Paper No. 7
`Date Filed: June 24, 2016
`
`Filed on behalf of: Aventis Pharma S.A.
`
`By:
`
`Dominick A. Conde
`dconde@fchs.com
`(212) 218-2100
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
`
`MYLAN LABORATORIES LIMITED
`Petitioner,
`v.
`AVENTIS PHARMA S.A.
`Patent Owner.
`________________
`
`Case IPR2016-00712
`U.S. Patent No. 8,927,592
`________________
`
`PRELIMINARY RESPONSE BY PATENT OWNER PURSUANT TO 37
`C.F.R. § 42.107
`
`
`Date Filed: June 24, 2016
`
`Filed on behalf of: Aventis Pharma S.A.
`
`By:
`
`Dominick A. Conde
`dconde@fchs.com
`(212) 218-2100
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
`
`MYLAN LABORATORIES LIMITED
`Petitioner,
`v.
`AVENTIS PHARMA S.A.
`Patent Owner.
`________________
`
`Case IPR2016-00712
`U.S. Patent No. 8,927,592
`________________
`
`PRELIMINARY RESPONSE BY PATENT OWNER PURSUANT TO 37
`C.F.R. § 42.107
`
`
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION ...........................................................................................1
`
`BACKGROUND OF THE INVENTION.......................................................3
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`The Need for New Prostate Cancer Therapies......................................3
`
`Difficulties in Obtaining Efficacious Treatments .................................4
`
`Failures in CRPC...................................................................................6
`
`Little Was Known About the Use of Cabazitaxel for
`Prostate Cancer Post-Docetaxel Therapy..............................................7
`
`Prosecution History...............................................................................8
`
`III.
`
`PERSON OF ORDINARY SKILL ...............................................................11
`
`IV. CLAIM CONSTRUCTION ..........................................................................11
`
`A.
`
`B.
`
`“dose” and “CV” .................................................................................12
`
`The Full Preambles of Claim 1 and Claim 27 Are
`Limiting ...............................................................................................12
`
`1.
`
`2.
`
`Claim Language Shows that the Preambles Are
`Limiting.....................................................................................12
`
`The Specification Shows that Treating and
`Increasing the Survival of the Claimed Patients
`Are Fundamental Characteristics of the Claimed
`Invention ...................................................................................13
`
`3.
`
`The Preambles Were Critical During Prosecution....................14
`
`C.
`
`“A method for treating a patient”........................................................15
`
`1.
`
`2.
`
`The Specification Shows that Therapeutic Efficacy
`Is a Fundamental Feature of the Invention ...............................16
`
`Applicants Relied on Therapeutic Efficacy During
`Prosecution................................................................................17
`
`- i -
`
`
`
`D.
`
`“A method of increasing the survival of a patient”.............................19
`
`1.
`
`2.
`
`The Specification Describes a Method that
`Provides a Statistically Significant Increase in
`Overall Survival ........................................................................19
`
`Applicants Relied on Overall Survival Data to
`Distinguish Prior Art.................................................................20
`
`V.
`
`LEGAL STANDARD ...................................................................................21
`
`VI. MYLAN’S ALLEGED INVALIDITY GROUNDS.....................................22
`
`A.
`
`B.
`
`All Grounds Fail Because Mylan Does Not Address the
`Surprise in the Field ............................................................................22
`
`Ground 1: The Board Should Not Institute Review Based
`on Alleged Obviousness over Winquist and the TROPIC
`Listing..................................................................................................23
`
`1.
`
`2.
`
`Ground 1 Does Not Establish Prima Facie
`Obviousness of Claims 1 and 27...............................................23
`
`Ground 1 Plus the Background Knowledge in the
`Art Do Not Establish Obviousness of Claims 1 or
`27...............................................................................................26
`
`a.
`
`b.
`
`c.
`
`d.
`
`Mylan Fails to Rebut Prosecution Evidence
`Showing the Single Response in Attard Is
`Insufficient......................................................................27
`
`Mylan’s Reliance on Activity in Breast
`Cancer to Predict Activity in Prostate
`Cancer Is Unsupported ...................................................33
`
`Mylan’s Reliance on Similarities with
`Docetaxel to Predict Activity in Patients No
`Longer Responding to Docetaxel Is
`Unsupported....................................................................38
`
`Mylan’s Reliance on the Mere Existence of
`the Phase III Trial Is Speculative....................................42
`
`- ii -
`
`
`
`e.
