`
`
`
`
`
`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. IPR2020-00371
`U.S. Patent No. 9,901,585
`____________________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 9,901,585
`
`
`
`

`

`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`TABLE OF CONTENTS
`
`Table of Authorities .............................................................................................. iii
`List of Exhibits ..................................................................................................... iv
`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.
`Independent Claim 16 .............................................................10
`3.
`Independent Claim 27 .............................................................14
`4.
`Dependent Claim Limitations .................................................18
`Ground 2: Obviousness over Cramer in View of PDR 1999 ............30
`1.
`Independent Claim 1 ...............................................................30
`2.
`Independent Claim 16 .............................................................38
`3.
`Independent Claim 27 .............................................................43
`4.
`Dependent Claim Limitations .................................................48
`D. No Objective Indicia Demonstrating Nonobviousness ......................63
`1.
`No Unexpected Results over the Closest Prior Art ..................64
`2.
`No Long-Felt but Unmet Need ................................................66
`3.
`No Industry Praise ..................................................................66
`VI. Mandatory Notices ......................................................................................66
`A.
`Real Parties-in-Interest ......................................................................66
`B.
`Related Matters .................................................................................66
`C.
`Counsel and Service Information ......................................................67
`VII. The Grounds Are Not Redundant ................................................................68
`VIII. The Petition Should Not Be Denied under § 325(d) ....................................68
`
`C.
`
`- i -
`
`

`

`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`IX. Conclusion ..................................................................................................68
`Certificate of Compliance with Word Count
`Certificate of Service
`
`
`- ii -
`
`

`

`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`TABLE OF AUTHORITIES
`Cases
`
`Amneal Pharm., LLC v. Supernus Pharm., Inc.,
`IPR2013-00368, Paper 8 (PTAB Dec. 17, 2013) .............................................. 63
`Eli Lilly & Co. v. Trs. of the Univ. of Pa.,
`IPR2016-00458, Paper 7 (PTAB July 14, 2016) .............................................. 63
`
`
`Statutes
`
`35 U.S.C. §§ 311-319 ............................................................................................. 1
`35 U.S.C. § 325(d) ................................................................................................ 68
`
`Regulations
`
`37 C.F.R. § 42.100 et seq. ....................................................................................... 1
`
`
`
`- iii -
`
`

`

`LIST OF EXHIBITS
`Exhibit
`No.
`Ex. 1001
`Ex. 1002
`
`Exhibit Name
`’620 Patent
`’723 Patent
`
`Ex. 1003
`
`’428 Patent
`
`Ex. 1004
`
`’585 Patent
`
`Ex. 1005
`
`’620 File History
`
`U.S. Patent No. 9,901,585
`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,
`2011) (“August 2011 ’620 Amendment”)
`(pages 135-164);
`
`- iv -
`
`

`

`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Exhibit Name
`
`Exhibit
`(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)
`’428 File History Excerpts from the prosecution file wrapper of
`the ’428 Patent:
`
`’723 File History
`
`Exhibit
`No.
`
`Ex. 1006
`
`Ex. 1007
`
`- v -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`Ex. 1008
`
`’585 File History
`
`Ex. 1009
`
`Phillipps
`
`Ex. 1010
`
`PDR 1999
`
`Ex. 1011
`
`Ex. 1012
`
`Cramer
`
`Segal
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Exhibit
`(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)
`International Patent Application Publication No.
`WO 98/48839 (published November 5, 1998)
`
`- vi -
`
`

`

`Exhibit
`No.
`Ex. 1013
`
`Exhibit Name
`
`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
`
`Ex. 1022
`
`Cauwenberge
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Exhibit
`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)
`Cauwenberge, et al., “Consensus Statement on
`the Treatment of Allergic Rhinitis,” Allergy
`55(2):116-134 (2000)
`
`- vii -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`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
`
`Ex. 1031
`
`Juniper 1997
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Exhibit
`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)
`Juniper, “First-line Treatment of Seasonal
`(Ragweed) Rhinoconjunctivitis),” Canadian
`
`- viii -
`
`

`

`Exhibit
`No.
`
`Exhibit Name
`
`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
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Exhibit
`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
`Allergy and Clinical Immunology 83(3):627-
`633 (1989)
`
`- ix -
`
`

`

`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
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Exhibit
`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
`Allergic Rhinitis,” Drug Safety 26(12):863-893
`(2003)
`
`- x -
`
`

`

`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
`Ex. 1058
`Ex. 1059
`
`Cipla Preliminary
`Response in
`Argentum IPR
`Institution
`Decision in
`Argentum IPR
`Flonase Ad
`N/A
`N/A
`N/A
`
`Ex. 1060
`
`Donovan
`
`Ex. 1061
`Ex. 1062
`
`N/A
`N/A
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Exhibit
`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
`not used
`not used
`Declaration by Maureen Donovan, Ph.D. dated
`January 3, 2020 (submitted in IPR of
`’585 Patent)
`not used
`not used
`
`- xi -
`
`

