Filed: March 3, 2015
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`————————————————
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`————————————————
`
`MYLAN PHARMACEUTICALS INC.
`Petitioner,
`
`v.
`
`YEDA RESEARCH & DEVELOPMENT CO. LTD.
`Patent Owner.
`
`————————————————
`Case IPR2015-00644
`Patent No. 8,399,413
`————————————————
`
`CORRECTED PETITION FOR INTER PARTES REVIEW
`
`

`
`
`
`TABLE OF CONTENTS
`INTRODUCTION ........................................................................................... 1
`I.
`II. MANDATORY NOTICES ............................................................................. 2
`A.
`Real Parties-In-Interest (37 C.F.R. § 42.8(b)(1)) .................................. 2
`B.
`Related Matters (37 C.F.R. § 42.8(b)(2)) .............................................. 2
`C.
`Identification of Counsel (37 C.F.R. § 42.8(b)(3)) and Service
`Information (37 C.F.R. § 42.8(b)(4)) .................................................... 3
`Service Information (37 C.F.R. § 42.8(b)(4)) ....................................... 3
`D.
`III. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT ......... 3
`IV.
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED .................................................................. 4
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ............... 5
`V.
`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED ............... 5
`A.
`Summary of the Argument .................................................................... 5
`B.
`Background of the ’413 Patent .............................................................. 7
`1.
`The ’413 Patent ........................................................................... 7
`2.
`The Prosecution of the ’413 Patent ........................................... 10
`Level of Ordinary Skill in the Art ....................................................... 12
`Claim Construction ............................................................................. 12
`Patents and Printed Publications Relied On In This Petition .............. 15
`1.
`Pinchasi (Ex. 1005) ................................................................... 15
`2.
`1996 FDA SBOA (Ex. 1007A) ................................................. 16
`3.
`Flechter 2002A (Ex. 1008) ....................................................... 18
`4.
`Prior Art Informing the General Knowledge of the
`Ordinarily-Skilled Artisan ........................................................ 20
`Ground 1: Claims 1-6 and 8-20 Are Anticipated by Pinchasi. ........... 20
`1.
`Independent Claim 1 Is Anticipated by Pinchasi. ..................... 20
`2.
`Independent Claim 19 Is Anticipated by Pinchasi. ................... 24
`3.
`Independent Claim 20 Is Anticipated by Pinchasi. ................... 25
`4.
`Dependent Claims 2-6 and 8-15 Are Anticipated by
`Pinchasi. .................................................................................... 26
`
`C.
`D.
`E.
`
`F.
`
`
`
`i
`
`

`
`a.
`
`b.
`
`c.
`
`d.
`
`e.
`
`f.
`
`b.
`
`Pinchasi expressly disclosed the further limitations
`of claims 2-3 and 8. ........................................................ 26
`Pinchasi expressly discloses the further limitations
`of claims 5 and 12-13. .................................................... 28
`Pinchasi expressly disclosed the further limitations
`of claim 6. ....................................................................... 28
`Pinchasi expressly discloses the further limitations
`of claim 14-15. ................................................................ 29
`Pinchasi discloses every limitation of dependent
`claims 16-18. ................................................................... 30
`Pinchasi discloses every limitation of dependent
`claims 4 and 9-11 ............................................................ 32
`Summary of Petitioner’s Obviousness Positions. ............................... 34
`1.
`The Law of Obviousness .......................................................... 34
`2.
`The Prior Art Renders the Claims Obvious .............................. 37
`a.
`Investigation into Different Dosing Protocols for
`GA Therapy .................................................................... 37
`The Prior Art Motivated a Person of Ordinary Skill
`to Investigate Different Dosing Protocols and
`Provided A Reasonable Expectation of Success ............ 40
`H. Ground 2: Claims 1-20 Are Unpatentable As Obvious over
`Pinchasi. .............................................................................................. 45
`1.
`Independent Claims 1, 19 and 20 Are Obvious over
`Pinchasi. .................................................................................... 45
`a.
`Dependent claim 7 is Obvious in View of Pinchasi. ...... 49
`Dependent Claims 2-6 and 8-18 Are Obvious in View of
`Pinchasi. .................................................................................... 50
`Ground 3: Claims 1-20 Are Unpatentable As Obvious over
`Pinchasi and the 1996 SBOA. ............................................................. 51
`1.
`Independent Claims 1, 19 and 20 Are Obvious over
`Pinchasi in view of the 1996 FDA SBOA. ............................... 51
`Dependent Claims 2-18 Are Obvious over Pinchasi and
`the 1996 SBOA. ........................................................................ 54
`
`G.
`
`I.
`
`2.
`
`2.
`
`
`
`ii
`
`

