IPR2017-01912
`Petition for Inter Partes Review
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
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`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`FRESENIUS-KABI USA LLC,
`Petitioner
`
`v.
`
`ASTRAZENECA AB,
`Patent Owner
`
`
`
`
`
`
`
`
`
`Case IPR2017-01912
`Patent No. 8,466,139
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,466,139
`UNDER 35 U.S.C. §§ 311-319 AND 37 C.F.R. § 42.100 ET SEQ.
`
`Mail Stop: Patent Board
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`

`

`IPR2017-01912
`Petition for Inter Partes Review
`
`
`TABLE OF CONTENTS
`
`
`
`I.
`
`INTRODUCTION .......................................................................................... 1
`
`II. NOTICES, STATEMENTS AND PAYMENT OF FEES ............................. 5
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`F.
`
`Real Party In Interest Under 37 C.F.R. § 42.8(b)(1) ............................ 5
`
`Related Matters Under 37 C.F.R. § 42.8(b)(2) .................................... 5
`
`Lead and Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3) ................. 7
`
`Service Information Under 37 C.F.R. § 42.8(b)(4) .............................. 7
`
`Grounds for Standing Under 37 C.F.R. § 42.104(a) ............................ 7
`
`Fees Under 37 C.F.R. § 42.103 ............................................................ 7
`
`III.
`
`IDENTIFICATION OF CHALLENGE UNDER 37 C.F.R. §
`42.104(B) ........................................................................................................ 8
`
`IV. FRESENIUS KABI’S GROUNDS OF UNPATENTABILITY ARE
`DISTINCT FROM THOSE PRESENTED BY MYLAN .............................. 9
`
`V. OVERVIEW OF THE ‘139 PATENT AND PROSECUTION
`HISTORY ..................................................................................................... 12
`
`A.
`
`B.
`
`The ‘139 Patent .................................................................................. 12
`
`The Prosecution History of the ‘680 and ‘139 Patents ...................... 14
`
`1.
`
`2.
`
`The Prosecution History of the ‘680 Patent ............................. 14
`
`The Prosecution History of the ‘139 Patent ............................. 17
`
`VI. LEVEL OF ORDINARY SKILL IN THE ART .......................................... 17
`
`VII. CLAIM CONSTRUCTION ......................................................................... 18
`
`A.
`
`“Achieves” .......................................................................................... 18
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`
`B.
`
`“Attained” ........................................................................................... 18
`
`C. Wherein the method achieves a blood plasma fulvestrant
`concentration of at least 2.5 ngml-1 for at least 2 weeks” ................. 19
`
`D.
`
`“Wherein…the blood plasma fulvestrant concentration is
`attained for at least 4 weeks” .............................................................. 19
`
`VIII. SCOPE AND CONTENT OF THE PRIOR ART ........................................ 19
`
`A.
`
`The Prior Art Discloses All Limitations of the Challenged
`Claims ................................................................................................. 19
`
`1.
`
`Howell Closely Matches the Claimed Invention ..................... 19
`
`2. McLeskey Discloses the Claimed Formulation and Was
`Not a “Treatment Failure” ....................................................... 22
`
`3.
`
`O’Regan Confirms the Route of Administration ..................... 26
`
`B. AstraZeneca’s Attempts to Detract From These Prior Art
`Teachings Fail .................................................................................... 26
`
`1.
`
`2.
`
`3.
`
`AstraZeneca’s Purported “Lead Compound” Analysis is
`Inapplicable .............................................................................. 27
`
`AstraZeneca’s Efficacy Arguments Are Contrary to Law ...... 29
`
`AstraZeneca’s Claims of Unpredictability Are Specious ........ 29
`
`a.
`
`b.
`
`The Pharmacokinetic Limitations Are Expressly
`Disclosed in the Prior Art .............................................. 30
`
`It Was Well-Known That Fulvestrant Was
`Administered Intramuscularly ....................................... 32
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`
`c.
`
`The Claimed Combination of Excipients Were
`Neither Unexpected Nor Surprising .............................. 33
`
`IX. DETAILED EXPLANATION AND SUPPORTING EVIDENCE ............. 36
`
`A. Ground 1: The Challenged Claims Are Obvious Over Howell ........ 36
`
`1.
`
`2.
`
`3.
`
`A POSA Would Have Been Motivated to Develop a
`Formulation to Achieve the Results Reported in Howell ........ 36
`
`A POSA Would Have A Reasonable Expectation of
`Success in Developing a Formulation to Achieve the
`Howell Results ......................................................................... 39
`
`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 .................................................................................... 45
`
`1.