`

`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Exhibit
`
`not used
`Declaration by Robert Schleimer, Ph.D. dated
`December 22, 2019 (submitted in IPR of
`’585 Patent)
`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
`’585 Patent)
`
`Exhibit
`No.
`Ex. 1063
`
`Exhibit Name
`N/A
`
`Ex. 1064
`
`Schleimer
`
`Ex. 1065
`
`Ansel
`
`Ex. 1066
`Ex. 1067
`
`BPC
`N/A
`
`Ex. 1068
`
`Greenhill
`
`
`
`
`- xii -
`
`

`

`U.S. Patent No. 9,901,585
`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 1-30
`
`(“the challenged claims”) of U.S. Patent No. 9,901,585 (“’585 Patent”; Ex. 1004)
`
`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 ’585 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)
`1-30
`
`1-30
`
`
`
`
`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 -
`
`

`

`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`III. PRIORITY DATE
`The purported priority date of the ’585 Patent is June 14, 2002, based on
`
`Great Britain Patent Application No. GB 0213739.6. (’585 Patent, (30); id.,
`
`1:5-30.) 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 ’585 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.
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`(Schleimer, ¶ 22; Donovan, ¶ 23.)
`
`V. THE CHALLENGED CLAIMS ARE UNPATENTABLE
`Summary
`A.
`The challenged claims are directed to nasal spray formulations comprising
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`azelastine hydrochloride and fluticasone propionate. (’585 Patent, claims.) Nasal
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`sprays comprising each of these ingredients were known in the prior art and
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`approved by the U.S. Food and Drug Administration (“FDA”) as safe and effective
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`for allergic rhinitis (PDR 1999). Co-formulation of the two ingredients into a
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`single formulation, and the benefits of such co-formulations, were also known in
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`the prior art (Segal; Cramer). A POSA would have thus been motivated to
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`combine these prior art disclosures to arrive at the claimed invention with a
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`reasonable expectation of success, rendering the claims unpatentable as obvious
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`under 35 U.S.C. § 103.
`
`B. Ground 1: Obviousness over PDR 1999 in View of Segal
`Independent Claim 1
`1.
`Claim 1 recites “[a] nasal spray formulation comprising: from 0.001%
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`(weight/weight) to 1% (weight/weight) of azelastine hydrochloride; from 0.0357%
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`(weight/weight) to 1.5% (weight/weight) of fluticasone propionate; one or more
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`preservatives; one or more thickening agents; one or more surfactants; and one or
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`more isotonization agents.” Claim 1 would have been obvious over PDR 1999 in
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`view of Segal. (Schleimer, ¶ 112; Donovan, ¶ 161.)
`
`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; Donovan, ¶ 162.) PDR 1999 discloses prescribing information
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`for Astelin® Nasal Spray and Flonase® Nasal Spray (Schleimer, ¶ 41, 64; Donovan,
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`¶¶ 28, 45), and was publicly available to and in actual use by researchers no later
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`than the first week of April 2000 (Greenhill, ¶ 15). PDR 1999 discloses that
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`Astelin® is a “nasal spray” formulation comprising “0.1% azelastine
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`hydrochloride” which is within the claimed range. (PDR 1999, 3191; Schleimer,
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`¶ 114; Donovan, ¶ 30.) Astelin® “also contains benzalkonium chloride
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`(125 mcg/mL),1 edetate disodium, hydroxypropyl methyl cellulose, citric acid,
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`dibasic sodium phosphate, sodium chloride, and purified water.” (PDR 1999,
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`3191; Schleimer, ¶ 114; Donovan, ¶¶ 30, 110, 130, 144, 154.) The benzalkonium
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`chloride and edetate disodium disclosed in PDR 1999 act as preservatives, the
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`hydroxypropyl methyl cellulose acts as a thickening agent, and the sodium chloride
`
`
`1 Micrograms may be abbreviated as “mcg” or “μg”; milligrams may be
`abbreviated as “mg”; milliliters may be abbreviated as “mL” or “ml”; and grams
`may be abbreviated as “g.” (Schleimer, ¶ 26; Donovan, ¶ 26.)
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`acts as a tonicity adjusting agent.2 (PDR 1999, 3191-3192; Donovan, ¶¶ 30, 110,
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`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
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`132, 145.)
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`PDR 1999 also discloses that Flonase® is a “nasal spray” formulation
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`comprising “0.05% (w/w)” fluticasone propionate, which is within the claimed
