`
`Case IPR2015-
`Patent No. 8,603,506
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________________________
`
`DR. REDDY’S LABORATORIES, LTD. and
`DR. REDDY’S LABORATORIES, INC.
`Requestors
`
`v.
`
`GALDERMA LABORATORIES, INC.
`Patent Owner
`
`
`Patent No. 8,603,506
`Issue Date: December 10, 2013
`Title: METHOD OF TREATING ACNE
`____________________________
`
`Inter Partes Review No. Unassigned
`
`__________________________________________________________________
`
`PETITION FOR INTER PARTES REVIEW OF
`CLAIMS 1, 7, 8, 14, 15, AND 20 OF U.S. PATENT
`NO. 8,603,506 AND MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
`
`
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`TABLE OF CONTENTS
`
`Page
`
`TABLE OF AUTHORITIES ...................................................................................III
`
`EXHIBIT LIST ........................................................................................................ iv
`
`STATEMENT OF REASONS FOR RELIEF REQUESTED .................................. 6
`
`I.
`
`II.
`
`INTRODUCTION AND SUMMARY OF ARGUMENT .............................. 6
`
`THE CLAIMS UNDER CONSIDERATION ...............................................11
`
`III. THE SPECIFICATION AND
`PROSECUTION HISTORY OF THE ‘506 PATENT ..................................13
`
`A. The Specification Of The ‘506 Patent ....................................................13
`
`B. The Prosecution History Of The ‘506 Patent .........................................16
`
`IV. EFFECTIVE FILING DATE FOR DETERMINATION .............................21
`
`V.
`
`CLAIM CONSTRUCTION ..........................................................................22
`
`A. Rosacea ...................................................................................................22
`
`B. Papules And Pustules ..............................................................................23
`
`VI. ANALYSIS ....................................................................................................24
`
`A. Ground 1. Claims 1, 7, 8, 14, 15, And 20
`Would Have Been Obvious Over Sneddon (Exh.1006)
`In View Of Golub (Exh.1048), Torresani (Exh.1010)
`And The 2000 PERIOSTAT PDR (Exh.1042) .......................................24
`
`1. The Level Of Ordinary Skill In The Art ..........................................25
`
`2. The Scope And Content Of The Prior Art .......................................27
`
`3. The Differences Between The
`Claimed Invention And The Prior Art .............................................32
`
`
`
`i
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`a.
`The Dosage ............................................................................32
`
`b.
`
`c.
`
`Exclusion Of Bisphosphonate ...............................................38
`
`No Reduction In Microflora ..................................................39
`
`4. Dependent Claims 7, 14, And 20 .....................................................40
`
`5. Claim Chart ......................................................................................41
`
`B. Ground 2. Claims 1, 8, And 15 Would Have Been
`Obvious Over Golub (Exh.1048) In View Of Torresani
`(Exh.1010) And Further In View Of Jansen (Exh.1034) .......................45
`
`1. The Level Of Ordinary Skill In The Art ..........................................45
`
`2. The Scope And Content Of The Prior Art .......................................45
`
`3. Differences Between The Art And The Claims ...............................49
`
`4. Claim Chart ......................................................................................52
`
`C. Ground 3. Dependent Claims 7, 14, And 20 Would
`Have Been Obvious Over Golub (Exh.1048) In View Of
`Torresani (Exh.1010) And Jansen (Exh.1034), And
`Further In View Of 2000 PERIOSTAT PDR (Exh.1042) ......................55
`
`VII. CONCLUSION ..............................................................................................56
`
`CERTIFICATE OF COMPLIANCE ...................................................................... 57
`
`
`
`
`
`
`
`
`ii
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`TABLE OF AUTHORITIES
`
`
`CASES
`Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362
`(Fed. Cir. 2012), cert denied, 133 S. Ct. 1736 (2013) ........................................ 25
`
`Page(s)
`
`Asyst Techs., Inc. v. Emtrak, Inc.,
`544 F.3d 1310 (Fed. Cir. 2008) .......................................................................... 19
`
`Cable Elec. Prods., Inc. v. Genmark, Inc.,
`770 F.2d 1015 (Fed. Cir. 1985), overruled on other grounds ............................ 19
`
`In re Cuozzo Speed Techs., LLC,
`No. 2014-1301, Slip. Op. (Fed. Cir. Feb. 4, 2015) ............................................. 22
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) ................................................................................................ 24
`
`J.T. Eaton & Co. v. Atl. Paste & Glue Co.,
`106 F.3d 1563 (Fed. Cir. 1997) .......................................................................... 19
`
`KSR Int'l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................... 24, 25
`
`Mintz v. Dietz & Watson, Inc.,
`679 F.3d 1372 (Fed. Cir. 2012) .......................................................................... 25
`
`In re Oelrich,
`666 F.2d 578, 581 (C.C.P.A. 1981) .................................................................... 39
`
`Par Pharm. Inc. v. TWI Pharms., Inc.,
`773 F.3d 1186, No. 2014-1391, 2014 U.S. App.