`
`A POSA Would Have Been Motivated to Combine
`Howell and McLeskey ............................................................. 45
`
`a.
`
`b.
`
`The Target Fulvestrant Concentration in Howell
`Would Have Led a Skilled Formulator to
`McLeskey ...................................................................... 45
`
`The Record Confirms the Motivation to Combine
`Howell and McLeskey ................................................... 48
`
`2.
`
`A POSA Would Have A Reasonable Expectation of
`Success in Administering the McLeskey Formulation
`Intramuscularly to Achieve the Results Reported in
`Howell ...................................................................................... 53
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`
`3.
`
`Every Limitation Is Disclosed By the Combination of
`Howell and McLeskey ............................................................. 58
`
`C. Ground 3: The Challenged Claims Are Obvious Over Howell,
`McLeskey, and O’Regan .................................................................... 61
`
`1.
`
`2.
`
`3.
`
`A POSA Would Have Been Motivated to Combine
`Howell, McLeskey, and O’Regan ............................................ 61
`
`A POSA Would Have A Reasonable Expectation of
`Success in Combining Howell, McLeskey, and O’Regan ....... 62
`
`Every Limitation Is Disclosed By the Combination of
`Howell, McLeskey, and O’Regan ............................................ 63
`
`X.
`
`SECONDARY CONSIDERATIONS FAIL TO OVERCOME THE
`EVIDENCE OF OBVIOUSNESS ............................................................... 66
`
`A.
`
`There Is No Nexus to the Claimed Invention ..................................... 66
`
`B. AstraZeneca’s Secondary Considerations Arguments Fail ................ 68
`
`1.
`
`2.
`
`AstraZeneca Cannot Show Long-Felt Need ............................ 68
`
`The Results Were Not Unexpected .......................................... 68
`
`a.
`
`b.
`
`Dr. Robertson’s Arguments Are Contradicted By
`His Own Published Work .............................................. 69
`
`The Release Profile and Effect of Benzyl Benzoate
`Were Expected ............................................................... 69
`
`XI. CONCLUSION ............................................................................................. 70
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`TABLE OF AUTHORITIES
`
`Cases
`
`Alcon Research, Ltd. v. Apotex Inc.,
` 687 F.3d 1362 (Fed. Cir. 2012) ........................................................................... 51
`Allergan, Inc. v. Apotex Inc.,
` 754 F.3d 952 (Fed. Cir. 2014) ............................................................................. 67
`Allergan, Inc. v. Sandoz Inc.,
` 726 F.3d 1286 (Fed. Cir. 2013) ........................................................................... 32
`Alza Corp. v. Mylan Labs., Inc.,
` 464 F.3d 1286 (Fed. Cir. 2006) ........................................................................... 29
`AstraZeneca LP v. Breath Ltd.,
` 603 F. App’x 999 (Fed. Cir. 2015) ..................................................................... 67
`AstraZeneca Pharms. LP v. Dr. Reddy’s Laboratories, Inc.,
`No. 1:17-cv-926-RMB-KMW (D.N.J.) ................................................................. 6
`AstraZeneca Pharms. LP v. Glenmark Pharms. Inc.,
`USA, No. 1:15-cv-615 (D.N.J.) .............................................................................. 5
`AstraZeneca Pharms. LP v. InnoPharma Licensing LLC,
`No. 1:16-cv-1962-RMB-KMW (D.N.J.) ............................................................... 5
`AstraZeneca Pharms. LP v. InnoPharma, Inc.,
`No. 1:16-cv-894-MB-KMW (D.N.J.) .................................................................... 5
`AstraZeneca Pharms. LP v. Mylan Institutional LLC,
`No. 1:16-cv-4612-RMB-KMW (D.N.J.) ............................................................... 6
`AstraZeneca Pharms. LP v. Mylan Pharms. Inc.,
`No. 1:15-cv-7009-RMB-KMW (D.N.J.) ............................................................... 6
`AstraZeneca Pharms. LP v. Sagent Pharms., Inc.,
`No. 1:14-cv-05539-RMB-KMW (D.N.J.) ............................................................. 5
`AstraZeneca Pharms. LP v. Sandoz Inc.,
`No. 1:14-cv-03547-RMB-KMW (D.N.J.) ............................................................. 5
`AstraZeneca Pharms. LP v. Teva Pharms. USA, Inc.,
`No. 1:15-cv-7889-RMB-KMW (D.N.J.) ............................................................... 5
`AstraZeneca Pharms. LP. v. Agila Specialties, Inc.,
`No. 1:15-cv-06039-RMB-KMW (D.N.J.) ............................................................. 5
`Aventis Pharma S.A. v. Hospira, Inc.,
` 743 F. Supp. 2d 305 (D. Del. 2010), aff’d, 675 F.3d 1324 (Fed. Cir.
