`
`Filed: June 29, 2016
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC.
`
`Petitioner,
`V.
`
`ASTRAZENECA AB
`
`Patent Owner.
`
`Patent No. 8,466,139
`
`PETITION FOR INTER PAR TES REVIEW
`
`OF U.S. PATENT NO. 8,466,139
`
`|nnoPharma Exhibit 1078.0001
`
`
`
`TABLE OF CONTENTS
`
`INTRODUCTION ......................................................................................... .. 1
`
`MANDATORY NOTICES ........................................................................... ..2
`
`A.
`
`B.
`
`C.
`
`Real Parties-In-Interest (37 C.F.R. § 42.8(b)(1)) ................................ ..2
`
`Related Matters (37 C.F.R. § 42.8(b)(2)) ............................................ ..2
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3)) and Service
`Information (37 C.F.R. § 42.8(b)(4)) .................................................. ..3
`
`D.
`
`Service Information (37 C.F.R. § 42.8(b)(4)) ..................................... ..3
`
`GROUNDS FOR STANDING ...................................................................... ..4
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`
`PRECISE RELIEF REQUESTED ................................................................ ..4
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ............. .. 5
`
`III.
`
`IV.
`
`VI.
`
`STATEMENT OF REASONS FOR THE RELIEF REQUESTED ............. ..5
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`F.
`
`Summary of the Argument .................................................................. ..5
`
`Background on Breast Cancer and Its Treatment Options .................. ..8
`
`Background of The ’ 139 Patent ........................................................ .. 10
`
`1.
`
`2.
`
`The ’139 Patent ....................................................................... .. 10
`
`The Prosecution of the ’ 139 Patent ......................................... .. 12
`
`The Person of Ordinary Skill in the Art ............................................ .. 12
`
`Claim Construction............................................................................ .. 13
`
`Patents and Printed Publications Relied On In This Petition ............ .. 16
`
`1.
`
`2.
`
`3.
`
`McLeskey (EX. 1005) .............................................................. .. 17
`
`Howell 1996 (Ex. 1006) .......................................................... .. 18
`
`Prior Art Informing the Knowledge of the POSA .................. .. 19
`
`a.
`
`Fulvestrant Was Well Known As a Breast Cancer
`
`Treatment. ..................................................................... ..20
`
`b.
`
`c.
`
`Oily Vehicles Were Used for Intramuscular
`Injections to Achieve Long-Acting Efficacy ................ ..22
`
`Conventional Excipients and Standard Formulation
`Principles Allowed Routine Formulation of
`Intramuscular Injections ............................................... .26
`
`|nnoPharma Exhibit 10780002
`
`
`
`(i) The Profile of Conventional Excipients ................. ..26
`
`(ii) Standard Formulation Principles ........................... ..29
`
`Petitioner’s Obviousness Positions ................................................... ..30
`
`1.
`
`2.
`
`The Law of Obviousness ........................................................ ..3O
`
`The Prior Art Renders the Claims Obvious ............................ ..31
`
`Ground 1: Claims 1-20 Were Unpatentable As Obvious Over
`McLeskey .......................................................................................... ..34
`
`1.
`
`Independent Claim 1 Was Obvious ........................................ ..34
`
`a.
`
`b.
`
`c.
`
`d.
`
`e.
`
`McLeskey Disclosed the Exact Formulation
`Recited in Claim 1 ........................................................ ..35
`
`The Art Disclosed Treatment of a Malignant
`Disease of the Breast With Fulvestrant ........................ ..36
`
`The Art Disclosed Intramuscular Injection of Oily
`Fulvestrant Formulations .............................................. ..38
`
`The Blood Plasma Concentration Recited in Claim
`
`1 Is a Statement of Intended Use .................................. ..38
`
`(i) To the Extent It Is Given Patentable Weight, Claim
`1’s Recitation of Blood Plasma Concentration Was
`
`Disclosed in the Art ...................................................... ..39
`
`McLesl<ey’s Formulation Did Not Result in
`Unexpectedly Improved Solubility ............................... ..4O
`
`2.
`
`4.
`
`Independent Claim 11 Was Obvious ...................................... ..4l
`
`Dependent Claims 2-3 and 12-13 Were Obvious .................. ..42
`
`Dependent Claims 4, 6, 10, 14, 16 and 20 Were Obvious ...... ..43
`
`a.
`
`The Statements of Intended Result in Claims 4, 6,
`
`10, 14, 16, and 20 Are Not Entitled to Patentable
`Weight ........................................................................... ..43
`
`b.
`
`c.
