Filed November 17, 2017
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`______________________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________________________________________
`
`
`FRESENIUS-KABI USA, LLC
`Petitioner
`
`v.
`
`ASTRAZENECA AB
`Patent Owner
`______________________________________________
`
`Case IPR2017-01913
`U.S. Patent No. 8,329,680
`______________________________________________
`
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE
` TO PETITION FOR INTER PARTES REVIEW
` OF U.S. PATENT NO. 8,329,680
`
`
`
`
`

`

`TABLE OF CONTENTS
`
`
`Case IPR2017-01913
`
`
`Page
`
`
`I.
`II.
`
`INTRODUCTION .......................................................................................... 1
`THE ’680 PATENT ........................................................................................ 7
`A.
`Specification ......................................................................................... 7
`B.
`Claims ................................................................................................... 8
`C.
`Prosecution History .............................................................................. 9
`III. THE DECISION OF THE BOARD IN THE MYLAN AND
`INNOPHARMA IPRS .................................................................................. 14
`IV. PERSON OF ORDINARY SKILL IN THE ART ....................................... 19
`V.
`CLAIM CONSTRUCTION ......................................................................... 20
`VI. STATE OF THE ART .................................................................................. 20
`A. Active: Fulvestrant Was Far From Established As An
`Efficacious Treatment ........................................................................ 20
`B. Amount: The Claimed Blood Plasma Levels Are
`Unconventional .................................................................................. 25
`C. Administration: Route, Excipients, And Result Are Intertwined
`And Not “Successfully Answered” By The Prior Art ........................ 28
`Conclusion On State Of The Art ........................................................ 36
`D.
`VII. THE ’680 PATENT IS VALID AND NOT OBVIOUS .............................. 36
`A.
`Law Of Obviousness .......................................................................... 36
`B. Ground One: Howell .......................................................................... 38
`1.
`The Gellert Declaration Does Not Provide A Motivation
`To Make The Formulation Of The Invention .......................... 39
`No Expectation Of Success ...................................................... 42
`2.
`C. Ground Two: Howell In Combination With McLeskey .................... 46
`1.
`Petitioner Cannot Cure The Lack Of Efficacy Or
`Pharmacokinetic Data In McLeskey ........................................ 48
`
`i
`
`

`

`TABLE OF CONTENTS
`(Continued)
`
`Case IPR2017-01913
`
`
`Page
`
`
`2.
`
`3.
`
`Petitioner Cannot Cure The Unpredictability Of
`Compositional Differences On Intramuscular
`Administration .......................................................................... 53
`Petitioner Cannot Change The Fact McLeskey Involves
`Subcutaneous Injection While Howell Involves
`Intramuscular Injection ............................................................ 55
`D. Ground Three: Howell In Combination With McLeskey And
`O’Regan .............................................................................................. 58
`Ground Four: Howell In Combination With McLeskey,
`O’Regan, And DeFriend .................................................................... 59
`VIII. OBJECTIVE INDICIA DEMONSTRATE THE NONOBVIOUS
`NATURE OF THE CLAIMED METHOD OF TREATMENT .................. 61
`IX. CONCLUSION ............................................................................................. 62
`
`
`E.
`
`ii
`
`

`

`Case IPR2017-01913
`
`Page(s)
`
`
`TABLE OF AUTHORITIES
`(Continued)
`
`Cases
`Apple, Inc. v. Contentguard Holdings, Inc.,
`IPR2015-00357, 2015 WL 9899009 (P.T.A.B. June 29, 2015) ......................... 58
`Bumble Bee Foods, LLC v. Kowalski,
`IPR2014-00224, 2014 WL 2584188 (P.T.A.B. June 5, 2014) ........................... 42
`Daiichi Sankyo Co. v. Matrix Labs., Ltd.,
`619 F.3d 1346 (Fed. Cir. 2010) .......................................................................... 57
`Eisai Co. v. Dr. Reddy’s Labs., Ltd.,
`533 F.3d 1353 (Fed. Cir. 2008) .......................................................................... 57
`Innogenetics, N.V. v. Abbott Labs.,
`512 F.3d 1363 (Fed. Cir. 2008) ......................................................................... 50
`In re Cyclobenzaprine HCl Extended-Release Capsule Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) ................................................................... 37, 42
`In re Klein,
`647 F.3d 1343 (Fed. Cir. 2011) .......................................................................... 51
`In re NTP, Inc.,
`654 F.3d 1279 (Fed. Cir. 2011) ................................................................... 54, 61
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ..................................................................................... 36, 47
`LG Elecs., Inc. v. Innovative Display Techs. LLC,
`IPR2015-00496, 2015 WL 4481790 (P.T.A.B. July 20, 2015) .......... 1, 3, 19, 62
`Medtronic, Inc. v. Nuvasive, Inc.,
`IPR2014-00076, 2014 WL 1410363 (P.T.A.B. Apr. 8, 2014) ........................... 41
`Merck Sharp & Dohme Corp v. Sandoz Inc.,
`No. 3:12–cv–03289–PGS–LHG,
`2015 WL 5089543 (D.N.J. Aug. 27, 2015) ........................................................ 41
`
`i
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`

