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. 6,774,122
`
`PETITION FOR INTER PAR TES REVIEW
`
`OF US. PATENT NO. 6,774,122
`
`InnoPharma Exhibit 1078.0001
`
`

`

`TABLE OF CONTENTS
`
`INTRODUCTION ......................................................................................... .. l
`
`II.
`
`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 AND PROCEDURAL STATEMENT ....... ..4
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`
`PRECISE RELIEF REQUESTED ................................................................ ..4
`
`THRESHOLD REQUIREIVIENT 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 US. Patent No. 6,774,122 (“the ’ 122 patent”) ........ .. 10
`
`l.
`
`2.
`
`The ’122 Patent ....................................................................... .. 10
`
`The Prosecution of the ’ l22 Patent ......................................... .. 12
`
`The Person of Ordinary Skill in the Art ............................................ .. 14
`
`Claim Construction............................................................................ .. 15
`
`Patents and Printed Publications Relied On In This Petition ............ .. 18
`
`l.
`
`2.
`
`3.
`
`McLeskey (EX. 1005) .............................................................. ..19
`
`Howell 1996 (EX. 1006) .......................................................... ..20
`
`Prior Art Informing the Knowledge of the POSA .................. ..21
`
`a.
`
`Fulvestrant Was Well Known As a Breast Cancer
`
`Treatment ...................................................................... . .22
`
`b.
`
`c.
`
`Oily Vehicles Were Used for Intramuscular
`Injections to Achieve Long-Acting Efficacy ................ ..24
`
`Conventional Excipients and Standard Formulation
`Principles Allowed Routine Formulation of
`Intramuscular Injections. .............................................. ..28
`
`InnoPharma Exhibit 1078.0002
`
`

`

`(i) The Profile of Conventional Excipients ................. ..28
`
`(ii) Standard Formulation Principles ........................... .3l
`
`Petitioner’s Obviousness Positions. .................................................. .32
`
`l.
`
`2.
`
`The Law of Obviousness ........................................................ .32
`
`The Prior Art Renders the Claims Obvious ............................ ..33
`
`Ground 1: Claims l—9 Were Unpatentable As Obvious Over
`McLeskey. ......................................................................................... .36
`
`1.
`
`Independent Claim 1 Was Obvious over McLeskey. ............. .36
`
`a.
`
`b.
`
`c.
`
`McLeskey Disclosed the Exact Formulation
`Recited in Claim 1. ....................................................... .37
`
`The Art Disclosed Treatment of a Malignant
`Disease of the Breast With Fulvestrant. ....................... .39
`
`The Art Disclosed Intramuscular Injection of Oily
`Fulvestrant Formulations. ............................................. ..40
`
`d.
`
`The Blood Plasma Concentration Recited in Claim
`
`1 Is a Statement of Intended Use. ................................. ..41
`
`(i) To the Extent It Is Given Patentable Weight, Claim
`l’s Recitation of Blood Plasma Concentration Was
`
`Disclosed in the Art. ..................................................... ..41
`
`e.
`
`McLeskey’s Formulation Did Not Result in
`Unexpectedly Improved Solubility ............................... ..42
`
`2.
`
`Independent Claim 5 Was Obvious over McLeskey. ............. ..44
`
`Dependent Claims 2 and 9 Were Obvious over
`McLeskey................................................................................ ..45
`
`4.
`
`Dependent Claims 3 and 4 Were Obvious over
`McLeskey ................................................................................ ..45
`
`a.
`
`The Statements of Intended Result in Claims 3 and
`
`4 Are Not Entitled to Patentable Weight ...................... ..45
`
`b.
`
`To the Extent They Are Given Patentable Weight,
`the Recitations of Claims 3 and 4 Were Obvious. ....... ..46
`
`5.
`
`Dependent Claims 6—8 Were Obvious over McLeskey. ........ ..46
`
`Ground 2: Claims l—9 Were Unpatentable As Obvious over
`Howell 1996 in view of McLeskey. .................................................. ..47
`
`ii
`
`InnoPharma Exhibit 1078.0003
`
`