`LEXIS 22737 (Fed. Cir. Dec. 3, 2014) ......................................................... 25, 39
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .................................................................... 41, 55
`
`
`
`
`
`
`
`iii
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`STATUTES, RULES & OTHER AUTHORITIES
`35 U.S.C. § 102(b) ............................................................................................passim
`
`35 U.S.C. § 103 .......................................................................................................... 4
`
`35 U.S.C. § 103(a) ............................................................................... 4, 6, 21, 24, 28
`
`35 U.S.C. § 314(a) ..................................................................................................... 6
`
`35 U.S.C. § 315(b) ..................................................................................................... 3
`
`37 C.F.R. § 42.100(b) .............................................................................................. 22
`
`M.P.E.P. § 716.03(b)................................................................................................ 19
`
`M.P.E.P. § 2143.01 IV ............................................................................................. 20
`
`
`
`iv
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`EXHIBIT LIST
`
`
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`Exhibit # Reference
`U.S. Patent No. 8,603,506
`1001
`1002
`Specification of Application No. 60/281,916 filed Apr. 5, 2001
`1003
`Specification of Application No. 60/325,489 filed Sept. 26, 2001
`1004
`Declaration of Michael Payette, M.D.
`1005
`C.V. of Michael Payette, M.D.
`I. B. Sneddon, A CLINICAL TRIAL OF TETRACYCLINE IN
`1006
`ROSACEA, 78 British J. Dermatology 649-52 (Jan.-Dec. 1966)
`R. Marks & J. Ellis, COMPARATIVE EFFECTIVENESS OF
`TETRACYCLINE AND AMPICILLIN IN ROSACEA A Controlled
`Trial, II(7733) Lancet 1049-52 (Nov. 13, 1971)
`E.M. Saihan and J.L. Burton, A double-blind trial of metronidazole
`versus oxytetracycline therapy for rosacea, 102 British J.
`Dermatology 443-45 (1980)
`P.G. Nielsen, A double-blind study of I% metronidazole cream versus
`systemic oxytetracycline therapy for rosacea, 109(1) British J.
`Dermatology 63-65 (1983)
`Claudio Torresani et al., Clarithromycin versus doxycycline in the
`treatment of rosacea, 36(12) International J. Dermatology 942-46
`(Dec. 1997)
`Joseph B. Bikowski, Treatment of Rosacea With Doxycycline
`Monohydrate, 66(2) Cutis 149-52 (Aug. 2000)
`U.S. Serial No. 13/277,789 Notice of Allowance, Oct. 9, 2013
`1012
`1013 WO 2000/018230 (Ramamurthy et al.)
`E-mail from PDR Customer Service Department to Lerner, David,
`1014
`Littenberg, Krumholz & Mentlik Library (May 14, 2015, 13:04 EST)
`(on file with recipient)
`Beth A. Kapes, Doxycycline hyclate reduces comedones by 50
`percent, Dermatology Times, 2001 Suppl. 22 (November (11)):S19
`U.S. Patent No. 7,211,267
`R. Russel Martin et al., Effects of Tetracycline on Leukotaxis, 129(2)
`J. Infectious Disease 110-16 (Feb. 1974)
`Gerd Plewig, M.D. & Erwin Schöpf, M.D., ANTI-INFLAMMATORY
`EFFECTS OF ANTIMICROBIAL AGENTS: AN IN VIVO STUDY,
`65(6) J. Investigative Dermatology 532-36 (Dec. 1975)
`
`1015
`
`1016
`1017
`
`1018
`
`
`
`v
`
`

`

`1020
`1021
`
`1022
`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Exhibit # Reference
`Nancy B. Esterly et al., THE EFFECT OF ANTIMICROBIAL
`1019
`AGENTS ON LEUKOCYTE CHEMOTAXIS, 70(1) J. Investigative
`Dermatology 51-55 (1978)
`U.S. Patent No. 7,232,572
`L.M. Golub et al., Minocycline reduces gingival collagenolytic
`activity during diabetes Preliminary observations and a proposed
`new mechanism of action, 18(5) J. Periodontal Research 516-26
`(1983)
`L.M. Golub et al., A Non-antibacterial Chemically-modified
`Tetracycline Inhibits Mammalian Collagenase Activity, 66(8) J.