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`range. (PDR 1999, 1122; Schleimer, ¶ 115; Donovan, ¶ 46.) Flonase® “also
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`contains microcrystalline cellulose and carboxymethylcellulose sodium, dextrose,
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`0.02% w/w benzalkonium chloride, polysorbate 80, and 0.25% w/w phenylethyl
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`alcohol.” (PDR 1999, 1122; Schleimer, ¶ 115; Donovan, ¶¶ 47, 105, 110, 130,
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`144, 155.) The benzalkonium chloride and phenylethyl alcohol disclosed in
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`PDR 1999 act as preservatives, the microcrystalline cellulose and carboxy
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`methylcellulose sodium act as thickening agents, the polysorbate 80 acts as a
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`surfactant, and the dextrose acts as a tonicity adjusting agent. (PDR 1999, 1122-
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`1124; Donovan, ¶¶ 47, 106, 110, 130, 145.)
`
`PDR 1999 thus teaches a nasal spray formulation comprising azelastine
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`hydrochloride within the claimed range or fluticasone propionate within the
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`claimed range, as well as one or more preservatives, one or more thickening
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`agents, one or more surfactants, and one or more tonicity adjusting agents.
`
`
`2 “Tonicity adjusting agent,” “isotonic agent,” and “isotonization agent” have the
`same meaning to a POSA. (Donovan, ¶ 26.)
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`(PDR 1999, 1122-1124, 3191-3192; Schleimer, ¶¶ 114-115; Donovan, ¶¶ 30, 47,
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`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
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`106, 110, 130, 145, 162.)
`
`Segal discloses “nasal spray” formulations “comprising a topical anti-
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`inflammatory agent,” such as “fluticasone propionate,” and “at least one additional
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`therapeutic agent,” such as “azelastine.” (Segal, 2:18-20, 2:23-26, 3:19-20, 4:20-
`
`24; Schleimer, ¶ 116; Donovan, ¶¶ 68-70.) Segal’s formulations may contain
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`“[i]sotonic agents such as sugars and sodium chloride”; “a humectant,” such as
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`“glycerin”; and “[a]dditional agents including pharmaceutically acceptable
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`preservatives.” (Segal, 4:12-14; Schleimer, ¶ 116; Donovan, ¶¶ 73-75, 111, 118,
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`131, 156.) Segal thus teaches a nasal spray formulation comprising both
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`fluticasone propionate and azelastine, as well as one or more preservatives and one
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`or more tonicity adjusting agents. (Segal, 2:18-26, 3:19-20, 4:6-14; 4:20-24;
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`Schleimer, ¶ 116; Donovan, ¶¶ 73-75, 111, 118, 131, 156, 162.)
`
`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; Donovan,
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`¶¶ 107, 114, 120, 127, 133, 141, 146, 151, 158.) As discussed above under “Scope
`
`of the Prior Art” (section V.B.1.a), PDR 1999 teaches nasal spray formulations
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`comprising azelastine hydrochloride within the claimed range or fluticasone
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`propionate within the claimed range, as well as preservatives, thickening agents,
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`surfactants, and tonicity adjusting agents. (PDR 1999, 1122-1124, 3191-3192;
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`Schleimer, ¶¶ 114-115; Donovan, ¶¶ 47, 105, 110, 130, 144, 162.) Segal teaches a
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`nasal spray formulation comprising both fluticasone propionate and azelastine, as
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`well as preservatives and tonicity adjusting agents. (Segal, 2:18-26, 3:19-20, 4:6-
`
`14; 4:20-24; Schleimer, ¶ 116; Donovan, ¶¶ 68-70, 111, 131, 162.)
`
`A POSA would have been motivated to modify these teachings of PDR 1999
`
`in view of Segal to co-formulate the two ingredients into a nasal spray because
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`Segal teaches the benefits of such co-formulation. (Segal, 1:12-2:3, 3:3-12;
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`Schleimer, ¶¶ 117-122; Donovan, ¶¶ 107, 114, 120, 133, 146, 157, 162.) For
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`example, Segal discloses that co-formulation “allow[s] the convenient
`
`administration…in a single topical nasal composition,” and “provides additive and
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`synergistic effects in the treatment of nasal and sinus conditions.” (Segal, 3:3-12;
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`Schleimer, ¶ 118). Segal also discloses that co-formulation overcomes “significant
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`disadvantages” of administering the ingredients separately, such as limits on “[t]he
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`volume of liquid that can effectively be applied nasally,” requirements for