`
`d.
`
`To the Extent They Are Given Patentable Weight,
`the Recitations of Claims 4 and 14 Were Obvious ...... ..43
`
`To the Extent They Are Given Patentable Weight,
`the Recitations of Claims 6 and 16 Were Obvious ...... ..45
`
`To the Extent They Are Given Patentable Weight,
`the Recitations of Claims 10 and 20 Were Obvious .... ..46
`
`|nnoPharma Exhibit 10780003
`
`
`
`5.
`
`6.
`
`7.
`
`8.
`
`Dependent Claims 5 and 15 Were Obvious ............................ ..47
`
`Dependent Claims 7 and 17 Were Obvious ............................ ..48
`
`Dependent Claims 8 and 18 Were Obvious ............................ ..48
`
`Dependent Claims 9 and 19 Were Obvious ............................ ..49
`
`Ground 2: Claims 1-20 Were Unpatentable As Obvious over
`Howell 1996 in view of McLeskey ................................................... ..49
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`Independent Claim 1 Was Obvious ........................................ ..49
`
`Independent Claim 11 Was Obvious ...................................... ..53
`
`Dependent Claims 2-3 and 12-13 Were Obvious .................. ..53
`
`Dependent Claims 4, 6, 10, 14, 16, and 20 Were
`Obvious. .................................................................................. ..54
`
`Dependent Claims 5 and 15 Were Obvious ............................ ..56
`
`Dependent Claims 7 and 17 Were Obvious Over ................... ..56
`
`Dependent Claims 8 and 18 Were Obvious ............................ ..57
`
`Dependent Claims 9 and 19 Were Obvious ............................ ..57
`
`Any Secondary Considerations Fail to Overcome the Showing
`of Obviousness .................................................................................. ..57
`
`1.
`
`Faslodex Sales Do Not Save the ’139 Patent .......................... ..58
`
`a.
`
`There is No Nexus Between the Claims and
`
`Secondary Considerations of Nonobviousness ............ ..5 8
`
`b.
`
`Any Commercial Success of Faslodex Is
`Attributable to AstraZeneca’s Extensive Marketing
`Efforts ........................................................................... ..6O
`
`2.
`
`4.
`
`The Claimed Methods Produced No Unexpected Results ...... ..61
`
`The ’ 139 Patent Satisfied No Long-Felt but Umnet Need ..... ..62
`
`Copying Is Irrelevant .............................................................. ..62
`
`iii
`
`|nnoPharma Exhibit 1078.0004
`
`
`
`LIST OF EXHIBITS
`
`Exhibit
`
`Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`U.S. Patent No. 8,466,139
`
`File History For U.S. Patent No. 8,466,139
`
`Expert Declaration of Dr. Laird Forrest, Ph.D.
`
`Expert Declaration of Dr. Leslie Oleksowicz, MD.
`
`McLeskey et al., “Tamoxifen-resistant fibroblast growth factor-
`transfected MCF-7 cells are cross-resistant in vivo to the
`
`antiestrogen ICI 182,780 and two aromatase inhibitors,” 4 CLIN.
`CANCER RESEARCH 697-711 (1998) (“McLeskey”)
`
`Howell et al., “Pharmacokinetics, pharmacological and anti-
`tumour effects of the specific anti—oestrogen ICI 182780 in
`women with advanced breast cancer,” 74 BRIT. J. CANCER 300-
`08 (1996) (“Howell 1996”)
`
`EP 0 346 014 (Dukes), published 12/13/1989 (“Dukes 1989”)
`
`Wakeling et al., “A Potent Specific Pure Antiestrogen with
`Clinical Potential,” 51 CANCER RESEARCH 3867-3873 (1991)
`(“Wakeling 1991”)
`
`Alan E. Wakeling & Jean Bowler, “ICI 182,780: A New
`Antioestrogen with Clinical Potential,” 43 J. STEROID BIOCHEM.