`

`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`Independent Claim 1 Was Obvious Over Howell 1996 in
`View of McLeskey.................................................................. ..47
`
`Independent Claim 5 Was Obvious Over Howell 1996 in
`View of McLeskey.................................................................. ..51
`
`Dependent Claims 2 and 9 Were Obvious Over Howell
`1996 in View of McLeskey..................................................... .. 51
`
`Dependent Claims 3 and 4 Were Obvious over Howell
`1996 in View of McLeskey..................................................... ..52
`
`Dependent Claim 6 Was Obvious Over Howell 1996 in
`View of McLeskey.................................................................. ..52
`
`Dependent Claim 7 Was Obvious Over Howell 1996 in
`View of McLeskey.................................................................. ..53
`
`Dependent Claim 8 Was Obvious Over Howell 1996 in
`View of McLeskey .................................................................. ..53
`
`Any Secondary Considerations Fail to Overcome the Showing
`of Obviousness .................................................................................. ..54
`
`l.
`
`FaslodeX Sales Do Not Save the ’12 Patent .......................... ..54
`
`a.
`
`There is No Nexus Between the Claims and
`
`Secondary Considerations of Nonobviousness ............ .. 54
`
`b.
`
`Any Commercial Success of FaslodeX Is
`Attributable to AstraZeneca’s Extensive Marketing
`Efforts ........................................................................... ..57
`
`2.
`
`4.
`
`The Claimed Methods Produced No Unexpected Results ...... .. 57
`
`The ’ 122 Patent Satisfied No Long-Felt but Unmet Need ..... .. 58
`
`Copying Is Irrelevant .............................................................. ..59
`
`iii
`
`InnoPharma Exhibit 1078.0004
`
`

`

`LIST OF EXHIBITS
`
`
`
`Exhibit
`Description
`
`
`1001
`U. S. Patent No. 6,774,122
`
`
`1002
`File History For US. Patent No. 6,774,122
`
`
`1003
`Expert Declaration of Dr. Laird Forrest, PhD.
`
`1004
`Expert Declaration of Dr. Leslie Oleksowicz, MD.
`
`
`1005
`
`McLeskey et a[., “Tamoxifen-resistant fibroblast growth factor-
`transfected MCF-7 cells are cross-resistant in V1VO to the
`
`antiestrogen ICI 182,780 and two aromatase inhibitors,” 4 CLIN.
`CANCER RESEARCH 697—7 11 (1998) (“McLeskey”)
`
`1006
`
`Howell et a[., “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”)
`
`
`
`1007 EP 0 346 014 (Dukes), published 12/13/1989 (“Dukes 1989”)
`
`1008
`
`Wakeling et al., “A Potent Specific Pure Antiestrogen with
`Clinical Potential,” 51 CANCER RESEARCH 3867—3873 (1991)
`(“Wakeling 1991”)
`
`1009
`
`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”)
`
`1010
`
`Spiegel & Noseworthy, “Use ofNonaqueous Solvents in
`Parenteral Products,” 52 J. PHARM. SCI. 917—927 (1963)
`(“Spiegel & Noseworthy”)
`
`1011
`Order, AstraZeneca Pharmaceuticals LP v. Sana’OZ Inc, No. 14—
`
`03547 (D.N.J. July 29, 2015), ECF N0. 102
`
`
`
`
`
` (“Howell 1995”)
`
`1012
`
`A. Howell, “Response to a specific antioestrogen (ICI 182780)
`in tamoxifen-resistant breast cancer,” 345 LANCET 29—30 (1995)
`
`1013
`
`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
`
`InnoPharma Exhibit 1078.0005
`
`

`

`
`
`
`
`Exhibit Description
`
`1014
`
`Lu et al., “The effects Of aromatase inhibitors and antiestrogens
`in the nude mouse mOdel,” 50 BREAST CANCER RESEARCH &
`TREATMENT 63—7 1 (1998) (“Lu 1998”)
`
`1015
`
`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”)
`
`1016
`
`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”)
`
`1017
`
`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”)
`
`1018
`
`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”)
`
`1019
`US. Patent RE 28,690 (“Lehmann”)
`
`
`
`
`
`
`
`
`1020
`GB 1 569 286 (“GB ’286”)
`
`
`REMINGTON’S PHARMACEUTICAL SCIENCES (excerpts) (Alfonso
`1021
`
`R. GennarO ed., 18th ed. 1990) (“Remington’s”)
`
`1022
`
`Riffl<in, “Castor Oil as a Vehicle for Parenteral Administration
`Of Steroid Hormones,” 53 J. PHARM. SCI. 891—895 (1964)
`
`(“Riffl<in”)
`
`1023
`
`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)
`
`InnOPharma Exhibit 1078.0006
`
`

