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`I 2‘R2017-00905
`
`Petition for Inter Farms Review
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`UNITED STAT,_;S PATENT AND TRADEMARK OFFICE
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`B TFORB THE PATENT TICAL AND APPEAL BOARD
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`INNOPI ‘ARMA ICENSING, LLC,
`Peti “igner
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`V.
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`ASTRAZENECA AB,
`Patent Owner
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`Case IPR2017-00905
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`Eatent No. 8,466,139
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`PETITION FOR INTER PARTES REVI'I‘W 0F
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`us. PATENT N0. 8,466,139
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`UN )ER 3: U.S.C. §§ 311-319 AND 3? (3.11.3. § 4 2.109 ET SEQ.
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`
`
`Mail Stop: Patent Board
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`
`PO. BOX 1450
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`Alexandria, VA 22313-1450
`
`AstraZeneca Exhibit 2174 p. 1
`Fresenius-Kabi USA LLC V. AstraZeneca AB IPR2017-01912
`
`

`

`1PR2012-00905
`
`Petition for Inter Primes Review
`
`W
`
`I.
`
`INTRODUCTION ........................................................................................... 1
`
`11.
`
`
`
`NOTICES, STATEMENTS AND PAYM ENT OF FEES .............................. 4
`
`
`
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`A. Read Party In Interest Under 3’? OER. § 2.8(b)(1) ............................... 4
`
`B. Related Matters Under 3’? GER. § 42.8(b}(2) ........................................ 4
`
`
`
`
`
`C. Lead and jack-Up Counsel Under 37 CPR, § 428(1))(3) ..................... 6
`
`
`Service Infermation Under 37 OER. § 2.863(4) ................................. ”I”
`
`D.
`
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`E. Grounds for Standing Under 3’? OER, § 42. 104(21) ................................ 3’
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`F.
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`Fees Under 37 OER. § 42.103 ................................................................ ’33
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`
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`IDENTIFICATTON OF CMLLENGE UNDER 3'? CF'JR. § 42.104{B) ...... 7
`
`TH.
`
`1V.
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`INNOPHAW’S GROUNDS OF UNPATENTABILITY AR‘
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` Lil
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`
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`DISTINCT FROM THOSE PRESENTED BY MYLAN ............................... 9
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`V.
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`
`
`OVERVIEW OF THE ‘ 139 PATENT AND PROSECUTION HISTORY ,12
`
`A. The “139 Patent ...................................................................................... 12
`
`B. The Prosecution History efthe ‘680 and ‘ 139 Patents .......................... 1n.
`
`1.
`
`2.
`
`The Preseeutien History ofthe “680 Patent ................................... 1—-
`
`The Prosecution History of the ‘ 139 Patent ................................... 17
`
`
`
`Vii
`
`LEVEL OF ORDINARY SKILL IN THE ART ........................................... 17’
`
`VII. CLAIM CONSTRUCTION .......................................................................... 18
`
`A.
`
`“Achieves,” ............................................................................................. 18
`
`B.
`
`“Attained” .............................................................................................. 18
`
`C.
`
`“Wherein the method achieves a b1ood plasma fulvestrant cancentration
`of at least 2.5 iigml‘j for at 1east 2 weeks” ............................................. 18
`
`i
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`AstraZeneca Exhibit 2174 p. 2
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`

`

`lPR2017-00905
`
`Petition for Inter Fortes Review
`
`D.
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`“Wherein. . .the blood plasma fulvestrant concentration is attained at
`least 4 weeks” ........................................................................................ 18
`
`
`
`VIII. SCOPE AN? CONTENT OF THE PRIOR ART ......................................... 19
`
`A. The Prior Art Diseloses All Limitations of the Challenged Claims ...... 19
`
`l. Howell Closely Matches the Claimed Invention ........................... l9
`
`2. McLeskey Diseloses the Claimed Formulation and Was Not a
`“Treatment Failure” ....................................................................... 22
`
`3. O’Regan Confirms the Route of Administration ........................... 26
`
`B. AstraZeneca’s Attempts to Detraet From These Prior Art Teachings
`Fail ......................................................................................................... 26
`
`i. AstraZeneea’s Purported “Lead Compound” Analysis is
`Inapplicahle ....................................................................................27
`
`2. AstraZeneca’s Efficacy Arguments Are Contrary to Law.............29
`
`3. AstraZeneoa’s Claims of Unpredictabiiity Are Speeious .............. 2‘9
`
`a.
`
`
`The Pharmacokinetie Limitations Are Expressly Disclosed in
`the Prior Art ............................................................................ 30
`
`b.
`
`It Was Well-Known That Fulvestrant Was Administered
`
`lntramuscularly ....................................................................... 32
`
`e.
`
`The Claimed Combination ofExeipients Were Neither
`Unexpected Nor Surprising .................................................... 33
`
`
`
`
`
`
`
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`IX. DQTAILED “XPLANATION AND SUPPORTING EVIDENCE .............. 35
`
`
`
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`A. Ground 1: The Challenged Claims Are Obvious Over} owell ............. 36
`
`1. A POSA Would Have Been Motivated to Develop a Formulation
`to Achieve the Results Reported in Howell ................................... 36
`
`2. A PQSA Would Have A Reasonable Expectation of Success in
`Developing a Formulation to Achieve the Howell Results. .......... 38
`
`ii
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`AstraZeneca Exhibit 2174 p. 3
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`