`

`Case IPR2017-01913
`
`Page(s)
`
`
`TABLE OF AUTHORITIES
`(Continued)
`
`Nautilus Hyosung Inc. v. Diebold, Inc.,
`IPR2016-00633, 2016 WL 5219979 (P.T.A.B. Aug. 22, 2016) ........................ 17
`Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc.,
`520 F.3d 1358 (Fed. Cir. 2008) ................................................................... 38, 40
`Synaptics Inc. v. Amkor Tech., Inc.,
`IPR2017-00085, 2017 WL 1403668 (P.T.A.B. Apr. 18, 2017) .......................... 7
`Unigene Labs., Inc. v. Apotex, Inc.,
`655 F.3d 1352 (Fed. Cir. 2011) ................................................................... 36, 38
`Universal Remote Control, Inc. v. Uei Cayman, Inc.,
`IPR2014-01111, 2014 WL 6737921 (P.T.A.B. Nov. 24, 2014) ......................... 58
`Regulations
`21 C.F.R. §314.94(a)(9)(iii) .................................................................................... 33
`21 C.F.R. §314.127(a)(8)(ii)(B) .............................................................................. 33
`35 U.S.C. §325(d) ..................................................................................................... 7
`MPEP §2141.02 ................................................................................................ 24, 37
`
`
`ii
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`

`

`Case IPR2017-01913
`
`LIST OF EXHIBITS
`
`Declaration of Lisbeth Illum, Ph.D. In Support Of Patent
`Owner’s Prelimin Res 0 onse
`
`Declaration of John F. R. Robertson, M.D. In Support Of
`Patent Owner’s Prelimin Res - onse
`
`Declaration of Ronald J. Sawchuk, Ph.D. In Support Of Patent
`Owner’s Prelimin Res 0 onse
`
`Angelo Di Leo et al., Results ofthe CONFIRM Phase III Trial
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`Postmenopausal Women With Estrogen Receptor-Positive
`Advanced Breast Cancer, 28 J. CLIN. ONCOL. 4594 (2010) (“Di
`Leo 2010”
`
`Angelo Di Leo et al., Final Overall Survival: Fulvestrant 500
`mg vs 250 mg in the Randomized CONFIRM Trial, 106 J.
`NAT’L CANCER INST. l 2014 “Di Leo 2014”
`
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`postmenopausal Japanese women with advanced breast
`cancer: resultsfrom a double-blind, phase II comparative
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`
`Kathleen I. Pritchard et al., Results ofa phase II study
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`“FINDER 2”
`
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`
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`
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`
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`Su. . 1995
`“Jordan Su. 0 . 1995”
`
`Gabriel N. Hortobagyi et al., Anastrozole (Arimidex‘s), a New
`Aromatase Inhibitorfor Advanced Breast Cancer: Mechanism
`ofAction and Role in Management, 16 CANCER INVESTIGATION
`385 1998
`“Hortoba 3 i Cancer Investi ation 1998”
`
`
`
`Exhibit
`
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
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`2009
`
`2010
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`2011
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`2012
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`

`

`2013
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`2014
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`2015
`
`2016
`
`2017
`
`2018
`
`2019
`
`2020
`
`2021
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`2022
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`2023
`
`2024
`
`
`
`Case IPR2017-01913
`
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`and reduces thefrequency ofacquired anti-oestrogen
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`
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`
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`1997”
`
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`ONCOL. 348 1998 “Buzdar Clin. Oncol. 1998”
`
`A. Howell et al., Response after withdrawal oftamoxifen and
`progestogens in advanced breast cancer, 3 ANNALS ONCOL.
`611 1992
`“Howell 1992”
`
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`Cancer, 35 ANN. REV. PHARMACOL. TOXICOL. 195 (1995)
`“Jordan 1995”
`
`Monica Morrow et al., Molecular Mechanisms ofResistance to
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`1993
`“Morrow”
`
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`14 CRIT. REVS. ONCOL. HEMATOL. 173 1993
`“Wiebe”
`
`V. Craig Jordan, The Strategic Use ofAntiestrogens to Control
`the Development and Growth ofBreast Cancer, 70 CANCER 977
`Su o. 1992
`“Jordan S . . 1992”
`
`V. Craig Jordan, The Role of Tamoxifen in the Treatment and
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`
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`“Minton”
`
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`(SERMs), 4 CURRENT PHARM. DESIGN 71 (1998) (“Grese
`1998”
`
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`1998”
`
`
`
`ii
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`
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`
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`
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`
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`
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`
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`ofFulvestrant Prolonged-Release Intramuscular Injection in
`Postmenopausal Women Awaiting Surgeryfor Primary Breast
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`2003”
`
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`
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`
`
`
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`
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`
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`
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`
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`
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`
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`
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`
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`ONCOL. 4530 2009 “Robertson 2009”
`
`John F.R- Robertson et al., Fulvestrant 500 mg versus
`anastrozole 1 mgfor thefirst-line treatment ofadvanced breast
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`2012”
`
`John F.R. Robertson et al., Fulvestrant 500 mg versus
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`
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`
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`
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`
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`
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`
`
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