`Dental Research 1310-14 (Aug. 1987)
`1023 Waldemar Pruzanski et al., INHIBITION OF ENZYMATIC
`ACTIVITY OF PHOSPHOLIPASES A2 BY MINOCYCLINE AND
`DOXYCYCLINE, 44(6) Biochemical Pharmacol. 1165-70 (1992)
`Ashok R. Amin et al., A novel mechanism of action of tetracyclines:
`Effects on nitric oxide synthases, 93(24) Proc. Nat’l Acad. Sci. USA.
`14014-019 (Nov. 1996)
`Ashok R. Amin et al., Post-transcriptional regulation of inducible
`nitric oxide synthase mRNA in murine macrophages by doxycycline
`and chemically modified tetracyclines, 410(2-3) FEBS Letters
`259-64 (June 1997)
`U.S. Patent No. 7,014,858
`L.M. Golub et al., TETRACYCLINES INHIBIT CONNECTIVE TISSUE
`BREAKDOWN BY MULTIPLE NON-ANTIMICROBIAL MECHANISMS, 12(2)
`Advances in Dental Research 12-26 (Nov. 1998)
`Kari K. Eklund & Timo Sorsa, Tetracycline Derivative CMT-3
`Inhibits Cytokine Production, Degranulation, and Proliferation in
`Cultured Mouse and Human Mast Cells, 878 Annals N.Y. Academy
`Sciences 689-91 (1999)
`Keith L. Kirkwood et al., Non-antimicrobial and Antimicrobial
`Tetracyclines Inhibit IL-6 Expression in Murine Osteoblasts, 878
`Annals N.Y. Academy Sciences 667-70 (1999)
`Y.H. Thong & A. Ferrante, Inhibition of mitogen-induced human
`lymphocyte proliferative responses by tetracycline analogues, 35(3)
`Clin. exp. Immunol. 443-46 (1979)
`
`1024
`
`1025
`
`1026
`1027
`
`1028
`
`1029
`
`1030
`
`
`
`vi
`
`

`

`1032
`
`1033
`
`1034
`
`1035
`
`1036
`1037
`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Exhibit # Reference
`A. Naess et al., In vivo and in vitro effects of doxycycline on
`1031
`leucocyte membrane receptors, 62(2) Clin. exp. Immunol. 310-14
`(1985)
`Hirohko Akamatsu et al., Effect of Doxycycline on the Generation of
`Reactive Oxygen Species: A Possible Mechanism of Action of Acne
`Therapy with Doxycycline, 72(3) Acta Dermo-Venereologica 178-79
`(1992)
`Y. Ueyama et al., Effects of antibiotics on human polymorphonuclear
`leukocyte chemotaxis in vitro, 32(2) British J. Oral Maxillofacial
`Surgery 96-99 (1994)
`Thomas Jansen MD & Gerd Plewig MD, Rosacea: classification and
`treatment, 90(3) J. Royal Society Med. 144-50 (Mar. 1997)
`R. Marks, Histogenesis of the Inflammatory Component of Rosacea,
`66(8) Proc. roy. Soc. Med. 742-45 (Aug. 1973)
`U.S. Patent No. 8,052,983
`R.K. Curley & J.L. Verbov, Stevens-Johnson syndrome due to
`tetracyclines ____ a case report (doxycycline) and review of the
`literature. 12(2) Clinical and Experimental Dermatology 124-25
`(Mar. 1987)
`R.M. Truëb & G. Burg, Acute Generalized Exanthematous Pustulosis
`due to Doxycycline, 186(1) Dermatology 75-78 (1993)
`Lori E. Shapiro et al., Comparative Safety of Tetracycline,
`Minocycline, and Doxycycline, 133(10) Archives of Dermatology
`1224-30 (Oct. 1997)
`Application Serial No. 11/876,478 Specification, filed Oct. 22, 2007
`Jerry D. Smilack M.D., The Tetracyclines, 74(7) Mayo Clinic Proc.