`

`I?R20l7-OO9G§
`
`Petition for Inter Fortes Review
`
`3.
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`Every Limitation Is Disclosed By Howell and The Knowledge of a
`POSA .............................................................................................. 41
`
`B. Ground 2: The Challenged Claims Are Obvious Over Howell and
`McLeSkey ............................................................................................... 44
`
`l. A POSA Would Have Been Motivated to Combine Howell and
`
`McLeskey .......................................................................................44
`
`a.
`
`The Target Fulvestrant Concentration in Howell Would Have
`Led a Skilled Formulator to McLeskey ..................................44
`
`b. The Record Confirms the Motivation to Combine Howell and
`
`McLeekey. ..............................................................................a 7
`
`
`
`2. A POSA Would Have A Reasonable Expectation of Success in
`
`Administering the MeLeskey ormulation Intramuscularly to
`Achieve the Results Reported in Howell ....................................... 52
`
`3.
`
`Every Limitation Is Disclosed By the Combination of Howell and
`McLeskey. . .. .................................................................................. 5’?
`
`C Ground 3: The Challenged Claims Are Obvious Over Howell
`
`Me__.eekey, and O Regan ....................................................................... 60
`
`l. A POSA Would Have Been Motivate” to Combine Howell,
`
`McLeskey, and O’Regan ................................................................ 60
`
`
`2. A POSA Would Have A Reasonable ”xpeotation of Success in
`Combining Howell, MoLeskey. and O’Regan ............................... 6i)
`
`
`
`3.
`
`
`Every Limitation ls Disclosed By the Combination of Howell
`MoLeskey, and O Regan ................................................................ 62
`
`
`
`SECONDARY CONSIDERATIONS FAIL TO OWRCOME Til-1,;
`
`X.
`
`EVIDENCE OF OBVIOUSNESS ................................................................ 64
`
`A. There Is No Nexus to the Claimed Invention ........................................ 64
`
`B. AstraZeneca’s Secondary Considerations Arguments Fail ................... 66
`
`l. AstraZeneea Cannot Show Long-Felt Need .................................. 66
`
`iii
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`AstraZeneca Exhibit 2174 p. 4
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`

`

`IPR2017-00905
`
`Petition for Inter Partes Review
`
`2.
`
`The Results Were No1: Unexpected .. ............... .
`
`....... . .................. 66
`
`
`
`a. Dr. Robertson’s Arguments Are Contradicted By J. is Own
`Published Werk.66
`
`b.
`
`The Release Profile and Effect of Benzyl Benzoate Were
`Expected ..................................... . ........................................... 67
`
`iv
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`AstraZeneca Exhibit 2174 p. 5
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`

`

`1PR2017~00905
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`Petitien for [riser Farms Review
`
`TABLE OF AUTHORITIES
`
`
`
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`Pagis)
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`
`
`wEDERAL CASES
`
`Aicon Research, Ltd. v. Apatex Inc,
`687 F.3d 1362 (Fed. Cir. 2012) .......................................................................... SO
`
`Affergan, Inc. v. Apatex {no}
`754 F.3d 952 (Fed. Cir. 2014) ............................................................................ 65
`
`Affergan, Inc. v. Sande: Ina,
`
`
`
`7267.3(1 1286 Fed. Cir. 2013) .......................................................................... 32
`
`Alza Corp. v. Mylan Labs), Inc,
`
`--64 "$.3d 1286 (Fed. Cir. 2006)29
`
`
`
`In re Appiied Materiafs, Ina;
`
`692 F.3d 1289 (Ted. Cir. 2012) .......................................................................... 4O
`
`Asa‘raZeneca LP 12. firms}; Ltd. ;
`
`603 F. App’x 999 (Fed. Cir. 2015) ..................................................................... 65
`
`
`
`Asszeneca Pharms. LP, 61 al. v. A?gila Speciafties) Inc, e: 532.,
`
`
`N0. 1:15—cy-06039-RM3-KMW (3.N.J.) ........................................................ 4, 5
`
`AsfmZeI/zeccz Pharms. LP, 8;? 633. v. Glenmark Pharms. Inc.) USA,
`
`No. 1:15-CV-615 (DNJ) ...................................................................................... 5
`
`
`
`ASfraZefieca Pharms. LP, 82’ (If. v. fmofi’kwma, 3928.,
`
`
`
`
`N0. 1:16-CV-894-RM 3-KMW ( )NJ.) ................................................................ 5
`
`Ase‘raZeneca Pharms. LP, 616:3. v. IflnaPharma Licensing LLC‘,
`N0. 1:16-cv-1962—RMB-KMW {DNHS
`
`AstraZeneca Pharms. LP, e: {11. v. Mylar: Instituiz‘omf LLC,
`NO, 1:16-CV-4612wRM 3-KMW (DNJ) .............................................................. 5
`
`AstraZeneca Pharms. LP, e: 0:3. 12. Mflan Pfizarmx Inc. e5 (23.,
`N0. 1:1.5-cv-?009~RM3-KMW (TD.N.J.) .............................................................. 5
`
`
`
`R}
`
`AstraZeneca Exhibit 2174 p. 6
`
`

