Paper No. ____
`Filed: March 15, 2016
`
`Filed on behalf of: Mylan Laboratories Limited
`By: Steven W. Parmelee
`
`Michael T. Rosato
`
`Jad A. Mills
`WILSON SONSINI GOODRICH & ROSATI
`701 Fifth Avenue, Suite 5100
`Seattle, WA 98104-7036
`Tel.: 206-883-2500
`
`
`
`
`
`
`
`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 No. IPR2016-00712
`Patent No. 8,927,592
`
`_____________________________
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,927,592
`
`

`

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`
`TABLE OF CONTENTS
`
`Page
`
`I.
`
`Introduction .................................................................................................. 1
`
`A.
`
`Brief Overview of the ’592 Patent....................................................... 3
`
`B.
`
`C.
`
`Brief Overview of the Prosecution History ......................................... 4
`
`Brief Overview of the Scope and Content of the Prior Art .................. 6
`
`i. Winquist et al., Canadian J. of Urology, 15(1), 2008 (Ex.
`1009) ........................................................................................ 6
`
`ii.
`
`The TROPIC Listing (Ex. 1008) ............................................... 7
`
`iii.
`
`Pivot et al., Annals of Oncology 19:1547-1552, 2008
`(Ex. 1010) ................................................................................. 8
`
`iv. U.S. Patent No. 7,241,907 to Didier et al. (“Didier,” Ex.
`1011) ........................................................................................ 8
`
`v. Mita et al., Clin. Cancer Res., 15(2), 2009 (Ex. 1012) ............... 9
`
`vi.
`
`Tannock et al., N. Engl. J. Med. 351, 2004, 1502-1512
`(Ex. 1013) ................................................................................. 9
`
`D.
`
`Brief Overview of the Level of Skill in the Art ................................... 9
`
`II.
`
`Grounds for Standing .................................................................................. 11
`
`III. Mandatory Notices under 37 C.F.R. § 42.8 ................................................. 11
`
`IV. Statement of the Precise Relief Requested .................................................. 13
`
`V.
`
`Statement of Non-Redundancy ................................................................... 14
`
`VI. Claim Construction ..................................................................................... 14
`
`A.
`
`“dose” ............................................................................................... 15
`
`B.
`
`“prostate cancer that has progressed” ................................................ 15
`
`-i-
`
`

`

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`“advanced metastatic disease” .......................................................... 16
`
`C.
`
`D.
`
`“castration-resistant” and “hormone-refractory” ............................... 16
`
`E.
`
`F.
`
`“Cmax” ............................................................................................... 16
`
`“CV” ................................................................................................. 17
`
`G.
`
`“A method for treating” .................................................................... 17
`
`H.
`
`“A method of increasing the survival of” .......................................... 19
`
`VII. Background Knowledge in the Art Prior to October 29, 2009 ..................... 20
`
`VIII. Detailed Explanation Of Grounds For Unpatentability ................................ 25
`
`A. Grounds Asserting Winquist and the Tropic Listing. ........................ 25
`
`i.
`
`ii.
`
`iii.
`
`iv.
`
`v.
`
`vi.
`
`[Ground 1] Claims 1-2, 5, 7-9, 12-13, 17-20, 22-25, and
`27-29: Obvious over Winquist and the TROPIC Listing. ........ 25
`1.
`Claim 1 ......................................................................... 25
`2.
`Claim 2 ......................................................................... 29
`3.
`Claims 7-9 .................................................................... 30
`4.
`Claim 13 ....................................................................... 31
`5.
`Claims 17 and 20 .......................................................... 31
`6.
`Claim 24 ....................................................................... 32
`7.
`Claim 27 ....................................................................... 32
`8.
`Claims 5, 19, 23, 25, and 29 .......................................... 34
`9.
`Claims 12, 18, 22, and 28 .............................................. 35
`
`[Ground 2] Claims 3-4: Obvious over Winquist, the
`TROPIC Listing, and Didier. .................................................. 38
`
`[Ground 3] Claims 7-9: Obvious over Winquist, the
`TROPIC Listing, and Mita. ..................................................... 40
`
`[Ground 4] Claims 10-11, 14, and 16: Obvious over
`Winquist, the TROPIC Listing, and Tannock. ......................... 41
`1.
`Claims 10 and 11 .......................................................... 41
`2.
`Claims 14 and 16 .......................................................... 42
`
`[Ground 5] Claims 21, 26, and 30: Obvious over
`Winquist, the TROPIC Listing, and Pivot. .............................. 43
`
`[Ground 6] Claim 15 : Obvious over Winquist, the
`TROPIC Listing, Pivot, and Tannock. .................................... 44
`
`-ii-
`
`