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`“sufficient contact time between topical preparations and the surface area of the
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`nostril,” limits on “the delivery volume per actuation,” “patient inconvenience,”
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`and compromised “[p]atient compliance.” (Segal, 1:12-2:3; Schleimer, ¶ 118.)
`
`A POSA would have been motivated to use azelastine hydrochloride and
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`fluticasone propionate at concentrations within the claimed ranges specifically,
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`because PDR 1999 teaches that both were FDA-approved by as safe and effective
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`for allergic rhinitis within those concentration ranges. (PDR 1999, 1122-1124,
`
`3191-3192; Schleimer, ¶ 119.)
`
`The teachings of PDR 1999 in view of Segal are supported by similar prior
`
`art disclosures. (Drouin, 341, 347; Brooks, 199; Dykewicz, 505; Berger, 536;
`
`Cauwenberge, 119-120, 125; Spector, 387; Bousquet, S189-S192; Schleimer,
`
`¶ 120.) For example, a POSA would have been motivated to co-formulate
`
`ingredients to “maximize” therapeutic and clinical efficacy (Drouin, 341, 347), and
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`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,
`
`that azelastine and fluticasone should be co-administered when use of only one did
`
`not adequately control symptoms. (E.g., Dykewicz, 505; Berger, 536;
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`Cauwenberge, 125; Schleimer, ¶ 122.) A POSA would have also been motivated
`
`to co-formulate the ingredients because a POSA would have known, as
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`exemplified in the prior art, that their mechanisms of action are complementary.
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`(Spector, S387; Cauwenberge, 119-120; Bousquet, S189-S192; Schleimer, ¶ 121.)
`
`Reasonable Expectation of Success
`c)
`A POSA would have had a reasonable expectation of success in modifying
`
`the teachings of PDR 1999 in view of Segal to arrive at the claimed invention.
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`(Schleimer, ¶ 123; Donovan, ¶ 166.) PDR 1999 teaches that both Astelin® and
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`Flonase® were FDA-approved as safe and effective for allergic rhinitis.
`
`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
`
`(PDR 1999, 1122-1124, 3191-3192; Schleimer, ¶ 125.) A POSA would have
`
`reasonably expected based on this teaching in PDR 1999 that a co-formulation
`
`with the ingredients in the disclosed concentrations would likewise be useful for
`
`treating allergic rhinitis. (PDR 1999, 1122-1124, 3191-3192; Schleimer, ¶ 125.)
`
`A POSA would have also had a reasonable expectation of success based on
`
`Segal’s disclosures that co-formulations of the ingredients “provide[] additive and
`
`synergistic effects in the treatment of nasal and sinus conditions,” “can be
`
`conveniently administered nasally to a human subject…to elicit the desired
`
`therapeutic effect,” and “may be administered in the form of a nasal spray or nose
`
`drops.” (Segal, 3:9-12, 4:20-24; Schleimer, ¶ 124.) The reasonable expectation of
`
`success for the modification of PDR 1999 in view of Segal is supported by similar
`
`prior art disclosures, as discussed above under “Motivation to Modify”
`
`(section V.B.1.b). (Schleimer, ¶ 126.) Moreover, the ’585 Patent does not
`
`disclose that the claimed concentrations of the ingredients are critical. (See
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`generally ’428 Patent; Schleimer, ¶ 125.)
`
`A POSA would have also had a reasonable expectation of success in
`
`preparing the formulations of the claim. (Donovan, ¶ 166.) For example,
`
`PDR 1999 discloses “nasal spray” formulations comprising “azelastine
`
`hydrochloride” or “fluticasone propionate,” along with excipients in the claimed
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`categories. (PDR 1999, 1122-1124, 3191-3192; Donovan, ¶¶ 107, 114, 120, 133,
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`IPR2020-00371 (U.S. Patent No. 9,901,585)
`Petition for Inter Partes Review
`
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`146, 157, 166.) A POSA would have had a reasonable expectation of success in
`
`preparing a co-formulation of the two ingredients based on this disclosure in
`
`PDR 1999. (PDR 1999, 1122-1124, 3191-3192; Donovan, ¶ 163.) A POSA would
`
`have also had a reasonable expectation of success in preparing the formulations
`
`based on Segal’s disclosure that “[t]he formulation of pharmaceutical compositions
`
`is generally known in the art and reference can be conveniently made to standard
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`text such as [Remington].” (Segal, 4:1-3; Donovan, ¶ 164.) Moreover, the
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`’585 Patent acknowledges that all of its examples involving azelastine and
`
`fluticasone “are prepared by techniques well known in the art.” (’585 Patent, 7:67-
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`8:2, Examples 1, 3-14; Donovan, ¶ 167.)
`
`Independent Claim 16
`2.
`Claim 16 recites “[a] nasal spray formulation comprising: 0.1%
`
`(weight/weight) azelastine hydrochloride; from 0.0357% (weight/weight) to 1.5%
`
`(weight/weight) of fluticasone propionate; from 0.002% (weight/weight) to 0.05%
`
`(weight/weight)