`

`IPR2017-00905
`
`Petition for 12238?” Fairies Review
`
`AstraZeneca Pharms. LP, er a]. v. Sagan: Pharms., Inc. e: 521.,
`N0. 1:14-CV~05539-RMB—KMW (D.N.J.) ............................................................ 5
`
`AstraZeneea Pharms. LP. 8: a3. 12. Sandoz Inc...
`
`No. 1:1—--eV—03547-RMB-KMW (D.N.J.) ............................................................ 5
`
`AstraZei/zeca Pharms. LP, 61‘ al. v. Teva Pkarms. USA, Inc. at 612.,
`
`No. 1:1 S-eV-7 889—RMB«KMW (D.N..1.) .............................................................. 5
`
`Aveniz’s Pharma SA. 1;. Hospim, Inc,
`743 F. Supp. 2d 305 (D. Del. 2010), afl’d, 675 F.3d 1324 (Fed. Cir.
`2012) ................................................................................................................... 34
`
`Cubist Pharms., Inc. v. Hospim, Inc,
`805 F.3d 1112 (Fed. Cir. 2015) .......................................................................... 56
`
`Dwamed Pharms., Inc. 1?. Warm}? Labs., 3:46..
`
`413 F. App’x 289 (Fed. Cir. 2011) ..................................................................... 51
`
`In re Ethicon, Inc,
`
`
`844 F.3d 1344 (Fed. Cir. 2017). ................................................................... 48, 5‘9
`
`Galderma 1252153., LP. 12. Toimar, Inc,
`737 F.3d 731 (Fed. Cir. 2013) ...................................................................... 28, 31
`
`Hoffmamiia Racke Inc. v. Apofex 1:46..
`”2'48 F.3d 1326 (Fed. Cir. 2014) ...................................................................... 3, 29
`
`In re Huai-szg K520,
`639 F. 3d 1057 (Fed. Cir. 2011) ......................................................................... 65
`
`In re ICON Health & Fitness,
`
`496 F.3d 1374 (Fed. Cir. 2007) .......................................................................... 36
`
`from. Gm}; Bareeie’ Co. 12. USA Sports, 1326.,
`392 F.3d 1317 (Fed. Cir. 2004) .......................................................................... 39
`
`KSR 172:7 Co. v. Teleflex Inc,
`550 US. 398 (2007) ............................................................................................ 47
`
`Merck (1’: Cafe 12. Gnosz’s S.P.A.,
`
`808 F.3d 829 (Fed. Cir. 2015) ............................................................................ 31
`
`Vi
`
`AstraZeneca Exhibit 2174 p. 7
`
`

`

`IPR2017-OO90‘5
`
`Petition for Inter Parties Review
`
`Merck (f; Co. v. Séocmfif 1252235., Inc?
`
`874 F.2d 804 Fed. Cir. 1989) ............................................................................ 28
`
`M6330 Minerafsg inc. v. Powerscrem has? Dist, Lick
`
`526 F. App’x 988 (Fed. Cir. 2013) ..................................................................... 31
`
`Ormca Corp. v. Align Tech, Inc.,
`
`498 F.3d 1307 (Fed, Cir. 2007') .....
`
`.................. . ................................. . ..... . ...... 3’?
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007)
`
`................................................................. 40, 66
`
`Pkmmanem Thémpeutics, 3:26. VJF’EaCeSL 5%.,
`
`491 F.3d 13-—2(Fed. 6120073.. ..... L .........................
`
`.............. . ...................... 33
`
`Purdue Pharma Prod. LP 1) Par Pkarm Inc
`
`
`
`3??r Appx9?8(sci Cir 2010) .................................. . .................................. E7
`
`Rmdaif Mg. v. Rea,
`733 F.3d 13% (Fed. Cir. 2013) .......................................................................... 3’?
`
`Samézma Inc. v. Par Pkarm., 3336.}
`
`
`
`694 F.3d 134-— (Fed. Cir. 2012) ...... . ........
`
`................................................... 55
`
`Smith & Nephew, 1m. 12. Rea,
`321?.3d13’F1 (Fed. Cir. 2013)
`
`...... ‘ ....... . ..............
`
`....... * ................. 30, 31
`
`Unigene Lam, Inc. v. Aporex, Inc,
`655 F.3d 1352 (Fed Cir. 2011) .......................................................................... 28
`
`
`FEDERAL STATUTES
`
`
`
`35 1.8.0 § 102(b) ..................................................................................................... 8
`
`35 USS. § 103,........ .............. . .................................................................................. '3
`
`35 U.S.C. §§ 311~19..... .............
`
`............ . ...... . ..... . .......... . ..... . ..................... fl .....
`
`..... 1
`
`35 U.S.C. §325(d) ..... L ............................. . ..................................
`
`.....
`
`................... 9
`
`Vii
`
`AstraZeneca Exhibit 2174 p. 8
`
`

`

`iPR2017~00905
`
`Petition for Inter Fortes Review
`
`
`
`
`PETITIONER’S EXHIBIT LIST
`
`
`
`001
`
`
`Exhibit 1002
`
`Complaint filed in AstraZeneca Pharms. LP 82? a3. 12.
`ImoPitarma, Ina, Case No. 1:16~CV-894 {DNJJ
`
`Exhibit 1003 i Proof of Service in AstraZeneca Pharms. LP er al. v.
`
`fnnoPkczrma, Inc, Case No. 1:16-CV-894 (DNJJ
`
`
`Exhibit 1004““ Order DismissingCase Without Prejudigo? AsfraZeneca Pfiérms.
`LP 32‘ a]. v. InnoPharma, Inc., Case No. 1:16—cvw894 (D.N.J.)
`
`
`
`Exhibit 1005
`
`Exhibit 1006
`
`Exhibit 1007
`
`Complaint filed in AsrraZeneca Pharms. LP 8: ad. 1;. Innon/zorma
`Licensing, LLC’, Case No. 1:16—0V—1962 (D.N.J.)
`
`
`
`
`
`Copy of Prosecution History for US. Patent No. 6,7743122
`
`
`downloaded from BAIR)
`
`
`
`”Ioweil et a1., Pharmacokfinerics, pharmacological and anti-
`
`{amour efiecz‘s ofthe specific anti—oestrogen ICI 182 ?8€} in
`
`
`women wim advanced breast cancer, 7’4 3RIT. J. CANCER 300—08
`
`(1996) (“Howell”)
`
`
`
`Exhibit 1008 McLeskey at 3.1., Tomoxfian-resismm‘fibrobiasz growthfactor-
`transfecs‘ed MCF-E’ {39335 are cross-resiszam‘ in vivo to {he
`antiestrogen 1C1 I82, 280 and fwo aromatase inhibitors, 4 CLIN.
`CANCER RESEARCH 697—71 1 (1998) (“McLeskey”)
`
`
`
`
`
`
`O’Regan at 211., Effects offhe Am‘iesz‘mgeos Tamoxifen,
`Toremifene, and {Cl 182, 2‘30 on Endometria! Cancer Growth,
`
`
`90 I. NAT’L CANCER iNST. 1552—1558 (1998) (“O’Regan”)
`
`
`Exhibit 1009
`
`Exhibit 1010
`
`Croat, Ass‘raZéneca Pharms. LP 12. 561125302: Inc, No. 14—03547
`(DNJ. July 29} 2015), ECF N0. 102
`
`AstraZeneca Exhibit 2174 p. 9
`
`

