE
`The purported priority date of the ’723 Patent is June 14, 2002, based on
`
`Great Britain Patent Application No. GB 0213739.6. (’723 Patent, (30); id., 1:4-
`
`15.) Because the undisputed publication date of each reference relied upon in this
`
`Petition is well before that date, Petitioner takes no position for purposes of this
`
`Petition regarding the sufficiency of this priority claim and refers to June 14, 2002
`
`as “the priority date.”
`
`IV. LEVEL OF ORDINARY SKILL
`The application field for the ’723 Patent is pharmaceutical formulations for
`
`allergy/immunology. A person having ordinary skill in the art (“POSA”) as of the
`
`priority date would have been part of a multidisciplinary team including a
`
`clinician/scientist and formulator. (Schleimer, ¶ 21; Donovan, ¶ 21.) The
`
`clinician/scientist would have had an M.D., a Pharm. D., or a Ph.D. in the field of
`
`allergy/immunology and/or pharmacology (or the equivalent), and at least three
`
`years of experience in treating or researching the treatment of allergic rhinitis,
`
`including with nasally administered steroids and antihistamines. (Schleimer, ¶ 22.)
`
`The formulator would have had a bachelor’s degree in chemistry, biology,
`
`chemical engineering, pharmaceutics, or a related field, and three to five years of
`
`experience in developing nasal dosage forms. (Donovan, ¶ 23.) A higher level of
`
`- 2 -
`
`

`

`education or specific skill might make up for less experience, and vice versa.
`
`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`
`(Schleimer, ¶ 22; Donovan, ¶ 23.)
`
`V. THE CHALLENGED CLAIMS ARE UNPATENTABLE
`Summary
`A.
`The challenged claims are directed to methods of using formulations
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`comprising azelastine and fluticasone. (’723 Patent, claims.) Nasal sprays
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`comprising each of these ingredients were known in the prior art and approved by
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`the U.S. Food and Drug Administration (“FDA”) as safe and effective for allergic
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`rhinitis (PDR 1999). Co-formulation of the two ingredients into a single
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`formulation, and the benefits of such co-formulations, were also known in the prior
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`art (Segal; Cramer). A POSA would have been motivated to combine these prior
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`art teachings to arrive at the claimed invention with a reasonable expectation of
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`success, rendering the claims unpatentable as obvious under 35 U.S.C. § 103.
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`B. Ground 1: Obviousness over PDR 1999 in View of Segal
`Independent Claim 1
`1.
`Claim 1 recites “[a] method for the prophylaxis or treatment in a mammal of
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`a condition for which administration of one or more anti-histamines and/or one or
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`more steroids is indicated, comprising intranasal administration to said mammal of
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`a therapeutically effective amount of a pharmaceutical composition comprising
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`(a) azelastine, or a pharmaceutically acceptable salt thereof; and (b) a
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`pharmaceutically acceptable ester of fluticasone.” Claim 1 would have been
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`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
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`obvious over PDR 1999 in view of Segal. (Schleimer, ¶¶ 111, 113; Donovan,
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`¶ 90.)
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`Scope of the Prior Art
`a)
`PDR 1999 in view of Segal teaches all the limitations of claim 1.
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`(Schleimer, ¶ 114.) PDR 1999 discloses prescribing information for Astelin®
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`Nasal Spray and Flonase® Nasal Spray (Schleimer, ¶ 41, 64; Donovan, ¶¶ 28, 45),
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`and was publicly available to and in actual use by researchers no later than the first
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`week of April 2000 (Greenhill, ¶ 15). PDR 1999 discloses that Astelin® is a
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`pharmaceutical composition “for intranasal administration” that comprises
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`“azelastine hydrochloride,” which is a pharmaceutically acceptable salt of
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`azelastine, and “is indicated for the treatment of the symptoms of seasonal allergic
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`rhinitis,” which is a condition for which administration of one or more
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`antihistamines is indicated. (PDR 1999, 3191-3192; Schleimer, ¶ 114.) PDR 1999
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`thus teaches a method for treating a condition for which administration of one or
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`more antihistamines is indicated using a pharmaceutical composition for intranasal
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`administration comprising a pharmaceutically acceptable salt of azelastine.
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`(PDR 1999, 3191-3192; Schleimer, ¶ 114.)
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`PDR 1999 discloses that Flonase® is a pharmaceutical composition for
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`“intranasal” administration that comprises “fluticasone propionate,” which is a
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`pharmaceutically acceptable ester of fluticasone, and “is indicated for the
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`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
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`management of the nasal symptoms of seasonal and perennial allergic rhinitis,”
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`which is a condition for which administration of one or more steroids is indicated.