`

`
`
`
`
`Exhibit Description
`
`1025
`
`Dukes et a[., “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”)
`
`1026
`
`Dukes et a[., “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”)
`
`1027
`
`DeFriend et a[., “Investigation of a New Pure Antiestrogen (ICI
`182780) in Women with Primary Breast Cancer,” 54 CANCER
`RESEARCH 408—414 (1994) (“DeFriend 1994”)
`
`1028
`
`Alan E. Wakeling, “The future of new pure antiestrogens in
`clinical breast cancer,” 25 BREAST CANCER RESEARCH &
`TREATMENT 1—9 (1993) (“Wakeling 1993”)
`
`
`
`1029 US. Patent No. 4,659,516 (“’516 patent”)
`
`1030
`
`Lu et a[., “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”)
`
`1031
`Int’l Patent App. Pub. NO. WO 97/21440 to Ferdinando et al.
`
`
`UNITED STATES PHARMACOPEIA XXIV, NAT’L FORMULARY XIX
`1032
`
`14 (2000) (“USP 24”)
`
`1033
`
`Selective Estrogen Receptor Modulators (SERMS),
`BREASTCANCERORG,
`
`
`
`
`
`
`
`http://wwwbreastcancer.Org/treatment/hormonal/serms (last
`visited June 22, 2016)
`
`1034
`FASLODEX, http://wwwfaslodexcom (last visited June 22, 2016)
`
`
`1035
`
`1036
`
`http://wwwazandmeapp.com/resources/prescription_product_list
`
`Lykkesfeldt et a[., “Altered Expression OfEstrogen-regulated
`Genes in a Tamoxifen-resistant and ICI 164,384 and ICI 182,780
`
`Sensitive Human Breast Cancer Cell Line,” 54 CANCER
`
`RESEARCH 15 87—1 595 (1994) (“Lykkesfeldt”)
`
`vi
`
`InnoPharma Exhibit 10780007
`
`

`

`
`
`
`
`Exhibit Description
`
`1037
`
`James C. Boylan et al., Parenteral Products, in MODERN
`PHARMACEUTICS (Gilbert S. Banker & Christopher T. Rhodes
`eds., 3d ed. rev. 1996) (“Modern Pharmaceutics”)
`
`1038
`
`Rodger & King, “Drawing up and administering intramuscular
`injections: a review of the literature,” 31 J. ADVANCED NURSING
`574—582 (2000) (“Rodger & King”)
`
`1039
`
`Machholz et al., “Manual Restraint and Common Compound
`Administration Routes in Mice and Rats,” 67 J. VISUALIZED
`EXPERIMENTS 1—8 (2012) (“Machholz”)
`
`US. Patent No. 4,229,626 (Schulze et al.), issued 10/10/1978
`1040
`
`(“Schfflze”)
`
`US. Patent No. 4,310,523 (Neumann), issued 1/12/1982
`1041
`(“Neumann”)
`
`1042
`
`ALFRED MARTIN, PHYSICAL PHARMACY: PHYSICAL CHEMISTRY
`PRINCIPLES IN THE PHARMACEUTICAL SCIENCES (4th ed. 1995)
`(“Martin 1995”)
`
`1043
`
`Powell et al., “Compendium of Excipients for Parenteral
`Formulations,” 52 PDA J. PHARM. SCI. & TECH. 238—3 11 (1998)
`(“Powell”)
`
`1044
`
`ALLAN FM. BARTON, HANDBOOK OF SOLUBILITY PARAMETERS
`AND OTHER COHESION PARAMETERS (2d ed. 1991) (“Barton
`1991”)
`
`Hansen, “The Universality of the Solubility Parameter,” 8 l &
`1045
`EC PROD. RESEARCH & DEV. 2—1 1 (1969) (“Hansen 1969”)
`
`
`
`
`
` PHARM. SCI. 487—491 (1980) (“Martin 1980”)
`
`1046
`
`Martin et al., “Extended Hildebrand Solubility Approach:
`Testosterone and Testosterone Propionate in Binary Solvents,”
`71 J. PHARM. SCI. 1334—1340 (1982) (“Martin 1982”)
`
`1047
`
`Martin et al., “Extended Hildebrand Solubility Approach:
`Solubility of Theophylline in Polar Binary Solvents,” 69 J.
`
`1048
`
`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
`
`InnOPharma Exhibit 1078.0008
`
`