`727-29 (July 1999)
`PERIOSTAT. (2000). In Physicians’ Desk Reference 944-46 (54th
`ed. 2000) Montvale, NJ: PDR Network
`ORACEA™ (2007). In Physicians’ Desk Reference 1000-100 (61st
`ed 2007), Retrieved from http://www.pdr.net
`A.K. Gupta & M.M Chaudhry, Rosacea and its management: an
`overview, 19(3) J. European Academy of Dermatology and
`Venereology 273-85 (2005)
`
`1038
`
`1039
`
`1040
`1041
`
`1042
`
`1043
`
`1044
`
`
`
`vii
`
`

`

`1047
`
`1048
`
`1049
`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Exhibit # Reference
`Complaint of Galderma Laboratories, Inc. in Civil Action No. 00670,
`1045
`filed on July 31, 2015, in the United States District Court for the
`District of Delaware
`1046 Webster’s Ninth New Collegiate Dictionary 852, 958 (1983),
`“papules” and “pustules,” respectively
`Stedman’s Medical Dictionary 1023, 1175 (24th ed 1982), “papules”
`and “pustules,” respectively
`L.M. Golub et al., Low-dose doxycycline therapy:Effect on gingival
`and eravicular fluid collagenase activity in humans, 25 J. Periodontal
`Research 321-30 (1990)
`Clay Walker et al., Long-Term Treatment With Subantimicrobial
`Dose Doxycycline Exerts No Antibacterial Effects on the Subgingival
`Microflora Associated With Adult Periodontitis, 71(9) J. of
`Periodontology 1465-71 (Sept. 2000)
`U.S. Patent No. 4,666,897 (Golub et. al.)
`Vibramycin®.(1974). In Physicians’ Desk Reference 942-43 (28th
`ed. 1974). Oradell, N.J.: PDR Network.
`Vital Therapies Incorporated.(2015). Management, Robert A. Ashely,
`M.A., Chief Technical Officer, Executive Vice President. Retrieved
`from http://vitaltherapies.com/corporate/management/
`Center for Drug Evaluation and Research, Fed. Food and Drug
`Admin., Approval Package for Application Number: NDA 50-744,
`Trade Name: PERIOSTAT CAPSULES, 20MG (Sept. 30, 1998),
`www.accessdata.fda.gov/drugsatfda_docs/nda/98/50744_
`appltr.pdf
`1054 Mark L. Nelson & Stuart B. Levy, The history of the tetracyclines,
`1241 Annals N.Y. Academy Sciences 17-32 (2011)
`Alicia Mack, Examination of the Evidence for Off-Label Use of
`Gabapentin, 9(6) J. Managed Care Pharmacy 559-68 (Nov./Dec.
`2003)
`Thomas B. Fitzpatrick et al., Dermatology in General Medicine (3rd
`ed. 1987)
`John Berth-Jones MRCP et al., The successful use of minocycline in
`pyoderma gangrenosum—a report of seven cases and review of the
`literature, 1(1) J. Dermatological Treatment 23–25 (June 1989)
`
`1050
`1051
`
`1052
`
`1053
`
`1055
`
`1056
`
`1057
`
`
`
`viii
`
`

`

`1059
`
`1061
`
`1062
`
`1063
`
`1064
`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Exhibit # Reference
`R.K. Joshi et al. Successful treatment of Sweet’s syndrome with
`1058
`doxycycline, 128 British J. Dermatology 584-86 (1993)
`P. Senet et al., Minocycline for the treatment of cutaneous silicone
`granulomas, 140 British J. Dermatology 985-87 (1999)
`1060 Mark Allen Berk & Allan L. Lorincz, The Treatment of Bullous
`Pemphigoid With Tetracycline and Niacinamide. A preliminary
`report. 122(6) Archives Dermatology 670-74 (June 1986)
`Carl R. Thornfeldt & Andrew W. Menkes, Bullous pemphigoid
`controlled by tetracycline, 16(2)(1) J. American Academy
`Dermatology 305-10 (Feb. 1987)