`

`IPMOYLOOE’JOS
`
`Petition for Inter Farms Review
`
`
`
`
`
`““xhibit 1011
`
`Institution Decigion in Myfian Pharms. Inc. v. AsémZeneca AB,
`Paper No. 11, IPR2016-01325 (RTAB. Dec. 14., 2016)
`
`
`
`
`
`
`
`" xhibit 1012
`
`"‘Xhibit 1013
`
`
`Dec aration ofDiane Burgess Ph. D. and Accompanying Exhibits
`
`Dec aratinn 036 Richard Bergsirom, PhD. and Accompanying
`Exh‘bits
`
`
`
`Exhibit 1014
`
`
`Decfaration of Dorraya 31-1115th. PhD. and Accompanying
`
`Exh'bits
`
`Exhibit 1015 Dec aration of Adrian Harris, M.B., PhD. and Accompanying
`Exhibits
`
`
`
`
`.’ Xhibit 1016 US. Patent No. 4,659,516 (“the ‘516 patent”)
`
`
`
`Exhibit 101’? AstraZeneca’s “reliIrinary Response in Myian Pharms. Inc. v.
`
`
`AstraZeneca AB. Paper No. 14, IPR2016-01326 (RTAB. Oct.
`18, 2016)
`
`
`
`
`
`
`
`xhibit 1018 DeLuca Fermulaiion omeal! Volnme Parenterals
`
`
`
`
`"HARMACEUTICAL DOSAGE FORMS: PARENTZRAL MEDECATIQNS
`
`VOLUM: 1 (Avis ed, 2d ed. 1992)
`
`
`
`Declaration Under 37 CPR. § 1.132 of Ronald J. Sawchuk in
`Application No. 1.’2‘./.285,88’1v
`
`Ekhibit 1020"""""" "Beclaratiofiffifier 37 CFR {$1. 132 of Paul'fiighard Gellert 1r;"""""
`Applicatien No. 101872384
`
`Exhibit 1021
`
`Félléiédexfi“ Labetflghailabie at:
`wwaccessdatafda. gm?drugsatfda_d0csz’1211361520 12102 1 34430 1
`930201b1.pclf
`
` Exhibit 1019
`
`
`
`
`Exhibit 1022 DiPirQ Cancepfis m Ciinicm’ Pharmacekérzeiz’cs {2010)
`
`Exhibit 1023
`
`Qiu. Developing Salid Om? Dogage Forms: Pharmaceuticai
`T1180132 and“ Pracffce (2009)
`
`W i
`
`x
`
`AstraZeneca Exhibit 2174 p. 10
`
`

`

`
`
`
`
`1PR2017-00905
`
`Petition for Inset” Parties Review
`
`
`Exhibit 1024
`
`
`
`Exhibit 1025
`
`Tozer, Introductian to Pkarmaeokineties and
`Pharmacadynamics: The Quantitative Basis ofDmg Therapy
`(2006)
`
`Caldwell, An Introdection 2‘0 Drug Disposition: The Basic
`Principles ofAbsorption, Distribm‘ion, Metabolism, and
`Excrezion, 23 Toxicologic Pathaiogy 102 (1995)
`
`Exhibit 1026 Wills, “Basic Pharmacodynamic Concepts and Models,”
`Pharmacodynamics and Drug Develepmem: Perspectives in
`Clinica! Pharmaeafogy (1994)
`
`
`
`Exhibit 1027 Derendorf, Handbook ofPharmacokineticfPharmacodynamic
`Correlation 53 (1995)
`
`
`Exhibit 1028 Mager, Seas’ing Pharmacodynamiesfiem fr? Vitm andPreeiinicaz’
`Animaf Studies :0 Humans) DRUG METAB. PHARMACOKINET.
`
`(2009)
`
`
`
`
`
`«lxhibit 1029
`
`Exhibit 1030
`
`
`
`
`Coiburn, Simuiz‘aneow Pfiarmaeakinetic/Pharmacodynamic
`Modding, PHARMACODYNAMICS AND DRUG DEVELOPMENT:
`PERSPECTIVES 1N CLINICAL PHARMACOLOGY (1994)
`
`
`
`
`“12317111033 Pharmaeekinefic and Pharmeeedynamic Considerasiom
`in Aniz’maiarial Dose Optimization, 57 ANTIMICROBIAL AGENTS
`
`& CHEMOTHERAPY 5802 (2013)
`
`
`Exhibit 1031 Wakeling at 211., A Pofem‘ Specific Pure Antieszrogen Wis}:
`Cfiniea! Potential, 51 CANCER RESEARCH 3867e3873 (1991)
`(“Wakeling 1991”)
`
`Exhibit 1032 Nichoison, R1. 61231., Responses To Pure Amiesxmgem (EC?
`164384, [CI 82 780) In Estrogen-Sensitive And —Resistanf
`Experimental! And Clinical Breast Cancer, ANNALS OF THE NEW
`
`
`
`YORK ACADEMY OF SCI‘NCES, Vol. 61:148-163 (1995)
`(“Nichoison”)
`
`AstraZeneca Exhibit 2174 p. 11
`
`