`MOLEC. BIOL. 173-177 (1992) (“Wakeling 1992”)
`
`Spiegel & Noseworthy, “Use of Nonaqueous Solvents in
`Parenteral Products,” 52 J. PHARM. SCI. 917-927 (1963)
`(“Spiegel & Noseworthy”)
`
`Order, AstraZeneca Pharmaceuticals LP 12. Sandoz Inc., No. 14-
`03547 (D.N.J. July 29, 2015), ECF No. 102
`
`A. Howell, “Response to a specific antioestrogen (ICI 182780)
`in tamoxifen-resistant breast cancer,” 345 LANCET 29-30 (1995)
`(“Howell 1995”)
`
`O’Regan et al., “Effects of the Antiestrogens Tamoxifen,
`Toremifene, and ICI 182,7 80 on Endometrial Cancer Growth,”
`90 J. NAT’L CANCER INST. 1552-1558 (1998) (“O’Regan 1998”)
`
`iv
`
`|nnoPharma Exhibit 1078.0005
`
`
`
`Exhibit
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`Description
`
`Lu et al., “The effects of aromatase inhibitors and antiestrogens
`in the nude mouse model,” 50 BREAST CANCER RESEARCH &
`TREATMENT 63-71 (1998) (“Lu 1998”)
`
`Mellor & Thomas, “Interactions between oestradiol and
`epidermal growth factor in endometrial stromal proliferation and
`differentiation,” 104 J. REPRODUCTION AND FERTILITY 157-164
`
`(1995) (“Mellor & Thomas”)
`
`Poyser, “Effects of onapristone, tamoxifen and ICI 182780 on
`uterine prostaglandin production and luteal function in
`nonpregnant guinea-pigs,” 98 J. REPRODUCTION AND FERTILITY
`307-312 (1993) (“Poyser”)
`
`Johnston et al., “Comparison of Estrogen Receptor DNA
`Binding in Untreated and Acquired Antiestrogen-resistant
`Human Breast Tumors,” 57 CANCER RESEARCH 3723-3727
`(1997) (“Johnston”)
`
`Osborne et al., “Comparison of the Effects of a Pure Steroidal
`Antiestrogen With Those of Tamoxifen in a Model of Human
`Breast Cancer,” 87 J. NAT’L CANCER INST. 746-750 (1995)
`(“Osbome 1995”)
`
`U.S. Patent RE 28,690 (“Lehmann”)
`
`GB 1 569 286 (“GB ’286”)
`
`REMINGTON’S PHARMACEUTICAL SCIENCES (excerpts) (Alfonso
`R. Gennaro ed., 18th ed. 1990) (“Remington’s”)
`
`Riffl<in, “Castor Oil as a Vehicle for Parenteral Administration
`of Steroid Hormones,” 53 J. PHARM. SCI. 891-895 (1964)
`(“Riffl<in”)
`
`HANDBOOK OF PHARMACEUTICAL EXCIPIENTS 7-9, 35-39, 82-83
`(Ainley Wade & Paul J. Weller eds., 2d ed. 1994)
`
`1024
`
`PHARMACEUTICAL DOSAGE FORMS: PARENTERAL MEDICATIONS
`
`Vol. 1 (Kenneth E. Avis et al. eds., 2d ed. 1992)
`
`|nnoPharma Exhibit 1078.0006
`
`
`
`Exhibit
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`Description
`
`Dukes et al., “Antiuterotrophic effects of a pure antioestrogen,
`ICI 182,7 80: magnetic resonance imaging of the uterus in
`ovariectomized monkeys,” 135 J. ENDOCRINOLOGY 239-247
`(1992) (“Dukes 1992”)
`
`Dukes et al., “Antiuterotrophic effects of the pure antiestrogen
`ICI 182,780 in adult female monkeys (Macaca nemestrma):
`quantitative magnetic resonance imaging,” 138 J.
`ENDOCRINOLOGY 203-209 (1993) (“Dukes 1993”)
`
`DeFriend et al., “Investigation of a New Pure Antiestrogen (ICI
`182780) in Women with Primary Breast Cancer,” 54 CANCER
`RESEARCH 408-414 (1994) (“DeFriend”)
`
`Alan E. Wakeling, “The future of new pure antiestrogens in
`clinical breast cancer,” 25 BREAST CANCER RESEARCH &
`TREATMENT 1-9 (1993) (“Wake1ing 1993”)
`
`U.S. Patent No. 4,659,516 (“’516 patent”)
`
`Lu et al., “The effect of combining aromatase inhibitors with
`antiestrogens on tumor growth in a nude mouse model for breast
`cancer,” 57 BREAST CANCER RESEARCH & TREATMENT 183-192
`(1999) (“Lu 1999”)
`
`lnt’l Patent App. Pub. No. WO 97/21440 to Ferdinando et al.