`2012) .................................................................................................................... 34
`Covidien LP v. Ethicon Endo-Surgery, Inc.,
` IPR2013-00209, Paper 28 at 11 (June 9, 2014) .................................................. 17
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`IPR2017-01912
`Petition for Inter Partes Review
`
`Cubist Pharms., Inc. v. Hospira, Inc.,
` 805 F.3d 1112 (Fed. Cir. 2015) ........................................................................... 57
`Duramed Pharms., Inc. v. Watson Labs., Inc.,
` 413 F. App’x 289 (Fed. Cir. 2011) ..................................................................... 52
`Galderma Labs., L.P. v. Tolmar, Inc.,
` 737 F.3d 731 (Fed. Cir. 2013) ...................................................................... 28, 31
`Hoffmann-La Roche Inc. v. Apotex Inc.,
` 748 F.3d 1326 (Fed. Cir. 2014) ...................................................................... 4, 29
`In re Applied Materials, Inc.,
` 692 F.3d 1289 (Fed. Cir. 2012) ........................................................................... 40
`In re Ethicon, Inc.,
` 844 F.3d 1344 (Fed. Cir. 2017) .................................................................... 49, 50
`In re Huai-Hung Kao,
` 639 F.3d 1057 (Fed. Cir. 2011) ........................................................................... 67
`In re ICON Health & Fitness,
` 496 F.3d 1374 (Fed. Cir. 2007) ........................................................................... 37
`Iron Grip Barbell Co. v. USA Sports, Inc.,
` 392 F.3d 1317 (Fed. Cir. 2004) ........................................................................... 40
`KSR Int’l Co. v. Teleflex Inc.,
` 550 U.S. 398 (2007) ............................................................................................ 48
`Merck & Cie v. Gnosis S.P.A.,
` 808 F.3d 829 (Fed. Cir. 2015) ............................................................................. 31
`Merck & Co. v. Biocraft Labs., Inc.,
` 874 F.2d 804 (Fed. Cir. 1989) ............................................................................. 27
`Merck & Co. v. Teva Pharms. USA, Inc.,
` 395 F.3d 1364 (Fed. Cir. 2005) ........................................................................... 67
`Metso Minerals, Inc. v. Powerscreen Int’l Distrib., Ltd.,
` 526 F. App’x 988 (Fed. Cir. 2013), cert. denied, 137 S. Ct. 297 (2016) ........... 31
`Ormco Corp. v. Align Tech., Inc.,
` 498 F.3d 1307 (Fed. Cir. 2007) ........................................................................... 37
`Perfect Web Techs., Inc. v. InfoUSA, Inc.,
` 587 F.3d 1324 (Fed. Cir. 2009) ........................................................................... 68
`Pfizer, Inc. v. Apotex, Inc.,
` 480 F.3d 1348 (Fed. Cir. 2007) .................................................................... 40, 68
`PharmaStem Therapeutics, Inc. v. ViaCell, Inc.,
` 491 F.3d 1342 (Fed. Cir. 2007) ........................................................................... 33
`Purdue Pharma Prods. L.P. v. Par Pharm., Inc.,
` 377 F. App’x 978 (Fed. Cir. 2010) ..................................................................... 27
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`Randall Mfg. v. Rea,
` 733 F.3d 1355 (Fed. Cir. 2013) ........................................................................... 37
`Santarus, Inc. v. Par Pharm., Inc.,
` 694 F.3d 1344 (Fed. Cir. 2012) ........................................................................... 56
`Smith & Nephew, Inc. v. Rea,
` 721 F.3d 1371 (Fed. Cir. 2013) ........................................................................... 31
`Unigene Laboratories, Inc. v. Apotex, Inc.,
` 655 F.3d 1352 (Fed. Cir. 2011) ........................................................................... 28
`
`
`Statutory Authorities
`
`35 U.S.C. § 102(b) ..................................................................................................... 8
`35 U.S.C. § 103 .......................................................................................................... 8
`35 U.S.C. § 325(d) ..................................................................................................... 9
`35 U.S.C. §§ 311-19 ................................................................................................... 1
`
`Rules and Regulations
`
`37 C.F.R. § 42.10(b) .................................................................................................. 7