`

`IPR2017«00905
`
`Petition for later Fairies Review
`
`Exhibit 1033
`
`"Exhibit 1034
`
`Riffkin Castor 022 a? a VehiciefarPaigmmrgngtggf
`SteroidHarmones, 53 I. PWARM SCI. 89l—~895 (I964)
`(“Riffkin”)
`
`Finley, New Drug Being flamed z Breast Cancer Study; SAN
`ANTONIO EXPRESS-NEWS, Sept. 20, 1997
`
`
`
` :lxhibit 1035 Uges, 33.3623ch 03" Serwn if? Therapezizic Drug Moniforz‘ng {Md
`
`Cfinécaf Toxicofogyg 10 PHARMACEUTISCH WEEKBLAD
`
`SCIENTIFIC EDITION 185—88 (1988) (“Uges”)
`
`
`
`
`
`ixhibit 1036 Dukes at al Awfiusemts6:me eflecés ofa pure amioesz‘mgefi ICE
`382 $780: magneiic 163012631268 imaging of the Mews in
`
`ovariectomized monkeys, 135 J. :zNDOCRINOLOGY 239~247
`(1992) (“Dukes”)
`
`Exhibit 1037 W0 03(006064
`
`
`
`film—wifII‘ibit 1038
`
`DeFrienEI et a1. Inveséz’gasion afa New Pure Anrzesz‘mgen (1C!
`
`3 82 ?80) in Women 142253;: F}zmary Breast Cancer 54 CANE::R
`
`
`
`
`
`R SSARFH 41084114 (1994) (“)eFriend”)
`
`Exhibit 1039
`
`Osborne 6‘: 3.1., Camparisan sz‘ke Effects efa Pure Szemidaa’
`Amiesfmgm W151: W205i? ofTamoxiflzs/s in a Modei offiuman
`
`Breast Cancer, 87 .I. NAT’L CANCER INST. 746—750 (1995)
`(“Osborne 1995”)
`
`
`Exhibit 1040 Alan ’3‘, Wakeiing & Jean Bowler, EC} 382, 7'80: A New
`
`Antioestrogen wirh Ciinicai Potenéiaa’, 43 I. ST’I'ROID
`
`BIOCHEM. MOLEC. BIOL. 173ml 77 (1992) (“Wakeling
`1992”)
`
`
`Exhibit 10-:1
`
`Howell, A. 61:511., Gil/256a! Studies With Th6 Speczfic ‘Pure’
`Amiesz‘roggn 1C] 18.2780, THE BREAST, Vol. 5:192495 (1996)
`(“Hewell Breast 1996”)
`
`
`Exhibit 104-2
`
`Copy ofProsecution History for US. Patent No. 8,329,680
`(downloaded from PAIR)
`
`AstraZeneca Exhibit 2174 p. 12
`
`

`

`
`IPR201’”-00905
`
`Petition for Inter Partes Review
`
`Exhibit 1043
`
`Robertson, J.F.R. at 3.1., Duration OfRemissioa To 10’ 1829, F80
`
`Compared To Megestrol Acetate In Tamoxifen Resistant Breast
`
`Cancer, THO BREAST? Vol. 62186-189 (1997) (“Robertson
`199?”)
`
`Exhibit 1044
`
`Exhibit 1045
`
`Robertson, Fulvestrant Versa; Anastrozolefor the Treatment of
`Advanced Breast Carctaoma its Postmenopaasai Women: A
`Prospective Comoiaea’ Aaatysis ofTwo Mafticenter Triats, 98
`CANCER 229-38 {2003) (“Robertson 2003”)
`
`
`
`
`
`7 Ioweil, Response to a Speotfic Antioestrogea (ICI 182780) in
`
`
`
`
`
`Tamoxifen—Resistant Breast Cancer, 3 5 ANCBT 989—90 (1995)
`(“Howell 1995”)
`
`“Exhibit: 1046
`
`Copy of Prosecution Historymfor the US. Patent No. ’?,456,160
`(downloaded from PAIR)
`
`Exhibit 1047 US Patent No. 5,183,814 (“Dukes ‘814”)
`
`
`
`
`
`‘xhibit 1048
`
`Parczykfl K. 61: 31., Progesterone Receptor Repression by
`Estrogens in Rat Uterine Epithet’iat‘ Cells} 63 J. STEROID
`
`BIOCHEMISTRY & MOLECULAR BIOLOGY 309 (1997)
`
`Exhibit 1049 Anderson, Moaeis ofNew Aatt’oestrogen Acttoo a; 14120: Primary
`Tumours: 5 THE BREAST 186—91 (1996)
`
`
`Eithihit 1050
`
`
`Buzdar, Update or: Endocrine Therapyfor Breast Cancer, ‘r
`CLINICAL CANCER RESEARCH 52134 (1998)
`
`
` Exhibit 1051 J. CANCER 576-88 (1996)
`
`
`
`Exhibit 1052
`
`Howell, The Definition ofthe ‘No Change’ Category in Patients
`Treated with Endocrine Therapy and Chemotherapy for
`
`
`
`Advanced Carcinoma ofthe Breast, 24 EUR. J. GANG R CLIN.
`ONCOL. 156732 (1988)
`
`xii
`
`AstraZeneca Exhibit 2174 p. 13
`
`