`
`UNITED STATES PHARMACOPEIA XXIV, NAT’L FORMULARY XIX
`14 (2000) (“USP 24”)
`
`Selective Estrogen Receptor Modulators (SERMS),
`BREASTCANCER.ORG,
`
`http://www.breastcancer.org/treatment/horrnonal/serms (last
`visited June 22, 2016)
`
`FASLODEX, http://www.faslodeX.com (last visited _)
`
`http://www.azandmeapp.corn/resources/prescription_product_list
`
`Lykkesfeldt et al., “Altered Expression of Estrogen-regulated
`Genes in a Tamoxifen-resistant and ICI 164,384 and ICI 182,780
`
`Sensitive Human Breast Cancer Cell Line,” 54 CANCER
`RESEARCH 1587-1595 (1994) (“Lykkesfeldt”)
`
`vi
`
`|nnoPharma Exhibit 1078.000?
`
`
`
`Exhibit
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`Description
`
`James C. Boylan et al., Parenteral Products, in MODERN
`PHARMACEUTICS (Gilbert S. Banker & Christopher T. Rhodes
`eds., 3d ed. rev. 1996) (“Modem Pharmaceutics”)
`
`Rodger & King, “Drawing up and administering intramuscular
`injections: a review of the literature,” 31 J. ADVANCED NURSING
`574-582 (2000) (“Rodger & King”)
`
`Machholz et al., “Manual Restraint and Common Compound
`Administration Routes in Mice and Rats,” 67 J. VISUALIZED
`EXPERIMENTS 1-8 (2012) (“Machholz”)
`
`U.S. Patent No. 4,229,626 (Schulze et al.), issued 10/10/1978
`(“Schtflze”)
`
`U.S. Patent No. 4,310,523 (Neumann), issued 1/12/1982
`(“Neumann”)
`
`ALFRED MARTIN, PHYSICAL PHARMACY: PHYSICAL CHEMISTRY
`PRINCIPLES IN THE PHARMACEUTICAL SCIENCES (4th ed. 1995)
`(“Martin 1995”)
`
`Powell et al., “Compendium of Excipients for Parenteral
`Formulations,” 52 PDA J. PHARM. SCI. & TECH. 238-311 (1998)
`(“Powell”)
`
`ALLAN FM. BARTON, HANDBOOK OF SOLUBILITY PARAMETERS
`AND OTHER COHESION PARAMETERS (2d ed. 1991) (“Barton
`1991”)
`
`Hansen, “The Universality of the Solubility Parameter,” 8 I &
`EC PROD. RESEARCH & DEV. 2-1 1 (1969) (“Hansen 1969”)
`
`Martin et al., “Extended Hildebrand Solubility Approach:
`Testosterone and Testosterone Propionate in Binary Solvents,”
`71 J. PHARM. SCI. 1334-1340 (1982) (“Martin 1982”)
`
`Martin et al., “Extended Hildebrand Solubility Approach:
`Solubility of Theophylline in Polar Binary Solvents,” 69 J.
`PHARM. SCI. 487-491 (1980) (“Martin 1980”)
`
`Gordon & Scott, “Enhanced Solubility in Solvent Mixtures. I.
`The System Phenanthrene—CycloheXane—Methylene Iodide,”
`74 J. AM. CHEM. SOC. 4138-40 (1952) (“Gordon 1952”)
`
`vii
`
`|nnOPharma Exhibit 1078.0008
`
`
`
`Exhibit
`
`1049
`
`Description
`
`Hancock et al., “The use of solubility parameters in
`pharmaceutical dosage form design,” 148 INT’L J.
`PHARMACEUTICS 1-21 (1997) (“Hancock 1997”)
`
`1050
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`Hildebrand, “Dipole Attraction and Hydrogen Bond Formation
`in Their Relation to Solubility,” 83 SCIENCE 21-24 (1936)
`(“Hildebrand 1936”)
`
`Waynforth et al., “Good Practice Guidelines: Administration of
`Substances (Rat, Mouse, Guinea Pig, Rabbit),” 1 LAB. OF
`ANIMAL SCI. Ass’N GOOD PRACTICE GUIDELINES 1-4 (1998)
`(“Waynforth 1998”)
`
`Davy et al., “A pharmacokinetic evaluation of IM administration
`of bleomycin oil suspension,” 14 CANCER CHEMOTHERAPY
`PHARMACOLOGY 274-276 (1985) (“Davy 1985”)
`
`Robinson et al., “Procaine Penicillin: Therapeutic Efficiency and
`a Comparative Study of the Absorption of Suspensions in Oil
`and in Oil Plus Aluminum Monostearate and of an Aqueous
`Suspension Containing Sodium Carboxymethylcellulose,” 33 J.