`
`Mylan Cites No Information Regarding a
`Survival Benefit..............................................................43
`
`3.
`
`Mylan Fails to Show that the Pharmacokinetic
`Properties of Claims 7-9 Are Inherent......................................44
`
`C.
`
`Ground 7: The Board Should Not Institute Review Based
`on Alleged Obviousness over Winquist and Pivot..............................45
`
`1.
`
`2.
`
`3.
`
`Ground 7 Does Not Establish Prima Facie
`Obviousness of Claims 1 and 27...............................................46
`
`Ground 7 Plus the Background Knowledge in the
`Art Do Not Establish Obviousness of Claims 1 and
`27...............................................................................................47
`
`Mylan Fails to Show that the Pharmacokinetic
`Properties of Claims 7-9 Are Inherent......................................49
`
`D.
`
`E.
`
`Grounds 2 and 8: The Board Should Not Institute Review
`Based on Alleged Obviousness over Winquist, TROPIC
`Listing, Pivot, and Didier ....................................................................49
`
`Grounds 3, 4, 5, 6, 9, and 10: The Board Should Not
`Institute Review Based on Alleged Obviousness over
`Winquist, the TROPIC Listing, Pivot, Mita, and Tannock.................52
`
`VII. THE BOARD SHOULD EXERCISE ITS DISCRETION TO
`DENY INSTITUTION PURSUANT TO 35 U.S.C. § 325(d)......................52
`
`VIII. MYLAN’S INHERENCY ARGUMENTS SHOULD BE
`DISREGARDED ...........................................................................................53
`
`IX. MYLAN FAILS TO REBUT OJECTIVE EVIDENCE OF
`NON-OBVOUSNESS...................................................................................55
`
`A.
`
`B.
`
`C.
`
`Long-Felt Need....................................................................................56
`
`Failure of Others..................................................................................56
`
`Unexpected Properties.........................................................................57
`
`- iii -
`
`
`
`1.
`
`It Was Unexpected that Cabazitaxel Would
`Increase Survival.......................................................................57
`
`D.
`
`Aventis Did Not Disclaim Unexpected Properties ...................58
`2.
`The Pharmaceutical Industry Has Praised Jevtana®............................59
`At Least Nine Companies have Copied Jevtana® ...............................60
`Jevtana® Is a Commercial Success......................................................60
`CONCLUSION..............................................................................................60
`
`E.
`
`F.
`
`X.
`
`- iv -
`
`
`
`TABLE OF AUTHORITIES
`
`Cases
`Alcon Research Ltd. v. Neev, IPR2014-00217,
`Paper 21 (P.T.A.B. May 9, 2014)..................................................................24
`
`Alcon, Inc. v. Teva Pharms., USA, Inc.,
`664 F. Supp. 2d 443 (D. Del. 2009) ..............................................................31
`
`Amgen Inc. v. F. Hoffman-La Roche Ltd.,
`580 F.3d 1340 (Fed. Cir. 2009) .....................................................................21
`
`Amgen, Inc. v. Chugai Pharm. Co.,
`927 F.2d 1200 (Fed. Cir. 1991) .....................................................................32
`
`Apple Inc. v. ITC,
`725 F.3d 1356 (Fed. Cir. 2013) .....................................................................55
`
`Atofina v. Great Lakes Chem. Corp.,
`441 F.3d 991 (Fed. Cir. 2006) ................................................................ 17, 20
`
`Benitec Biopharma Ltd. v. Cold Spring Harbor Lab.,
`IPR2016-00014, Paper 7 (P.T.A.B. Mar. 23, 2016)............................... 29, 44
`
`Boehringer Ingelheim Int’l GMBH v. Biogen Inc.,
`IPR2015-00418, Paper 14 (P.T.A.B. July 13, 2015).....................................26
`
`Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough
`Corp.,
`320 F.3d 1339 (Fed. Cir. 2003) .....................................................................13
`
`Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc.,
`246 F.3d 1368 (Fed. Cir. 2001) .....................................................................54
`
`Coal. for Affordable Drugs V LLC v. Biogen Ma Inc.,
`IPR2015-01136, Paper 23 (P.T.A.B. Sept. 2, 2015) .............................. 25, 47
