IPR201?-00904
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`Petition for Enter Partes Review
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`UNITED STATES PATENT AND TRADQMARK 0F ICE
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`BEFORE THE PATENT TRIAL AND AH’EAL BOARD
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`INNOPHARM LICENSING, LLC,
`Petitioner
`
`V.
`
`ASTRAZENECA ABg
`Patent Owner
`
`Case IPR2017-00904
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`Patent No. 6,7?4}122
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`PETITION fl‘OR INTER PARTES REVIEW OF
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`US. PATENT NO. 6,774,122
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`UNDER 35 U.S.C. §§ 311-319 AND 3" C.F.R. § 2.100 ETSEQ.
`
`Mail Stop: Patent Boarci
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`
`RC3. BOX 1430
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`
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`Alexandria, VA 223 13-1 50
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`AstraZeneca Exhibit 2174 p. 1
`Fresenius—Kabi USA LLC V. AstraZeneca AB IPR2017-01910
`
`

`

`IPR201i-00904
`
`Petition for Inter Fortes Review
`
`
`TABLE OF CONTENTS
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`INTRODUCTION ........................................................................................... 1
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`NOTICES, STATEMENTS AND PAYMENT OF FEES .............................. 4
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`A. Real Party In Interest Under 3’? C.F.R. § 42.8(b)(1) ............................... 4
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`Related Matters
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`nder 37 CFR. § —-2.8(b)(2) ........................................ 4
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`3 C
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`. Lead and Back-Up Counsel Under 37 CFR. § 412.8(b)(3)..............._..i.16
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`Service Information Under 3’? C.F.R. § --218(b)( ) ..
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`..
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`.7?
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`3
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`.1. Grounds for Standing Under 3? ORR. § 42.104(a) ................................ 7
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`7?.
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`Fees Under 37 CPR. §42.103 ................................................................ 7
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`
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`II.
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`III.
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`IV.
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`IDENTIFICATION OF CHALLENGE UNDER 3'? ORR. § “2.1911(3) ...... 7
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`LLJ
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`INNOPHARMA’S GROUNDS OF UNPATENTABILITY 23R;
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`DISTINCT FROM THOSE PRESEN" ED BY MYLAN ............................... 9
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`OVERVIEW 0’“ THE ‘ 122 PATENT AND PROSECUTION EJSTORY 112
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`A. The ‘122 Patent ...................................................................................... 12
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`B. The Prosecution History ........................................................................ 14
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`1.
`
`2.
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`The Prosecution History of the ‘ 122 Patent ................................... 14
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`The Prosecution History of Related Applications ......................... 15
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`VI.
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`LEVEL 03‘ ORDINARY SKILL IN THE ART ........................................... 1’?
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`VII .
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`CLAIM CONSTRUCTION 1’?
`
`A.
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`“Attained” .............................................................................................. 18
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`B.
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`“Therapeutieelly Significant” ................................................................ 18
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`CL
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`“What-eh}! a theraoemieaiiy significant blood 2313mm flimesizram
`concentration of‘at least 2.5 ngml'l is attained for at 1east2 weeks after
`..
`.
`,,
`...................................................... 18
`Injection ..........................................
`
`i
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`AstraZeneca Exhibit 2174 p. 2
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`

`

`IPRZG lit-00904
`
`Petition for Inter Fortes Review
`
`VIII. SCOPE AND CONTENT OF THE PRIOR ART ......................................... 19
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`A. The Prior Art Diseloses All Limitations of the Challenged Claims ...... 19
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`l. Howell Closely Matches the Claimed Invention ........................... l9
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`2. McLeskey Discloses the Claimed Formulation and Was Not a
`“Treatment F ailure” ....................................................................... 22
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`3. OiRegan Confirms the Route of Administration ........................... 26
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`B. AstraZeneoa’s Attempts to Detract From These Prior Art Teachings
`Fail ......................................................................................................... 26
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`l. AstraZeneca’s Purported “Lead Compound” Analysis is
`Inapplieable .................................................................................... 2?
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`2. AstraZeneea’s Efficacy Arguments Are Contrary to Law............. 29
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`3. AstraZeneea’s Claims of Unpredictability Are Speeious .............. 30
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`a.
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`The Pharmaeokinetie Limitations Are Expressly Disclosed in
`the Prior Art ............................................................................ 30
`
`b.
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`It Was Weil~Known That Fulvestrant Was Administered
`
`Intramuscularly ....................................................................... 32
`
`c.
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`The Claimed Combination of Exeipients Were Neither
`Unexpected Nor Surprising .................................................... 33
`
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`IX. DETAILED EXPLANATION AND SUPPORTING EVIDENCE .............. 36
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`A. Ground 1: Claims 1: 2, 5, and 9 Are Obvious Over Howell ................. 36
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`
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`1. A POSA Would Have Been Motivated to Develon a Formulation
`to Achieve the Results Reported in Howell ................................... 36
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`2. A ROSA Would Have A Reasonable Expectation of Success in
`Developing a Formulation to Achieve the Howell Results. .......... 39
`
`3.
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`Every Limitation Is Disclosed By Howell And The Knowledge of
`a POSA. .......................................................................................... 41
`
`ii
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`AstraZeneca Exhibit 2174 p. 3
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`

