`
`Case IPR2015-
`Patent No. 8,603,506
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`
`
`
`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-017
`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 ...............................................10
`
`III. THE SPECIFICATION AND
`PROSECUTION HISTORY OF THE ‘506 PATENT ..................................11
`
`A. The Specification Of The ‘506 Patent ....................................................11
`
`B. The Prosecution History Of The ‘506 Patent .........................................14
`
`IV. EFFECTIVE FILING DATE FOR CLAIMS 1, 7, 8 AND 14 .....................20
`
`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 Bikowski (Exh.1011), In View Of The 2000
`PERIOSTAT PDR (Exh.1042) And Golub et.al. (Exh.1048) ................24
`
`1. The Level Of Ordinary Skill In The Art ..........................................25
`
`2. The Scope And Content Of The Prior Art .......................................27
`
`3. Differences Between The Art And The Claims ...............................31
`
`4. Dependent Claims 7, 14 and 20 .......................................................36
`
`5. Claim Chart ......................................................................................37
`
`
`
`i
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`B. Ground 2. Claims 1, 7, 8, 14, 15, And 20 Would
`Have Been Obvious Over Bikowski (Exh.1011)
`And The 2000 PERIOSTAT PDR (Exh.1042) .......................................41
`
`1. The Level Of Ordinary Skill In The Art ..........................................41
`
`2. The Scope And Content Of The Prior Art .......................................41
`
`3. The Differences Between The
`Claimed Invention And The Prior Art .............................................45
`
`a.
`
`a.
`
`b.
`
`The Dosage ............................................................................45
`
`Exclusion Of Bisphosphonate ...............................................50
`
`No Reduction In Microflora ..................................................50
`
`4. Dependent Claims 7, 14, And 20 .....................................................52
`
`5. Claim Chart ......................................................................................53
`
`VII. CONCLUSION ..............................................................................................57
`
`CERTIFICATE OF COMPLIANCE ...................................................................... 58
`
`
`
`
`
`
`
`
`ii
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`TABLE OF AUTHORITIES
`
`
`CASES
`Alcon Research, Ltd. v. Apotex Inc.,
`687 F.3d 1362, 1369 (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) .......................................................................... 17
`
`Cable Elec. Prods., Inc. v. Genmark, Inc.,
`770 F.2d 1015 (Fed. Cir. 1985), overruled on other grounds ............................ 17
`
`In re Cuozzo Speed Techs., LLC,
`778 F.3d 1271 (Fed. Cir. 2015), rh’g en banc denied ........................................ 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) .......................................................................... 17
`
`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
`
`New Railhead Mfg., LLC v. Vermeer Mfg Co.,
`298 F.3d 1290 (Fed. Cir. 2002) .......................................................................... 21
`
`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) (Exh. 1032)............................... 25, 35, 51
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .................................................................... 37, 52
`
`
`
`iii
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`STATUTES, RULES & OTHER AUTHORITIES
`
`35 U.S.C. § 102 .......................................................................................................... 5
`
`35 U.S.C. § 103 ............................................................................................ 4, 5, 6, 24
`
`35 U.S.C. § 119(e) ............................................................................................. 20, 21
`
`35 U.S.C. § 314(a) ..................................................................................................... 6
`
`37 C.F.R. § 42.100(b) .............................................................................................. 22
`
`M.P.E.P. § 716.03(b)................................................................................................ 17
`
`M.P.E.P. § 2143.01 IV ............................................................................................. 19
`
`
`
`
`
`iv
`
`

`

`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`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-017
`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-017
`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-017
`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-017
`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-017
`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-017
`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-017
`
`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 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 19, 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-017
`‘506 Patent
`under
`different
`theories
`
`bearing
`
`attorney
`
`docket
`
`nos. REDDYPP 7.1R-009 and REDDYPP 7.1R-015.
`
`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-017
`Ground 1. Claims 1, 7, 8, 14, 15, and 20 are obvious over Bikowski
`
`(Exh.1011) in view of the 2000 PERIOSTAT PDR (Exh.1042) and Golub et al.
`
`(Exh.1048). See 35 U.S.C. § 103(a).2
`
`Ground 2. Claims 1, 7, 8, 14, 15, and 20 are obvious over Bikowski
`
`(Exh.1011) and the 2000 PERIOSTAT PDR (Exh.1042). See 35 U.S.C. § 103(a).