`37 C.F.R. § 42.100 ..................................................................................................... 1
`37 C.F.R. § 42.103 ..................................................................................................... 7
`37 C.F.R. § 42.104(a) ................................................................................................ 7
`37 C.F.R. § 42.104(b) ................................................................................................ 8
`37 C.F.R. § 42.22(a) .................................................................................................. 8
`37 C.F.R. § 42.24(c) ................................................................................................ 71
`37 C.F.R. § 42.6(e) .................................................................................................. 72
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 5
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 5
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 7
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 7
`37 C.F.R. §§ 42.104(b)(1)-(2) .................................................................................... 8
`
`
`Additional Authorities
`
`U.S. Patent No. 5,183,814 ........................................................................................ 13
`U.S. Patent No. 8,329,680 .......................................................................................... 1
`U.S. Patent No. 8,466,139 .......................................................................................... 2
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`PETITIONER’S EXHIBIT LIST
`
`Exhibit No. Description
`
`Exhibit 1001 U.S. Patent No. 8,466,139 (“the ‘139 patent”)
`
`Exhibit 1002 Reserved
`
`Exhibit 1003 Reserved
`
`Exhibit 1004 Reserved
`
`Exhibit 1005 Reserved
`
`Exhibit 1006 Copy of Prosecution History for U.S. Patent No. 6,774,122
`(downloaded from PAIR)
`
`Exhibit 1007 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”)
`
`Exhibit 1008 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”)
`
`Exhibit 1009 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”)
`
`Exhibit 1010 Order, AstraZeneca Pharms. LP v. Sandoz Inc., No. 14–03547
`(D.N.J. July 29, 2015), ECF No. 102
`
`Exhibit 1011
`
`Institution Decision in Mylan Pharms. Inc. v. AstraZeneca AB,
`Paper No. 11, IPR2016-01325 (P.T.A.B. Dec. 14, 2016)
`
`Exhibit 1012 Declaration of Diane Burgess, Ph.D. and Accompanying
`Exhibits
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`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1013 Declaration of Richard Bergstrom, Ph.D. and Accompanying
`Exhibits
`
`Exhibit 1014 Declaration of Dorraya El-Ashry, Ph.D. and Accompanying
`Exhibits
`
`Exhibit 1015 Declaration of Adrian Harris, M.B., Ph.D. and Accompanying
`Exhibits
`
`Exhibit 1016 U.S. Patent No. 4,659,516 (“the ‘516 patent”)
`
`Exhibit 1017 AstraZeneca’s Preliminary Response in Mylan Pharms. Inc. v.
`AstraZeneca AB, Paper No. 14, IPR2016-01326 (P.T.A.B. Oct.
`18, 2016)
`
`Exhibit 1018 DeLuca, Formulation of Small Volume Parenterals,
`PHARMACEUTICAL DOSAGE FORMS: PARENTERAL MEDICATIONS
`VOLUME 1 (Avis ed., 2d ed. 1992)
`
`Exhibit 1019 Declaration Under 37 C.F.R. § 1.132 of Ronald J. Sawchuk in
`Application No. 12/285,887
`
`Exhibit 1020 Declaration Under 37 C.F.R. § 1.132 of Paul Richard Gellert in
`Application No. 10/872,784
`
`Exhibit 1021
`
`Faslodex® Label, available at:
`www.accessdata.fda.gov/drugsatfda_docs/label/2012/021344s01
`9s020lbl.pdf
`
`Exhibit 1022 DiPiro, Concepts in Clinical Pharmacokinetics (2010)
`
`Exhibit 1023 Qiu, Developing Solid Oral Dosage Forms: Pharmaceutical
`Theory and Practice (2009)
`
`Exhibit 1024 Tozer, Introduction to Pharmacokinetics and
`Pharmacodynamics: The Quantitative Basis of Drug Therapy
`(2006)
`
`Exhibit 1025 Caldwell, An Introduction to Drug Disposition: The Basic
`Principles of Absorption, Distribution, Metabolism, and
`Excretion, 23 Toxicologic Pathology 102 (1995)
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`IPR2017-01912
`Petition for Inter Partes Review
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`Exhibit 1026 Wills, “Basic Pharmacodynamic Concepts and Models,”
`Pharmacodynamics and Drug Development: Perspectives in
`Clinical Pharmacology (1994)
`
`Exhibit 1027 Derendorf, Handbook of Pharmacokinetic/Pharmacodynamic
`Correlation 53 (1995)
`
`Exhibit 1028 Mager, Scaling Pharmacodynamics from In Vitro and
`Preclinical Animal Studies to Humans, DRUG METAB.