`

`IPR20l?-{}O904
`
`Petition for Inter Fortes Review
`
`B. Ground 2: Claims 1, 23 S, and 9 Are Obvious Over Howeli and
`
`McLeskey ...............................................................................................4
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`l. A POSA Would Have Been Motivated to Combine Howell and
`
`MoLeskey .......................................................................................44
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`a.
`
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`The Target Fulvestrant Concentration in Howell Would Have
`Led a Skilled Formulator to MoLeskey..................................44
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`b. The Record Confirms the Motivation to Combine Howell and
`
`
`
`7
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`MeLeskey.
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`2. A POSA Would Have A Reasonable Expectation of Suecese in
`
`
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`Administering the McLeskey “ormulation lntramuscularly to
`Aehieve the Results ‘KepOtted in Howell ....................................... 51
`
`3.
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`Each and Every Lim'tation ls Disclosed By the Combination of
`
`Powell and McLeskey ................................................................... 5?
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`
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`C. Ground 3: Claims 1, 2, 5a and 9 Are Obvious Over Hmvella McLeskey,
`and O’Regan .......................................................................................... 58
`
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`l. A ROSA Would Have Been Motivated to Combine Howell,
`McLeskey, and O’Regan ................................................................ 59
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`2‘ A POSA Would Have A Reasonable Expectation of Success in
`Combining Howell, MeLeskey, end O’Regan ............................... 59
`
`3.
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`Each and Every Limitation ls Disclosed By the Combination of
`Howell} MoLeskey} and O’Regan .................................................. 60
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`X.
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`SECONDARY CONSIDERATIONS, FAIL TO OVERCOME THE
`
`EVIDENCE OF OBVIOUSNESS. ............................................................... 62
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`A. There Is No Nexus to the Claimed Invention ........................................ 62
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`,3. AstraZeneca’s Secondary Considerations Arguments Fail ................... 6/”
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`1. AstreZeneea Cannot Show Long-“Eek Need .................................. ea
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`2 like Ree-nits;- Were Not Unexpected ................................................ <35:
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`a. Dr. Robertson’s Arguments Are Contradieted "By His Own
`
`iii
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`AstraZeneca Exhibit 2174 p. 4
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`

`

`IPR2017-00984
`
`Petition for Inter Parzes Review
`
`.
`
`Published Work. .. .......
`
`................ . ......
`
`................... ”H.635
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`b.
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`The Release Profile and Effect of Benzyi Benzoate Were
`Expected66
`
`XI
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`CONCLUSION ........... . ..... a ............................................................................ 66
`
`iv
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`AstraZeneca Exhibit 2174 p. 5
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`

`

`IPR2017—00904
`
`Petition for Inter Parres Review
`
`TABLE OF AUTHORITIES
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`‘a9e(s)
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`TFEDE AL CASES
`
`Alcoa Research! Ltd. v. Apos‘ex £336.,
`687 F.3d 1362(F6d.C11’.2012) .......................................................................... 50
`
`Affergm, Inc. v. Apofex Inc,
`754 F.3d 952 (Fed. Cir. 2014), cert. denied, 135 S. Ct. 956 (201.5) .................. 63
`
`Affergan, Inc. v. SGRdOZ Inc;
`726 F.3d 1286 (Fed. Cir. 2013) ......................................................................... 32
`
`31262 Corp. V. Myfian Labs., Ina,
`
`
`464 33.3d 1286 (Fed. Cir. 2006) .......................................................................... 29
`
`
`In re Appfied Maferfafs, inc. ,
`
`
`
`692 F.3d 1289 ( 1 ed. Cir. 2012) .......................................................................... 4O
`
`AstraZeneca LP 1). Breath Ltd. ,
`
`603 F. App”): 999 (Fed. Cir. 2015) ..................................................................... 64
`
`AsiraZeneca Phayms. LP 12. Agile: Speciafz‘ées, 3320.;
`
`N0. 1:15-cv—0603 9-1W—KMW (D.N.J .) ............................................................
`
`
`
`
`Asszeneca Pharms. LP v. Dr. Reddy ’5 Laboratories, Inc,
`
`N0. 1:1”‘-cv-926-WB~KMW (DNJ) ................................................................ 5
`
`AstraZeneca Pharms. LP v. Gienmark Pharms. Inc, USA,
`No. 1:15~CV~615 (DNJ) ...................................................................................... 5
`
`Agtherzeca: Pharms. LP 12. ImoPharma, Inc. ,
`
`
`
`
`N0. 1:16-cv—894-RMi3-KMW (3.11.1) ................................................................ 4
`
`
`AstraZ’meccx Pharms. LP 12. InnoPharma Licensing LLC?
`
`No. 1:16-0V-1962~RW-KMW (A).N.J.) .......................................................... 4, 5
`
`AstraZeneca Pharms. LP 12. Mylan Institutiaml LLC,
`N1:1,...,,,I..:.l-énwmfiifiiIznlfimkfi-Kifirfiw(ENE)‘3
`
`AstraZeneca Exhibit 2174 p. 6
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`

`

`1PR2012-00904
`
`Péztition for Inter Partes Review
`
`Ass‘mZeneca Pharms. LP v. Myfan Pharms. Inc,
`No. 1:15~CV-7009—RMB~KMW (D.N.J.) ............................................................. 5
`
`AstraZeneca Pharms. LP v. Sagan: Pfiarms., 1226.,
`
`
`No. 1:14-cv~05539-RMB—KMW (T).N.J.) ............................................................ 5
`
`AstraZenéca Pharms. LP 1}. Sandaz Inc,
`
`No. 1:14~cv~03547-R1\21B—KMW (D.N.J.) ............................................................ 5
`
`AstraZeneca Pharms. LP v. Teva Parenteral Medicines Inc,
`
`No. 1:10—cv—18-JMS-KMW (D. Del.) .................................................................. 5
`
`AstraZeneccz Pharms. LP 12. Teva Pizarms. USA, Inc,
`
`No. 1:15-CV—7889wRMB-KMW (D.N.J.) .............................................................. 5
`
`Avemz‘s Pharma 51A. 1). Hospim, Inc,
`
`743 F. Supp. 2d 305 (D. D81. 2010), afl’d. 675 F.3d 1324 (Fed. Cir.
`2012) ................................................................................................................... 35
`
`Cubist_P1/2arms.. Inc. v. Hospira. 11:16.,
`805 F.3d 1112 (Fed. Cir. 2015), 66%. denied, 136 S. Ct. 2393 (2016) .............. 56
`
`Duramed Pharma, Inc. v. Warsen Laban. 13116.,
`
`413 F. App’x 289(Fed. (3.1122011) ..................................................................... 51
`
`In re Ethicox/s, 1126..
`
`
`84—- F.3d 134—- (Fed. Cir. 201?) .......................................................................... 4’?
`
`Gafderma £355., LP. 1:. Tofmar, Ina,
`
`237 F.3d "1'31 (Fed. Cir. 2013) ...................................................................... 28, 31
`
`
`Haflmam-La Roche Inc. v. Apotex Inc,
`
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`148 ‘.3d 1326 (Fed. Cir. 2014) ...................................................................... 3., 29
`
`In re Hum-Hung K510,
`639 F.3d 105’? (Fed. Cir. 2011) .......................................................................... 63
`
`fr: re ICON {1185355112 (E: Fitness,
`
`496 F.3d 13?4 (Fed. Cir. 2007) .......................................................................... 3?
`
`from Grip Barbefé Co. :2. USA Sperm Inc,
`392 F.3d 1317 (Fed. Cir. 2004) .......................................................................... 40
`
`V1
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`AstraZeneca Exhibit 2174 p. 7
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`