`

`
`Grounds Asserting Winquist and Pivot. ............................................ 45
`
`B.
`
`i.
`
`ii.
`
`iii.
`
`iv.
`
`[Ground 7] Claims 1-2, 5, 7-9, 12-13, and 17-30:
`Obvious over Winquist and Pivot............................................ 45
`
`[Ground 8] Claims 3-4: Obvious over Winquist, Pivot,
`and Didier. .............................................................................. 49
`
`[Ground 9] Claims 7-9: Obvious over Winquist, Pivot,
`and Mita. ................................................................................. 50
`
`[Ground 10] Claims 10-11 and 14-16: Obvious over
`Winquist, Pivot, and Tannock. ................................................ 50
`1.
`Claims 10 and 11 .......................................................... 50
`2.
`Claims 14-16 ................................................................ 51
`
`IX. Phase III Clinical Data Are Not Required To Have a Reasonable
`Expectation of Success in an Obviousness Analysis ................................... 52
`
`X. No Unexpected Results ............................................................................... 55
`
`XI. Conclusion .................................................................................................. 57
`
`XII. Payment of Fees under 37 C.F.R. §§ 42.15(a) and 42.103........................... 58
`
`XIII. Appendix – List of Exhibits ........................................................................ 59
`
`
`
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`
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`-iii-
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`
`I.
`
`INTRODUCTION
`
`Mylan Laboratories Limited (“Petitioner”) requests review of U.S. Patent
`
`No. 8,927,592 to Gupta (“the ’592 patent,” Ex. 1001), that issued on January 6,
`
`2015, and is currently assigned to Aventis Pharma S.A. (“Patent Owner”). This
`
`Petition demonstrates a reasonable likelihood that claims 1-5 and 7-30 of the ’592
`
`patent are unpatentable for failing to distinguish over prior art.
`
`Independent claim 1 is to a method of treatment that requires:
`
`• administering 20 to 25 mg/m2 of cabazitaxel, or its hydrate or solvate;
`
`• in combination with a corticoid;
`
`• to a patient with prostate cancer; and
`
`• that the cancer progressed during or after treatment with docetaxel
`
`(Taxotere®).
`
`The claimed method administers a known drug, in a known dosage range, in a
`
`known combination, with known activity against a known indication, to patients
`
`with that indication. Independent claim 27 specifies metastatic “castration resistant
`
`or hormone refractory” prostate cancer, and a prednisone or prednisolone corticoid.
`
`The claimed method was published more than one year before the earliest
`
`alleged priority date of the ’592 patent. As just one example, Winquist discloses
`
`an ongoing Phase III clinical study (“the TROPIC study”) in which 25 mg/m2 of
`
`cabazitaxel (referenced as XRP-6258) was administered to patients in combination
`
`with prednisone (a corticoid) for treating hormone-refractory (castration-resistant)
`
`metastatic prostate cancer (“mCRPC”) previously treated with docetaxel. Ex. 1009.
`
`As another example, the TROPIC Listing describes the same TROPIC study
`
`
`
`-1-
`
`

`

`
`
`as Winquist. The TROPIC Listing discloses that the TROPIC study had been
`
`ongoing for almost two years (since December 2006). In order to participate in the
`
`study, the TROPIC Listing discloses that the included mCRPC patients, who were
`
`all previously treated with docetaxel, must have “[d]ocumented progression of
`
`disease,” including “rising PSA[prostate-specific antigen] levels or appearance of
`
`[a] new lesion.” Ex. 1008. Thus, the TROPIC Listing confirms that the 25 mg/m2
`
`dose of cabazitaxel administered to mCRPC patients in the TROPIC Study, as
`
`disclosed in Winquist, was administered to patients whose mCRPC had progressed
`
`during or after treatment with docetaxel. In view of Winquist and the TROPIC
`
`Listing, claims 1-2, 5, 7-9, 12-13, 17-20, 22-25, 27-29 of the ‘592 patent are each
`
`obvious. The remaining features of claims 3-4, 10-11, 14-16, 21, 26, and 30 are
`
`minor, obvious limitations in view of the prior art.
`
`In addition, Pivot describes a Phase II study of cabazitaxel, in which doses
`
`of 20-25 mg/m2 of cabazitaxel were administered to patients with taxane-resistant
`
`breast cancer (two-thirds of which were docetaxel-resistant). In view of Pivot and
`
`Winquist, claims 1-2, 5, 7-9, 12-13, 17-30 of the ‘592 patent are each obvious.
`
`The remaining features of claims 3-4, 10-11, 14-16 are minor, obvious limitations
`
`in view of the prior art.
`
`Despite the prior art, Patent Owner is attempting through the ’592 patent to
`
`monopolize a previously-disclosed therapeutic method based on the subsequent
`
`disclosure of Phase III clinical data collected using that method. Patent Owner has
`
`stated that there was no “unexpected property” or “unexpected benefit here,” and
`
`there is none. But even if the Phase III results had been surprising and unexpected
`
`-2-
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`