`
`Ground 4: Claims 1-20 Are Unpatentable As Obvious over
`Pinchasi and Flechter 2002A. .............................................................. 55
`1.
`Independent Claims 1, 15, and 19 Are Obvious in View
`of Pinchasi and Flechter 2002A. ............................................... 55
`Dependent Claims 2-18 Are Obvious over Pinchasi and
`Flechter 2002A. ......................................................................... 56
`K. Any Secondary Considerations Fail to Overcome the Showing
`of Obviousness. ................................................................................... 56
`1.
`The Methods Recited in the ’413 Patent Produced No
`Relevant Unexpected Results. .................................................. 56
`The ’413 Patent Satisfied No Long-Felt But Unmet Need. ...... 57
`Copying By Generic Drug Makers Is Irrelevant. ...................... 58
`
`
`2.
`
`2.
`3.
`
`J.
`
`
`
`
`
`iii
`
`

`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`CASES
`Baldwin Graphic Sys., Inc. v. Siebert, Inc.,
`512 F.3d 1338 (Fed. Cir. 2008) ..................................................................... 15
`
`Bayer Healthcare Pharms., Inc. v. Watson Pharms., Inc.,
`713 F.3d 1369 (Fed. Cir. 2013) ..................................................................... 58
`
`Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014) ....................................................................... 57
`
`Galderma Labs. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) ....................................................................... 58
`
`Gillette Co. v. Energizer Holdings Inc.,
`405 F.3d 1367 (Fed. Cir. 2005) ................................................... 13, 14, 15, 23
`
`Graham v. John Deere Co. of Kan. City,
`383 U.S. 1 (1966) ........................................................................................... 34
`
`Hoffmann-La Roche Inc. v. Apotex Inc.,
`748 F.3d 1326 (Fed. Cir. 2014) ............................................................... 37, 57
`
`In re Baxter Travenol Labs.,
`952 F.2d 388 (Fed. Cir. 1991) ................................................................. 29, 33
`
`In re Cronyn,
`890 F.2d 1158 (Fed. Cir. 1989) ..................................................................... 18
`
`In re Cuozzo Speed Techs., LLC, No. 2014-31,
`Slip opinion (Fed. Cir. Feb. 4, 2015) ............................................................. 13
`
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) ......................................................... 33, 34, 37
`
`In re Lister,
`583 F.3d 1307 (Fed. Cir. 2009) ..................................................................... 17
`
`In re PepperBall Techs., Inc.,
`469 F. App’x 878 (Fed. Cir. 2012) ................................................................ 58
`iv
`
`
`
`

`
`In re Petering,
`301 F.2d 676 (CCPA 1962) ........................................................................... 29
`
`Invitrogen Corp. v. Biocrest Mfg., L.P.,
`327 F.3d 1364 (Fed. Cir. 2003) ............................................................... 13, 23
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007)................................................................................. 34, 35
`
`Medichem, S.A. v. Rolabo, S.L.,
`353 F.3d 928 (Fed. Cir. 2003) ....................................................................... 13
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ..................................................................... 56
`
`Warner Chilcott Co. v. Teva Pharms. USA, Inc., Nos. 2014-1439,
`1441, 1444-46, 2014 WL 6435042
`(Fed. Circ. Nov. 18, 2014) ................................................................. 35, 36, 37
`
`STATUTES
`
`35 U.S.C. § 103(a) ................................................................................................... 34
`
`35 U.S.C. § 314(a) ..................................................................................................... 5
`
`RULES
`
`37 C.F.R. § 42.100(b) .............................................................................................. 13
`
`MPEP 2111.03 ................................................................................................... 13, 14
`
`MPEP 2131.01(II) .................................................................................................... 29
`
`
`
`
`
`
`
`v
`
`