`Isabelle Thomas et al., Treatment of generalized bullous pemphigoid
`with oral tetracycline, 28(1) J. American Academy Dermatology
`74-77 (January 1993)
`David P. Fivenson et al., Nicotinamide and Tetracycline Therapy of
`Bullous Pemphigoid, 130 Arch. Dermatol. 753-58 (June 1994
`Ronald M. Reisner, MD, Systemic Agents in the Management of
`Acne, California Medicine 28-34 (Jan. 1967)
`1065 Marsha L. Chaffins et al., Treatment of pemphigus and linear IgA
`dermatosis with nicotinamide and tetracycline: a review of 13 cases,
`28(6) J. Am. Acad. Dermatol. 998-1000 (June 1998)
`L. Reiche L et al., Combination therapy with nicotinamide and
`tetracyclines for cicatricial pemphigoid: further support for its
`efficacy, 23(6) Clin. and Experimental Dermatol. 254-57 (Nov. 1998)
`Howard Maibach, MD, Second-Generation Tetracyclines, A
`Dermatologic Overview: Clinical Uses and Pharmacology, 48(5)
`cutis 411-17 (Nov. 1991)
`U.S. Serial No. 13/277,789 Fifth Preliminary Amendment, Apr. 30,
`2012
`U.S. Serial No. 13/277,789 Official Action, May 14, 2012
`U.S. Serial No. 13/277,789 Resp. to May 14, 2012 Office Action,
`Sept. 19, 2012
`U.S. Serial No. 13/277,789 Resp. to November 19, 2012 Final Office
`Action and Substance of February 7, 2013 Interview in Reply to
`February 19, 2013 Interview Summary, Feb. 22, 2013
`U.S. Serial No. 13/277,789 Declaration under 37 C.F.R. § 1.132 [of
`Vasant Manna], Feb. 22, 2013
`
`1066
`
`1067
`
`1068
`
`1069
`1070
`
`1071
`
`1072
`
`
`
`ix
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Exhibit # Reference
`1073 MONODOX®, VIBRAMYCIN®. (2000). In Physician’s Desk
`Reference 2082-2083, 2384-2386 (54th ed. 2000) Montvale, NJ:
`PDR Network
`
`
`
`x
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s Laboratories, Inc. (“DRL,”
`
`“Requestor,” or “Petitioner”) requests inter partes review of claims 1, 7, 8, 14, 15,
`
`and 20 of U.S. Patent No. 8,603,506 (“the ‘506 Patent”) (Exh.1001).
`
`NOTICE OF LEAD AND BACKUP COUNSEL
`
`Lead Counsel:
`William L. Mentlik
`(Reg. No. 27,108)
`WMentlik.ipr@ldlkm.com
`Postal and Hand-Delivery Address
`600 South Avenue West
`Westfield, NJ 07090
`Telephone: 908.518.6305
`Fax: 908.654.7866
`
`
`
`Backup Counsel:
`Michael H. Teschner
`(Reg. No. 32,862)
`MTeschner.ipr@ldlkm.com
`Postal and Hand-Delivery Address
`600 South Avenue West
`Westfield, NJ 07090
`Telephone: 908.518.6313
`Fax: 908.654.7866
`
`Brian R. Tomkins
`(Reg. No. 58,550)
`BTomkins.ipr@ldlkm.com
`Postal and Hand-Delivery Address
`600 South Avenue West
`Westfield, NJ 07090
`Telephone: 908.518.6380
`Fax: 908.654.7866
`
`Maegan A. Fuller
`(Reg. No. 71,596)
`MFuller.ipr@ldlkm.com
`Postal and Hand-Delivery Address
`600 South Avenue West
`Westfield, NJ 07090
`Telephone: 908.518.6324
`Fax: 908.654.7866
`
`
`
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`
`NOTICE OF EACH REAL-PARTY-IN-INTEREST
`The Real-Parties-In-Interest for this Petition are Requestor, Dr. Reddy’s
`
`Laboratories, Ltd. (“DRL LTD”) an Indian company, and Dr. Reddy’s
`
`Laboratories, Inc. (“DRL Inc.”) a U.S. company, and wholly owned subsidiary of
`
`DRL LTD. (collectively referred
`
`to herein as “DRL,” “Requestor,” or
`
`“Petitioner”).