`

`IPR2017—0090S
`
`Petition for [333323 P533383 Review
`
`
`
`
`
`
`Xhihit 1053
`
`
`
`Nicholson, “Pure Antioestrogens in, Breast Cancer: Experimental
`and Clinical Observations,” Sex Hormones and Antihormones 1'33
`Endocring Dependenz Parkway}: Baséc and Cffrzica! Aspecz‘s,
`Proceedings of an International Symposium, Milano 34160
`(1994) (“Nicholson”)
`
`
`
`Santen, Use ofAromarase Inhibiiors 3'33 Breast Carcmomaj 6
`
`ENDOCRINE-RELATED CANCER ?5-92 {1999)
`
`Exhibit 1055
`
`
`Tamongémfi‘esisrom Breast Comer 345 LANCE} 29—30 (1995)
`
`Exhibit 1054
`EP 0 346 014 Exhibit 1056 Hawaii Response 30 3:3 Specsfic A333ioes3roge32 {ICE 382?80) 3'33
`
`
`
`
`
`
`ixhibit 1057 Dukes Aoziuz‘emzroph3c Effects offl/ze Pure Antéoesz‘rogen [CI
`3 82 380333 Adm: F83333326 Mookeys {Macaw 39333853333333)
`Quantiz'csz‘fve Magnetic Resonance Imagirzg, 138 J.
`ENDOCRINOLOGY 203-09 (1993)
`
`
`
` 3 Xhibit 1060 Howell? FRivesfmm Revisfied: Efficacy and Safety ofihe 500w333g
`
`Wakeiingg The F3333331? ofNew P333332 Amioesz‘rogem 3'33 Chmicaf
`Breast Cancer, 25 BREAST CANCER RESEARCf-I & TREATMENT 1-
`9 (1993) (“Wakeling”)
`
`Exhibit 1059
`
`832533033129 Sorrogeo Recepmr Modufim‘ors (SEEMS)?
`BREASTCANCERDRG (last modified NOV. 5, 2015),
`http:/fwww.breastcancer.org/treatment/hormonaI/SBrms
`
`
`
`
`Dose, 11 CLINICAL BREAST CANCER 204-10 (2011)
`
`Exhibit 1061
`
`Thomas The Eflecfs offo 382 780 a Pure A3333 Oefirogen 033
`3338 Hypoffiaiamic—«meitary—Gonacfai Aims 33333:? on E33520metr3’53!
`Profifizméion in Pre-Menopausa? Women, 9 HUMAN
`REPRODUCTION 1991-96 (1994)
`
`Exhibit 1062
`
`Freireich Qmmimzwe Compomson of T02333733113 ofAnzz'cmcer
`Agent‘s in Moum R333 Hamster Dog, Monkey) and Man 50
`
`CANCER CHEMOTHERAPY REPORTS 219-44 (1966)
`
`l
`
`AstraZeneca Exhibit 2174 p. 14
`
`

`

`iPR201?-00905
`
`Petition for Inter Partes Review
`
`Exhibit 1063
`
`Equivalent Surface Area. Dosage Conversion Factors (206?)
`
`Ekhibit 1064
`
`Exhibit 1065
`
`Exhibit 1066
`
`Clarke, Anxiestrogen Resisinnce in Breasi Cancer and the Rafe of
`
`Estrogen Receptor Signaling, 22 ONCOGENE 7316—39 (2303)
`
`
`
`Gusterson, Do we now have a reievani animai modeifar 23mm:
`
`
`
`
`
`
`cancer? 1 BREAST CANC ,R . " SEARCH 2-4 (1999)
`
`
`
`Johnston, Ckangcs in Es rogen Receptor, Progesz‘emne
`Receptor, andpél? Expression in Tamoxifin-Resistam Human
`Breast Cancer, 55 CANCER RESEARCH 333188 {1995)
`
`Exhibit 1067 Waynforth, LASA Good Practice Guideiines Administration of
`Substances {Rat Moose Guinea Pig, Rabbi}? (065.1998)
`WWW.procedureswithcare.org.uk/iasa_administrationpdf
`
`Exhibit 1068 Mackey, Toierabifiw ofinimmwcuiar injectiom of Testosterone
`Ester in Oil Vehicle, 10 HUMAN REPRODUCTION 862-65 (1995)
`
`
`
`
`
`
`
`
`
`
`
`Exhibit 1069
`
`“ii—Eihibit 1070
`
`Karma “Role of Angiogencsis in the Transition to Hormone
`Independence and Acquisition of the Metastatic Phenotype,”
`Endocrinofogy (3fo66383 Cancer 169-86 (Manni ed” 1999)
`
`whwieilbaucitif, Changes in Tumour Bioiogicai Markers during
`Primary Systemic Ckemoiizempy (P83, 28 ANTICANCER
`
`Exhibit 1071
`
`Exhibit 1072
`
`Exhibit 1073
`
`
`
`: RESEARCH 1797—804 (2008)
`
`
`
`
`Smith, Analysis ofOiZ~Based Pharmaceuticaisfib J. AM“RICAN
`OIL CHEMISTS” SOCIETY 409-13 (1972)
`
`Spiegci & Noscworthy, Use ofNonaqueous Solvents in
`
`Parem‘erai Products, 52 J. PHARM. 8018. 917-2? (1963)
`(“Spiegel”)
`
`Tauchcr Sequentiaf Steroid Hormone Recepfor Measurements3}?
`Primary Breast Cancer with or without Intervening Primary
`
`
`
`
`{ Chemotherapfi 10 ENDOCRINE-R'3LA'fiZD CANCER 91-98 (2003)
`
`xiv
`
`AstraZeneca Exhibit 2174 p. 15
`
`