`
`LIST OF EXHIBITS
`
`Exhibit No.
`
`Description
`
`1001
`
`1002
`
`1003
`
`1003A
`
`1003B
`
`1004
`
`1004A
`
`1004B
`
`1005
`
`1006
`
`1007
`
`1007A
`
`1008
`
`
`
`U.S. Patent No. 8,399,413, Low Frequency Glatiramer
`Acetate Therapy (filed Aug. 19, 2010) (issued May 19,
`2013)
`
`File History for U.S. Patent No. 8,399,413
`
`Declaration of Stephen J. Peroutka, M.D., Ph.D.
`
`Curriculum Vitae of Stephen J. Peroutka, M.D., Ph.D.
`
`Materials Reviewed by Stephen J. Peroutka, M.D., Ph.D.
`
`Expert Declaration of Ari Green, M.D.
`
`Curriculum Vitae of Ari Green, M.D.
`
`Materials Reviewed by Ari Green, M.D.
`
`Irit Pinchasi: International Publication No. WO
`2007/081975 (published July 19, 2007)
`
`J.A. Cohen et al., Randomized, double-blind, dose-
`comparison study of glatiramer acetate in relapsing-
`remitting MS, 68:12 NEUROLOGY, 939-44 (2007)
`
`Affidavit of Marlene S. Bobka dated December 9, 2014
`
`John J. Jessop, Review and Evaluation of Pharmacology
`Toxicology Data Original NDA Review (1996) (the 1996
`FDA SBOA) (attached as Exhibit A to Exh. 1007)
`
`Shlomo Flechter et al., Copolymer 1 (Glatiramer Acetate)
`in Relapsing Forms of Multiple Sclerosis: Open Multicenter
`Study of Alternate-Day Administration. 25:1 CLINICAL
`NEUROPHARMACOLOGY, 11-15 (2002) (Flechter 2002A)
`
`vi
`
`

`
`Exhibit No.
`
`Description
`
`Zeev Meiner et al., Copolymer 1 in relapsing-remitting
`multiple sclerosis: a multi-centre trial, in FRONTIERS IN
`MULTIPLE SCLEROSIS: CLINICAL RESEARCH AND THERAPY
`(Oded Abramsky and Haim Ovadia, eds., 1997)
`
`Omar Khan et al., Randomized, prospective, rater-blinded,
`four-year, pilot study to compare the effect of daily versus
`every-other-day glatiramer acetate 20 mg subcutaneous
`injections in relapsing-remitting multiple sclerosis, 14
`MULTIPLE SCLEROSIS, S296 (2008)
`
`Christina Caon et al., Randomized, Prospective, Rater-
`Blinded, Four Year Pilot Study to Compare the Effect of
`Daily Versus Every Other Day Glatiramer Acetate 20 mg
`Subcutaneous Injections in RRMS, 72:11(3) NEUROLOGY,
`A317 (2009)
`
`Shlomo Flechter et al., Comparison of glatiramer acetate
`(Copaxone) and interferon β-1b (Betaferon) in multiple
`sclerosis patients: an open-label 2-year follow up, 197
`JOURNAL OF THE NEUROLOGICAL SCIENCES, 51-55 (2002).
`(“Flechter 2002B”)
`
`James R Miller, The importance of early diagnosis of
`multiple sclerosis, 10(3) (Suppl. S-b) J. MANAG. CARE
`PHARM., S4-11 (2004)
`
`M.B. Bornstein, Multiple Sclerosis: Trial of a Synthetic
`Polypeptide, 11:3 ANNALS OF NEUROLOGY, 317-19 (1982)
`
`M.B. Bornstein et al., Clinical Trial of Copolymer I in
`Multiple Sclerosis, 436 ANNALS NEW YORK ACADEMY OF
`SCIENCES, 366-372 (1984)
`
`M.B. Bornstein et al., A Pilot Trial of COP 1 in
`Exacerbating-Remitting Multiple Sclerosis, 317:7 THE NEW
`ENGLAND JOURNAL OF MEDICINE, 408-14 (1987)
`
`vii
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`
`
`