`
`Although Petitioner provides multiple grounds of unpatentability, they are
`
`meaningfully distinct from each other and from those made in the corresponding
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`IPR Petitions filed on the same date as this Petition bearing attorney docket
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`nos. REDDYPP 7.1R-009 and REDDYPP 7.1R-015.
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`Grounds 1 and 2 herein are based on the premise that claims 1, 7, 8 and 14
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`of the ‘506 Patent are entitled to a priority date no earlier than April 5, 2002, the
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`filing date of the earliest nonprovisional application in its chain, now U.S. Patent
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`No. 7,211,267 (Exh.1016). The provisional applications from which priority is also
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`claimed on the face of the ‘506 Patent do not disclose a dose range that is some
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`fraction of a 50mg dose ____ that disclosure, which is embodied in independent
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`claims 1 and 8 of the ‘506 Patent was only added when the nonprovisional
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`2 The pre-AIA version of 35 U.S.C. § 103 applies to each ground in this
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`proceeding, because the ‘506 Patent has an effective filing date before March 16,
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`2013.
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`4
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`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`application was filed. Bikowski (Exh.1011) is a printed publication published in
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`August 2000, Vol. 66, No. 2 of CUTIS, Cutaneous Medicine for the Practitioner.
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`The copy of Bikowski in this Petition bears a date stamp from the University of
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`Minnesota Bio-Medical Library of August 18, 2000. Bikowski was listed as of
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`record on the cover of the ‘506 Patent, but was not discussed during its
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`prosecution. As such, Bikowski (Exh.1011) is prior art against claims 1, 7, 8,
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`and 14 pursuant to 35 U.S.C. § 102(b) and against claims 15 and 20 pursuant to 35
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`U.S.C. § 102(a). Even if claims 1, 7, 8 and 14 are accorded the benefit of the
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`provisional applications, Bikowski is still prior art pursuant to 35 U.S.C.
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`§§ 102(a)/103(a) against all of the challenged claims.
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`For Ground 1, Bikowski teaches the oral administration of 50mg of
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`doxycycline to a patient to treat rosacea, including its papules and pustules, and
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`that rosacea is an inflammatory condition. This combined with the knowledge that
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`periodontal disease, known to be another inflammatory condition treatable with
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`doxycycline, and which was successfully treated by PERIOSTAT, a 40mg/day
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`doxycycline product of Patent Owner, renders the claims obvious.
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`Ground 2 starts with the premise that by April 5, 2001: (1) it was known to
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`treat rosacea with doxycycline (Exh.1004 ¶ 31, 32; 1011)); (2) it was known that
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`the papules and pustules of rosacea were not bacterial, but more inflammatory
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`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`conditions (Exh.1004 ¶ 33, 1011); and (3) it was known that doxycycline was an
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`effective anti-inflammatory agent at the claimed doses (Exhs.1004 ¶ 42, 1042,
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`1048), that is, doses below those allegedly considered to have an antibiotic effect.
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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
`It was known to treat rosacea with doxycycline. (Exhs.1011, at 149-50; 1004
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`¶¶ 31, 32.) Historically, tetracyclines, including doxycycline, were administered to
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`treat rosacea, albeit at what the Patent Owner alleges to be “antibiotic doses.”
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`(Exhs.1004 ¶¶ 28, 29, 31; 1001 col.5 ll.43-45; 1048.) However, as of the
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`‘506 Patent’s earliest asserted effective filing date (April 5, 2001), doxycycline had
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`already been successfully used to treat rosacea at doses as little as 50mg daily and
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`50mg every other day, which, given that doxycycline’s half-life is 18 hours, the
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`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`expected dose at the end of one day would be less than half of the initial does
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`given. (Exhs.1011, at 149; 1042, at 945; 1004 ¶ 32). Rosacea was known by
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`April 5, 2001, to be an inflammatory condition, not bacterial. (Id.; see also
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`Exh.1004 ¶ 33, 1048.) And, it was known that doxycycline’s success in treating the
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`papules and pustules of rosacea was attributed to its anti-inflammatory properties,
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`not its antibiotic properties. (Exh.1004 ¶ 37, 40; 1048)
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`In treating rosacea, there was no medical necessity for using an antibiotic
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`amount of an antibiotic drug if less was needed to take advantage of its
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`anti-inflammatory properties. (Exh.1004 ¶¶ 40, 42, 43, 44, 45, 58.) This strongly
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`suggests using a lower dose of an antibiotic in treating rosacea. (Id.) But there were
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`several other readily apparent advantages that would motivate one to try giving an
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`allegedly sub-antibiotic dose of an antibiotic with anti-inflammatory properties,
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`such as doxycycline (itself already known to successfully treat rosacea). These
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`included possible reduced drug cost, smaller dosage forms, and reduced potential
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`exposure to antibiotic level side effects and reducing the prospect of creating drug
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`resistant bacteria, all of which were well known. (Id. ¶¶ 46, 47, 48; Exh.1048.)