`LAB. CLIN. MED. 1232-40 (1948) (“Robinson 1948”)
`
`Newton, “Reviewing the ‘Big Three’ Injection Routes,” 22(2)
`NURSING 34-41 (1992) (“Newton”)
`
`Uges, “Plasma or serum in therapeutic drug monitoring and
`climcal toxicology,” 10 PHARMACEUTIsCH WEEKBLAD
`SCIENTIFIC EDITION 185-88 (1988) (“Uges 1988”)
`
`1056
`
`Patent Comparison
`
`viii
`
`|nnoPharma Exhibit 1078.0009
`
`
`
`TABLE OF AUTHORITIES
`
`Case
`
`AstraZeneca Pharmaceuticals LP v. Sandoz Inc. ,
`14-03547 (D.N.J.) ............................................................................................ .. 14
`
`Bayer Healthcare Pharms., Inc. v. Watson Pharms., Inc.,
`713 F.3d 1369 (Fed. Cir. 2013) ........................................................................ ..63
`
`Catalina Mktg. Int ’l, Inc. V. Coolsavingscom, Inc.,
`289 F.3d 801 (Fed. Cir. 2002) .......................................................................... ..15
`
`Cuozzo Speed Techs., LLC v. Lee,
`Slip Op. N0. 1446 (U.S. June 20, 2016) ........................................................... .. 13
`
`Ex parte Standish,
`No. 870178, 1988 WL 252397 (B.P.A.I. July 26, 1988) .................................. ..58
`
`Galderma Labs. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) .......................................................................... ..62
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) .............................................................................................. ..31
`
`Hofler v. Microsoft Corp. ,
`405 F.3d 1326 (Fed. Cir. 2005) ........................................................................ .. 15
`
`In re Huai—Hung Kao,
`639 F.3d 1057 (Fed. Cir. 2011) ........................................................................ ..58
`
`In re PepperBall Techs., Inc.,
`469 F. App’); 878 (Fed. Cir. 2012) ................................................................... ..62
`
`J.T. Eaton & Co. v. Atl. Paste & Glue Co.,
`106 F.3d 1563 (Fed. Cir. 1997) ........................................................................ ..60
`
`KSR Int ’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) .................................................................................... ..30, 31
`
`McNeil—PPC, Inc. v. L. Perrigo Co., SA,
`337 F.3d 1362 (Fed. Cir. 2003) ........................................................................ ..60
`
`ix
`
`|nnoPharma Exhibit 1078.001O
`
`
`
`Merck & Co. v. Teva Pnarms. USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005) ........................................................................ ..59
`
`I\/finton 1/. Nat 7 Ass ’n ofSecs. Dealers, Inc.,
`336 F.3d 1373 (Fed. Cir. 2003) ........................................................................ ..15
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ........................................................................ ..58
`
`Stratoflex, Inc. v. Aeroquip Corp.,
`713 F.2d 1530 (Fed. Cir. 1983) ........................................................................ ..58
`
`Texas Instruments Inc. v. US. Int 7 Trade Comm ’n,
`988 F.2d 1165 (Fed. Cir. 1993) ........................................................................ ..15
`
`Tnerasense, Inc. v. Becton, Dickinson & Co,
`593 F.3d 1289 (Fed. Cir. 2010) ................................................................. ..59, 60
`
`Statutes and Regulations
`
`35 U.S.C. § 103 ........................................................................................................ ..4
`
`35 U.S.C. §§ 311-319 .............................................................................................. ..1
`
`35 U.S.C. §314(a) ................................................................................................... ..5
`
`37 C.F.R. §42.6(c) ................................................................................................... ..4
`
`37 C.F.R. § 42.8(b)(1) .............................................................................................. ..2
`
`37 C.F.R. §42.8(b)(2) .............................................................................................. ..2
`
`37 C.F.R. §42.8(b)(3) .............................................................................................. ..3
`
`37 C.F.R. §42.8(b)(4) .............................................................................................. ..3
`
`37 C.F.R § 42.10(b) ................................................................................................. ..1
`
`37 C.F.R. §42.15(a) ................................................................................................. ..1
`
`37 C.F.R. §42.100(b) ............................................................................................ ..13
`
`37 C.F.R. §42.103 ................................................................................................... ..1
`
`X
`
`|nnoPharma Exhibit 1078.0011
`
`
`
`37 C.F.R. §42.104(a) ............................................................................................... ..4
`
`Other Authorities
`
`MPEP § 716 ........................................................................................................... ..58
`
`MPEP 716.03(b) ..................................................................................................... ..58
`
`Xi
`
`|nnoPharma Exhibit 1078.0012
`
`
`
`TABLE OF ABBREVIATIONS
`
`70t- [9-(4,4,5 ,5 ,5 -pentafluoropentyl sulphinyl)nonyl]oestra- 1 ,3 ,5 ( 1 0)-
`triene-3 ,17B-diol ............................................................................ ..FulVestrant
`
`Estrogen receptor-positive ........................................................ .. ER+ or ER-positive
`
`Estrogen-receptor downregulators ................................................................... .. ERDs
`
`Horrnone-dependent ............................................................................................. .