`

`
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`(they were not), efficacy of the method is inherent in the method itself, and clinical
`
`data from a known process directed to a known purpose is not patentable.
`
`A. Brief Overview of the ’592 Patent
`
`The ’592 patent is entitled “Antitumoral Use of Cabazitaxel,” and has an
`
`earliest claimed priority date of October 29, 2009. Application No. 13/456,720
`
`(“the ’720 application”) was filed on April 26, 2012, and issued on January 6,
`
`2015, as U.S. Patent No. 8,927,592. The ’720 application is a continuation of
`
`International Application No. PCT/IB2010/054866, filed on October 27, 2010, and
`
`claims priority to seven different U.S. Provisional Patent Applications, ultimately
`
`to 61/256,160 (“the ’160 application,” Ex. 1005), filed October 29, 2009.
`
`The ’592 patent is directed to treating prostate cancer by administering
`
`cabazitaxel. For example, claim 1 is to a method for treating a patient with
`
`prostate cancer that has progressed during or after treatment with docetaxel,
`
`comprising administering cabazitaxel at a dose of 20 to 25 mg/m2, in combination
`
`with a corticoid. Claim 2 recites that the prostate cancer is an advanced metastatic
`
`disease, and claims 17 and 20 recite castration resistant or hormone-refractory
`
`prostate cancer. Dependent claims 13 and 24 recite that the corticoid is prednisone
`
`or prednisolone, and claim 14 recites the prednisone or prednisolone is
`
`administered at a dose of 10 mg/day. Independent claim 27 recites a method for
`
`increasing survival of a patient with castration resistant or hormone refractory,
`
`metastatic prostate cancer that has progressed during or after treatment with
`
`docetaxel, comprising administering cabazitaxel at a dose of 20 to 25 mg/m2, in
`
`combination with prednisone or prednisolone.
`
`-3-
`
`

`

`
`
`Dependent claims 12, 15, 16, 18, 21, 22, 24, 26, 28 and 30 specify that
`
`cabazitaxel is administered at a dose of either 20 mg/m2 or 25 mg/m2. Dependent
`
`claims 5, 19, 23, 25, and 29 recite that the administration of cabazitaxel is repeated
`
`in 3-weekly cycles. Dependent claims 3-4 recite that the cabazitaxel is in the form
`
`of an acetone solvate. Dependent claim 10 recites monitoring blood counts and
`
`neutrophil levels in the patient, and dependent claim 11 recites discontinuing
`
`treatment if neutrophils are below a specified amount.
`
`Dependent claims 7-9 recite that cabazitaxel is administered in an amount to
`
`provide specified pharmacokinetic parameters. Claims 7-9 of the ’592 patent are
`
`not entitled to the priority date of October 29, 2009, or to the benefit of provisional
`
`application 61/293,903 (“the ’903 application,” Ex. 1006), filed January 11, 2010.
`
`The pharmacokinetic parameters of claims 7-9 were not disclosed in either of these
`
`provisional applications, nor could they be deduced from the disclosures provided
`
`therein. Ex. 1002, ¶ 13. The ’834 application (Ex. 1007), filed June 17, 2010, is the
`
`earliest filed provisional containing written support for distributions of
`
`pharmacokinetic parameters (AUC, Cmax, and plasma clearance), as recited in
`
`claims 7-9. Ex. 1002, ¶¶ 11-13. Accordingly, the relevant timeframe for assessing
`
`validity of claims 7-9 is prior to June 17, 2010. Ex. 1002, ¶ 14.
`
`B.
`
`Brief Overview of the Prosecution History
`
`During prosecution of the ’720 application, claims to treating prostate cancer
`
`by administering cabazitaxel and prednisone were rejected over Mita et al. (Ex.
`
`1012) and Tannock et al. (Ex. 1013). Ex. 1004 at 01874, 02224. Mita discloses
`
`Phase I data evaluating safe dose ranges for administering cabazitaxel to patients
`
`-4-
`
`