`

`IPR201’?-00904
`
`Petition for Inter Farms Review
`
`KSR Inf? Co. v. Teieflex Inc. ,
`550 US. 398 (2007) ............................................................................................ 47
`
`212(9er (fir C58 12. ($320523 SPA...
`808 F.3d 829 (Fed. Cir. 2015) ............................................................................ 31
`
`114%:er (fl: Co. v. Biocrafl‘ 1.303., Ina,
`874 F.2d 804 (Fed. Cir. 1989) ............................................................................ 28
`
`Merck 0% C0. 19. Tera Pharms. USfl, Ema,
`395 F.3d 1364 (Fed. Cir. 2005) .......................................................................... 63
`
`Memo Mfieraé’s. Irsc. v. Pewemcreerz Irzz’f Disfrib., Ltd,
`
`526 F. App’x 988 (Fed. Cir. 2013) ..................................................................... 32
`
`Merasofl Cerp. v. Mafmi’ech $325.. Ina,
`357 F.3d 1340 (Fed. Cir. 2004) .......................................................................... 37
`
`Perfect Web 102:2th Inc. v. Info USA. 1126..
`587 F.3d 1324 (Fed. Cir. 2009) .......................................................................... 64
`
`
`Pfizer, Inc. v. Apotex, 1116..
`
`
`
`
`
`
`480 F.3d 1348(1‘e: . Cir. 2007) .................................................................... 41, 6
`
`
`
`
`
`PharmaStem Therapeutics, Inc. v. ViaCeZZ, Inc.,
`491 F.3d 1342 (Fed. Cir. 2007) .......................................................................... 33
`
`Purdue Pharma Prods. LP. 12. Per Pharm, Inc. ,
`377 F. App’x 978 (Fed. Cir. 2010) ..................................................................... 2'?
`
`Randaii Mfg. V. Rea.
`733 F.3d 1355 (Fed. Cir. 2013) .......................................................................... 37‘
`
`Santerus, Inc. v. Par Pharm, Inc,
`
`694 3.3(1 1344 (Fed. Cir. 2012) .......................................................................... 55
`
`Smith & Nephew, Inc. v. Rea,
`
`3’21F3d137‘1 (zed. Cir. 2013) .......................................................................... 31
`
`Unigene Laboratories, Inc. v. Aporex, Inc,
`655 13:30 3352 (Fee. Cir. 2011‘} .......................................................................... 28
`
`V11
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`AstraZeneca Exhibit 2174 p. 8
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`

`

`IPR2017-00904
`
`Petitien for Im‘er Fairies Review
`
`FEDERAL STAIUIES
`
`35 [JWSC § 10203) ....................... H. ........... “H. ..... . ....... u...n...¢uu.._.8
`
`3S UWSC § 103 .............................................. . ................................... "mu ............. .m;
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`.
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`.
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`.
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`.................................... . ..............................................................
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`35 U..S.C § 325(d) ..n.u.....n.n ............. .... ..... .....«....in ..... 9
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`viii
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`AstraZeneca Exhibit 2174 p. 9
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`

`

` IPR2017~00904
`
`Petition for 1mg? Ferries Review
`
`
`PETITIONER’S EXHIBIT LIST
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`
`
`Exhibit 1001 US. Patent N0. 6,7?4,122 (“the ‘ 122 patent”)
`
`Exhibit 1002
`
`Campiaim filed in Ass‘raZeneca Phgrms. LP ez‘ (:3. v.
`InnoPharma, Inc., Case No. 1:16-cvu894 (D.N.J.)
`
`
`
`fllfit 1003 limié’roof of Service in AgimZeneca 130mm; LPez‘ al, v.
`
`
`
`‘‘‘‘‘‘‘‘‘‘‘‘‘‘‘
`
`ImoPharma, Inc, Case No. 1:16-cv—894 (DNJJ
`
`
`‘xhibit 1004
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`
`
`Exhibit 1005
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`
`
`
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`Xhibit 1006
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`Order Dismissing Cage \Vwithou’: Prejudice, AsfraZeneca Pharms.
`
`
`Complaint filed in AstraZeneca Pharms. LP er al v. IanPI/zarma
`
`Licensing, LLC, Case No. 1:16«cv~1962 (DNJJ
`
`Copy of Prosecution Histary for US. Patem No. 6,?74,122
`(downloaded from PAIR)
`
`
`
`Exhibit 1007 Howell et 211,, Pharmacakinerz‘cs, pharmacological and anti“
`tameur eflécz‘s offize specific gnfiweszrogen 3C; 382 $290 are
`
`
`women with advanced breast cancer, 74 BRIT. I. CANCizR
`
`
`
`
`300—08 (1996) (“I aweii”)
`
`Exhibit 1008 McLeSkey at £11., Tamaxifem-resismmfifirofifas: grows‘fzfacrorw
`transfected MCF»? 66225 are cross-reSistam in vivo to five
`
`amfesfmgen ICE 1’ 82, 780 and {we gromaiase inhééés‘ors, 4 CLIN.
`
`
`
`CANCER RESCARCH 697~71 1 (1998) (“McLeskey”)
`
`
`
`
`‘3 xhibit 1009
`
`O’Regan at 211., Effecm thhe Antiestmgens Tammi/Em,
`
`Taremg’flme, wad {CI 382, ?80 or: Emdomegriai Cancer Growzk,
`
`
`
`
`90 J. NATL CANCER INST. 10552-4558 (1998) (“0’ egan”)
`
`Exhibit 1010
`
`Order, AstraZeneca Pharms. LP v. Sande: Inc., No. 14—03547
`(DNJ. July :19? 301% EC}? Na. 1072...
`WW“... “mm .MWWWMWMW................
`
`
`
`ix
`
`AstraZeneca Exhibit 2174 p. 10
`
`