`
`. HD
`
`ICI 182,780 .............................................................................................. ..FulVestrant
`
`Intramuscular ...................................................................................................... .. i.m.
`
`percent Volume in Volume ................................................................................. .. %V/V
`
`percent weight in Volume ................................................................................. .. %w/V
`
`Progesterone receptor-positive ............................................... ..PgR+ or PgR-positive
`
`Selective estrogen-receptor modulators ........................................................ .. SERMs
`
`Subcutaneous ....................................................................................................... .. s.c.
`
`U.S. Food and Drug Administration .................................................................. ..FDA
`
`U.S. Patent and Trademark Office ..................................................................... .. PTO
`
`U.S. Patent No. 6,774,122 .................................................................. ..the ’122 patent
`
`U.S. Patent No. 7,456,160 .................................................................. ..the ’160 patent
`
`U.S. Patent No. 8,329,680 .................................................................. ..the ’680 patent
`
`U.S. Patent No. 8,466,139 .................................................................. ..the ’139 patent
`
`X11
`
`|nnoPharma Exhibit 10780013
`
`
`
`I.
`
`INTRODUCTION
`
`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 1-20 of U.S. Patent No. 8,466,139 (“the ’139 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 ’ 139 patent are unpatentable over the
`
`prior art. Specifically, in a 1998 publication, Dr. Sandra McLeskey published a
`
`formulation of fulvestrant
`
`that
`
`falls
`
`squarely within the ranges
`
`recited in
`
`AstraZeneca’s formulation of fulvestrant—a drug long known to treat breast
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`cancer in humans—that AstraZeneca now tries to claim. EX. 1005 (“McLeskey”).
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`There is no question that the fulvestrant formulation Dr. McLeskey published is the
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`claimed fulvestrant
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`formulation,
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`the formulation was provided by Zeneca
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`Pharmaceuticals, predecessor to AstraZeneca. This disclosure renders claims 1-20
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`obvious to a person having ordinary skill in the art (“POSA”) as of the priority
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`date.
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`McLeskey is joined in the prior art by other references expressly disclosing
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`the use of Zeneca-supplied castor oil-based fulvestrant formulations to treat breast
`
`|nnoPharma Exhibit 1078.0014
`
`
`
`cancer. Howell 1996 expressly taught the POSA to treat breast cancer with a long-
`
`acting castor oil-based fulvestrant depot,1 exactly what was disclosed in
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`McLeskey. The POSA looking for guidance on formulating an oily fulvestrant
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`depot like that disclosed in Howell would look no further that the explicit recipe
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`disclosed in McLeskey. The claims of the ’139 patent are alternatively obvious
`
`over Howell 1996 in View of McLeskey.
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`II. MANDATORY NOTICES
`
`A.
`
`Real Parties-In-Interest (37 C.F.R. § 42.8(b)(1))
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`The real parties-in-interest for Petitioner are Mylan Pharmaceuticals Inc.,
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`Mylan Institutional LLC, Mylan Laboratories Limited, Agila Specialties Inc.,
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`Mylan Teoranta, Mylan Inc., and Mylan N.V.
`
`B.
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`Related Matters (37 C.F.R. § 42.8(b)(2))
`
`Petitioner
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`is not aware of any reexamination certificates or pending
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`prosecution concerning the ’139 patent. Petitioner is a defendant to the following
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`1 A “depot” is an injection of a pharmaceutical product that tends to keep the
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`injected drug product at the site of the injection and which allows the drug product
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`to be released or absorbed over several days or weeks. See Ex. 1003 1161, Ex. 1004
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`1111139445. Steroids are often administered in intramuscular depots. Ex. 1003
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`111161-63, see also Exs. 1012 at 1, 1006 at 2, 1007 at 7, 9, 1025 at 3, 1026 at 2,
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`1041 at 9::22—24; 1040 at 7:42-43.
`
`|nnoPharma Exhibit 10780015
`
`
`
`litigations involving the ’139 patent: AstraZeneca Pharmaceuticals LP v. Agila
`
`Specialties Inc., 15-06039 (D.N.J.) (consolidated); AstraZeneca Pharmaceuticals
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`LP v. Mylan Pharmaceuticals Inc., 15-00183 (N.D.W. Va.). Other pending
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`litigations involving the ’139 patent include AstraZeneca Pharmaceuticals LP v.