`

`
`
`with advanced solid tumors, including breast and prostate cancer. Ex. 1012 at 723.
`
`Mita also discloses pharmacokinetic properties of cabazitaxel. Id. Mita does not
`
`disclose Phase II clinical data, and does not state that it involved administering
`
`cabazitaxel to patients with mCRPC that had progressed during or after treatment
`
`with docetaxel. Ex. 1012. Tannock discloses co-administering docetaxel, of
`
`which cabazitaxel is a close analogue, with prednisone. Ex. 1013.
`
`Subsequently the claims were rejected as both anticipated by Beardsley et al.
`
`(Ex. 1022), and as obvious over Beardsley, Mita and Tannock. Ex. 1004 at 00252-
`
`68. Beardsley reviews treatments for castration- (or hormone-) resistant prostate
`
`cancer, stating: “The current first-line standard of care for patients with
`
`symptomatic or progressive disease is docetaxel-based chemotherapy.” Ex. 1022.
`
`Beardsley noted a variety of second-line treatments, i.e., treatments for patients
`
`with disease progression after or during docetaxel chemotherapy. See id.; Ex. 1002,
`
`¶ 27. Beardsley reported that administering cabazitaxel to patients with docetaxel-
`
`resistant metastatic breast cancer resulted in an objective response rate of 14%, and
`
`that based on this result, a Phase III study had been initiated among prostate cancer
`
`patients with mCRPC previously treated with docetaxel. Ex. 1022 at 163.
`
`Beardsley does not disclose the dose of cabazitaxel being administered in the
`
`Phase III trial. Id.
`
`The applicant held an in-person interview with the examiner on July 10,
`
`2014. Ex. 1004 at 00143, 00230. According to the interview summary, the
`
`examiner agreed the claims would be allowable if they were amended “to recite (1)
`
`treatment of prostate cancer in patients who had progressed during or after
`
`-5-
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`

`

`
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`docetaxel treatment and (2) administering a dose of 20 to 25 mg/m2
`
` cabazitaxel . . . in combination with a corticoid.” Id. (emphases added).
`
`On July 16, 2014, applicant submitted an amendment making the agreed
`
`changes from the interview (id. at 137-138, 140), accompanied by the §1.132
`
`declaration of Dr. Sartor (id. at 0164-92). In remarks, applicant repeatedly argued
`
`that the absence of the 20 to 25 mg/m2 dosage range in the prior art was important
`
`evidence rebutting the examiner’s rejections. Id. at 0145 (“Importantly, the doses
`
`of cabazitaxel and prednisone are not disclosed in Beardsley. . . . Beardsley does
`
`not describe any dose of cabazitaxel, let alone an effective amount of cabazitaxel.”
`
`(emphasis in original)); id. at 0148. A Notice of Allowance ensued. Id. at 0091-94.
`
`C. Brief Overview of the Scope and Content of the Prior Art
`
`In obviousness cases, Graham v. John Deere Co. of Kansas City, requires an
`
`evaluation of any differences between the claimed subject matter and the asserted
`
`prior art. 383 U.S. 1, 17-18 (1966). As noted in KSR Int’l Co. v. Teleflex Inc., it is
`
`not necessary to have precise teachings in the art directed to the specific subject
`
`matter claimed because inferences and creative steps that a person of ordinary skill
`
`in the art would employ can be taken into account. 550 U.S. 398, 418 (2007).
`
`i. Winquist et al., Canadian J. of Urology, 15(1), 2008 (Ex. 1009)
`
`Winquist provides a listing for the Phase III TROPIC study: “A
`
`randomized, open-label multicentre study of XRP-6258 [cabazitaxel] at 25 mg/m2
`
`in combination with prednisone every 3 weeks compared to mitoxantrone in
`
`combination with prednisone for the treatment of hormone-refractory metastatic
`
`prostate cancer previously treated with a Taxotere [docetaxel]-containing
`
`-6-
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`