`PHARMACOKINET. (2009)
`
`Exhibit 1029 Colburn, Simultaneous Pharmacokinetic/Pharmacodynamic
`Modeling, PHARMACODYNAMICS AND DRUG DEVELOPMENT:
`PERSPECTIVES IN CLINICAL PHARMACOLOGY (1994)
`
`Exhibit 1030 White, Pharmacokinetic and Pharmacodynamic Considerations
`in Antimalarial Dose Optimization, 57 ANTIMICROBIAL AGENTS
`& CHEMOTHERAPY 5802 (2013)
`
`Exhibit 1031 Wakeling et al., A Potent Specific Pure Antiestrogen with
`Clinical Potential, 51 CANCER RESEARCH 3867–3873 (1991)
`(“Wakeling 1991”)
`
`Exhibit 1032 Nicholson, R.I. et al., Responses To Pure Antiestrogens (ICI
`164384, ICI 82780) In Estrogen-Sensitive And –Resistant
`Experimental And Clinical Breast Cancer, ANNALS OF THE NEW
`YORK ACADEMY OF SCIENCES, Vol. 61:148-163 (1995)
`(“Nicholson”)
`
`Exhibit 1033 Riffkin, Castor Oil as a Vehicle for Parenteral Administration of
`Steroid Hormones, 53 J. PHARM. SCI. 891–895 (1964)
`(“Riffkin”)
`
`Exhibit 1034
`
`Finley, New Drug Being Tested in Breast Cancer Study, SAN
`ANTONIO EXPRESS-NEWS, Sept. 20, 1997
`
`Exhibit 1035 Uges, Plasma or Serum in Therapeutic Drug Monitoring and
`Clinical Toxicology, 10 PHARMACEUTISCH WEEKBLAD
`SCIENTIFIC EDITION 185–88 (1988) (“Uges”)
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1036 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”)
`
`Exhibit 1037 WO 03/006064
`
`Exhibit 1038 DeFriend et al., Investigation of a New Pure Antiestrogen (ICI
`182780) in Women with Primary Breast Cancer, 54 CANCER
`RESEARCH 408–414 (1994) (“DeFriend”)
`
`Exhibit 1039 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”)
`
`Exhibit 1040 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”)
`
`Exhibit 1041 Howell, A. et al., Clinical Studies With The Specific ‘Pure’
`Antiestrogen ICI 182780, THE BREAST, Vol. 5:192-195 (1996)
`(“Howell Breast 1996”)
`
`Exhibit 1042 Copy of Prosecution History for U.S. Patent No. 8,329,680
`(downloaded from PAIR)
`
`Exhibit 1043 Robertson, J.F.R. et al., Duration Of Remission To ICI 182,780
`Compared To Megestrol Acetate In Tamoxifen Resistant Breast
`Cancer, THE BREAST, Vol. 6:186-189 (1997) (“Robertson
`1997”)
`
`Exhibit 1044 Robertson, Fulvestrant Versus Anastrozole for the Treatment of
`Advanced Breast Carcinoma in Postmenopausal Women: A
`Prospective Combined Analysis of Two Multicenter Trials, 98
`CANCER 229-38 (2003) (“Robertson 2003”)
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1045 Howell, Response to a Specific Antioestrogen (ICI 182780) in
`Tamoxifen-Resistant Breast Cancer, 345 LANCET 989-90 (1995)
`(“Howell 1995”)
`
`Exhibit 1046 Copy of Prosecution History for the U.S. Patent No. 7,456,160
`(downloaded from PAIR)
`
`Exhibit 1047 U.S. Patent No. 5,183,814 (“Dukes ‘814”)
`
`Exhibit 1048
`
`Parczyk, K. et al., Progesterone Receptor Repression by
`Estrogens in Rat Uterine Epithelial Cells, 63 J. STEROID
`BIOCHEMISTRY & MOLECULAR BIOLOGY 309 (1997)
`
`Exhibit 1049 Anderson, Models of New Antioestrogen Action in Vivo: Primary
`Tumours, 5 THE BREAST 186-91 (1996)
`
`Exhibit 1050 Buzdar, Update on Endocrine Therapy for Breast Cancer, 4
`CLINICAL CANCER RESEARCH 527-34 (1998)
`
`Exhibit 1051 Howell, New Endocrine Therapies for Breast Cancer, 32A EUR.