`
`Exhibit No.
`
`Description
`
`1017
`
`1018
`
`1019
`
`1019A
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`
`
`FDA, GUIDELINE FOR INDUSTRY: Dose-Response
`Information to Support Drug Registration (1994)
`
`K.P. Johnson, et al., Copolymer 1 reduces relapse rate and
`improves disability in relapsing-remitting multiple
`sclerosis, 43 NEUROLOGY, 1268-1276 (1995)
`
`Affidavit of Marlene S. Bobka dated January 5, 2015
`
`1996 FDA Meeting Agenda minutes from the Peripheral
`and Central Nervous System Drug Advisory Committee
`(dated September 19, 1996) (Exhibit A to Exhibit 1019)
`Ruth Arnon, The development of Cop 1(Copaxone®), an
`innovative drug for the treatment of multiple sclerosis:
`personal reflections, 50 IMMUNOLOGY LETTERS 1-15 (1996)
`
`Leslie Z. Benet et al., Pharmacokinetics: The Dynamics of
`Drug Absorption, Distribution, and Elimination, in THE
`PHARMACOLOGICAL BASIS OF THERAPEUTICS, 3 (Alfred
`Goodman Gilman ed. 1996)
`
`E. Lobel, et al., Copolymer-1, 21(2) DRUGS OF THE FUTURE,
`131-134 (1996)
`
`Haines et al., Linkage of the MHC to familial multiple
`sclerosis suggests genetic heterogeneity. The multiple
`sclerosis genetics group, HUM. MOL. GENET. 7:1229-34
`(Aug 1998)
`
`U.S. Patent No. 6,342,476, Copolymer-1 Improvements in
`Compositions of Copolymers (2002).
`
`Y. Ge et al., Glatiramer acetate (Copaxone) treatment in
`relapsing-remitting MS: Quantitative MR assessment, 54
`NEUROLOGY, 813-17 (2000)
`
`viii
`
`

`
`Exhibit No.
`
`Description
`
`Giancarlo Comi et al., European/Canadian multicenter,
`double-blind, randomized, placebo-controlled study of the
`effects of glatiramer acetate on magnetic resonance
`imaging-measured disease activity and burden in patients
`with relapsing multiple sclerosis: European/Canadian
`Glatiramer Acetate Study Group, 49:3 ANN. NEUROL., 290-
`97 (2001)
`
`Boissel and Nony, Using pharmacokinetic-
`pharmacodynamic relationships to predict the effect of poor
`compliance, CLIN. PHARMACOL. 41:1-6 (2002)
`
`McBride, INT’L J. MS CARE 4:85 (2002)
`
`Dene Simpson, Adis Drug Evaluation Glatiramer Acetate –
`A Review of its use in Relapsing-Remitting Multiple
`Sclerosis, 16:12 CNS DRUGS, 825-50, 834 (2002)
`
`Catherine M. Edgar, et al., Lipoatrophy in Patients with
`Multiple Sclerosis on Glatiramer Acetate, 31 CAN. J.
`NEUROL. SCI., 58-63 (2004)
`
`Rich et al., Stepped-care approach to treating MS: A
`managed care treatment algorithm, J. MANAGED CARE
`PHARM. 10:S26-S32 (June 2004)
`
`Stuart, Clinical management of multiple sclerosis: The
`treatment paradigm and issues of patient management, J.
`MANAGED CARE PHARMACY 10:S19-S25 (June 2004)
`
`Rohit Bakshi et al., Imaging of Multiple Sclerosis: Role in
`Neurotherapeutics, 2(2) NEURORX, 277–303 (2005)
`
`Paul Beringer et al., Clinical Pharmacokinetics and
`Pharmacodynamics, in REMINGTON: THE SCIENCE AND
`PRACTICE OF PHARMACY, 1191-1205, 1197, 1201 (Paul
`Beringer ed., 2005)
`
`ix
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`
`
`