`

`
`
`regimen.” Ex. 1009 at 3948. The study included 720 patients with “[h]ormone-
`
`refractory prostate cancer previously treated with docetaxel,” and “overall
`
`survival” was the primary end-point. Id. Winquist does not explicitly teach
`
`cabazitaxel as an acetone solvate, its pharmacokinetic parameters, or monitoring
`
`neutrophils. Winquist is prior art to the claims under 35 U.S.C. § 102(b).
`
`ii. The TROPIC Listing (Ex. 1008)
`
`A second listing for the Phase III TROPIC study (Ex. 1008; hereinafter “the
`
`TROPIC Listing”) was published in the ClinicalTrials.gov database of the National
`
`Library of Medicine, and archived by The Internet Archive on October 23, 2008
`
`(as authenticated by the affidavit of C. Butler, Ex. 1026). The TROPIC Listing
`
`discloses that the Phase III TROPIC study had been ongoing for nearly two years
`
`(since December 2006), and was “a randomized, open-label, multi-center study
`
`comparing the safety and efficacy of XRP6258 [cabazitaxel] plus prednisone to
`
`mitoxantrone plus prednisone in the treatment of hormone refractory metastatic
`
`prostate cancer previously treated with a Taxotere [docetaxel]-containing
`
`regimen.” Ex. 1008 at 0001-0002. The TROPIC listing also states that cabazitaxel
`
`is to be administered every three weeks and that patients must have a
`
`“[d]ocumented progression of disease (demonstrating at least one visceral or soft
`
`tissue metastatic lesion, including a new lesion) . . . [or] rising PSA levels or
`
`appearance of a new lesion.” Id. at 0001-02. The primary objective of the TROPIC
`
`study was overall survival. Id. at 0001. The TROPIC Listing does not explicitly
`
`describe acetone solvate of cabazitaxel, administration doses and the resulting
`
`pharmacokinetic parameters, or monitoring neutrophil cell counts. The TROPIC
`
`-7-
`
`

`

`
`
`Listing is prior art under 35 U.S.C. § 102(b).
`
`iii. Pivot et al., Annals of Oncology 19:1547-1552, 2008 (Ex. 1010)
`
`Pivot discloses a Phase II clinical study administering cabazitaxel every
`
`three weeks to patients with metastatic breast cancer, including patients previously
`
`treated with docetaxel. Ex. 1010 at 1547-49. Pivot discloses administering 20 and
`
`25 mg/m2 of cabazitaxel and concludes that the safety profile at these doses was
`
`“very favorable” compared to the marketed taxanes (i.e., paclitaxel and docetaxel).
`
`Id. at 1548, 1551. Pivot observed a 14% objective response rate among
`
`cabazitaxel-treated metastatic breast cancer patients, and concluded that
`
`cabazitaxel “appears to be active in docetaxel- or paclitaxel-resistant breast cancer,
`
`even when the most stringent criterion of resistance (P[rogressive ]D[isease] on
`
`therapy) was used.” Id. at 1551. Pivot teaches that tumors with high expression of
`
`P-glycoprotein were resistant to taxanes, and that cabazitaxel was selected for its
`
`low affinity for P-glycoprotein, which was encoded by the multidrug resistant gene
`
`ABCB1. Id. at 1547-48. Pivot also teaches that cabazitaxel was known to be
`
`effective against docetaxel-resistant cancer cells. Id. Pivot does not teach
`
`cabazitaxel as an acetone solvate, describe treatment of prostate cancer with
`
`cabazitaxel, or expressly teach its pharmacokinetic parameters. Pivot is prior art to
`
`the claims under 35 U.S.C. § 102(b).
`
`iv. U.S. Patent No. 7,241,907 to Didier et al. (“Didier,” Ex. 1011)
`
`Didier teaches an acetone solvate of cabazitaxel and its preparation from an
`
`aqueous/acetone solution. Ex. 1011, abstract. Didier further discloses the solvate
`
`containing from about 5% to about 7% by weight of acetone, including specific
`
`-8-
`
`