`J. CANCER 576-88 (1996)
`
`Exhibit 1052 Howell, The Definition of the ‘No Change’ Category in Patients
`Treated with Endocrine Therapy and Chemotherapy for
`Advanced Carcinoma of the Breast, 24 EUR. J. CANCER CLIN.
`ONCOL. 1567-72 (1988)
`
`Exhibit 1053 Nicholson, “Pure Antioestrogens in Breast Cancer: Experimental
`and Clinical Observations,” Sex Hormones and Antihormones in
`Endocrine Dependent Pathology: Basic and Clinical Aspects,
`Proceedings of an International Symposium, Milano 347-60
`(1994) (“Nicholson”)
`
`Exhibit 1054
`
`Santen, Use of Aromatase Inhibitors in Breast Carcinoma, 6
`ENDOCRINE-RELATED CANCER 75-92 (1999)
`
`Exhibit 1055 EP 0 346 014
`
`Exhibit 1056 Howell, Response to a Specific Antioestrogen (ICI 182780) in
`Tamoxifen-Resistant Breast Cancer, 345 LANCET 29-30 (1995)
`
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`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1057 Dukes, Antiuterotrophic Effects of the Pure Antioestrogen ICI
`182,780 in Adult Female Monkeys (Macaca nemestrina):
`Quantitative Magnetic Resonance Imaging, 138 J.
`ENDOCRINOLOGY 203-09 (1993)
`
`Exhibit 1058 Wakeling, The Future of New Pure Antioestrogens in Clinical
`Breast Cancer, 25 BREAST CANCER RESEARCH & TREATMENT 1-
`9 (1993) (“Wakeling”)
`
`Exhibit 1059
`
`Selective Estrogen Receptor Modulators (SERMs),
`BREASTCANCER.ORG (last modified Nov. 5, 2015),
`http://www.breastcancer.org/treatment/hormonal/serms
`
`Exhibit 1060 Howell, Fulvestrant Revisited: Efficacy and Safety of the 500-mg
`Dose, 11 CLINICAL BREAST CANCER 204-10 (2011)
`
`Exhibit 1061 Thomas, The Effects of ICI 182,780, a Pure Anti-Oestrogen, on
`the Hypothalamic—Pituitary—Gonadal Axis and on Endometrial
`Proliferation in Pre-Menopausal Women, 9 HUMAN
`REPRODUCTION 1991-96 (1994)
`
`Exhibit 1062
`
`Freireich, Quantitative Comparison of Toxicity of Anticancer
`Agents in Mouse, Rat, Hamster, Dog, Monkey, and Man, 50
`CANCER CHEMOTHERAPY REPORTS 219-44 (1966)
`
`Exhibit 1063 Equivalent Surface Area Dosage Conversion Factors (2007)
`
`Exhibit 1064 Clarke, Antiestrogen Resistance in Breast Cancer and the Role of
`Estrogen Receptor Signaling, 22 ONCOGENE 7316-39 (2003)
`
`Exhibit 1065 Gusterson, Do we now have a relevant animal model for breast
`cancer? 1 BREAST CANCER RESEARCH 2-4 (1999)
`
`Exhibit 1066
`
`Johnston, Changes in Estrogen Receptor, Progesterone
`Receptor, and pS2 Expression in Tamoxifen-Resistant Human
`Breast Cancer, 55 CANCER RESEARCH 3331-38 (1995)
`
`Exhibit 1067 Waynforth, LASA Good Practice Guidelines: Administration of
`Substances (Rat, Mouse, Guinea Pig, Rabbit) (Oct. 1998),
`www.procedureswithcare.org.uk/lasa_administration.pdf
`
`-xiii-
`
`

`

`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1068 Mackey, Tolerability of Intramuscular Injections of Testosterone
`Ester in Oil Vehicle, 10 HUMAN REPRODUCTION 862-65 (1995)
`
`Exhibit 1069 Kern, “Role of Angiogenesis in the Transition to Hormone
`Independence and Acquisition of the Metastatic Phenotype,”
`Endocrinology of Breast Cancer 169-86 (Manni ed., 1999)
`
`Exhibit 1070 Neubauer, Changes in Tumour Biological Markers during
`Primary Systemic Chemotherapy (PST), 28 ANTICANCER
`RESEARCH 1797-804 (2008)
`
`Exhibit 1071
`
`Smith, Analysis of Oil-Based Pharmaceuticals, 49 J. AMERICAN
`OIL CHEMISTS’ SOCIETY 409-13 (1972)
`
`Exhibit 1072
`
`Spiegel & Noseworthy, Use of Nonaqueous Solvents in
`Parenteral Products, 52 J. PHARM. SCIS. 917-27 (1963)
`(“Spiegel”)
`
`Exhibit 1073 Taucher, Sequential Steroid Hormone Receptor Measurements in
`Primary Breast Cancer with or without Intervening Primary
`Chemotherapy, 10 ENDOCRINE-RELATED CANCER 91-98 (2003)
`
`Exhibit 1074 Turner, Administration of Substances to Laboratory Animals:
`Routes of Administration and Factors to Consider, 50 J.
`AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
`600-13 (2011)
`
`Exhibit 1075 Robertson, J.F.R. et al., A Partially-Blind, Randomised,
`Multicentre Study Comparing the Anti-Tumor Effects of Single
`Doses (50, 125 and 250 mg) Of Long-Acting (LA) ‘Faslodex’
`(ICI 182,780) With Tamoxifen In Postmenopausal Women With
`Primary Breast Cancer Prior To Surgery, in 22ND ANNUAL SAN
`ANTONIO BREAST CANCER SYMPOSIUM, Abstract No. 28 (Dec. 8-
`11, 1999) (“Robertson 1999”)
`
`-xiv-
`
`

`

`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1076 Kohler, Plasma and Tissue Concentrations Following
`Intramuscular Administration of Etofenamat. Pharmacokinetics
`of Etofenamat and Flufenamic Acid in Plasma, Synovium, and
`Tissues of Patients with Chronic Polyarthritis after
`Administration of an Oily Solution of Etofenamat, 42
`ARZNEIMITTEL-FORSCHUNG (English Abstract) (1992)
`(“Kohler”)
`
`Exhibit 1077
`
`Jorgensen, Pharmacokinetic Studies in Volunteers of Intravenous
`and Oral Cis (Z)-Flupentixol and Intramuscular Cis (Z)-
`Flupentixol Decanoate in Viscoleo®, 18 EUR. J. CLIN.
`PHARMACOL. 355-60 (1980) (“Jorgensen”)
`
`Exhibit 1078
`
`Petition for Inter Partes Review in Mylan Pharms. Inc. v.
`AstraZeneca AB, Paper No. 2, IPR2016-01326 (P.T.A.B. June
`29, 2016)
`
`Exhibit 1079 Handbook of Pharmaceutical Excipients (Wade ed., 2d. ed.
`1994)
`
`Exhibit 1080
`
`FDA’s Inactive Ingredient Database (1996) (“IIG”)
`
`Exhibit 1081 Drugs@FDA Glossary of Terms, U.S. FOOD & DRUG
`ADMINISTRATION (last updated Feb. 2, 2012),
`http://www.fda.gov/Drugs/InformationOnDrugs/ucm079436.htm
`
`Exhibit 1082 Adam, “Pharmacokinetics of Agents in Relation to Response,”
`Endocrine Management of Cancer: Biological Bases 112-24
`(1988)
`
`Exhibit 1083 Baselga, Phase II Study of Weekly Intravenous Recombinant
`Humanized Anti-p185HER2 Monoclonal Antibody in Patients with
`HER2/neu-Overexpressing Metastatic Breast Cancer, 14 J.