`
`Exhibit No.
`
`Description
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`
`
`Michael Franklin et al., Drug Absorption, Action, and
`Disposition, in REMINGTON: THE SCIENCE AND PRACTICE OF
`PHARMACY, 1142-1170, 1167 (Paul Beringer ed., 2005)
`
`James Rasmussen: International Patent Publication No. WO
`2005/120542 A2 (published December 22, 2005)
`
`Devonshire et al., The Global Adherence Project – A
`multicentre observational study on adherence to disease-
`modifying therapies in patients suffering from relapsing-
`remitting multiple sclerosis, MULTIPLE SCLEROSIS 12:S1
`(P316) (2006)
`
`C.C. Ford et al., A prospective open-label study of
`glatiramer acetate: over a decade of continuous use in
`multiple sclerosis patients, 12 MULTIPLE SCLEROSIS, 309-
`320 (2006)
`
`Frohman, Multiple Sclerosis – The Plaque and its
`Pathogenesis, NEW ENGLAND J. MED. 354:942-55 (2006)
`
`J.J. Kragt et al., How similar are commonly combined
`criteria for EDSS progression in multiple sclerosis?, 12(6)
`MULTIPLE SCLEROSIS782-786 (2006)
`
`Peter J. Manso et al., Life cycle management of ageing
`pharmaceutical assets, 3:7 PHARMACEUTICAL LAW INSIGHT,
`(2006)
`
`Soares et al., Localized panniculitis secondary to
`subcutaneous glatiramer acetate injections for the
`treatment of multiple sclerosis: a clinicopathologic and
`immunohistochemical study, J. AM. ACAD. DERM. 55:968-
`74 (2006)
`
`Klauer and Zettl, Compliance, adherence and the treatment
`of multiple sclerosis, J. NEUROL. 255 [Suppl. 6]:87-92
`(2008)
`
`x
`
`

`
`Exhibit No.
`
`Description
`
`Pelidou et al., Multiple sclerosis presented as clinically
`isolated syndrome: the need for early diagnosis and
`treatment, THER. CLIN. RISK MANAGEMENT 4:627-30 (June
`2008)
`
`Tjalf Ziemssen et al., Effects of glatiramer acetate on
`fatigue and days of absence from work in first-time treated
`relapsing-remitting multiple sclerosis, 6 HEALTH AND
`QUALITY OF LIFE OUTCOMES 67 (2008)
`
`Teva Provides Update on Forte Trial Jerusalem, Israel
`(July 7, 2008)
`Copaxone® U.S. Product Label (2001)
`Betaseron® U.S. Product Label (2003)
`Rebif® U.S. Product Label (2003)
`Avonex® Product Label (2006)
`Tysabri® Product Label (2008)
`Copaxone® U.S. Product Label (Feb. 2009)
`Extavia® Product Label (2009)
`
`Jacobs et al., Intramuscular interferon beta-1a therapy
`initiated during a first demyelinating event in multiple
`sclerosis, NEW ENGL. J. MED 343:898-904 (2000)
`(“Jacobs”)
`
`Stedman’s Medical Dictionary for Health Professionals
`(2008)
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`U.S. Patent Publication No. 2009/0149541A1 (filed Nov.
`26, 2008)
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`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`1049
`
`1050
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`
`
`

`
`Exhibit No.
`
`Description
`
`Concepts in clinical pharmacokinetics, in INTRODUCTION TO
`PHARMACOKINETICS AND PHARMACODYNAMICS, Tozer and
`Rowland eds (Lippincott Williams & Wilkins 2006)
`
`M. Tintore et al., Baseline MRI predicts future attacks and
`disability in clinically isolated syndromes, 67 NEUROLOGY
`968-972, (2006).
`
`FDA GUIDANCE FOR INDUSTRY - POPULATION
`PHARMACOKINETICS (1999)
`
`REBIF® Product Label (June 2005)
`
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexcl
`new.cfm?Appl_No=020622&Product_No=003&table1=OB
`_Rx (accessed February 5, 2015)
`
`https://scamparoo.wordpress.com/2008/04/11/ms-therapies-
`copaxone/ (dated April 11, 2008 (accessed February 5,
`2015))
`
`
`
`xii
`
`1057
`
`1058
`
`1059
`
`1060
`
`1061
`
`1062
`
`
`
`
`
`