`
`Cuozzo Speed Techs. LLC v. Lee,
`579 U.S. _ (2016) (No. 15-446, Slip. Op.)....................................................11
`
`- v -
`
`
`
`Cyanotech Corp. v. Bd. of Trs. of the Univ. of Ill.,
`IPR2013-00401, Paper 17 (P.T.A.B. Dec. 19, 2013)....................................41
`
`Eisai Co. v. Dr. Reddy’s Labs., Ltd.,
`533 F.3d 1353 (Fed. Cir. 2008) .....................................................................32
`
`Eizo Corp. v. Barco N.V., IPR2014-00358,
`Paper No. 11 (P.T.A.B. July 2, 2014)..................................................... 22, 26
`
`General Elec. Co. v. Tas Energy Inc., IPR2014-00163,
`Paper 11 (P.T.A.B. May 13, 2014)................................................... 27, 39, 42
`
`Gilead Scis., Inc. v. Mylan, Inc.,
`107 F. Supp. 3d 541 (N.D. W. Va. 2015)......................................................17
`
`Honeywell Int’l Inc. v. ITT Indus., Inc.,
`452 F.3d 1312 (Fed. Cir. 2006) .....................................................................16
`
`In re Cruciferous Spout Litig.,
`301 F.3d 1343 (Fed. Cir. 2002) .....................................................................14
`
`In re Dow Chem. Co.,
`837 F.2d 469 (Fed. Cir. 1988) .......................................................................21
`
`In re Fisher,
`427 F.2d 833 (C.C.P.A. 1970).......................................................................32
`
`In re Kahn,
`441 F.3d 977 (Fed. Cir. 2006) .......................................................................22
`
`In re Montgomery,
`677 F.3d 1375 (Fed. Cir. 2012) .....................................................................54
`
`In re Sang Su Lee,
`277 F.3d 1338 (Fed. Cir. 2002) .....................................................................22
`
`In re Shetty,
`566 F.2d 81 (C.C.P.A. 1977).........................................................................44
`
`Institut Pasteur v. Focarino,
`738 F.3d 1337 (Fed. Cir. 2013) .....................................................................24
`
`- vi -
`
`
`
`Kaiser Aluminum v. Consellium Rolled Prods. Ravenswood,
`LLC,
`IPR2014-01002, Paper 64 (P.T.A.B. Nov. 2, 2015)......................................54
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007).......................................................................................21
`
`MBO Labs., Inc. v. Becton Dickinson & Co.,
`474 F.3d 1323 (Fed. Cir. 2007) .....................................................................14
`
`Merial Ltd. v. Virbac, IPR2014-01279,
`Paper 23 (P.T.A.B. Jan. 22, 2015).................................................................30
`
`Mycogen Plant Sci. v. Monsanto Co.,
`243 F.3d 1316 (Fed. Cir. 2001) .....................................................................32
`
`Neil Ziegman N.P.Z., Inc. v. Stephens,
`IPR2015-01860, Paper 11 (P.T.A.B. Feb. 24, 2016) ....................................52
`
`Nichia Corp. v. Everlight Elecs. Co.,
`No. 2:13-cv-702, 2014 WL 7149169
`(E.D. Tex. Dec. 12, 2014)..............................................................................13
`
`Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc.,
`348 F. Supp. 2d 713 (N.D. W. Va. 2004)......................................................60
`
`Pacing Techs., LLC v. Garmin Int’l, Inc.,
`778 F.3d 1021 (Fed. Cir. 2015) .....................................................................12
`
`Panduit Corp. v. Dennison Mfg. Co.,
`810 F.2d 1561 (Fed. Cir. 1987) .....................................................................50
`
`Par Pharm., Inc. v. TWI Pharms., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) .....................................................................44
`
`Perfect Web Techs., Inc. v. InfoUSA, Inc.,
`587 F.3d 1324 (Fed. Cir. 2009) .....................................................................22
`
`Praxair Distrib., Inc. v. INO Therapeutics, Inc.,
`IPR2015-00522, Paper 12 (P.T.A.B. July 29, 2015).....................................29
`
`Praxair, Inc. v. ATMI, Inc.,
`543 F.3d 1306 (Fed. Cir. 2008) .....................................................................16
`
`- vii -
`
`
`
`Tempur Sealy Int’l Inc. v. Select Comfort Corp.,
`IPR2014-01419, Paper 7 (P.T.A.B. Feb. 17, 2015) ......................................53