`

`IPR201?-009{}5
`
`Petition for latter ,Parres Review
`
`r“IM 3:. 33":13 g—i C3 7"
`
`Turner, Adméfifsrmz‘éon Oszsbsrances 30 Laboramry Animais:
`Routes ofAdministration and Factors to Consider, 50 I.
`AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
`
`600-13 (2011)
`
`
`
`
`
`Robertson, 33R. at 31., A Pars‘z‘aiiywfie’ma: Randams‘sea’,
`Multicentre Sma’y Comparing the Anti-Tumor Ejfieca‘s OfSingZe
`Doses (50, 125 and 259 mg) Offlong-Acting {LA} ‘Fasfaa’ex’
`(SC? 382, $80) With Tamongen In Postmenopazzsai Womm W321?
`
`Primary Breast Cancer Prior To Surgery,
`in 22ND ANNUAL SAN
`
`
`ANTONIO RR AST CANCER SYMPOSIUM, Abstract No. 28 (Dec. 8~«
`11, 1999) (“Robertson 1999”)
`
`Kohier, Pfasiim and Tissue Concenfraiions Foifowing
`Intramuscuiar Administration QfEmfienamar. Pharmacokénetic’s
`OfEfofenamat and Fluflmamic Acid in Pfasma, Syaovium, and
`Tissues qf‘Pczs‘iemfs with Chronic Peiyarfhritis qfi‘er
`Administration chm Oily Solution ofEtofimamat, 42
`
`
`ARZNZIMITTZL-«FORSCHUNG (English Abstract) (1 992)
`(“Kohler”)
`
`Jargensenfi Pizarmaceé’cinefic Szudies in Vofunteers affmmvenozss
`and Oral Cis (Z)~Fiupentixol and fm‘ramuscuiar Cis (Z)-
`FMpentiva Decanoafe in Viscoieo®, 18 EUR. J. CLIN.
`PHARMACOL. 355-60 (1980) (“Jorgensen”)
`
`
`Petition for {was Pastas Review in Myfcm Paarms. Inc. v.
`
`
`
`AstraZeneca 38, Paper No. 2, IPR2016-01326 PTA.
`. June
`29, 2016)
`
`Handboek ofPharmaceurical Exmpz’em‘s (Wade ed, 2d. ed.
`1994)
`‘
`
`
`
`
`Exhibit 10:6
`
`
` uxhibit 187”?
`
`
`
`
` ixhibit 1078
`
`Exhibit 1079
`
`
`
`Exhibit 1080
`
`FDA’S Inactive Ingredient Database (1996) (“11G”)
`
`Exhibit 1081
`
`Drugs@FDA Gfassary affirms, US. FOOD & DRUG
`ADMINISTRATION (last updated Feb. .2, 2012),
`http:ffwww.fda.gow’DrugstnformationOnDrugs/110ml}?9436.11tm
`
`
`
`AstraZeneca Exhibit 2174 p. 16
`
`

`

`IPR2017-00905
`
`
`Petition for [refer Barres Review
`
`
`
`Exhibit 1082
`
`Exhibit 1083
`
`Exhibit 1084
`
`
`
`
`
`
`
`Exhibit 1086
`
`Exhibit 188'?
`
`
`Exhibit 1088 '
`
`
`
`
`
`Adam, “Pharmacokinetics of Agents in Relation to Respense,”
`Endocrine Management of Cancer: Biclogicai Bases 112—24
`1988)
`
`jaselga, Phase II Study of Weekb» Inxravenous Recombifiam
`Humanized Ami-p] 85mm Monoclonal Antibcdy in Patients with
`HERKnezszverexpressing Meg‘asiaz‘ic Breast Cancer, 14 J.
`CLINICAL ONCOLOGY 73 144
`
`Fabian, Ciinicai Pharmacology of Tamoxifen in Patients with
`
`Breast Cancer: Correfaz‘ion waif: Cfim'cai Data, 48 CANCER 876-
`82 (1 981 )
`
`Goldenberg: Trastuzumab a Recombinant DNA-Derived
`Humanized Macadam! Antibody, a Novef Agem‘fcr the
`Treaz‘mem ofMeszafic Brew: Came?) 21 CLINICAL
`THERAPEUTICS 309-18 (1999)
`
`Wilkinson? Tamoxifen (Noivadex *) Therapy — Rationaiefor
`Leadmg Dosc Fcfiowed by Mcém‘cncnce Dcsefor Patéem‘s wish
`
`Metastatic Breast Cancer, 10 CANCER CHEMOTHERAPY
`
`PHARMACOLOGY 3365 (1982)
`
`
`
`Cepy ofPrcsecution History for the US. Patent No. 8366339
`(downloaded from PAIR)
`
`
`
`Wunsche Estrcgenic Regcfcta‘cn ofousz‘erétz mRNA in 3%)?ch
`
`and Mcfxgxam Enc’cmcs‘rfai Tsssuc "2'6 INT 3' CANCER 684-88
`(1998) (“Wunsche”)
`
`
`Chwalisz, Mcdciczfion of Oestrogemc Eficcfs by Progesterone
`
`
`
`Antagonists m {he Raf Uterus, 4 IUMAN REPRODUCTION UPDATE
`570v83 (1998) (“Chwalisz”)
`
`
`
`
`Robertson ruivcszmm (Fasiodex)mHow to Make a Good Drag
`Bezzer, 12 ONCOLOGIST W4 84 (200’?)
`
`
`
`xvi
`
`AstraZeneca Exhibit 2174 p. 17
`
`