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`(PDR 1999, 1122-1124; Schleimer, ¶ 115.) PDR 1999 thus teaches a method for
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`treating a condition for which administration of one or more steroids is indicated
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`using a pharmaceutical composition for intranasal administration comprising a
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`pharmaceutically acceptable ester of fluticasone. (PDR 1999, 1122-1124;
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`Schleimer, ¶ 115.)
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`Segal discloses pharmaceutical compositions for intranasal administration
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`“comprising a topical anti-inflammatory agent,” such as “fluticasone propionate,”
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`and “at least one additional therapeutic agent,” such as “azelastine.” (Segal, 2:18-
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`20, 2:23-26, 3:19-20, 4:20-24; Schleimer, ¶ 116.) Segal’s formulations “are useful
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`for the treatment of nasal and sinus conditions, for example allergic rhinitis,”
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`which is a condition for which administration of one or more antihistamines and/or
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`one or more steroids is indicated. (Segal, 2:20-21; Schleimer, ¶ 116.) Segal thus
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`discloses a method for treating a condition for which administration of one or more
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`antihistamines and/or one or more steroids is indicated using a pharmaceutical
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`composition for intranasal administration comprising azelastine and a
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`pharmaceutically acceptable ester of fluticasone. (Segal, 2:18-21, 2:23-26, 3:19-
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`20, 4:20-24; Schleimer, ¶ 116.)
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`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
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`b) Motivation to Modify
`A POSA would have been motivated to modify the teachings of PDR 1999
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`in view of Segal to arrive at the claimed invention. (Schleimer, ¶ 117.) As
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`discussed above under “Scope of the Prior Art” (section V.B.1.a), PDR 1999
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`teaches (1) a method of treating a condition for which administration of one or
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`more antihistamines is indicated using a pharmaceutical composition for intranasal
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`administration comprising a pharmaceutically acceptable salt of azelastine, and
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`(2) a method for treating a condition for which administration of one or more
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`steroids is indicated using a pharmaceutical composition for intranasal
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`administration comprising a pharmaceutically acceptable ester of fluticasone.
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`(PDR 1999, 1122-1124, 3191-3192; Schleimer, ¶ 118.) Segal teaches a method for
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`treating a condition for which administration of one or more antihistamines and/or
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`one or more steroids is indicated using a pharmaceutical composition for intranasal
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`administration comprising both azelastine and a pharmaceutically acceptable ester
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`of fluticasone. (Segal, 2:18-21, 2:23-26, 3:19-20, 4:20-24; Schleimer, ¶ 118.)
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`A POSA would have been motivated to modify these teachings of PDR 1999
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`in view of Segal to co-formulate the ingredients into a pharmaceutical composition
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`for intranasal administration because Segal teaches the benefits of such a co-
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`formulation. (Segal, 1:12-2:3, 3:3-12; Schleimer, ¶ 118.) For example, Segal
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`discloses that co-formulation “allow[s] the convenient administration of an
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`antiinflammatory agent and at least one additional therapeutic agent in a single
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`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
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`topical nasal composition,” and “provides additive and synergistic effects in the
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`treatment of nasal and sinus conditions.” (Segal, 3:3-12; Schleimer, ¶ 118.) Segal
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`also discloses that co-formulation overcomes “significant disadvantages” of
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`administering the ingredients separately, such as limits on “[t]he volume of liquid
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`that can effectively be applied nasally,” requirements for “sufficient contact time
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`[with] the surface area of the nostril,” limits on “the delivery volume per
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`actuation,” “patient inconvenience,” and compromised “[p]atient compliance.”
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`(Segal, 1:12-2:3; Schleimer, ¶ 118.)
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`A POSA would have been motivated to use azelastine hydrochloride and
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`fluticasone propionate specifically, because PDR 1999 teaches that both were
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`FDA-approved as safe and effective for allergic rhinitis, a condition for which
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`administration of one or more antihistamines and/or one or more steroids is
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`indicated. (PDR 1999, 1122-1124, 3191-3192; Schleimer, ¶ 119.)