`

`1PR2017-00904
`
`Petition for Inter Fortes Review
`
`
`Institution Decision in Myiaa Pharms. Inc. v. AstraZeneca AB,
`Paper No. 11:, IPR2016—01325 (P.T.A.B. Dec. 14, 2016)
`
`
`
`Declaration of Diane Burgess, Ph J and Accompanying Exhibits
`
`
`
`Deciaration of Dorraya Ei-Ashry, PhD. and Kecompanying
`
`Exhibits
`
`
`”Exhibit 1011
`
`“Exhibit 1012
`
`Exhibit 1013
`
`Exhibit 1014
`
`Exhibit 1015
`
`W‘
`
`Exhibit 1017
`
`Exhibit 1018
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`
`
`
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`Declaration of Richard Bergstrom, PhD. and Accompanying
`Exhibits
`
`
`Declaration of Adrian Harrie, M.
`xhibits
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`
`
`
`
`
`
`’., PhD. and Accompanying
`
`AstraZeneca’s Preliminary Response in Mylar: Pharms. Inc. v.
`
`AstraZeneca AB, Paper No. 10, 1191120164113 16 (P.T.A.B. Oct.
`17, 2016)
`
`
`DeLuca, Formulation omeall Volume Parenterals,
`
`
`PHARMACEUTICAL JOSAG: FORMS: PARENTERAL MEDICATIONS
`
`VOLUME 1 (Avis ed., 2d ed. 1992)
`
`Eeciaration Under 3’? CPR. § 1.132 of Ronald I. Sawchuk in
`Application No. 12/285,887
`
`Declaration Under 37 CPR. § 1.132 of Paul Richard Gellert in
`Application No. 10f872,’?84
`
`Faslodex® Label, avaifable at:
`WWW.aecessdata.fda.govfdrugsatfda_docsflabelz’2012/021344801
`930201b1.pdf
`
`
`
`Exhibit 1022
`
`DiPiro, Concepts in Ciz'nfcal Phormacokineiics (2010)
`
`Eihibit 1023
`
`Qiu Developing Solid Ora! Dosage Forms: Pharmncanncal
`
`Theory and Practice (2009)
`
`AstraZeneca Exhibit 2174 p. 11
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`

`

`1PR2012-00904
`
`Petition for Inter Partes Review
`
`axhwmggmgom“mm““““““““““““““
`
`Pharmacodynamics: The Quantitative Basis ofDrug Therapy
`
`(2006)
`
`
`
`Exhibit 1025
`Caldwell, An Introduction to Drug Disposiziorz: The Basic
`
`Priecipies QfAbsorpiz'en, Diszrébmion, Mezabafism, c2326?
`
`
`Excretion, 23 Taxicologic Pathalogy 102 (1995)
`
`
`Exhibit 1026
`
`Exhibit 1027
`
`
`
`Derendorf, Handbook ofPharmacakinefic/PharmaeOdy/1amit:
`Correiafien S3 (1995)
`
`
`
`Wills, “Basic Pharmacodynamic Ceneepts and Models,”
`Pharmacodynamies and Drug Development: Perspectives in
`
`
`Ciinieai’ Pharmacafogy (1994)
`
`
`
`
`
`Exhibit 1028 Mager, Scaiing Pharmaeocz’ynamicsfiflom Ire Viim and Preciinicai
`
`
`Animafi Studies 2‘0 Humans, DRUG META). PHARMACOKINET.
`(2009)
`
`Exhibit $29
`
`
`
`
`
`Colburn, Simeifarzeous Pharmaeokinetic/Pharmacodynamic
`Modeling, FHA RMACODYNAMICS AND DRUG DEVELOPMENT:
`PERSPECTIVES m CLINICAL PHARMACOLOGY (1994)
`
`
`
`
`
`Exhifil 030
`
`
`
`”white, Pharigggekmerie and Pharmacadymméc Comiderai‘ions
`
`
`
`
`in Aetimal’am‘az‘ Ease Opzémizaiéom, 3’? ANTIMICROBIAL AG NTS
`& CHEMOTHERAPY 5802 (2013)
`lTEXhlblt 1031 Wakeling at 211., A Poienz Specific Pare Amiestrogen with
`
`
`Ci’micai Pelem‘iai, 51 CANCER RESEARCH 386?—38?3 (1991)
`{“Wakeiing 1991”)
`
`Exhibit 1032
`
`
`
`Nicholson, R1. at 311., Responses To Pure Amiesfmgens {”in
`I 64384, {C3 82 ?’80) If”; Esfrogen-Sensitive Arid "Resisicmi
`Experimental And Clinical Breast Cancer, ANNALS OF THE NEW
`YORK ACADEMY OF SCIENCES, Vol. 61:148-163 (1995)
`(“Nicholson”)
`
`xi
`
`AstraZeneca Exhibit 2174 p. 12
`
`