`

`
`
`
`
`Exhibit Description
`
`1049
`
`Hancock et al., “The use Of solubility parameters in
`pharmaceutical dosage form design,” 148 INT’L J.
`PHARMACEUTICS 1—21 (1997) (“Hancock 1997”)
`
`1050
`
`Hildebrand, “Dipole Attraction and Hydrogen Bond Formation
`in Their Relation tO Solubility,” 83 SCIENCE 21—24 (1936)
`(“Hildebrand 1936”)
`
`1051
`
`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”)
`
`
`
`
`
` SCIENTIFIC EDITION 185—88 (1988) (“Uges 1988”)
`
`1052
`
`Davy et al., “A pharmacokinetic evaluation Of 1M administration
`of bleomycin oil suspension,” 14 CANCER CHEMOTHERAPY
`PHARMACOLOGY 274—276 (1985) (“Davy 1985”)
`
`1053
`
`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)
`1054
`
`NURSING 34—41 (1992) (“Newton”)
`
`1055
`
`Uges, “Plasma or serum in therapeutic drug monitoring and
`clinical toxicology,” 10 PHARMACEUTISCH WEEKBLAD
`
`
`
`1056 Patent Comparison
`
`viii
`
`InnOPharma Exhibit 1078.0009
`
`

`

`TABLE OF AUTHORITIES
`
`
`Cases
`
`AstraZeneca Pharmaceuticals LP v. Sana’oz Inc. ,
`14—03547 (D.N.J.) ............................................................................................ .. 15
`
`Bayer Healthcare Pharms., Inc. v. Watson Pharms., Inc.,
`713 F.3d 1369 (Fed. Cir. 2013) ........................................................................ ..59
`
`Catalina Mktg. Int ’l, Inc. v. Coolsavings.com, Inc.,
`289 F.3d 801 (Fed. Cir. 2002) .......................................................................... ..17
`
`Cuozzo Speed Techs., LLC v. Lee,
`Slip Op. N0. 1446 (US. June 20, 2016) ........................................................... .. 15
`
`Ex parte Standish,
`No. 870178, 1988 WL 252397 (B.P.A.I. July 26, 1988) .................................. ..55
`
`Gala’erma Labs. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) .......................................................................... ..59
`
`Graham v. John Deere Co.,
`383 US. 1 (1966) .............................................................................................. ..33
`
`Hofi’er v. Microsoft Corp. ,
`405 F.3d 1326 (Fed. Cir. 2005) ........................................................................ .. 16
`
`In re Huai-Hung Kao,
`639 F.3d 1057 (Fed. Cir. 2011) ........................................................................ ..54
`
`In re PepperBall Techs., Inc.,
`469 F. App’X 878 (Fed. Cir. 2012) ................................................................... ..58
`
`J.T. Eaton & Co. v. Atl. Paste & Glue Co.,
`106 F.3d 1563 (Fed. Cir. 1997) ........................................................................ ..56
`
`KSR Int ’l Co. v. Teleflex Inc.,
`550 US. 398 (2007) .......................................................................................... ..33
`
`McNeil-PFC, Inc. v. L. Perrigo Co., S.A.,
`337 F.3d 1362 (Fed. Cir. 2003) ........................................................................ ..57
`
`1X
`
`InnoPharma Exhibit 1078.0010
`
`

