Filed: June 29, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`————————————————
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`————————————————
`
`MYLAN PHARMACEUTICALS INC.
`Petitioner,
`v.
`
`ASTRAZENECA AB
`Patent Owner.
`
`————————————————
`Patent No. 8,466,139
`————————————————
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 8,466,139
`
`
`
`
`
`
`
`

`
`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 ........................................................................ 4
`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 on Breast Cancer and Its Treatment Options .................... 8
`C.
`Background of The ’139 Patent .......................................................... 10
`1.
`The ’139 Patent ......................................................................... 10
`2.
`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. McLeskey (Ex. 1005) ................................................................ 17
`Howell 1996 (Ex. 1006) ............................................................ 18
`2.
`3.
`Prior Art Informing the Knowledge of the POSA .................... 19
`a.
`Fulvestrant Was Well Known As a Breast Cancer
`Treatment. ....................................................................... 20
`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
`
`D.
`E.
`F.
`
`b.
`
`c.
`
`i
`
`

`
`G.
`
`b.
`
`c.
`
`d.
`
`(i) The Profile of Conventional Excipients ...................26
`(ii) Standard Formulation Principles .............................29
`Petitioner’s Obviousness Positions ..................................................... 30
`1.
`The Law of Obviousness .......................................................... 30
`2.
`The Prior Art Renders the Claims Obvious .............................. 31
`H. Ground 1: Claims 1–20 Were Unpatentable As Obvious Over
`McLeskey ............................................................................................ 34
`1.
`Independent Claim 1 Was Obvious .......................................... 34
`a. 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
`e. McLeskey’s Formulation Did Not Result in
`Unexpectedly Improved Solubility ................................. 40
`Independent Claim 11 Was Obvious ........................................ 41
`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
`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
`
`2.
`3.
`4.
`
`b.
`
`c.
`
`d.
`
`ii
`
`

`
`I.
`
`J.
`
`Dependent Claims 5 and 15 Were Obvious .............................. 47
`5.
`Dependent Claims 7 and 17 Were Obvious .............................. 48
`6.
`Dependent Claims 8 and 18 Were Obvious .............................. 48
`7.
`Dependent Claims 9 and 19 Were Obvious .............................. 49
`8.
`Ground 2: Claims 1–20 Were Unpatentable As Obvious over
`Howell 1996 in view of McLeskey ..................................................... 49
`1.
`Independent Claim 1 Was Obvious .......................................... 49
`2.
`Independent Claim 11 Was Obvious ........................................ 53
`3.
`Dependent Claims 2–3 and 12–13 Were Obvious .................... 53
`4.
`Dependent Claims 4, 6, 10, 14, 16, and 20 Were
`Obvious. .................................................................................... 54
`Dependent Claims 5 and 15 Were Obvious .............................. 56
`5.
`Dependent Claims 7 and 17 Were Obvious Over ..................... 56
`6.
`Dependent Claims 8 and 18 Were Obvious .............................. 57
`7.
`Dependent Claims 9 and 19 Were Obvious .............................. 57
`8.
`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 .............. 58
`Any Commercial Success of Faslodex Is
`Attributable to AstraZeneca’s Extensive Marketing
`Efforts ............................................................................. 60
`The Claimed Methods Produced No Unexpected Results ........ 61
`The ’139 Patent Satisfied No Long-Felt but Unmet Need ....... 62
`Copying Is Irrelevant ................................................................ 62
`
`
`2.
`3.
`4.
`
`b.
`
`
`
`
`
`iii
`
`

`
`Exhibit
`1001
`1002
`1003
`1004
`1005
`
`1006
`
`1007
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`LIST OF EXHIBITS
`
`Description
`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, M.D.
`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 v. 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 182,780 on Endometrial Cancer Growth,”
`90 J. NAT’L CANCER INST. 1552–1558 (1998) (“O’Regan 1998”)
`
`iv
`
`