`

`
`
`IPR2017~00905
`
`Petition for Maker Partes Review
`
`Exhibit 1091
`
`Ansel, “Dosage Form Design: Biopharmaceutic and........................................................................
`Pharmacokinetic Considerations,” Pharmaceutical! Dosage
`Farms and Drag Deiivery Systems 101—41 (7th ed. 1999)
`
`
`
`
`Exhibit 1092
`
`Lee, Szandard Deviation and Sz‘ana’ard Ermr ofz‘ke Meafi, 68
`KOREAN I. ANESTHESIOLOGY 220-23 (2015)
`
`
`Exhibit 11193
`
`Aitman, Standard Deviaz‘éwzs and Siaxdard Erma, 331 BMJ 903
`
`
`
`(2005)
`
`
`
`111133109
`
`
`
`
`
`
`
`
`
`Tse Bioavaz {nifty afParenz‘eva Dmgs I. Ingravmmgs mic?
`Intramusmfar 905885 34 I PARENTERAL DRUG ASSOCZATKEN
`
`409-21 {1980)
`
`Exhibit 1095
`
`
`Licciardi OMS Versus {aframuscuiar Prageszemnefax In Viz‘m
`
`
`
`
`Ferisifzaifion A Prospecs‘fve Randamzzesf Study 31 L ixRTILiTY 84:
`STERILIIY 614 18 (1999)
`
`Exhibit 1096 August 21,, 2008 Applicant Amendment and Response in
`Application No. 105872384
`
`Exhibit 1098
`
`Exhibit 1097
`
`
`
`Exhibit 1099
`
`
`Baiant-Gorgia, Pharmacokinezic Optimisation qfrhe Treatment
`ofPsychosz's, 25 CLIN. PHARMACOKINET. 2133-36 (1993)
`
`Chien, Soiubz‘iizaiion ofSlerozfds by Mumpie Co—Solveni Sysrems,
`23 CHEM. PHARM. BULL. 1085-90 (1975)
`
`Ford, “Parenterai Products,” Pharmaceiiz‘icx: The Science Of
`Dasage Form Design 359-«80 (Auiton ed“, 1988)
`
` Exhibit 1100
`
`
`Cuniiffe-Beamen “Biomethodoiogy and Surgicai Techniques,”
`The Mame in Biemea’icaf Research, Vemme [I]: Narmafi’ve
`
`Bioiagy, Immmolegy, and Husbandry 401—37 (Foster 1311., 1983)
`
`
`Exhibit 1101 Way! “Cosoivent Use in Inj estabie Farmuiations,” Ifijecméz’e
`Drag Deveiopmem: Techniqws £0 Reduce Pam and Irrimffoxz
`
`215436 (Gupta 6d,, 1999)
`
`xvii
`
`i
`
`AstraZeneca Exhibit 2174 p. 18
`
`

`

`1PR201 7-00905
`
`Petition fer Inter Partes Review
`
`Exhibit 1102
`
`Exhibit 1103
`
`1 Nema§ Escapfenrs and Tkeér Use in Ifijeczabie Products, 51 PDA
`J. PHARM. SCI. & TECH. 166-71 (1997)
`
`Ogasawara, Ejfiécfs ofExperimear/ztaf Ckemoendocrine 1"hempy
`mm a Combination ofa Pure Antiess‘rogen and 5-Fluomumcil
`m2 Han/1am Bream Cancer C5335 {inflamed in Nude Mice, 29
`
`
`SURGERY TODAY 1 9—56 (1999)
`
`
`
`Exhibit 1104 Oidham, “Mass Transport 1:0 Electrodes,” Ckemicai Kinefics ’39—
`143 (Bamford ed, 1986)
`
`Exhibit 1105
`
`Pewell, Campendmm OfExcipfemeor Parentera! Formuiations,
`
`52 PDA 113111112114. SCI. & Tear-1.238611 (1998)
`
`
`
`
`
`Exhibit 1106
`
`
`
`
`éxhihit 1107
`
`
`1 Exhibit 1108
`
`Remington ’5 Pharmaceutical Sciences 1538—39, 1545-50, 1686—
`88(18111 ed. 1990)
`
`Roberts, Investigation ofCosoivem Ejj’ects 0n fhe Salvation of
`A0? Reverse Miceffes £12 Supercrfs‘z'caf Ethane? 102 J.PI~1YS.
`CHEM. B 90?4-80 (1998)
`
`gawka, Pkysioiegfcaf Comeguenees onypokydmtfion: Exercise
`
`Performance and Thermoreguialion, 24 MEDICINE & SCIENCE IN
`SPORTS & EXERCISE 65110 (1992)
`
`
`
`127-28 (19:70)
`
`
`Exhibit 1110
`
`Ting, Solubiligz ofNaproxerz in Supercritica! Carban Dioxide
`
`with and 9921710312? (30302981235, 32 1ND. ENG. CHEM. RES. 1431—81
`
`(1993)
`
`Exhibit 1111
`
`Tse, Bioavaflabifiw afParem‘era! Drugs H. Parenteral? Doses
`
`
`
`Other Than Intravenous and Intramuscular Routes, 3
`J.
`
`
`PARENTERAL DRUG ASSOCIATEQN 48/ ~95 (1980)
`
`AstraZeneca Exhibit 2174 p. 19
`
`

`

`IPRQGI $03905
`
`Petition for Inter Partes Review
`
`USP 23W?mates¥harmgzopm~7fhe"""""""""""""""""""
` Exhibit 1113
`
`National Formulary 13-44 (1995)
`
`
`
`xix
`
`AstraZeneca Exhibit 2174 p. 20
`
`

`

`IPREGI’E-OOQGS
`
`Petition for Inter Panes Review
`
`TABLE OF ABBREVIATIONS
`
`3w[9-(454,5,S,5-pentafluoropentylsulphinyl)nonyl]oestra~ l,3,5(10)- Wiener-3,1375-
`
`diol ......
`
`.........................................
`
`........ _ ........... . .............. Fulvestrant
`
`Estrogen receptor—positive ...................................
`
`................ER+ or EEK-positive
`
`Estrogen receptor ........................................................................ER
`
`Estrogen-receptor downregulators ................................................................. ....ERDS
`
`Hormone-dependent........m...W... .....
`
`.......HD
`
`ICI 182,780 ............ , .......................
`
`............... . ......... . .......
`
`........... Fulvestrant
`
`Intramuscular ....................................
`
`....................... . .........................................1M
`
`Percent volume in volume ................ _ ................. r ....... r ............... r ........................ %V£\r
`
`Percent weight in volume ........................... l ....................................................... %w/V
`
`Person