`
`INTRODUCTION
`
`
`
`I.
`
`Pursuant
`
`to 35 U.S.C. §§ 311-319 and 37 C.F.R. § 42, Mylan
`
`Pharmaceuticals Inc. (“Petitioner”) petitions for Inter Partes Review (“IPR”) of
`
`claims 1 through 20 of U.S. Patent No. 8,399,413 to Klinger, titled “Low
`
`Frequency Glatiramer Acetate Therapy” (“the ’413 patent,” Ex. 1001).
`
`Concurrently filed herewith is a Power of Attorney pursuant to 37 C.F.R
`
`§ 42.10(b). Pursuant to 37 C.F.R. § 42.103, the fee set forth in § 42.15(a)
`
`accompanies this Petition.
`
`This Petition demonstrates that a preponderance of the evidence shows a
`
`reasonable likelihood that claims 1-20 of the ’413 patent are unpatentable over the
`
`prior art. Specifically, Teva, the commercial partner of Yeda for Copaxone®, in
`
`2007 disclosed to the public in a published patent application to Irit Pinchasi (Ex.
`
`1005) the claimed subject matter more than one year before Yeda filed its patent
`
`application that led to the ’413 patent. This disclosure anticipates claims 1-6 and
`
`8-20 and rendered all the claims obvious to a person having ordinary skill in the art
`
`(“POSA”) as of the priority date. All of the ’413 patent’s claims are alternatively
`
`obvious over Pinchasi in view of either of two additional prior art publications: the
`
`published Summary Basis of Approval for 20 mg Copaxone® (Ex. 1007A) or a
`
`2002 article by Flechter, et al. (Ex. 1008).
`
`
`
`1
`
`

`
`II. MANDATORY NOTICES
`A. Real Parties-In-Interest (37 C.F.R. § 42.8(b)(1))
`The real parties-in-interest for Petitioner are Mylan Pharmaceuticals Inc.,
`
`Mylan Inc. and Mylan Teoranta.
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2))
`Petitioner is not aware of any reexamination certificates or pending
`
`prosecution concerning the ’413 patent. Petitioner is a defendant to the following
`
`litigations involving the ’413 patent: Teva Pharms. USA, Inc. v. Mylan Pharms.
`
`Inc., 14-01278 (D. Del. Oct. 6, 2014); Teva Pharms. USA, Inc. v. Mylan Pharms.
`
`Inc., 14-00167 (N.D. W. Va. Oct. 7, 2014). Other pending litigations involving the
`
`’413 patent include Teva Pharms. USA, Inc. v. Sandoz, Inc, No. 14-cv-01171 (D.
`
`Del. Sept. 10, 2014); Teva Pharms. USA, Inc. v. Dr. Reddy’s Labs., No. 14-cv-
`
`01172 (D. Del. Sept. 10, 2014); Teva Pharms. USA, Inc. v. Dr. Reddy’s Labs., No.
`
`14-cv-05672 (D.N.J. Sept. 11, 2014); Teva Pharms. USA, Inc. v. Synthon Pharms.
`
`Inc., No. 14-cv-01419 (D. Del. Nov. 18, 2014); Teva Pharms. USA, Inc. v. Synthon
`
`Pharms., No. 14-cv-00975 (M.D.N.C. Nov. 19, 2014); and Teva Pharms. USA,
`
`Inc. v. Amneal Pharms., LLC., No. 15-cv-00124 (D. Del. Feb. 3, 2015)
`
`A patent application in the same patent family is pending as U.S. Patent
`
`Application No. 13/770,677.
`
`
`
`
`
`2
`
`