`

`
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`percentages within this range. Id. at 2:39-42 and claim 2. Didier is prior art under
`
`35 U.S.C. § 102(b).
`
`v. Mita et al., Clin. Cancer Res., 15(2), 2009 (Ex. 1012)
`
`Mita describes a Phase I pharmacokinetic study of cabazitaxel “designed
`
`primarily to determine the maximum tolerated dose and the dose-limiting toxicity
`
`of XRP6258 [cabazitaxel] given as a 1-hour i.v. infusion.” Ex. 1012 at 724. Mita
`
`discloses administering cabazitaxel at several doses, including 20 and 25 mg/m2,
`
`and reports distributions of pharmacokinetic parameters obtained at these doses,
`
`e.g., area under the curve (AUC), maximum plasma concentration (Cmax) and
`
`clearance (CL). Id. at 729. Mita does not teach cabazitaxel as an acetone solvate.
`
`For claims 7-9, Mita is prior art under 35 U.S.C. § 102(b).
`
`vi. Tannock et al., N. Engl. J. Med. 351, 2004, 1502-1512 (Ex. 1013)
`
` Tannock describes a Phase III clinical study in which patients with
`
`metastatic hormone-refractory prostate cancer were treated in 3-week cycles with
`
`docetaxel, with prednisone given at a dose of 10 mg/day via two 5 mg
`
`administrations. Ex. 1013 at 1502-03. Tannock concluded, “[w]hen given with
`
`prednisone, treatment with docetaxel every three weeks led to superior survival
`
`and improved rates of response in terms of pain, serum PSA level and quality of
`
`life.” Id., at 1502. Tannock teaches determining neutrophil counts and reducing or
`
`delaying treatment in patients with counts below 1,500/mm3. Id., at 1504. Tannock
`
`is §102(b) prior art.
`
`D. Brief Overview of the Level of Skill in the Art
`
`A person of ordinary skill in the art as of October 29, 2009 (or June 17, 2010
`
`-9-
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`

`

`
`
`as to claims 7-9 of the ’592 patent), would be an oncologist, would hold a medical
`
`degree (e.g., a D.O. or an M.D.), and would have experience treating patients with
`
`prostate cancer by administering chemotherapeutic drugs. Ex. 1002, ¶ 40. The
`
`skilled artisan would likely have some combination of the following skills and
`
`experience: (a) treatment of metastatic prostate cancer by administering taxanes,
`
`including docetaxel; (b) treatment of docetaxel-resistant prostate cancer; (c)
`
`treatment of castration resistant prostate cancer; and (d) the ability to understand
`
`publications in the field, including those discussed herein. Id. In particular, the
`
`means of administering taxane drugs and prednisone to prostate cancer patients
`
`would be a routine matter for a person of ordinary skill in the art. Id.
`
`Submitted concurrent with this petition is a declaration from Dr. Rahul Seth.
`
`Dr. Seth is an Assistant Professor of Medicine at SUNY Upstate Medical
`
`University, where he has been a member of the faculty since 2009. Dr. Seth is also
`
`a practicing oncologist, with his practice including work at the prostate cancer
`
`program at Upstate University Hospital in Syracuse, NY. Ex. 1002, ¶ 1; see also,
`
`Ex. 1003. He received a Doctor of Osteopathy degree from the New York College
`
`of Osteopathic Medicine in 1999, and has been board-certified in oncology since
`
`2006. Ex. 1002, ¶ 2; see also, Ex. 1003. Dr. Seth completed his residency in
`
`internal medicine in 2002, and completed a fellowship in hematology and
`
`oncology in 2005, both at Stony Brook University Hospital. Ex. 1002, ¶ 1; see
`
`also, Ex. 1003. Prior to medical training, Dr. Seth received a B.S. in Biology from
`
`Carnegie Mellon University in 1991 and a M.S. in Biochemistry and Toxicology
`
`from Brown University in 1995. Ex. 1002, ¶ 2; see also, Ex. 1003.
`
`-10-
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`