`

`Merck & Co. v. Teva Pharms. USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005) ........................................................................ ..55
`
`Minton v. Nat ’1 Ass ’n ofSecs. Dealers, Inc.,
`336 F.3d 1373 (Fed. Cir. 2003) .................................................................. ..16, 41
`
`Pentec, Inc. v. Graphic Controls Corp,
`776 F.2d 309 (Fed. Cir. 1985) ......................................................................... ..57
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ........................................................................ ..54
`
`Stratoflex, Inc. v. Aeroquip Corp.,
`713 F.2d 1530 (Fed. Cir. 1983) ........................................................................ ..54
`
`Texas Instruments Inc. v. US. Int ’1 Trade Comm ’n,
`988 F.2d 1165 (Fed. Cir. 1993) ........................................................................ ..16
`
`Tnerasense, Inc. v. Becton, Dickinson & Co.,
`593 F.3d 1289 (Fed. Cir. 2010) ....................................................................... ..56
`
`Statutes and Regulations
`
`35 U.S.C. § 103 ........................................................................................ ..1, 4, 12, 32
`
`35 U.S.C. §§ 311—319 .............................................................................................. ..1
`
`35 U.S.C. §314(a) ................................................................................................... ..5
`
`37 CPR. §42.6(c) ................................................................................................... ..4
`
`37 CPR. § 42.8(b)(1) .............................................................................................. ..2
`
`37 CPR. §42.8(b)(2) .............................................................................................. ..2
`
`37 CPR. §42.8(b)(3) .............................................................................................. ..3
`
`37 CPR. §42.8(b)(4) .............................................................................................. ..3
`
`37 CPR § 42.10(b) ................................................................................................. ..1
`
`37 CPR. §42.15(a) ................................................................................................. ..1
`
`37 CPR. §42.100(b) ............................................................................................ ..15
`
`X
`
`InnoPharma Exhibit 1078.0011
`
`

`

`37 CPR. § 42.103 ................................................................................................... ..4
`
`37 CPR. §42.104(a) ............................................................................................... ..4
`
`Other Authorities
`
`MPEP § 716 ........................................................................................................... ..55
`
`Xi
`
`InnoPharma 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+ 0r 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+ 0r PgR—positive
`
`US. Patent and Trademark Office ..................................................................... .. PTO
`
`Selective estrogen-receptor modulators ........................................................ .. SERMs
`
`Subcutaneous ....................................................................................................... .. s.c.
`
`US. Food and Drug Administration .................................................................. ..FDA
`
`US. Patent and Trademark Office ..................................................................... .. PTO
`
`US. Patent No. 6,774,122 .................................................................. ..the ’122 patent
`
`US. Patent No. 7,456,160 .................................................................. ..the ’160 patent
`
`US. Patent No. 8,329,680 .................................................................. ..the ’680 patent
`
`US. Patent No. 8,466,139 .................................................................. ..the ’139 patent
`
`Xii
`
`InnoPharma Exhibit 1078.0013
`
`

`

`I.
`
`INTRODUCTION
`
`Pursuant
`
`to
`
`35 U.S.C.
`
`§§311—319
`
`and
`
`37 CPR.
`
`§42, Mylan
`
`Pharmaceuticals Inc. (“Petitioner”) petitions for Inter Partes Review (“IPR”) of
`
`claims 1-9 of US. Patent No. 6,774,122 (“the ’122 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—9 of the ’ 122 patent are unpatentable over the
`
`prior art. Specifically, in a 1998 publication, Dr. Sandra McLeskey published the
`
`exact formulation of fulvestrant—a drug long known to treat breast cancer in
`
`humans—that Patent Owner 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 Patent Owner. This disclosure renders claims 1—9 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
`
`cancer. Howell 1996 expressly taught the POSA to treat breast cancer with a long-
`
`InnoPharma Exhibit 1078.0014
`
`

`

`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 ’122 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 ’122 patent. Petitioner is a defendant to the following
`
`litigations involving the ’122 patent: AstraZeneca Pharmaceuticals LP v. Agila
`
`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 1156, Ex. 1004
`
`1111139—144. Steroids are often administered in intramuscular depots. Ex. 1003
`
`111157—58; 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.
`
`InnoPharma Exhibit 10780015
`
`