`
`C.
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3)) and Service
`Information (37 C.F.R. § 42.8(b)(4))
`
`Lead Counsel
`Jeffrey W. Guise (Reg. No. 34,613)
`
`Back Up Counsel
`Brandon M. White (Reg. No. 52,354)
`
`Wilson Sonsini Goodrich & Rosati
`
`PERKINS COIE LLP
`
`650 Page Mill Road
`
`700 13th St., NW, Suite 600
`
`Palo Alto, CA 94304
`
`Washington, DC 20005
`
`jguise@wsgr.com
`
`Tel: (858) 350-2307
`
`Fax: (858) 350-2399
`
`BMWhite@PerkinsCoie.com
`
`Tel: (202) 654-6206
`
`Fax: (202) 654-9681
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`Service Information (37 C.F.R. § 42.8(b)(4))
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`D.
`Please direct all correspondence to lead counsel and back-up counsel at the
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`contact information above. Petitioner consents to service by electronic mail at
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`jguise@wsgr.com and bmwhite@perkinscoie.com.
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`III. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT
`As required by 37 C.F.R. § 42.104(a), Petitioner certifies that the ’413 patent
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`is available for inter partes review and that the Petitioner is not barred or estopped
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`from requesting inter partes review on the grounds identified herein.
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`IV.
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`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED
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`Petitioner requests inter partes review and cancellation of claims 1-20 of the
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`’413 patent under 35 U.S.C. §§ 102 and 103, as set forth herein. The ’413 patent is
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`to be reviewed under pre-AIA §§ 102 and 103. Petitioner’s detailed statement of
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`the reasons for the relief requested is set forth below in the section titled
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`“Statement of Reasons for Relief Requested.” In accordance with 37 C.F.R.
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`§ 42.6(c), copies of the exhibits are filed herewith. In addition, this Petition is
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`accompanied by the Declaration of Stephen J. Peroutka, M.D., Ph.D. (Ex. 1003)
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`and the Declaration of Ari Green, M.D. (Ex. 1004).
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`The challenged claims of the ’413 patent are generally directed to methods
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`of alleviating symptoms of relapsing–remitting multiple sclerosis by administering
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`at least “three subcutaneous injections of 1 ml of a pharmaceutical composition
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`comprising 40 mg dose of glatiramer acetate over a period of seven days with at
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`least one day between every subcutaneous injection.” Claims 1-20 of the ’413
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`patent are unpatentable based on the following grounds:
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`Ground 1: Claims 1-6 and 8-20 are anticipated by Pinchasi.
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`Ground 2: Claims 1-20 are obvious over Pinchasi.
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`Ground 3: Claims 1-20 are obvious over Pinchasi in view of the 1996 FDA
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`SBOA.
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`Ground 4: Claims 1-20 are obvious over Pinchasi in view of Flechter
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`2002A.
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`V. 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 this threshold. As
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`explained below, there is a reasonable likelihood that Petitioner will prevail with
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`respect to at least one of the challenged claims.
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`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED
`A.
`Summary of the Argument
`Glatiramer acetate (“GA”) was first patented in 1974 as copolymer-1, U.S.
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`Patent No. 3,849,550 (“the ’550 patent”). Ex. 1003 at ¶ 43. In the 1980s, Yeda
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`partnered with Teva to develop GA commercially and seek FDA approval to
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`market it, as Copaxone®, to treat Multiple Sclerosis (“MS”). The FDA first
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`approved Copaxone® for use in treating MS in the U.S. in 1996. Id. In 1996 the
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`FDA approved Copaxone® in a dosing regimen of 20 mg daily administered by
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`subcutaneous (“SC”) injection. In the 1990s, following the expiration of the ’550
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`patent and in preparation for the U.S. launch of 20 mg Copaxone®, Teva sought
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`additional U.S. patent protection and received patents on the GA compound and on
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`methods of making and using it. In 2013, with the last of the patents covering
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`Teva’s 20 mg daily dosage form ready to expire, Teva sought FDA approval of a
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`40 mg, three times per week Copaxone® and upon approval, began to switch
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`patients from the old, 20 mg daily product to its “new,” 40 mg three times per
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`week Copaxone®.
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`One of the patents that is alleged by Teva to cover its 40 mg dosage form is
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`the ’413 patent. The ’413 patent is generally directed to “low frequency glatiramer
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`acetate therapy” and describes a method of reducing the frequency of relapses in
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`patients suffering from MS. Ex. 1001, Title, Abstract. In general, the claims of the
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`’413 patent recite an open-ended method comprising administration of 40 mg of
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`GA SC at least three times in a 7-day period with at least one day between each
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`injection to treat MS. Ex. 1001 at col. 16, l. 26 - col. 18, l. 28. All claims,
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`however, describe an MS treatment regimen that was already known in, or obvious
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`in view of, the prior art.
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`Before the earliest possible priority date (August 20, 2009), various GA
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`dosages and injection frequencies were tested and known. As explained in detail
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`below, a 2007 Teva patent application to Pinchasi (Ex. 1005) taught the
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`administration of a 40 mg dosage of GA every other day, anticipating claims 1-6