`
`TomTom, Inc. v. Adolph,
`790 F.3d 1315 (Fed. Cir. 2015) .....................................................................12
`
`Statutes
`
`35 U.S.C. § 103(a) ...................................................................................................21
`
`35 U.S.C. § 314(a) ...................................................................................................21
`
`35 U.S.C. § 325(d) ...................................................................................................52
`
`Other Authorities
`
`M.P.E.P. § 2143.02 ..................................................................................................24
`
`Rules
`
`37 C.F.R. § 42.100(b) ..............................................................................................11
`
`37 C.F.R. § 42.104(b)(2)..........................................................................................26
`
`37 C.F.R. § 42.104(b)(4)................................................................................... 21, 24
`
`37 C.F.R. § 42.6(a)(3)..............................................................................................53
`
`37 C.F.R. § 42.65 ........................................................................................ 27, 39, 54
`
`- viii -
`
`
`
`Aventis Pharma S.A. (“Aventis”) respectfully submits this Preliminary
`
`Response to the Petition of Mylan Laboratories Ltd. (“Mylan”) seeking inter
`
`partes review (“IPR”) of U.S. Patent No. 8,927,592 (“the ’592 patent”). The ’592
`
`patent claims recite methods of treating and increasing the survival of a patient
`
`with prostate cancer that has progressed during or after treatment with docetaxel,
`
`comprising administering cabazitaxel in combination with a corticoid. Aventis has
`
`asserted the ’592 patent in a pending Hatch-Waxman action against Mylan: C.A.
`
`No. 15-03392(MAS)(LHG) (D.N.J.).
`
`I.
`
`INTRODUCTION
`
`Before the 2009 priority date of the ’592 patent, no life-extending treatments
`
`were available for patients with metastatic castration resistant prostate cancer
`
`(“mCRPC”) worsening after docetaxel treatment. Jevtana® (cabazitaxel), the use
`
`of which is covered by the claims of the ’592 patent, changed that.
`
`Jevtana® is the first and only cytotoxic chemotherapy regimen that prolongs
`
`the lives of patients with mCRPC that has progressed during or after treatment with
`
`docetaxel. A phase III clinical trial (the TROPIC study) comparing cabazitaxel to
`
`the standard palliative therapy (mitoxantrone) surprisingly revealed that
`
`cabazitaxel provided a statistically significant increase in overall survival and
`
`significantly better disease response rates. Exh. 2055 at 1151, 1154. Because
`
`- 1 -
`
`
`
`cabazitaxel fulfilled an unmet need, the FDA granted priority review and approved
`
`Jevtana® after only eleven weeks of review. Exh. 2059 at 1.
`
`Ignoring those surprising results, Mylan seeks to institute an IPR based on
`
`alleged obviousness of Claims 1-5 and 7-30 of the ’592 patent. For at least the
`
`reasons below, the Board should reject Mylan’s Petition.
`
`First, Mylan fails to address evidence submitted during prosecution of the
`
`’592 patent. Specifically, Mylan ignores that, as discussed during prosecution,
`
`there were multiple compounds that showed some activity in phase I and II
`
`prostate cancer studies, but (to the great disappointment of experts in the field)
`
`failed in critical phase III studies. Mylan also ignores that experts in the field were
`
`surprised by the results of the TROPIC study. Prior to that study there was no
`
`known treatment for mCRPC patients whose disease progressed after docetaxel
`
`therapy. Thus, any agent working in this desperate and gravely ill patient group
`
`was surprising on its own. It was particularly surprising that cabazitaxel provided
`
`a survival benefit because it and docetaxel are both taxanes. No prior art suggested
`
`that once a prostate cancer patient’s disease progressed after treatment with one
`
`taxane, the same patient would obtain a survival benefit from using a second drug
`
`from the same taxane class. That cabazitaxel provided such a result defied
`
`common sense and conventional wisdom.