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`Sandoz Inc., 14-03547 (D.N.J.) (consolidated).
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`Previously pending litigation
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`involving the ’139 patent included AstraZeneca Pharms. LP v. Teva Parenteral
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`Medicines, Inc., 10-00018 (D.N.J.).
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`Petitions requesting inter partes review of U.S. Patent Nos. 6,774,122,
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`7 ,456,160, and 8,329,680 are being concurrently filed herewith.
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`C.
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`Identification of Counsel (37 C.F.R. §42.8(b)(3)) and Service
`Information (37 C.F.R. § 42.8(b)(4))
`
`Lead Counsel
`
`Back Up Counsel
`
`Brandon M. White
`(Reg. No. 52,354)
`PERKINS CoIE LLP
`
`700 13th St., NW, Suite 600
`Washington, DC 20005
`BMWhite@PerkinsCoie.com
`Tel: (202) 654-6206
`Fax: (202)654-9681
`
`Crystal R. Canterbury
`(Reg. No. 69,853)
`PERKINS COIE LLP
`
`700 13th St., NW, Suite 600
`Washington, DC 20005
`CCanterbury@PerkinsCoie.com
`Tel: (202)654-6383
`Fax: (202)654-9962
`
`D.
`
`Service Information (37 C.F.R. § 42.8(b)(4))
`
`Please direct all correspondence to lead counsel and back-up counsel at the
`
`contact
`
`information above.
`
`Petitioner consents to service by electronic mail
`
`at bmwhite@perkinscoie.com and ccanterbury@perkinscoie.com.
`
`|nnoPharma Exhibit 10780016
`
`
`
`III. GROUNDS FOR STANDING
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`As required by 37 C.F.R. § 42.104(a), Petitioner certifies that the ’ 139 patent
`
`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
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`PRECISE RELIEF REQUESTED
`
`Petitioner requests inter partes review and cancellation of claims 1-20 of the
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`’139 patent under 35 U.S.C. § 103, as set forth herein. The ’139 patent is to be
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`reviewed under pre-AIA § 103. Petitioner’s detailed statement of the reasons for
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`the relief requested is set forth below.
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`In accordance with 37 C.F.R. §42.6(c),
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`copies of the exhibits are filed herewith.
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`In addition, this Petition is supported by
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`the Declaration of Laird Forrest, Ph.D.
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`(EX. 1003) and the Declaration of Dr.
`
`Leslie Oleksowicz, MD. (Ex. 1004).
`
`The challenged claims of the ’139 patent are generally directed to methods
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`of treating, among other things, a malignant disease of the breast (e.g., breast
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`cancer) by administering an intramuscular (“i.m.”
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`injection of a “formulation
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`comprising: about 50 mgml'1 of fulvestrant, a mixture of from 17-23% w/v of
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`ethanol and benzyl alcohol, 12-18% w/v of benzyl benzoate, and a sufficient
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`amount of castor oil vehicle.” Petitioner challenges the claims of the ’139 patent
`
`as unpatentable based on the following grounds:
`
`Ground 1: Claims 1-20 were obvious over McLeskey.
`
`|nnoPharma Exhibit 1078.001?
`
`
`
`Ground 2: Claims 1-20 were obvious over Howell 1996 in View of
`
`McLeskey.
`
`V.
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`
`A petition for inter partes review must demonstrate “a reasonable likelihood
`
`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.
`
`VI.
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`STATEMENT OF REASONS FOR THE RELIEF REQUESTED
`
`A.
`
`Summary of the Argument
`
`Fulvestrantz was first patented in 1987 in U.S. Patent No. 4,659,516 (“the
`
`’516 patent”).3 EX. 1029. The use of fulvestrant to treat breast cancer is not new.
`
`EX. 1004 111136-49, 111-132, 134. The ’516 patent disclosed that fulvestrant has
`
`antiestrogenic activity, and that fulvestrant “is of value in the treatment of the same
`
`conditions in which tamoxifen is beneficial, in particular
`
`in the treatment of
`
`2 Fulvestrant is also known in the art by its project name, ICI 182,780, and by its
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`chemical
`
`name,
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`70t-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-
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`1,3,5(10)-triene-3,17B-diol. EX. 1001 at 2:1- 4.
`
`3 Fulvestrant was developed by ICI Pharmaceuticals, see, e. g., EX. 1008 at 1, EX.