`

`1PR201?-009{)4
`
`Petition for Inter Partes Review
`
`Exhibit 1033
`
`Riffkin, Castor Oi! as e Vekiciefor Paeeefemf Adminisrmz‘iee of
`Steroid Hormones, 53 J . PHARM. SCI. 891—895 (1964)
`(“Rifikin”)
`
`Exhibit 1034
`
`
`
`
`Exhibit 1035
`
`Finley, New Drug Being Tested 3'}: Breast Cancer Smdy, SAN
`ANTONIO EXPRESS-«NEWS, Sept. 20, 199’?
`
`Uges, Pfesma or Serum in Therapemée Dreg Meeimring and
`
`
`CZim’caZ Toxicefiegy, 11) PEAWCEUTISCH WE‘EKBLAD
`
`SCIENTIFIC EDITION 185—88 (1988) (“Uges”)
`
`
`
`Exhibit 1036 Dukes at 211., Antiwterotrepkic effects ofa pure amioestrogen, ICI
`18.2, 3780: magnetic resonance imaging afthe uterus in
`
`
`
`overieeiemized monkeys, 135 J. w"NZ)(I)CRIN(ILOG‘i’ 239—247
`(1992) (“Dukes”)
`
`Exhibit 103’? WO 0311306064
`
`Exhibit 1038 DeFriend at 211., [evess‘igeriee efa New Peee Antiestregee (ICI
`
`182780) in Warner: with Primary Breast Cancer, 54 CANCER
`
`
`
`
`
`
`RESEARCH 08
`1
`(1994)(“DeFriend”)
`
`Exhibit 1039 Osborne at 311., Comparison office Effects ofa Pure Stemidal
`
`emiesz‘mgee With These ofTemoxifim in e Model efHumarz
`
`
`
`Breasr Cancer, 87 J. NAT’L CANC R INST, 7—6—750 (1995)
`(“Osborne 1995”)
`
`Exhibit 1040 Alan E. Wakeling & Jean Bowler, ICI 182,781}: A New
`Antioess‘rogen with Clinieai’ Poteetfal, 43 J. STEROID
`
`BIOCH‘EM. MOLEC. BIOL. 173347? (1992) (“Wakeling
`1992”)
`
`Exhibit 1041
`
`“Howe11,A. 61: a1, cemcaz Studies Wee The Speeffic ‘Pwe’
`Antiestrogen ICI 182780, THE BREAST, V01. 5:192-195 (1996)
`(“Howeli Breast 1996”)
`
`Exhibit 1042
`
`Copy of Prosecution History for us. Patent 110. 8,329,680 ““““““““““W
`
`(dewnleaded from PAIA)
`
`AstraZeneca Exhibit 2174 p. 13
`
`

`

`IPR2017-0090
`
`
`
`
`
`Petition for {flier Fortes Review
`
`
`
`
`
`Exhibit 1043
`
`
`Exhibit 104-
`
`
`
`
`
`
`
`
`Robertson 3 F.R et a1 Emission Of126222555on To 1C! 382, 7813
`Compared To .Megesfrol Acetate In Tamoxifen Resistant Breast
`Comer; THE: BREAST, Voi. 6:186-189 (199’?) (“Robertson
`1997”)
`
`Robertson Fuivesz‘mnr Versus Anaszrozolefor the Treatment of
`Advanced Breosf Carcinoma in Poss‘meoopousoi Women. A
`Prospective Combined Analysis QfTwo Multicem‘er Triais, 98
`CANCER 229-38 (2003) (“Robertson 2893”)
`
`
`
`
`
`
`
`
`
`
`
`Ixhibit 10 S Howell, Response go a Specific Amioesz‘mgm (ICE 1‘ 82780) in
`TamoxifenuResistam Breast Cancer, 345 LANCET 989—90 (1995)
`
`
`
`
`(“ Iowell 1995”)
`
`
`
`
`Exhibit 1046
`
`Copy of Prosecution History for the U S Patent No. ’3?456 160
`(downloaded from PAIR)
`
`
`
`
`“Xhibit 1047 U S Patent No S 183814 (“Dukes ‘814”)
`
`
`
`
`
`
`
`Exhibit 10 8
`
`Parczyk, K. et 31.? Progesierone Receptor Repression by
`Esmogem in Rat Uterine Epitheiéa? Cefis, 63 I. STEROID
`BIOCHEMISTRY & MOLECULAR BIOLOGY 309 (1997)
`
`
`
`
`
`
`Xhibit 1049 Anderson Models ofNew Antioestrogen r czion in Vivo: Prime???»
`Toxiwxizrs> 5 THE BREAST 18691 (1996)
`
`
`
`
`Exhibit 1058
`
`
`Suzdar, Update on Endocrine Thempyfor Breasf Cancer, 4
`CLINICAL CANCER RESEARCH 527-34 (1998)
`
`Exhibit 1051
`
`Howell; New Endocrine Thempiesfor Breast Cancer, 32A EUR.
`5. CANCER 53"6-88 (1996)
`
`
`Exhibit 1052
`
`Howoiifi 712:3 Definition offlie ‘No Change ’ Cafegory in Patienfs
`Treafied wish Endocrme Therapy and Ckemothemgyfor
`Advanced Carcinoma ofrhe Sreost, 24 EUR. 3. CANCER CLIN.
`ONCOL. 1567—72 (1988)
`
`xiii
`
`AstraZeneca Exhibit 2174 p. 14
`
`