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`The teachings of PDR 1999 in view of Segal are supported by similar prior
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`art disclosures. (Drouin, 341, 347; Brooks, 199; Dykewicz, 505; Berger, 536;
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`Cauwenberge, 119-120, 125; Spector, 387; Bousquet, S189-S192; Schleimer,
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`¶¶ 120-122.) For example, a POSA would have been motivated to co-formulate
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`the ingredients to “maximize” therapeutic and clinical efficacy (Drouin, 341, 347),
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`and to “better and sooner” remit symptoms (Brooks, 199). (Schleimer, ¶ 120.) A
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`POSA would have known as of the priority date, as exemplified in the prior art,
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`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
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`that azelastine and fluticasone should be co-administered when one did not
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`adequately control symptoms. (E.g., Dykewicz, 505 (“[Intranasal antihistamines]
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`are appropriate…as part of combination therapy with nasal corticosteroids….”);
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`Berger, 536 (“[F]or those patients whose symptoms are not adequately
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`controlled…often a combination of both an antihistamine with an intranasal
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`corticosteroid is prescribed.”); Cauwenberge, 125 (“If the patient presents with
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`severe symptoms or if the treatment with nasal steroids in the case of moderate
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`disease does not have an adequate effect, a combination of nasal steroids and
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`antihistamines (oral and/or topical) is recommended….”); Schleimer, ¶ 122.)
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`A POSA would have also been motivated to co-formulate the two
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`ingredients because a POSA would have known, as exemplified in the prior art,
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`that their mechanisms of action are complementary. (Spector, S387;
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`Cauwenberge, 119-120; Bousquet, S189-S192; Schleimer, ¶ 121.) A POSA would
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`have known as of the priority date, as exemplified in the prior art, that allergic
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`rhinitis includes an early-phase reaction and a late-phase reaction, and that
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`“[o]ptimal treatment…can be achieved only by managing both.” (Spector, S387;
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`Schleimer, ¶ 121.) A POSA would have also known, as exemplified in the prior
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`art, that early-phase reaction symptoms “are most effectively managed by an H1-
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`receptor antagonist,” such as azelastine, and that late-phase reaction symptoms
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`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
`“are best managed with a corticosteroid,” such as fluticasone propionate. (Spector,
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`S387; see also Cauwenberge, 119-120 (disclosing that azelastine is a “highly
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`specific H1-receptor antagonist” and that fluticasone propionate is a “topical
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`corticosteroid[]”); Bousquet, S189-S192 (disclosing that allergic rhinitis includes
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`an early-phase reaction and a late-phase reaction); Schleimer, ¶ 121.)
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`Reasonable Expectation of Success
`c)
`A POSA would have had a reasonable expectation of success in modifying
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`PDR 1999 in view of Segal to arrive at the claimed invention. (Schleimer, ¶ 123.)
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`PDR 1999 teaches that both Astelin® and Flonase® were FDA-approved as safe
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`and effective for allergic rhinitis. (PDR 1999, 1122-1124, 3191-3192; Schleimer,
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`¶ 125.) A POSA would have reasonably expected based on this teaching in
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`PDR 1999 that a pharmaceutical composition for intranasal administration
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`comprising the two ingredients would likewise be useful for treating allergic
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`rhinitis, a condition for which one or more antihistamines and/or one or more
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`steroids is indicated. (PDR 1999, 1122-1124, 3191-3192; Schleimer, ¶ 125.)
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`A POSA would have also had a reasonable expectation of success based on
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`Segal’s disclosures that co-formulations of the ingredients “provide[] additive and
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`synergistic effects in the treatment of nasal and sinus conditions,” “can be
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`conveniently administered nasally to a human subject…to elicit the desired
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`therapeutic effect,” and “may be administered in the form of a nasal spray or nose
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`drops.” (Segal, 3:9-12, 4:20-24; Schleimer, ¶ 124.) The reasonable expectation of
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`IPR2020-00368 (U.S. Patent No. 8,163,723)
`Petition for Inter Partes Review
`
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`success for the modification of PDR 1999 in view of Segal is supported by similar
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`prior art disclosures, as discussed above under “Motivation to Modify”
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`(section V.B.1.b). (Schleimer, ¶ 126.)
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`A POSA would have also had a reasonable expectation of success in
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`preparing the pharmaceutical compositions of the claim. (Donovan, ¶ 158.) For
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`example, PDR 1999 discloses pharmaceutical compositions for “intranasal”
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`administration comprising “azelastine hydrochloride” or “fluticasone propionate.”
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`(PDR 1999, 1122-1124, 3191-3192; Donovan, ¶ 155.) A POSA would have had a
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`reasonable expectation of success in preparing a co-formulation of the two
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`ingredients based on this disclosure in PDR 1999. (PDR 1999, 1122-1124, 3191-
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`3192; Donovan, ¶ 155.) A POSA would have also had a reasonable expectation of
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`success in preparing the pharmaceutical compositions of the claim based on
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`Segal’s disclosure that “[t]he formulation of pharmaceutical compositions is
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`generally known in the art and reference can be conveniently made to standard text
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`such as [Remington].” (Segal, 4:1-3; Donovan, ¶ 156.) Moreover, the ’723 P