`

`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 ’122 patent include AstraZeneca Pharmaceuticals LP v.
`
`Sandoz Inc., 14—03547 (D.N.J.) (consolidated).
`
`Previously pending litigation
`
`involving the ’122 patent included AstraZeneca Pharms. LP v. Teva Parenteral
`
`Medicines, Inc., 10-00018 (D.N.J.).
`
`Petitions requesting inter partes review of US. Patent Nos. 7,456,160;
`
`8,329,680; and 8,466,139 are being concurrently filed herewith.
`
`Identification of Counsel (37 C.F.R. §42.8(b)(3)) and Service
`C.
`Information (37 C.F.R. § 42.8(b)(4))
`
`Lead Counsel
`
`Back Up Counsel
`
`
`
`
`
`
`
`Brandon M. White
`(Reg. No. 52,354)
`PERKINS COIE LLP
`
`Crystal R. Canterbury
`(Reg. No. 69,853)
`PERKINS COIE LLP
`
`700 13th St., NW, Suite 600
`700 13th St., NW, Suite 600
`Washington, DC 20005
`Washington, DC 20005
`CCanterbury@PerkinsCoie.com
`BMWhite@PerkinsCoie.com
`Tel:
`(202) 654-6383
`Tel: (202) 654-6206
`
`Fax: (202) 654-9681
`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.
`
`InnoPharma Exhibit 1078.0016
`
`

`

`III. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT
`
`As required by 37 CPR. § 42.104(a), Petitioner certifies that the ’ 122 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—9 of the
`
`’122 patent under 35 U.S.C. § 103, as set forth herein. The ’122 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 the section titled “Statement of Reasons
`
`for the Relief Requested.” In accordance with 37 CPR. § 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 ’122 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 (“im”) injection of a “pharmaceutical
`
`formulation comprising fulvestrant, a mixture of 10% weight of ethanol per
`
`volume of formulation, 10% weight of benzyl alcohol per volume of formulation
`
`and 15% weight of benzyl benzoate per volume of formulation and a sufficient
`
`InnoPharma Exhibit 1078.001?
`
`

`

`amount of a castor oil vehicle.” Petitioner challenges the claims of the ’ 122 patent
`
`as unpatentable based on the following grounds:
`
`Ground 1: Claims 1—9 were obvious over McLeskey.
`
`Ground 2: Claims
`
`1—9 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
`
`A.
`
`Summary of the Argument
`
`Fulvestrant2 was first patented in 1987 in US. Patent No. 4,659,516 (“the
`
`’516 patent”).3 EX. 1029. The use of fulvestrant to treat breast cancer is not new.
`
`2 Fulvestrant is also known in the art by its project name, 1C1 182,780, and by its
`
`chemical
`
`name,
`
`70t-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-
`
`1,3,5(10)—triene-3,17B-diol. EX. 1001 at 1:64—67.
`
`3 Fulvestrant was developed by 1C1 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 ’ 122 patent.
`
`InnoPharma Exhibit 10780018
`
`

`

`EX. 1004 111137—50, 112—133, 135. 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
`
`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
`
`1111112—133, 135, 164—166, 189—191. 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, Patent Owner 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 ’ 122 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 Patent Owner’s castor oil-based fulvestrant depots
`
`InnoPharma 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, Patent Owner filed a
`
`patent application on methods of using the fulvestrant formulation it had been
`
`providing to researchers for years. The ’122 patent was filed on January 9, 2001,
`
`claiming priority to January 10, 2000. The ’122 patent recites methods of treating
`
`breast cancer with fulvestrant formulations. The independent claims of the ’122
`
`patent recite excipient concentrations of 10% w/v ethanol, 15% w/v benzyl
`
`benzoate, and 10% w/v benzyl alcohol. EX. 1001 at 12:55—65 (claim 1) and 13:7—
`
`16 (claim 5). This is exactly the formulation disclosed in McLeskey. See EX. 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 111114, 42—43, 60—
`
`73, 92; EX. 1004 111153, 137, 162.
`
`4 To the extent Patent Owner suggests that the formulation in either McLeskey or
`
`Howell 1996 is different than the formulation recited in the claims of the ’122
`
`patent, Patent Owner should provide the details of those formulations, consistent
`
`with its duty of candor to the Board.
`
`InnoPharma Exhibit 1078.0020
`
`

`

`The Examiner allowed the ’ 122 patent on the basis of a purported
`
`unexpected increase in the solubility of fulvestrant in the formulation recited in the
`
`claims. Ex. 1002 at 572. The Examiner reached this determination without the
`
`benefit of McLeskey and its express disclosure of the fulvestrant formulation
`
`recited in the claims because, quite surprisingly, Patent Owner failed to disclose
`
`McLeskey during prosecution of the ’ 122 patent.
`
`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 Patent Owner now seeks to claw back
`
`from the public domain. The Board should cancel each claim of the ’ 122 patent.
`
`B.
`
`Background o