`

`
`
`IL’RZG‘I #00904
`
`Petition for Inter Partes Review
`
`1351111131111: 1053
`
`
`Exhibit 1054
`
`Exhibit 1055
`
`Exhibit 1056
`
`Exhibit 1057
`
`
`
`
`
`
`
`NichOISOn,‘Pure Antioestrogens111 Breast Cancer: "xperimentai
`and Clinical Observations,” Sex Hormones and Antikormorzes in
`
`Endocrz’ne Dependem‘ Pafieoe’ogy: Basic and Clinicaf Aspects,
`
`
`Jroceeciings of an International Symposium, Milano 347-60
`
`
`
`199 ) (“Nicholson”)
`
`Santen, Use ofA‘ romatase Inhibfz‘ors in Breast Carcinoma, 6
`
`ENDOCRINE—RELATED CANCER 75—92 (1999)
`
`
`'P 0 346 014
`
`Tamoxzfen~Resfsmm Breast Cancer, 345 LANCET 29—30 (1995)
`
`Hrzwsl'ella Response to a Specific Antioestrogen (1’C1 182780) in
`
`Dukes, Antiuterotrophic Efficts ofrhe Pure Antioestragen [CI
`1’82, 781’} in Adm: Femaie Menkeys (Macaca nemestrfna):
`Quam‘ifafive Magnez‘ic Resonance Imagfng, 138 J.
`ENDOCRINOLOGY 203-09 (1993)
`
`
`
`Exhibit 1058
`
`Wakeling, The Future ofNew Pure Antioesi’ragens in Clinical
`Breast Caflcerg 2S BREAST CANCER RESEARCH & TREATMENT 1—
`
`Exhibit 1059
`
`Exhibit 1060
`
`Exhibit 1061
`
`
`
`9 (1993) (“Wakeling”)
`
`
`
`See’ecfive Estrogen Reeepier Modefarors (SEEMS),
`
`
`
`3KZASTCANCBRORG (last modified Nov. 5, 2015),
`http://www.breastcancer.org/theatment/hormonal/serms
`
`Howell, Fulvestrant Revisited: Efficacy and Safety offhe 5170:1711;
`
`Dose, 1 1 CLINICAL BREAST CANCER 204*10 (201 1)
`
`
`
`
`Thomas The Effects OfICI 182 780 .22 Pure Anti— Oestrogen on
`the Hypothaz‘amic—PimifaryflGonadaf Axis and On Endemetréas’
`Profifemrion in Pre—Menopaasaf Women, 9 HUMAN
`REPRODUCTION 199196 (1994)
`
`Freireich, Quantitative Camparison 0f Toxiciaz OfAnticancer
`Agenm in Meme; Ra!) Hémszer, Dog, Monkey, and Man, 50
`CANCER CHEMOTHERAPY REPORTS 219414 (1966)
`
`
`
`AstraZeneca Exhibit 2174 p. 15
`
`

`

`iPR201?~00904
`
`Petition fer Inter Partes Review
`
`Exhibit 1063
`
`Equivalent Surface Area Dosage Conversion Factors (2007)
`
`
`
`Exhibit 1136
`
`
`
`
`
`Exhibit 1865
`
`
`
`
`
`
`
`
`Clarke, Aeriegs‘rogerz Resistarzee ie Breast Cancer and me Rafe {9f
`Estregen Receptor Sigfiaiing, 22 ONCOGENE 7316-39 (2003)
`
`
`Gustersen, Do we now have a reievem ammai modeifer brew:
`
`cancer? 1 BREAST CANCER RESEARCH 2-4 (1999)
`
`
`Exhibit 1066
`Johnsten Changes Sr; Estrogers Recepzor Progesterone
`Receptor andpSL’ Expressionm Tamoxifim-Resistam Human
`
`
`Brees: Cancer} 55 CANCER R’JEEARCH 3331-38 (1995)
`
`
`
`
`
`mixhibit 1068 Mackey; 3‘eferebiéiiy efirzi‘rammceier frgjeez‘iem efTesiosierorze
`
`Ester in Oil Vehicle, 10 HUMAN REPRODUCTION 862-65 (1995)
`
`
`
`
`
`
`Exhibit 1067 Waynforth LASA Good Praez‘ice Guidelines Edministrarz'on 0f
`Subsrerices (Ra: Moese GEmea Pig, Rabbis) (Oct 1998),
`www.procedureswithcare.0rg.uk/lasa_administration.pdf
`
`
`Exhibit 1070 Neubauer, Changes in Ten/202E” Biologice! Markers during
`Primary Systemic Chemotherapy (PST): 28 ANTICANCER
`
`
`
`
`RESEARCH 1797—803 (2008)
`
`Exhibit 1069
`
`
`
`
`
`
`w‘xhibit 1071
`
`
`
`Exhibit 10?.
`
`
`Kern, “Role of Angiogenesis in the Transition to Hormone
`Independence and Acquisition of the Metastatic Phenotype,”
`Endeerz‘rzoiegy efBreasr Cancer 169~86 (Manni ed, 1999)
`
`
`
`
`Smith, Arieiysis ofOiZ—Based Pharmaceuticals, 49 J. AMERICAN
`OIL CHEMISTS’ SOCIETY 409-13 (1972)
`
`Spiegel & Noseworthy, Us‘e ome/iaqueous Salverzts in
`
`Pareeferai Prods/5e33, 52 J. PHARM. SCISi 9112'? (1963)
`(“Spiegei”)
`
`
`
`Exhibit 10??
`
`Taucher Sequeméaa’ Séereid Hormone Reeepter Meamremems in
`Primary Breast Cancer with or wimom Imervemng Primary
`..lCfEeergEizzEmR};
`ii} EEEELEWE- R}; EMLECEEC2:. 919E{EEEE}
`
`XV
`
`AstraZeneca Exhibit 2174 p. 16
`
`