`
`Second, Mylan relies on a patchwork of “background knowledge” references
`
`- 2 -
`
`
`
`(that are not included in the stated Grounds) to suggest there would have been a
`
`reasonable expectation of success. But those references do not support Mylan’s
`
`conclusions.
`
`Specifically, Mylan depends on structural similarities of cabazitaxel with
`
`docetaxel. But such similarities would suggest another taxane would provide no
`
`benefit for patients who are no longer responding to docetaxel. Mylan also relies
`
`on data regarding breast cancer patients without showing why a person of ordinary
`
`skill in the art (“POSA”) would understand that data in breast cancer is predictive
`
`of success in prostate cancer (it is not). And, Mylan relies on data from a single
`
`patient in a phase I study (which was considered during prosecution) without
`
`showing it would provide a reasonable expectation of success in other patients. It
`
`does not — the prior art was full of examples where compounds tested in phase I
`
`or II studies subsequently failed in phase III trials with larger patient populations.
`
`Because Mylan’s arguments are unsupported and fail to address evidence
`
`considered by the Examiner in allowing the claims, Mylan fails to establish a
`
`prima facie case of obviousness, and the Petition should be denied.
`
`II.
`
`BACKGROUND OF THE INVENTION
`
`A.
`
`The Need for New Prostate Cancer Therapies
`
`In 2009, prostate cancer was the second leading cause of male cancer deaths
`
`in the United States. Exh. 2047 at 4. Metastatic prostate cancer patients are
`
`- 3 -
`
`
`
`typically treated with medical or surgical castration to lower the level of hormones
`
`that promote cancer growth. Exh. 2001 at ¶28. Most patients with metastatic
`
`prostate cancer have progression or recurrence despite castration-levels of
`
`testosterone. Exh. 2083 at 300. This is referred to as castration resistant or
`
`hormone-refractory prostate cancer (“CRPC”). Exh. 2001 at ¶¶29-30; Exh. 1001 at
`
`4:4-5. mCRPC was incurable, and therefore the goals of treatment were to
`
`enhance quality of life and overall survival. Exh. 1022 at 161; Exh. 2001 at ¶30.
`
`In 2004, docetaxel was approved by the FDA for mCRPC based on an
`
`overall survival benefit. Exh. 2083 at 304-307; Exh. 2058. Unfortunately, nearly
`
`all CRPC patients progress during or after treatment with docetaxel, often because
`
`of drug resistance. Exh. 1027 at 557; Exh. 2009 at 3; Exh. 1004 at 21. Prior to the
`
`claimed methods, once such progression occurred, patients had no options to
`
`prolong life, making the need for other options “urgent.” Exh. 1022 at 161-62.
`
`Exh. 2001 at ¶35.
`
`B.
`
`Difficulties in Obtaining Efficacious Treatments
`
`Developing treatments for CRPC was and is particularly difficult. First, the
`
`disease is heterogeneous, which means a variety of cancer cells must be attacked
`
`within a single patient, and the disease can be different between patients. See, e.g.,
`
`Exh. 1001 at 2:1-5; Exh. 2025 at 1033; Exh. 2001 at ¶¶31-32.
`
`Second, there are a variety of pathways by which castration resistance can
`
`- 4 -
`
`
`
`develop. Exh. 2083 at 300; Exh. 2025 at 1034. And, understanding docetaxel
`
`resistance mechanisms was a “very challenging task” because it can be caused by
`
`multiple mechanisms “in a single cell at the same time.” Exh. 1020 at 939; see
`
`also Exh. 2009 at 4 (noting “complex” and “overlapping” mechanisms of
`
`resistance). Nor was it clear that resistance to docetaxel in one type of cancer
`
`would be the same as resistance to docetaxel in another cancer. Exh. 2091 at 960,
`
`96l; see also Exh. 2009 at 5 (choice of cell lines influences mechanisms of
`
`resistance).