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`Indeed, there would have been nothing to dissuade a dermatologist from trying
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`lower doses, where, as here,
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`the condition being
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`treated
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`is not
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`life
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`threatening ____ they were skin blemishes. (Exh.1004 ¶ 50.) If lower doses were not
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`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`effective, doctors could always prescribe a higher dose. (Id.) In the meantime,
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`unlike when treating an infection, there would be little or no therapeutic downside
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`to starting with a lower dose ____ only, at worst, a slight delay in clearing up the
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`symptoms. (Exh.1004 ¶¶ 50-53.)
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`It was also known at the time of the earliest asserted effective filing date that
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`using 40mg/day of doxycycline successfully treated another chronic inflammatory
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`condition, periodontal disease, whose underlying inflammatory pathways were
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`known to be similar to those found in the papules and pustules of rosacea.
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`(Exhs.1048, 1004 ¶ 39.) And a commercial product used for that exact treatment,
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`PERIOSTAT, made that dose readily available. (Exhs.1042, 1053.)
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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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`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`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. (Exh.1004 ¶ 25.) Furthermore, a dermatologist may
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`prescribe an FDA-approved medication for any use. (Id.) Thus, prescribing
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`PERIOSTAT treatment for papules and pustules of rosacea was well within the
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`skill of any dermatologist. (Id. ¶ 59-60.) Indeed, there is evidence that, before the
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`‘506 Patent, dermatologists were already using PERIOSTAT “off
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`label.”
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`(Exh.10153, at 2 (“Periostat was approved by the FDA in 1998, and it could
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`currently be used for its anti-inflammatory benefits with excellent results . . . .”);
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`Exh.1004 ¶ 27.)
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`Accordingly, in view of these combined teachings, it would have been
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`obvious to reduce the 50mg daily dose of doxycycline taught in Bikowski , which
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`was already a significant decrease from historical dosage levels, to 40mg/day (as
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`claimed). (Exhs.1011; 1042; 1004 ¶¶ 42-45, 53, 59, 60.) This is an even more
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`obvious step when taking into account that Bikowski reported that a maintenance
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`level of doxycycline could be as low as 50mg every other day, which taking into
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`considering doxycycline’s half-life is 18 hours, would be less than half of the
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`3 Exhibit 1015 is not prior art for purposes of this IPR.
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`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDYPP 7.1R-017
`initial dose given by the end of one day. (Exh.1004 ¶ 32.) All of the treatments in
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`question were done without a bisphosphonate (as claimed). Finally, if, as the
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`challenged claims allege, treating a patient with 40mg/day of doxycycline does not
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`reduce skin microflora after six months of treatment, then that would have been the
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`inherent result of using the recommended dosage of prior art PERIOSTAT.
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`(Exh.1004 ¶ 62.) In light of these teachings, claims 1, 7, 8, 9, 15, and 20 of the
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`‘506 Patent are therefore unpatentable.
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`II. THE CLAIMS UNDER CONSIDERATION
`1.
`A method for treating papules and pustules of rosacea in a human
`in need thereof, the method comprising administering orally to said human
`doxycycline, or a pharmaceutically acceptable salt thereof, in an amount that
`(i) is effective to treat the papules and pustules of rosacea; (ii) is 10-80% of a
`50 mg dose of doxycycline per day; and (iii) results in no reduction of skin
`microflora during a six-month
`treatment, without administering a
`bisphosphonate compound.
`7.
`The method according to claim 1, wherein said doxycycline, or a
`pharmaceutically acceptable salt thereof, is administered in an amount which
`provides a serum concentration in the range of about 0.1 to about 0.8 µg/ml.
`8.
`A method for treating papules and pustules of rosacea in a human
`in need thereof, the method comprising administering orally to said human
`doxycycline, or a pharmaceutically acceptable salt thereof, in an amount that
`(i) is effective to treat the papules and pustules of rosacea; (ii) is 40-80% of a
`50 mg dose of doxycycline per day; and (iii) results in no reduction of skin
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`Case