`
`NOTICE OF RELATED MATTERS
`Patent Owner1 has asserted the ‘506 Patent as well as related U.S. Patent
`
`Nos. 7,211,267 and 7,232,572 in a civil action filed in the United States District
`
`Court for the District of Delaware (Civil Action No. 15-670), on July 31, 2015
`
`(“the Litigation”). (Exh.1045.) Requestor has also filed concurrent inter partes
`
`review (also referred to herein as “IPR”) petitions against the same claims of the
`
`
`1 Galderma is listed as the patent owner in the caption of this Petition, and as of
`
`August 18, 2015, is the recorded assignee of the ‘506 Patent in the USPTO
`
`Assignment Database. However, in the Litigation (defined herein), the Complaint
`
`states that Nestle Skin Health S.A. (“Nestlé”) is now the owner of the ‘506 Patent.
`
`While the purported assignment to Nestlé is not yet recorded, Petitioner is serving
`
`both Galderma and Nestlé with this Petition, and as used herein, “Patent Owner”
`
`refers to both Galderma and Nestlé.
`
`2
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`‘506 Patent under different theories bearing attorney docket nos. REDDYPP
`
`7.1R-015 and REDDYPP 7.1R-017.
`
`NOTICE OF SERVICE INFORMATION
`Please address all correspondence to the lead and backup counsel at the
`
`address
`
`shown
`
`above.
`
`Requestor
`
`also
`
`consents
`
`to
`
`electronic
`
`service by e-mail at: WMentlik.ipr@ldlkm.com, MTeschner.ipr@ldlkm.com,
`
`BTomkins.ipr@ldlkm.com, and MFuller.ipr@ldlkm.com.
`
`GROUNDS FOR STANDING
`Requestor certifies that the patent for which review is sought is available for
`
`inter partes review, and that Requestor is not barred or estopped from requesting
`
`an inter partes review on the grounds identified in the Petition. The Petition is filed
`
`within one year of the filing of the Complaint in the Litigation. (Exh.1045.) The
`
`Petition is thus timely under 35 U.S.C. § 315(b). The fee for this Petition has been
`
`paid. However, the U.S. Patent and Trademark Office is hereby authorized to
`
`charge Deposit Account No. 12-1095 for any fees that may be due and owing in
`
`connection with this Petition.
`
`STATEMENT OF PRECISE RELIEF REQUESTED
`Requestor requests that claims 1, 7, 8, 14, 15, and 20 of the ‘506 Patent be
`
`held unpatentable based on the following grounds:
`
`3
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Ground 1. Claims 1, 7, 8, 14, 15, and 20 would have been obvious over
`
`Sneddon (Exh.1006), in view of Golub (Exh.1048), Torresani (Exh.1010), and the
`
`2000 PERIOSTAT PDR (Exh.1042). See 35 U.S.C. § 103(a).2
`
`Ground 2. Claims 1, 8, and 15 would have been obvious over Golub
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`(Exh.1048) in view of Torresani (Exh.1010) and further in view of Jansen
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`(Exh.1034). See 35 U.S.C. § 103(a).
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`Ground 3. Claims 7, 14, and 20 would have been obvious over Golub
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`(Exh.1048) in view of Torresani (Exh.1010), and Jansen (Exh.1034) and in further
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`view of the 2000 PERIOSTAT PDR (Exh.1042). See 35 U.S.C. § 103(a).
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`Although Petitioner provides multiple grounds of unpatentability, they are
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`meaningfully distinct. Ground 1 is meaningfully distinct from Grounds 2 and 3
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`because Ground 1 involves a different primary reference and takes a different
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`approach to unpatentability. All of the Grounds in this Petition also represent
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`meaningfully different arguments than those made in the corresponding IPR
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`Petitions filed on the same date as this Petition bearing attorney docket
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`nos. REDDYPP 7.1R-015 and REDDYPP 7.1R-017.
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`2 The pre-AIA version of § 103 applies to each ground in this Petition, because the
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`‘506 Patent has an effective filing date before March 16, 2013.
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`4
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`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Ground 1 starts with the premise that: (1) it was known to treat rosacea with
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`tetracycline, including doxycycline (Exhs.1006, 1010); (2) it was known that the
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`papules and pustules of rosacea were not bacterial, but more inflammatory
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`conditions (Exhs.1010, 1048, 1004 ¶ 33); and (3) it was known that doxycycline
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`was an effective anti-inflammatory agent at the claimed doses (Exhs.1010, 1042,
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`1048, 1004 ¶ 42), that is, doses below those allegedly considered to have an
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`antibiotic effect.