`
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`Dr. Seth’s research and clinical practice is focused on urological oncology
`
`and gastrointestinal cancers. Ex. 1002, ¶ 3; see also, Ex. 1003. He has been
`
`administering taxanes for the treatment of prostate cancer since 2002, and has
`
`treated over 60 patients with metastatic prostate cancer using active chemotherapy,
`
`often with taxane drugs. Ex. 1002, ¶ 3; see also, Ex. 1003. Dr. Seth has also been
`
`actively involved in a number of clinical studies, including Phase III studies
`
`directed to treating cancer using taxane drugs. Ex. 1002, ¶ 3; see also, Ex. 1003.
`
`Dr. Seth is well qualified as an expert, possessing the necessary clinical
`
`expertise and other specialized knowledge, as of October 29, 2009 and as of June
`
`17, 2010, to assist in an understanding of the evidence presented herein, as well as
`
`possessing the expertise necessary to determine and explain the level of ordinary
`
`skill in the art during the relevant time frame. See Ex. 1002, ¶¶ 1-4; Ex. 1003.
`
`II. GROUNDS FOR STANDING
`
`Petitioner certifies that, under 37 C.F.R. § 42.104(a), the ’592 patent is
`
`available for Inter Partes Review, and Petitioner is not barred or estopped from
`
`requesting Inter Partes Review of the ’592 patent on the grounds identified.
`
`III. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
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`Real Parties-in-Interest (37 C.F.R. § 42.8(b)(1))
`
`The following real parties-in-interest are identified: Mylan Laboratories
`
`Limited, which is the Petitioner in this matter and which is a wholly owned
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`subsidiary of Mylan Inc.; Mylan Pharmaceuticals Inc., which is a wholly owned
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`subsidiary of Mylan Inc.; Mylan Inc., which is an indirectly wholly owned
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`subsidiary of Mylan N.V.; and, Mylan N.V.
`
`-11-
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`

`

`
`
`Related Matters (37 C.F.R. § 42.8(b)(2)):
`
`Petitioner has filed IPR2016-00627 for a patent directed to cabazitaxel, U.S.
`
`Patent No. 6,847,170. The ʼ592 patent issued from application 13/456,720 and is a
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`continuation of PCT/IB2010/054866, which claims priority to U.S. provisional
`
`applications 61/256,160 (Ex. 1005, filed October 29, 2009); 61/293,903 (Ex. 1006,
`
`filed January 11, 2010); 61/355,834 (Ex. 1007, filed June 17, 2010); 61/355,888,
`
`filed June 17, 2010; 61/369,929, filed August 2, 2010; 61/383,933, filed September
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`17, 2010; and 61/389,969, filed October 5, 2010. Petitioner is aware of pending
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`continuations 14/575,566 and 14/575,578.
`
`Petitioner and other entities have been involved in litigation over the ’592
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`patent in the action styled Sanofi-Aventis U.S. LLC et al. v. Mylan Laboratories
`
`Limited, C. A. No. 15-03392 (MAS)(LHG), filed in the District of New Jersey (Ex.
`
`1014). A waiver of service of the complaint asserting the ’592 patent against
`
`Petitioner was filed in court no earlier than June 2, 2015.
`
`Petitioner is aware of other pending actions involving the ’592 patent:
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`Sanofi-Aventis U.S. LLC et al. v. Apotex Corp. et al., C. A. No. 15-01835; Sanofi-
`
`Aventis U.S. LLC et al. v. Breckenridge Pharmaceutical, Inc., C. A. No. 15-01836;
`
`Sanofi-Aventis U.S. LLC et al. v. Accord Healthcare, Inc., C. A. No. 15-02520;
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`Sanofi-Aventis U.S. LLC et al. v. BPI Labs, LLC et al., C. A. No. 15-02521; Sanofi-
`
`Aventis U.S. LLC et al. v. Dr. Reddy Laboratories, Inc. et al., C. A. No. 15-02522;
`
`Sanofi-Aventis U.S. LLC et al. v. Glenmark Generics Inc. et al., C. A. No. 15-
`
`02523; Sanofi-Aventis U.S. LLC et al. v. Fresenius Kabi USA, LLC, C. A. No. 15-
`
`02631; Sanofi-Aventis U.S. LLC et al. v. Actavis LLC et al., C. A. No. 15-03107.
`
`-12-
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`