`
`Exhibit
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`1020
`1021
`
`1022
`
`1023
`
`1024
`
`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)
`(“Osborne 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”)
`Riffkin, “Castor Oil as a Vehicle for Parenteral Administration
`of Steroid Hormones,” 53 J. PHARM. SCI. 891–895 (1964)
`(“Riffkin”)
`HANDBOOK OF PHARMACEUTICAL EXCIPIENTS 7–9, 35–39, 82–83
`(Ainley Wade & Paul J. Weller eds., 2d ed. 1994)
`PHARMACEUTICAL DOSAGE FORMS: PARENTERAL MEDICATIONS
`Vol. 1 (Kenneth E. Avis et al. eds., 2d ed. 1992)
`
`v
`
`

`
`Exhibit
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`1030
`
`1031
`1032
`
`1033
`
`1034
`1035
`1036
`
`Description
`Dukes et al., “Antiuterotrophic effects of a pure antioestrogen,
`ICI 182,780: 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 nemestrina):
`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) (“Wakeling 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”)
`Int’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/hormonal/serms (last
`visited June 22, 2016)
`FASLODEX, http://www.faslodex.com (last visited ___)
`http://www.azandmeapp.com/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
`
`

`
`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) (“Modern 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 (Schülze et al.), issued 10/10/1978
`(“Schülze”)
`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 F.M. 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. 2–11 (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
`
`

`
`Exhibit
`1049
`
`1050
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`Description
`Hancock et al., “The use of solubility parameters in
`pharmaceutical dosage form design,” 148 INT’L J.
`PHARMACEUTICS 1–21 (1997) (“Hancock 1997”)
`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
`clinical toxicology,” 10 PHARMACEUTISCH WEEKBLAD
`SCIENTIFIC EDITION 185–88 (1988) (“Uges 1988”)
`Patent Comparison
`
`
`
`
`
`
`
`viii
`
`

`
`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. Coolsavings.com, Inc.,
`289 F.3d 801 (Fed. Cir. 2002) ............................................................................ 15
`
`Cuozzo Speed Techs., LLC v. Lee,
`Slip Op. No. 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
`
`Hoffer 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’x 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., S.A.,
`337 F.3d 1362 (Fed. Cir. 2003) .......................................................................... 60
`
`ix
`
`

`
`Merck & Co. v. Teva Pharms. USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005) .......................................................................... 59
`
`Minton v. Nat’l Ass’n of Secs. 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. U.S. Int’l Trade Comm’n,
`988 F.2d 1165 (Fed. Cir. 1993) .......................................................................... 15
`
`Therasense, 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
`
`

`
`37 C.F.R. § 42.104(a) ................................................................................................. 4
`
`Other Authorities
`
`MPEP § 716 ............................................................................................................. 58
`
`MPEP 716.03(b) ....................................................................................................... 58
`
`
`
`
`
`xi
`
`

`
`TABLE OF ABBREVIATIONS
`
`7α-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-1,3,5(10)-
`triene-3,17β-diol .............................................................................. Fulvestrant
`
`Estrogen receptor-positive .......................................................... ER+ or ER-positive
`
`Estrogen-receptor downregulators ..................................................................... ERDs
`
`Hormone-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
`
`
`
`xii
`
`

`
`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
`
`cancer in humans—that AstraZeneca now tries to claim. Ex. 1005 (“McLeskey”).
`
`There is no question that the fulvestrant formulation Dr. McLeskey published is the
`
`claimed fulvestrant formulation; the formulation was provided by Zeneca
`
`Pharmaceuticals, predecessor to AstraZeneca. This disclosure renders claims 1–20
`
`obvious to a person having ordinary skill in the art (“POSA”) as of the priority
`
`date.
`
`McLeskey is joined in the prior art by other references expressly disclosing
`
`the use of Zeneca-supplied castor oil-based fulvestrant formulations to treat breast
`
`1
`
`