`CLINICAL ONCOLOGY 737-44
`
`Exhibit 1084
`
`Fabian, Clinical Pharmacology of Tamoxifen in Patients with
`Breast Cancer: Correlation with Clinical Data, 48 CANCER 876-
`82 (1981)
`
`-xv-
`
`

`

`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1085 Goldenberg, Trastuzumab, a Recombinant DNA-Derived
`Humanized Monoclonal Antibody, a Novel Agent for the
`Treatment of Metastatic Breast Cancer, 21 CLINICAL
`THERAPEUTICS 309-18 (1999)
`
`Exhibit 1086 Wilkinson, Tamoxifen (Nolvadex*) Therapy – Rationale for
`Loading Dose Followed by Maintenance Dose for Patients with
`Metastatic Breast Cancer, 10 CANCER CHEMOTHERAPY
`PHARMACOLOGY 33-35 (1982)
`
`Exhibit 1087 Copy of Prosecution History for the U.S. Patent No. 8,466,139
`(downloaded from PAIR)
`
`Exhibit 1088 Wunsche, Estrogenic Regulation of Clusterin mRNA in Normal
`and Malignant Endometrial Tissue, 76 INT. J. CANCER 684-88
`(1998) (“Wunsche”)
`
`Exhibit 1089 Chwalisz, Modulation of Oestrogenic Effects by Progesterone
`Antagonists in the Rat Uterus, 4 HUMAN REPRODUCTION UPDATE
`570-83 (1998) (“Chwalisz”)
`
`Exhibit 1090 Robertson, Fulvestrant (Faslodex®)—How to Make a Good Drug
`Better, 12 ONCOLOGIST 774-84 (2007)
`
`Exhibit 1091 Ansel, “Dosage Form Design: Biopharmaceutic and
`Pharmacokinetic Considerations,” Pharmaceutical Dosage
`Forms and Drug Delivery Systems 101-41 (7th ed. 1999)
`
`Exhibit 1092 Lee, Standard Deviation and Standard Error of the Mean, 68
`KOREAN J. ANESTHESIOLOGY 220-23 (2015)
`
`Exhibit 1093 Altman, Standard Deviations and Standard Errors, 331 BMJ
`903 (2005)
`
`Exhibit 1094 Tse, Bioavailability of Parenteral Drugs I. Intravenous and
`Intramuscular Doses, 34 J. PARENTERAL DRUG ASSOCIATION
`409-21 (1980)
`
`-xvi-
`
`

`

`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1095 Licciardi, Oral Versus Intramuscular Progesterone for In Vitro
`Fertilization: A Prospective Randomized Study, 71 FERTILITY &
`STERILITY 614-18 (1999)
`
`Exhibit 1096 August 21, 2008 Applicant Amendment and Response in
`Application No. 10/872,784
`
`Exhibit 1097 Balant-Gorgia, Pharmacokinetic Optimisation of the Treatment
`of Psychosis, 25 CLIN. PHARMACOKINET. 217-36 (1993)
`
`Exhibit 1098 Chien, Solubilization of Steroids by Multiple Co-Solvent Systems,
`23 CHEM. PHARM. BULL. 1085-90 (1975)
`
`Exhibit 1099
`
`Ford, “Parenteral Products,” Pharmaceutics: The Science of
`Dosage Form Design 359-80 (Aulton ed., 1988)
`
`Exhibit 1100 Cunliffe-Beamer, “Biomethodology and Surgical Techniques,”
`The Mouse in Biomedical Research, Volume III: Normative
`Biology, Immunology, and Husbandry 401-37 (Foster ed., 1983)
`
`Exhibit 1101 Way, “Cosolvent Use in Injectable Formulations,” Injectable
`Drug Development: Techniques to Reduce Pain and Irritation
`215-66 (Gupta ed., 1999)
`
`Exhibit 1102 Nema, Excipients and Their Use in Injectable Products, 51 PDA
`J. PHARM. SCI. & TECH. 166-71 (1997)
`
`Exhibit 1103 Ogasawara, Effects of Experimental Chemoendocrine Therapy
`with a Combination of a Pure Antiestrogen and 5-Fluorouracil
`on Human Breast Cancer Cells Implanted in Nude Mice, 29
`SURGERY TODAY 149-56 (1999)
`
`Exhibit 1104 Oldham, “Mass Transport to Electrodes,” Chemical Kinetics 79-
`143 (Bamford ed., 1986)
`
`Exhibit 1105
`
`Powell, Compendium of Excipients for Parenteral Formulations,
`52 PDA J. PHARM. SCI. & TECH. 238-311 (1998)
`
`Exhibit 1106 Remington’s Pharmaceutical Sciences 1538-39, 1545-50, 1686-
`88 (18th ed. 1990)
`
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`
`

`

`IPR2017-01912
`Petition for Inter Partes Review
`
`Exhibit 1107 Roberts, Investigation of Cosolvent Effects on the Solvation of
`AOT Reverse Micelles in Supercritical Ethane, 102 J. PHYS.
`CHEM. B 9074-80 (1998)
`
`Exhibit 1108
`
`Sawka, Physiological Consequences of Hypohydration: Exercise
`Performance and Thermoregulation, 24 MEDICINE & SCIENCE IN
`SPORTS & EXERCISE 657-70 (1992)
`
`Exhibit 1109
`
`Simmons, The Laboratory Mouse: Selection and Mana