`
`Mylan’s expert, Dr. Rahul Seth, oversimplifies docetaxel resistance by
`
`asserting that it was “well established” that prostate and breast cancer develop
`
`resistance to docetaxel due to the P-glycoprotein (“PGP”) efflux pump. Exh. 1002
`
`at ¶77. PGP was considered a resistance mechanism when in vitro cell lines were
`
`exposed to docetaxel. Exh. 1020 at 923. But it was recognized that “the
`
`contribution of the distinct resistance phenotypes as well as their role in clinical
`
`oncology ha[d] yet to be fully evaluated.” Id. at 939 (emphasis added); Exh. 1021
`
`at 75 (noting the “clinical relevance [of PGP] is not fully understood”). Others
`
`cautioned that “mechanisms discovered in cell culture may not always represent
`
`the most commonly encountered mechanisms in patients undergoing treatment.”
`
`Exh. 2009 at 3. Additionally, Dr. Seth ignores prior art describing many other
`
`potential mechanisms of resistance to docetaxel such as alterations to the
`
`- 5 -
`
`
`
`tubulin/microtubulin system, signaling pathways, regulation of cell cycle, and
`
`control of apoptosis and cell death signals. Exh. 1020 at 921. Indeed, the
`
`mechanisms of resistance to docetaxel are still not well understood. Exh. 2096 at
`
`2974; see also Exh. 2001 at ¶¶37-40.
`
`C.
`
`Failures in CRPC
`
`The unpredictability in finding successful treatments for CRPC is
`
`demonstrated by numerous failed phase III studies. As discussed during
`
`prosecution, the art is replete with examples where a treatment regimen showed
`
`promising results in phase I and/or II studies and then failed in expensive phase III
`
`studies involving significantly more patients.
`
`For example, phase II studies with satraplatin demonstrated “activity and an
`
`acceptable toxicity profile in patients with CRPC,” but in a phase III study
`
`satraplatin failed to produce a statistically significant increase in overall survival.
`
`Exh. 1022 at 162-63. A phase II study of suramin reported three complete
`
`responses and thirteen patients with PSA reductions, but the drug did not prolong
`
`overall survival in a phase III CRPC study. Exh. 2020 at 209-10. Atrasentan
`
`reduced PSA levels in a phase II study, but did not reduce disease progression or
`
`prolong overall survival in a phase III mCRPC study. Exh. 2010 at 1960, 1962-63.
`
`DN-101 plus docetaxel showed a “promising improvement” in survival and no
`
`increase in toxicity in a phase II study in mCRPC, yet did not improve overall
`
`- 6 -
`
`
`
`survival in a phase III clinical study. Exh. 2006 at 672-73; Exh. 2043 at 1593;
`
`Exh. 2028 at 2. Phase I/II studies of GVAX in mCRPC reported a complete
`
`response and an increase in overall survival as compared to predicted survival, but
`
`development was terminated after two phase III mCRPC studies failed to show an
`
`effect on overall survival. Exh. 2034 at 3884, 3888, 3890; Exh. 2018 at 983; Exh.
`
`2027 at 1.
`
`Similarly, failures in CRPC continued after the filing of the ’592 patent.
`
`Antonarakis and Eisenberger report eight failed phase III trials in patients with
`
`mCRPC of different combination therapies with docetaxel: bevacizumab,
`
`aflibercept, atrasentan, zibotentan, dasatinib, GVAX, lenalidomide, and calcitriol.
`
`Exh. 2004 at 1709-10. The authors state that “accurate prediction of a positive
`
`phase III study is an impossible endeavor.” Id. at 1711; see also Exh. 1004 at 175-
`
`79.
`
`D.
`
`Little Was Known About the Use of Cabazitaxel for Prostate Cancer
`Post-Docetaxel Therapy
`
`Before the priority date of the ’592 patent, the only data available on the use
`
`of cabazitaxel in patients with prostate cancer that had progressed during or after
`
`treatment with docetaxel came from Mita et al. Exh. 2001 at ¶53. Mita reports the
`
`results of a phase I study of cabazitaxel administered to patients with a variety of
`
`advanced solid tumors. Exh. 1012 at 724-25. A single prostate cancer patient
`
`- 7 -
`
`
`
`refractory to docetaxel had a partial response at the 25 mg/m2 dose level. Id. at
`
`727. Mylan also identifies the existence of a phase III clinical trial being
`
`performed by Sanofi-Aventis of cabazitaxel in patients with mCRPC that had
`
`previously received docetaxel therapy.1 Exh. 1022 at 163; Exh. 2078 at 3; Exh.