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`Ground 2, on the other hand, starts with research showing that periodontal
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`disease, a condition of mixed bacterial and inflammatory origin, was treated by
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`low dose (40mg/day) doxycycline and that the inflammatory pathways of
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`periodontal disease were also known to exist in rosacea. (Exh.1048.) Indeed, the
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`impact of tetracyclines as anti-inflammatories for treating rosacea was offered as
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`part of the justification for trying low dose doxycycline in periodontal disease.
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`Both conditions are chronic conditions requiring potentially long term treatment.
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`(Exhs.1034, at 144; 1048, at 328.) And doxycycline was known to treat papules
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`and pustules of rosacea based on its anti-inflammatory activity. (Exhs.1010, 1004
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`¶ 31.) The prospect of long-term administration of an antibiotic dose of an
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`antibiotic drug would, in both cases, raise the very same concerns over side effects
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`and the creation of drug resistant microorganisms. (Exhs.1004 ¶¶ 48, 49; 1048.)
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`5
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`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`Thus, it would have been obvious to use low dose doxycycline to treat rosacea
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`based on the success in treating periodontal disease.
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`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`A petition for inter partes review must demonstrate “a reasonable likelihood
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`that the petitioner would prevail with respect to at least 1 of the claims challenged
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`in the petition.” 35 U.S.C. § 314(a). This Petition meets that threshold. All of the
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`elements of claims 1, 7, 8, 14, 15, and 20 of the ‘506 Patent are taught, either
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`expressly or inherently, in the prior art, or are obvious in view of the prior art, as
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`explained below in the grounds of unpatentability. The reasons to combine the
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`cited references, where applicable, are established under 35 U.S.C. § 103(a).
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`I.
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`STATEMENT OF REASONS FOR RELIEF REQUESTED
`INTRODUCTION AND SUMMARY OF ARGUMENT
`The claims for which this Petition was filed involve treating symptoms of a
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`common skin condition known as rosacea. (Exh.1004 ¶ 7.) Rosacea and its various
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`symptoms, including papules and pustules (Id. ¶¶ 7, 12, 13), have long been treated
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`by tetracyclines, including doxycycline, albeit administered at what the Patent
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`Owner alleges to be “antibiotic” doses. (Id. ¶¶ 28, 29, 31; Exhs.1001 col.5 ll.43-45;
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`1006; 1010; 1048.) Prior to the earliest application leading to the ‘506 Patent, it
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`was known that rosacea in general, and its papules and pustules specifically, were
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`inflammatory in nature, not bacterial. (Exhs.1004 ¶ 33; 1048, at 325; 1034, at 145.)
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`6
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`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`And before the claimed invention, it was known that tetracyclines, and in
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`particular, doxycycline, were effective as anti-inflammatory agents (Exhs.1004
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`¶¶ 34-39, 1010, 1048) including at doses lower than were allegedly used for
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`antibiotic therapy. (Exhs.1004 ¶ 42, 1042, 1048.) As such, no medical necessity
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`persisted for giving antibiotic doses of doxycycline to treat papules and pustules of
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`rosacea. (Exh.1004 ¶¶ 40, 45, 58.) Indeed, just the opposite was true. Advantages
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`of lower doses, such as cost and pill size, in addition to possibly avoiding the
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`known antibiotic-level side effects of that drug and reducing the prospect of
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`creating drug resistant bacteria, were well known. (Id. ¶¶ 46, 47, 48; Exh.1048.)
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`At the time of the alleged invention of the ‘506 Patent, dermatologists would
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`have been motivated to use, or at least try, lower doses of doxycycline to treat
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`inflammatory conditions like rosacea and its symptoms because they knew
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`doxycycline was effective in treating rosacea, and that doxycycline was active as
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`an anti-inflammatory at almost any level. (Exhs.1004 ¶ 40, 42, 43, 44, 45; 1031,
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`1032.) They also knew of both the availability of, and the success achieved by,
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`using 40mg of doxycycline in treating periodontitis, another chronic inflammatory
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`condition involving some of the same underlying mechanisms. (Exhs.1004 ¶¶ 38,
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`39, 42, 55-58, 60; 1042, 1048.) PERIOSTAT, for example, was already
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`FDA-approved and commercially available. (Exhs.1053, 1042, 1004 ¶¶ 42, 53,
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`7
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`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`60.)3 PERIOSTAT uses allegedly subantibiotic 40mg/day doses of doxycycline
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`just as claimed in the ‘506 Patent. (Exhs.1042, 1048, 1004 ¶¶ 42, 54, 55.)