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`and 8-20 of the ’413 patent under the claims’ broadest reasonable construction.
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`Moreover, all of the claims are obvious in light of the prior art, including
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`Pinchasi and others. A number of prior art references taught administering GA
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`every other day for inter alia improved patient compliance and adherence. See,
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`e.g., Ex. 1004 at ¶¶ 54-59; see also Ex. 1003 at ¶¶ 22-23, 54-62, 65-75. The prior
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`art also disclosed that no additional adverse side effects are associated with
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`administering 40 mg of GA per dose, as compared to 20 mg of GA per dose as had
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`been previously administered. Ex. 1004 at ¶ 99 (citing Ex. 1005 at p. 19, ll. 8-14);
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`Ex. 1003 at ¶ 105 (citing Ex. 1005 at p. 19, ll. 11-15). And so, in light of Pinchasi
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`alone, or in combination with other references detailed below, the claims of the
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`’413 patent were obvious at the time of the alleged invention.
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`B.
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`Background of the ’413 Patent
`1.
`The ‘413 patent was filed on August 19, 2010 and claimed priority to two
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`The ’413 Patent
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`early provisional applications. This application is the earliest filed non-provisional
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`patent application in the family. The ’413 patent names Ety Klinger as inventor
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`and Yeda Research & Development Co., Ltd. as assignee. The ’413 patent’s
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`earliest possible priority date is August 20, 2009.
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`The ’413 patent issued with 20 claims. Claims 1, 19 and 20 are independent
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`claims. Independent claim 1 relates to “[a] method of reducing the frequency of
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`relapses” in certain patients suffering from MS. Ex. 1001 at col. 16, ll. 26-36. The
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`claimed method includes the step of “administering to the human patient a
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`therapeutically effective dosage regimen of three subcutaneous injections of 1 ml
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`of a pharmaceutical composition comprising 40 mg of [GA] over a period of seven
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`days with at least one day between every subcutaneous injection.” Id.
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`Independent claims 19 and 20 recite a similar method and include additional
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`limitations directed to the pH of the GA formulation and that the GA is in a
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`prefilled syringe. Id. at col. 18, ll. 1-28. As each independent claim employs the
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`open-ended transition “comprising,” the claims are not limited to only three SC
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`injections per 7-day period. Instead, the claim recitations after the transition serve
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`only to set the floor for the number of injections administered each 7-day period
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`and a minimum time period between such injections.
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`The dependent claims recite the specific symptom alleged to be “reduced”
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`by the claimed method (claims 2-4, 8-11), that the method employs a pre-filled
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`syringe, just like prior art Copaxone® (claims 5 and 12-13), the method’s
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`relationship to certain side effects (claim 7) and characteristics of the patient
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`(claims 6 and 14-18).
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`The patent’s specification acknowledges that treating MS patients with GA
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`is not new. Ex. 1001 at col. 2, ll. 12-42. GA had been known for years to be a safe
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`and effective treatment for MS and had been FDA approved as a 20 mg daily
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`injection therapy for MS patients since 1996. Id. While the patent acknowledges
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`prior art Copaxone®, it fails to acknowledge the extensive body of prior art related
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`to alternate dosages and dosing regimens for treating MS with GA. See, e.g., Exs.
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`1005, 1006, 1007A, 1008, 1010, 1011. Much of this highly relevant prior art is
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`authored by Yeda or its commercial partner, Teva, or those working on their
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`behalf.
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`The patent includes one prophetic example (Ex. 1001 at col. 8, l. 50 - col.
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`15, l. 52), but does not provide any actual in vitro or in vivo data or data from a
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`concluded human clinical trial to show safety or efficacy of the claimed method or
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`its purported improvement in tolerability or reduction in side effects. No
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`unexpected results are alleged in the patent. The patent does not suggest that the
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`claimed methods are more efficacious than prior art methods, including daily
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`administration of 20 mg Copaxone®. Instead, the patent states only that
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`“[t]reatment with 40 mg s.c. GA three times weekly is at least as effective as 20
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`mg s.c. GA daily administration” for various clinical endpoints. See, e.g., Ex. 1001
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`at col. 13, l. 36 – col. 15, l. 40. While the patent generally alleges that “due to the
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`complex pharmacokinetic behavior of a drug, variation in the frequency of
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`administration is unpredictable and requires empirical testing,” no such empirical
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`testing is included in the patent. Instead, the patent cites an article addressing the
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`unrelated interferon class of drugs without correlating the stated proposition or the
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`teachings of the articl