`
`2001 at ¶¶54-58. However, no data from that study had been reported. Id.
`
`E.
`
`Prosecution History
`
`The ’592 patent issued on January 6, 2015, from U.S. Patent Application
`
`Number 13/456,720 filed on April 26, 2012. Exh. 1001. The ’720 application is a
`
`continuation of International Application No. PCT/IB2010/054866 filed on
`
`October 27, 2010, and claims priority to seven U.S. provisional patent applications,
`
`the earliest of which was filed on October 29, 2009. Exh. 1001; Petition at 3.
`
`The claims of the ’592 patent were extensively reviewed. The Examiner
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`considered the Didier, Mita, Tannock, and Pivot references relied upon by Mylan
`
`in its asserted Grounds, and the Attard and Beardsley references cited by Mylan as
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`“background knowledge in the art.” See Exh. 1001 at 1, 3. The Examiner also
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`considered the National Horizon Scanning Centre reference (“NHSC”), which
`
`contains substantially the same disclosure as Mylan’s Winquist reference. Exh.
`
`1001 at 3; compare Exh. 1009 with Exh. 2078; Exh. 2001 at ¶56. The Examiner
`
`also considered a printout of the Clinicaltrials.gov website for the TROPIC study
`
`1 Sanofi-Aventis was an affiliated company of Aventis.
`
`- 8 -
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`
`
`updated on December 28, 2006, which is similar to the TROPIC Listing relied on
`
`by Mylan. Exh. 1001 at 2 (listing
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`http://clinicaltrials.gov/archive/NCT00417079/2006_12_8); compare Exh. 1008
`
`with Exh. 2100; Exh. 2001 at ¶57.
`
`The claims were initially rejected over Mita and Tannock. Exh. 1004 at
`
`2222-28; 1874-79. Additionally, the claims were later rejected as anticipated and
`
`obvious over Beardsley. Exh. 1004 at 252-61.
`
`At an interview, Applicants submitted a draft declaration by Dr. Alton
`
`Oliver Sartor, an expert in treating prostate cancer, who was also in attendance.
`
`Exh. 1004 at 230. The Examiner indicated that the claims would be allowed if
`
`they were amended to recite 20-25 mg/m2 of cabazitaxel and prostate cancer that
`
`had progressed during or after treatment with docetaxel. Id.
`
`Applicants amended the claims as suggested, noting that there was no
`
`anticipation because Beardsley did not recite 20-25 mg/m2 of cabazitaxel. Exh.
`
`1004 at 137-45. Applicants also argued that the claims were not obvious over the
`
`single patient response in Mita, Beardsley (which included no prostate cancer
`
`data), and the docetaxel disclosure of Tannock because these references did not
`
`provide a reasonable expectation of success that the claimed methods would
`
`successfully treat the claimed patients. Id. at 145-49.
`
`In doing so, Applicants submitted a declaration from Dr. Sartor (“Sartor
`
`- 9 -
`
`
`
`Declaration”), who was a principal investigator for the phase III clinical trial
`
`leading to the approval of Jevtana®. Id. at 164-222. Dr. Sartor explained why
`
`prostate cancer that had progressed during or after treatment with docetaxel was
`
`particularly difficult to treat. Id. at 184-87. He also explained why it was difficult
`
`to predict the clinical success of new therapies for CRPC and described regimens
`
`that had promising phase II data, but failed in phase III studies. Id. at 172-79, 186-
`
`87. Dr. Sartor explained why the limited clinical data available for cabazitaxel in
`
`the prior art was insufficient for a POSA to reasonably predict that the claimed
`
`regimen would provide a clinically meaningful benefit to the relevant patients. Id.
`
`at 188-91. He also described the long-felt need for a treatment for prostate cancer
`
`patients that had progressed during or after treatment with docetaxel, and that
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`Jevtana® met that need as demonstrated by a statistically significant increase in
`
`overall survival, shown in Example 1 of the patent. Exh. 1004 at 184; Exh. 1001 at
`
`Table 1. Dr. Sartor noted that he encountered skepticism when initiating the study,
`
`and that his presentation of the results at a scientific conference was met with
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`surprise. Exh. 1004 at 185, 189.