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`Drugs are often thought of as falling into only one therapeutic category. But
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`just as often, they are used to treat conditions in other categories. Gabapentin, for
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`example, is FDA approved for treatment of epilepsy and shingles. But its “off
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`label” uses for pain and other conditions are so prevalent, they exceed the
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`approved uses. (Exh.1004 ¶ 25.) Aspirin is another example. Known since
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`antiquity for treating headaches, inflammation, and fever, it more recently has been
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`used as an antiplatelet aggregation drug for cardiac patients. (Id.) And doxycycline,
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`the drug whose use is claimed in the ‘506 Patent, was similarly known for off label
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`uses, even in dermatology, before the invention of the ‘506 Patent. (Id. ¶ 26.)
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`Before the ‘506 Patent, dosing was known to change with changes in usage
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`as well. Returning to aspirin, it is often dosed at 500mg or more up to six times a
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`day for fever, but it is commonly prescribed at a level of 81mg once per day for
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`antiplatelet aggregation. (Id. ¶ 25.) Thus, prescribing PERIOSTAT treatment for
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`papules and pustules of rosacea was well within the skill of any dermatologist.
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`
`3 References to PERIOSTAT were not meant to be references to the product per se,
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`but rather to the published prescribing information memorialized in, inter alia, the
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`2000 PERIOSTAT PDR. (Exh.1042.)
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`8
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`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`(Exh.1004 ¶¶ 59, 60.) Indeed, there is evidence that, before the ‘506 Patent, doctors
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`were already using PERIOSTAT “off label” in this manner. (Exh.10154, at 2
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`(“Periostat was approved by the FDA in 1998, and it could currently be used for its
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`anti-inflammatory benefits with excellent results.”); Exh.1004 ¶ 27.)
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`Importantly, prior to the ‘506 Patent, dermatologists would have known that
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`patients could be advantaged by using lower doses of doxycycline for reasons
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`including, but not limited to, not being needlessly exposed to antibiotic side effects
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`and the possible development of drug resistant bacteria, lower cost, smaller pills,
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`etc. (Exh.1004 ¶¶ 44-49.) Indeed, there would have been nothing to dissuade a
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`dermatologist from trying lower doses, where, as here, the condition being treated
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`is not life threatening ____ they were skin blemishes. (Id. at ¶ 50.) If lower doses
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`were not effective, doctors could always prescribe a higher dose. (Id.) In the
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`meantime, unlike when treating an infection, there would be little or no therapeutic
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`downside to starting with a lower dose ____ only, at worst, a slight delay in clearing
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`up the symptoms. (Exh.1004 ¶¶ 50-53.)
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`This is by no means the only path leading to the conclusion of the
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`obviousness of these claims. For many years prior to the filing of the ‘506 Patent,
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`research had been ongoing on the role of inflammation in periodontal disease.
`
`
`4 Exhibit 1015 is not prior art for purposes of this inter partes review.
`
`9
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`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-009
`(Exhs.1004 ¶¶ 38, 39, 54-56; 1048.) Periodontal disease is a chronic condition, and
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`a patient with this condition needs long term treatment. (Id.¶ 48, Exh.1048.)
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`Research had shown that several inflammatory pathways were implicated and that
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`doxycycline could be an effective anti-inflammatory for treating periodontal
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`disease. (Exh.1004 ¶¶ 38, 39.) Concerns for the side effects of long term antibiotic
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`exposure, such as traditional antibiotic side effects and the possible creation of
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`drug resistant bacteria, prompted the exploration of the use of low dose
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`doxycycline ____ i.e., 40mg/day. (Id. ¶¶ 48, 49, 54, 56; Exh.1048.) That research
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`proved that 40mg/day of doxycycline was effective as an anti-inflammatory in
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`treating periodontal disease. (Id. ¶¶ 54-56, Exh.1048.) It also purported to address
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`many of the concerns one might have in exposing patients with a chronic condition
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`to antibiotics over a long term. That research eventually led to the product
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`PERIOSTAT mentioned above. (Exhs.1004 ¶ 54, 1042, 1053.) PERIOSTAT was
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`FDA approved and commercialized before the filing of the ‘506 Patent.
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`(Exhs.1004 ¶¶ 7, 42, 53; 1042, 1053.)
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`The inflammatory pathways of periodontal disease were known to exist in
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`papules and pustules of rosacea. (Exhs.1004 ¶¶ 39, 57; 1048.) And the