`

`IPR2017—00904
`
`Petition for later Paries Review
`
`Exhibit 1074
`
`Turner, Administration ofSubszances to Lahoroz‘ory Animals:
`Routes ofAdministration and Factors to Consider, 50 J}
`
`AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
`
`600-13 (2011)
`
`Exhibit 1075
`
`Exhibit 1076
`
`
`
`Exhibit 1077
`
`
`
`Robertson, I.F.R. 61:211.) A Partially-Blind, Randomised
`Mufszcemre 8335?)» Comparing the Anti-Tumor Eficts osz‘ngle
`Doses (50‘, 325 and 256 mg) Offlosg-A sting (LA) ‘Fosiodex ’
`(ICI 182, 780) With Tamoxzfen In Postmenopausal Women With
`
`
`Primary Breast Cancer Prior T0 Surgery, in 22ND ANNUAL SAN
`
`
`
`
`
`ANTONIO REAST CANCER SYMPOSIUM, Abstract No. 28 ( )ec. 8-
`11, 1999) (“Robertson 1999”)
`
`Kohier, Plasma and Tissue Concentrations Following
`Infromusczdor Adminisrmtiorz ofEiofénamaz. Pharmacokmetics
`ofEiofeoomot and Fiaferzamic Acid in Pfosmo, Synovium, and
`Tissues ofPazients wish Chronic Polyarrhrz’tis ofier
`Administration afar: Oily Solurion ofEtofi‘nomat 42
`ARZNEIMITTELwFORSCHUNG (English Abstract) (1992)
`(“Kohler”)
`
`Jorgansen, Pharmacokinetic Studies in Volunteers ofIntravenous
`and Oroi Cz‘s (29-Hopenfixoi and Intramuscular Cz's (Z)—
`Fz’upeofixof Becareoofe fr: Viscoieo®, 18 EUR. J. GLEN.
`PHARMACOL. 355-60 (1980) (“Jorgensen”)
`
`Exhibit 1078
`
` Petition for Inter Fortes Review in Myi’orz Pharms. Inc. v.
`Ass‘roZeneco AB, Paper No. 1, 1PR2816-013} 6 (PTAB. June
`29, 2016)
`
`
`
`
`Exhibit 1080
`
`Exhibit 1081
`
`
`FDA’S Inactive Ingredient Database (1996) (“HG”)
`
` Drugs@FDA Glossary of Terms} US. FOOD & DRUG
`
`ADMINISTRATION (last updated Feb‘ 2,, 2012),
`http:Xfwww.fda.gow’DI‘ugsflnformationOnDrugsfucm079436.hfim
`
`xvi
`
`AstraZeneca Exhibit 2174 p. 17
`
`

`

`11311201?@0994
`
`Petition for Inter Farms Review
`
`
`
`
`
`
`fixhibit .1882 Adam, “Pharmacokinetics of Agents in Relation to Response,”
`
`Endocrine Management of Cancer: Bioiogicaf Bases 113-24
`(1988)
`
`
`
`
`Exhibit 1,083
`
`
`
`Baselga Phase II Study 9f Weekiy Intravenous Recombinant
`Humanized Ami-p} 858E332 Monaciomi Antibacfy 3'22 Pafiem‘s 1425f}:
`HER2/neu- Overexpreswing Metastatic Breast Cancer 14 J
`CLINICAL ONCOLOGY ?37-4--
`
`Exhibit 108
`
`
`
`
`
`Exhibit 1885
`
`Fabian Ciim'cal Pharmacology QfTamoxgfim in Patients with
`Breast Cancer: Carrefation W53}! Ciz‘nfcaf Dam, 48 CANCER 81'6-
`
`82 (1981)
`
`Goidenberg, Tmstummab, a Recoméfnant DNA-Derived
`Humanizecf Monoclonal Antibody, a Novel Agenzfor {he
`Treaimem‘ ofMemsmfic Bram? (Tamer, 21 CLINICAL
`THERAPEUTICS 309-18 {1999)
`
`
`
`
`Exhibit 1086 Wilkinson, Tamoxffim W03mdexfl Therapy - Razionafgfer
`
`Loading Dose Foilowed by Maintenance Dosefor Pgtients with
`Metaséazic Breast Cancer, 10 CANCER CHEMOTHERAPY
`PHARMACOLOGY 33-35 (1982)
`
`
`
`
`
`
`xhihit 108’?
`
`Cepy of Prosecution History for the US Patent No. 8,466;139
`(downloaded from PAIR)
`
`Exhibit 1038 Wuxzsche Essrogenic Regs/£36280}: ofCJassa‘erfn mRNié in Nerma!
`andMaZignamEndomerriai Tissue 761NT.J CANCER 684- 88
`(1998) (“Wunsche”)
`
`
`
`
`
`4xhibit 1089
`
`
`
`ixhibit 109G
`
`
`
`Chwalisz; Moduiation ofOesfmgenic Eflecis by Progesterone
`
`
`Anmganisfs m the Ra: Uz‘ems, _, hUMAN REPRODUCTION UPDATE
`570-83 (1998} (“Chwalisz”)
`
`Robertson Fut’vesz‘mm (Fasfaa’ex)—~H0w :0 Mafce a Goad Drug
`
`Betrer 12 ONCOI,06131 772—84 (200’?)
`
`xvii
`
`AstraZeneca Exhibit 2174 p. 18
`
`