`
`The Examiner allowed the claims stating “it is surprising and unexpected
`
`that the claimed combination of cabazitaxel and a corticoid are clinically effective
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`in the treatment of prostate cancer that has progressed during or after treatment
`
`with docetaxel.” Id. at 93; 21. The Examiner noted that Dr. Sartor “provide[d]
`
`- 10 -
`
`
`
`convincing evidence that while the art was full of promising early clinical results,
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`these failed to predict whether therapies would ultimately provide a clinically
`
`meaningful benefit to the desired patient populations and that mCRPC was known
`
`to be a particularly challenging and unpredictable indication.” Id.
`
`III. PERSON OF ORDINARY SKILL
`
`A POSA would be an oncologist or medical doctor specializing in oncology
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`and would have experience in the treatment of prostate cancer, including metastatic
`
`prostate cancer, in evaluating therapies for prostate cancer, and would have access
`
`to information regarding pharmacokinetics and mechanisms of drug resistance.
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`Exh. 2001 at ¶24. Although Mylan’s proposed definition is different, the definition
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`of a POSA should not affect the outcome.
`
`Submitted herewith is a declaration from Dr. Sartor. Dr. Sartor is well-
`
`qualified as an expert, possessing the necessary clinical expertise and other
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`specialized knowledge as of October 29, 2009. Exh. 2001 at ¶¶2-11.
`
`IV. CLAIM CONSTRUCTION
`
`The Board interprets claims according to the broadest reasonable
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`construction in light of the specification of the patent in which they appear and the
`
`file history. 37 C.F.R. § 42.100(b); Cuozzo Speed Techs. LLC v. Lee, 579 U.S. _, _
`
`(2016) (No. 15-446, Slip. Op. at 20).
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`- 11 -
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`
`
`A.
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`“dose” and “CV”
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`Although Mylan did not propose that “dose” or “CV” required construction
`
`in the related district court litigation, Mylan now proposes constructions. Petition
`
`at 15, 17. Construction of these terms is not necessary because the ordinary
`
`meaning is clear to a POSA.
`
`B.
`
`The Full Preambles of Claim 1 and Claim 27 Are Limiting
`
`Mylan truncates the preambles of Claims 1 and 27. Petition 17-19. The
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`complete preamble of Claim 1 recites “A method for treating a patient with
`
`prostate cancer that has progressed during or after treatment with docetaxel,” and
`
`of Claim 27 recites “A method of increasing the survival of a patient with . . .
`
`prostate cancer that has progressed during or after treatment with docetaxel,” both
`
`of which should be construed as a whole. The claim language, the specification,
`
`and the file history show that those preambles are claim limitations.
`
`1.
`
`Claim Language Shows that the Preambles Are Limiting
`
`The preambles of Claims 1 and 27 are limitations because they provide
`
`antecedent basis for “administering to said patient,” and “to the patient”
`
`respectively. Pacing Techs., LLC v. Garmin Int’l, Inc., 778 F.3d 1021, 1024 (Fed.
`
`Cir. 2015) (preamble limiting where it provided antecedent basis). Mylan’s
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`reliance on TomTom, Inc. v. Adolph, 790 F.3d 1315, 1324 (Fed. Cir. 2015) is
`
`misplaced because there the non-limiting language of the preamble was also in the
`
`- 12 -
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`
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`body of the claim, and therefore was “merely duplicative.” Here, treating or
`
`increasing survival of particular patients is only in the preamble.
`
`The preambles are also limiting because Claims 24 and 28 are redundant
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`unless treating and increasing the survival of patients are limiting. Nichia Corp. v.
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`Everlight Elecs. Co., No. 2:13-cv-702, 2014 WL 7149169, at *24 (E.D. Tex. Dec.
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`12, 2014) (preamble limiting where otherwise two claims would have identical
`
`scope).
`
`2.
`
`The Specification Shows that Treating and Increasing the
`Survival of the Claimed Patients Are Fundamental
`Characteristics of the Claimed Invention
`
`Where the specification shows that preamble language is an essential part of
`
`the invention, that language is limiting. Boehringer Ingelheim Vetmedica, Inc. v.
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`Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003) (preamble recited
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`the “essence of the invention without which performance of the recited steps is
`
`nothing but an academic exercise”).
`
`Here, the specification shows that the essence of the invention is a
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