`
`1009 at 1, which later became Zeneca Pharmaceuticals, see, e. g., Ex. 1006 at 7,
`
`and eventually AstraZeneca AB (“AstraZeneca” or “Patent Owner”), see, e. g., Ex.
`
`1001 at 1. AstraZeneca is the assignee of the ’139 patent.
`
`|nnoPharma Exhibit 10780018
`
`
`
`breast tumors.” EX. 1029 at 7: 29-30, 48-52 (emphasis added). The POSA would
`
`have understood tamoxifen to be useful in the treatment of breast cancer. EX. 1004
`
`117111-132, 134, 168-170, 196-198. The POSA would also have understood the
`
`’516 patent’s disclosure of fulVestrant’s efficacy in the treatment of breast tumors
`
`to mean breast cancer. EX. 1004 11111.
`
`During fulVestrant’s development, AstraZeneca provided samples of
`
`fulvestrant formulations to researchers. See, e. g., EX. 1005 at 2, EX. 1014 at 5, EX.
`
`1030 at 3, EX. 1015 at 7, EX. 1017 at 2 (“treatment with 5 mg of [fulvestrant]
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`(Zeneca Pharmaceuticals, Macclesfield, United Kingdom) in castor oil”), EX. 1018
`
`at 2 (“treatment with the indicated doses of [fulvestrant] (Zeneca Pharmaceuticals,
`
`Macclesfield England) in castor oil”). Some of those researchers published details
`
`of their work with fulvestrant years before the ’ 139 patent was filed. See, e. g., Ex.
`
`1005.
`
`In the case of McLeskey, the exact details of the formulation were published
`
`and thereby disclosed to the public.
`
`In the case of Howell 1996, the authors
`
`disclosed that they administered AstraZeneca’s castor oil-based fulvestrant depots
`
`|nnoPharma Exhibit 10780019
`
`
`
`intramuscularly to human female patients to treat breast cancer.4 EX. 1006 at 1-2.
`
`Howell 1996’s formulation was described as a long acting, castor oil-based
`
`fulvestrant depot. EX. 1006 at 1-2.
`
`Thirteen years after fulvestrant was first patented, AstraZeneca filed a patent
`
`application on methods of using the fulvestrant formulation it had been providing
`
`to researchers for years. The ’ 139 patent was filed on September 4, 2012, claiming
`
`priority to January 10, 2000. The ’139 patent recites methods of treating breast
`
`cancer with fulvestrant formulations. The independent claims of the ’139 patent
`
`recite excipient concentrations of from 17-23% w/V ethanol and benzyl alcohol
`
`and 12-18% w/V benzyl benzoate, EX. 1001 at 12:11-22 (claim 1) and 12:48-59
`
`(claim 11). The formulation disclosed in McLeskey falls squarely within each of
`
`these ranges. See EX. at 1005 at 2 (“...50 mg/ml preformulated [fulvestrant] drug
`
`in a Vehicle of 10% ethanol, 15% benzyl benzoate, 10% benzyl alcohol, brought to
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`Volume with castor oil, was supplied by B. M. Vose (Zeneca Phannaceuticals).”),
`
`EX. 1003 M14, 93, 119, 162, 173, 181, 185, EX. 1004 1l1l52,l36-137,166.
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`4 To the extent AstraZeneca suggests that the fonnulation in either McLeskey or
`
`Howell 1996 is different than the formulation recited in the claims of the ’139
`
`patent, AstraZeneca should provide the details of those formulations, consistent
`
`with its duty of candor to the Board.
`
`|nnoPharma Exhibit 1078.0020
`
`
`
`AstraZeneca describes the purported unexpected increase in the solubility of
`
`the specific solvent mixture recited in the claims. Ex. 1001 at 517-67. Despite
`
`McLeskey disclosing a formulation embodying the benefits AstraZeneca asserted
`
`were so “unexpected,” the ’139 patent issued just six months after the application
`
`was filed without a substantive rejection.5 See generally Ex. 1002.
`
`Now, with full benefit of the state of the art, it becomes plain that fulvestrant
`
`was long known in the art to be an efficacious treatment for breast cancer and that
`
`the prior art contained the exact formulation AstraZeneca now seeks to claw back
`
`from the public domain. The Board should cancel each claim of the ’ 139 patent.
`
`B.
`
`Background on Breast Cancer and Its Treatment Options
`
`Humans may experience diseases of the breast or reproductive tract, and
`
`these can be malignant or benign. At issue here is malignant breast disease,
`
`meaning breast cancer. A POSA would have known