`

`1PR201?-00904
`
`Petition for Inter Partes Review
`
`Exhibit 1091
`
`
`
`
`< Xhibit 1092
`
`Ansel: “Dosage Form Design: Biopharmaceutic anci
`Pharmacokinetic Considerations,” Pharmaceuticai Dosage
`Forms (23/361 {3ng Delivery Systems 101-41 (7th ed. 1999)
`
`Lee, Standard Deviation and Standard Ermr ofthe Mean, 68 ‘‘‘‘‘m
`KOREAN J . ANESTHESIOLOGY 220-33 (2015)
`
`
`
`iiiiiz’iltmang Standciitg Deviationsfland Standard Errors, 331 131131 903
`(2005)
`
`Exhibit 1094
`
`Tse stémvmggigtbiiigz ofParessremZ Drugs 1 Intravenous and VVVVVVVVVVVVVVm
`Intramuscular Doses 34 I PARENTERAL DRUG ASSOCIATION
`
`409—21 (1980)
`
`Exhibit 1095
`
`Exhibit 1096
`
`
`Exhibit 169’"
`
`
`
`Licciarcli, Oral Versus IntramuscuZar Progesterone for In Vitro
`Fertit‘izaz‘ion: A Prospective Randomized Study} 71 FERTILITY &
`
`STEMLITY 614-18 (1999)
`
`
`
`August 21, 2008 Applicant Amendment and Response in
`Application No. 10/872,784
`
`Balant-Gorgia, Pharmacoicfssetfc Optimisation affke Treatment
`ofPsychosis, 25 CLIN. PHARMACOKINET. 21766 (1993)
`
`Chien, Sofubiiizafian ofSi‘eroz'ds by 114213553938 (30—Selves: Systems
`
`
`23 CHEM 3HARM BULL 1085-90 (19"5)
`
`
`
`
`
`i‘xhibit 1098
`
`
`
`Exhibit 1099
`
`Ford, “Parenteral Precincts,” Pharmaceutics: The Science Qf
`Dosage Form Design 359—80 (Aulton ed; 1988)
`
`
`
`Exhibit 1100
`
`Cunliffe-Beamer, “Biomethodology and Surgical Techniques,”
`The Mouse in Biomedical Research, Vomme 3H.“ Normative
`
`Exhibit 1101
`
`Bialogy. Immwwfogy, and Husbandry 40167 (Faster sci, 1983)
`
`
`wégiiméosolvefiifisé in Injectsigigfiormuiatioiism}; Inflatable lllllllllllllll
`Drug Development.“ Techniques 2‘0 Reduce Pain and Irritation
`215—66 (Gupta ed, 1999)
`
`xviii
`
`AstraZeneca Exhibit 2174 p. 19
`
`

`

`IPR201?-00904
`
`Petition for Inter Partes Review
`
`
`
`
`
`
`Nema Exeipfienm :3?ch The??? Use in Izgees‘eeie Prodeca‘s 51 FDA
`.1 PHARM SCI &TECH 166710997)
`
`
`
`Ogasawara Ejfizcz‘s offixperimenmé’ Chemoendecrme Therapy
`with a Combinarien ofa Pure Antiesfrogee and 5-Fiu0memcii
`0e Heme}? Breeze: Cancer Ceiis Implanted in Nude Mice, 29
`SURGERY TODAY“ 149-56 (1999)
`
`Oldham “Mass Transpert 1:0 Eiectrodes” Chemicef Kinetics 79-
`143 (Bamford ed ,1986)
`
`Powell, Compendium ofExezpienrsfor Parem‘eml Fermuiaz‘ions,
`52 FDA 3'. PHARM. SCI. & TECH. 238-311 (1998)
`
`Remington ’s Pharmaceuricai Sciences 1538—393 1545-50, 1686-
`88 (18th ed. 1990)
`
`Roberts Inveetigafzon efCoselvem‘ Efleem on the Salvation ofm
`AOTReveree Mieefies in Sepeeerfricai Ethane 102 J. PHYS
`
`Cam. B 9074-80 (1998)
`
`
`
` Exhibit 1105
`
`
`
`
`
`
`
`exhibit 1106
`
`Exhibit 1107
`
`
`
`Exhibit 1108
`
`
`
`
`
`
`‘Xhlblt 1109
`
`Eihibit 1110
`
`Exhibit 111 1
`
`
`
`
`
`Sawka, Physioiegieei Conseqeeeees enypohydmtiorz: Exercise
`Performance and Thermoregulation, 24 MEDICINE & SCIENCE IN
`
`E SPORTS &EXERCISE. 65730 (1992)
`
`Slmmons, The Laboratory Mouse: Selecsion and Managemem
`1233-28 {19?0)
`
`Ting? Seiueiiim ofNapeeer/I in Sepereeiiz‘caf Carbon. Déexide
`
`wife and wis‘fzoazt Cosoivems, 32 IN} ENG. CHEM. RES. 147’1-81
`
`(1993)
`
`
`
`
`
`Tse, Bioaveiiebiiigs ofPerememZ Drugs If. Parememi 330563
`Other Than Intravenous and Inseamuseuiae Rome‘s, 34 J.
`
`PARENTERAL DRUG ASSOCIATION 484-95 (BBQ)
`
`xix:
`
`AstraZeneca Exhibit 2174 p. 20
`
`

`

`EPIC/301100904
`
`Petition for Inier Partes Review
`
`Exhibit 1113
`
`Natienal Formulary 13-14 (1995)
`
`USP 23 -—- NF 18, The United States Pharmacopeia —— The
`
`XX
`
`AstraZeneca Exhibit 2174 p. 21
`
`

`

`IPR201?-0090
`
`
`
`
`
`Petition for Inter Partes Review
`
`
`TABLE OF ABBREVIATIONS
`
`
`7€1~ [9-(— ,4, 5 ,5 ,S-pentafluompentylsulphinyljnenyl]oestra—13,500)»
`
`triene-B ,1?13-
`
`diol .................................................................................................. Fulvestrant
`
`Estrogen receptor ........................................................................... ER
`
`Estrogen receptor-positiveFR+ 0r ER~positixze
`
`
`estrogen—receptor downreguiaters .....................................................................ERDS
`
`
`
`flormone—dependent.........