`

`
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`Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3))
`
`Lead Counsel: Steven W. Parmelee (Reg. No. 31,990)
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`Back-Up Counsel: Michael T. Rosato (Reg. No. 52,182)
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`Back-Up Counsel: Jad A. Mills (Reg. No. 63,344)
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`Service Information – 37 C.F.R. § 42.8(b)(4).
`
`Petitioner hereby consents to electronic service.
`
`Email: sparmelee@wsgr.com; mrosato@wsgr.com; jmills@wsgr.com
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`Post: WILSON SONSINI GOODRICH & ROSATI
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`701 Fifth Avenue, Suite 5100, Seattle, WA 98104-7036
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`Tel.: 206-883-2542 Fax: 206-883-2699
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`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED
`
`Petitioner requests review of claims 1-5 and 7-30 of the ’592 patent under 35
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`U.S.C. § 311 and AIA § 6 on the grounds that they are unpatentable and invalid,
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`and should be canceled, as follows:
`
`Ground
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`Claims
`1, 2, 5, 7-9, 12, 13,
`17-20, 22-25, 27-29
`
`Obvious under §103 over
`
`Winquist and the TROPIC Listing
`
`3, 4
`
`7-9
`
`Winquist, the TROPIC Listing, and Didier
`
`Winquist, the TROPIC Listing, and Mita
`
`10, 11, 14, 16 Winquist, the TROPIC Listing, and Tannock
`
`21, 26, 30
`
`Winquist, the TROPIC Listing, and Pivot
`
`15
`
`Winquist, the TROPIC Listing, Pivot, and
`Tannock
`
`1, 2, 5, 7-9, 12, 13,
`17-30
`
`Winquist and Pivot
`
`3, 4
`
`Winquist, Pivot, and Didier
`
`-13-
`
`

`

`
`
`9
`
`10
`
`
`
`7-9
`
`Winquist, Pivot, and Mita
`
`10, 11, 14-16
`
`Winquist, Pivot, and Tannock
`
`V.
`
`STATEMENT OF NON-REDUNDANCY
`
`Each of the ten Grounds raised in this Petition is meaningfully distinct:
`
`Ground 1 presents obviousness of claims 1, 2, 5, 7-9, 12, 13, 17-20, 22-25,
`
`and 27-29, based on a combination of Winquist and the TROPIC Listing.
`
`Winquist and the TROPIC Listing each describe a method for treating mCRPC
`
`previously treated with docetaxel by administering cabazitaxel and prednisone.
`
`Winquist expressly discloses a dose of 25 mg/m2. The TROPIC Listing details
`
`progression of the cancer during or after docetaxel treatment.
`
`Grounds 2-6 each establish the obviousness of certain dependent claims,
`
`where additional prior art is applied to claim elements that are minor and well-
`
`known limitations in view of the prior art.
`
`Ground 7 presents obviousness of claims 1, 2, 5, 7-9, 12, 13, and 17-30
`
`based on a combination of Winquist and Pivot. This Ground is materially different
`
`from Ground 1 in that Pivot discloses treating docetaxel-resistant breast cancer by
`
`starting at a dose of 20 mg/m2 and increasing the dose to 25 mg/m2 if well
`
`tolerated, an aspect not expressly taught by the references in Ground 1. Winquist
`
`describes treating mCRPC previously treated with docetaxel by administering
`
`cabazitaxel at 25 mg/m2 together with prednisone. Grounds 8-10 address other
`
`dependent claims that recite minor and well known features of the prior art.
`
`VI. CLAIM CONSTRUCTION
`
`In an inter partes review, a claim in an unexpired patent is given its broadest
`
`-14-
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`

`

`
`
`reasonable construction in light of the specification. 37 C.F.R. § 42.100(b); In re
`
`Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1275-1280 (Fed. Cir. 2015), cert.
`
`granted, Cuozzo Speed Techs., LLC v. Lee, 2016 U.S. LEXIS 632 (U.S. Jan. 15,
`
`2016) (No. 15-446). Claims terms are also “generally given their ordinary and
`
`customary meaning,” i.e., the meaning the term would have to a person of ordinary
`
`skill in the art at the time of the invention in view of the specification. See In re
`
`Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Under either legal
`
`standard, there is a reasonable likelihood that Petitioner will prevail with respect to
`
`the challenged claims. Claim terms that warrant construction are discussed below.
`
`A.
`
`“dose”
`
`The term “dose” appears, e.g., in claim 1 of the ’592 patent, but is not
`
`defined in the patent. The plain and ordinary meaning of the term “dose” is the
`
`total amount of drug administered during an administration cycle. Ex. 1002, ¶ 42.
`
`B.
`
`“prostate cancer that has progressed”
`
`Claims 1 and 27 refer to “prostate cancer that has progressed.” The ’592
`
`patent states that in Example 1, “progression” was evaluated as “at least [a] 20%
`
`increase in the sum of the largest diameter of the lesion or appearance of one or
`
`more new lesions” or as “either an increase of the PSA, or of the tumour, or of the
`
`pain.” Ex. 1001 at 11:10-25. The Patent Owner ha