`
`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
`
`McLeskey. The POSA looking for guidance on formulating an oily fulvestrant
`
`depot like that disclosed in Howell would look no further that the explicit recipe
`
`disclosed in McLeskey. The claims of the ’139 patent are alternatively obvious
`
`over Howell 1996 in view of McLeskey.
`
`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 Institutional LLC, Mylan Laboratories Limited, Agila Specialties Inc.,
`
`Mylan Teoranta, Mylan Inc., and Mylan N.V.
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2))
`Petitioner is not aware of any reexamination certificates or pending
`
`prosecution concerning the ’139 patent. Petitioner is a defendant to the following
`
`
`1 A “depot” is an injection of a pharmaceutical product that tends to keep the
`
`injected drug product at the site of the injection and which allows the drug product
`
`to be released or absorbed over several days or weeks. See Ex. 1003 ¶61; Ex. 1004
`
`¶¶139–145. Steroids are often administered in intramuscular depots. Ex. 1003
`
`¶¶61–63; see also Exs. 1012 at 1; 1006 at 2; 1007 at 7, 9; 1025 at 3; 1026 at 2;
`
`1041 at 9::22–24; 1040 at 7:42–43.
`
`2
`
`

`
`litigations involving the ’139 patent: AstraZeneca Pharmaceuticals LP v. Agila
`
`Specialties Inc., 15-06039 (D.N.J.) (consolidated); AstraZeneca Pharmaceuticals
`
`LP v. Mylan Pharmaceuticals Inc., 15-00183 (N.D.W. Va.). Other pending
`
`litigations involving the ’139 patent include AstraZeneca Pharmaceuticals LP v.
`
`Sandoz Inc., 14–03547 (D.N.J.) (consolidated). Previously pending litigation
`
`involving the ’139 patent included AstraZeneca Pharms. LP v. Teva Parenteral
`
`Medicines, Inc., 10-00018 (D.N.J.).
`
`Petitions requesting inter partes review of U.S. Patent Nos. 6,774,122;
`
`7,456,160; and 8,329,680 are being concurrently filed herewith.
`
`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
`
`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
`
`Service Information (37 C.F.R. § 42.8(b)(4))
`
`D.
`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.
`
`3
`
`

`
`III. GROUNDS FOR STANDING
`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
`
`from requesting inter partes review on the grounds identified herein.
`
`IV.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED
`Petitioner requests inter partes review and cancellation of claims 1–20 of the
`
`’139 patent under 35 U.S.C. § 103, as set forth herein. The ’139 patent is to be
`
`reviewed under pre-AIA § 103. Petitioner’s detailed statement of the reasons for
`
`the relief requested is set forth below. In accordance with 37 C.F.R. § 42.6(c),
`
`copies of the exhibits are filed herewith. In addition, this Petition is supported by
`
`the Declaration of Laird Forrest, Ph.D. (Ex. 1003) and the Declaration of Dr.
`
`Leslie Oleksowicz, M.D. (Ex. 1004).
`
`The challenged claims of the ’139 patent are generally directed to methods
`
`of treating, among other things, a malignant disease of the breast (e.g., breast
`
`cancer) by administering an intramuscular (“i.m.”) injection of a “formulation
`
`comprising: about 50 mgml-1 of fulvestrant; a mixture of from 17–23% w/v of
`
`ethanol and benzyl alcohol; 12–18% w/v of benzyl benzoate; and a sufficient
`
`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.
`
`4
`
`

`
`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
`
`in the petition.” 35 U.S.C. § 314(a). This Petition meets this threshold.
`
`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED
`Summary of the Argument
`A.
`Fulvestrant2 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 ¶¶36–49, 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
`
`chemical
`
`name,
`
`7α-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-
`
`1,3,5(10)-triene-3,17β-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.
`
`5
`
`

`
`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
`
`¶¶111–132, 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 ¶111.
`
`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]
`
`(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
`
`6
`
`

`
`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
`
`volume with castor oil, was supplied by B. M. Vose (Zeneca Pharmaceuticals).”);
`
`Ex. 1003 ¶¶14, 93, 119, 162, 173, 181, 185; Ex. 1004 ¶¶52, 136–137, 166.
`
`
`4 To the extent AstraZeneca suggests that the formulation 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.
`
`7
`
`

`
`AstraZeneca describes the purported unexpected increase in the solubility of
`
`the specific solvent mixture recited in the claims. Ex. 1001 at 5:7–67. 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.
`
`Background on Breast Cancer and Its Treatment Options
`
`B.
`Humans may experi