`Tel: 571-272-7822
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`Entered: September 21, 2017
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`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
`Patent 8,927,592 B2
`______________
`
`
`
`Before BRIAN P. MURPHY, TINA E. HULSE, and
`CHRISTOPHER M. KAISER, Administrative Patent Judges.
`
`MURPHY, Administrative Patent Judge.
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a); 37 C.F.R. § 42.73(a)
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`IPR2016-00712
`Patent 8,927,592 B2
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`I.
`INTRODUCTION
`Mylan Laboratories Limited (“Petitioner”) filed a Petition requesting
`an inter partes review of claims 1–5 and 7–30 of U.S. Patent No. 8,927,592
`(Ex. 1001, “the ’592 patent”). Paper 3 (“Petition” or “Pet.”). Petitioner
`supported its challenge with the Declaration of Dr. Rahul Seth. Ex. 1002.
`Aventis Pharma S.A. (“Patent Owner”) filed a Preliminary Response to the
`Petition. Paper 7 (“Prelim. Resp.”). On September 22, 2016, we instituted
`an inter partes review of claims 1–5 and 7–30 of the ’592 patent. Paper 9
`(“Institution Decision”).
`After institution, Patent Owner filed a Response (Paper 21, “PO
`Resp.”) and a Contingent Motion to Amend claims 27–30 of the ’592 patent
`(Paper 22, “MTA”). Patent Owner supported its Response and MTA with
`the Declaration of Dr. Alton Oliver Sartor (Ex. 2176), the Declaration of Mr.
`Michael Tate (Ex. 2149), and the Declaration of Mr. Art Lathers (Ex. 2231).
`Petitioner filed a Reply (Paper 42, “Reply”) and Opposition to Patent
`Owner’s MTA (Paper 43, “MTA Opp.”1). Petitioner supported its Reply
`and MTA Opposition with the Reply Declaration of Dr. Seth (Ex. 1043), and
`the Declaration of Mr. Robert McSorley (Ex. 1044).2
`
`
`1 Petitioner filed the MTA Opposition under seal, subject to the Board’s
`ruling on Petitioner’s Motion to Seal (Paper 45). Petitioner filed a redacted
`public version of the MTA Opposition as Paper 44.
`2 Petitioner filed Dr. Seth’s Reply Declaration and Mr. McSorley’s
`Declaration under seal, subject to the Board’s ruling on Petitioner’s Motion
`to Seal (Paper 45). Petitioner filed redacted public versions of the
`declarations using the same respective exhibit numbers.
`2
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`Patent Owner filed a Reply to Petitioner’s Opposition to Patent
`Owner’s MTA. Paper 53 (“MTA Reply”).3 Patent Owner supported its
`MTA Reply with the Reply Declaration of Dr. Sartor (Ex. 2259) and the
`Declaration of Patricia Matthews, RN, BSN (Ex. 2234).
`Patent Owner filed a Motion to Exclude Exhibits 1089–1090 (Paper
`61), Petitioner filed an Opposition (Paper 77 (under seal), Paper 78 (public
`version)), and Patent Owner filed a Reply (Paper 86).
`Petitioner filed a Motion to Exclude Exhibits 2170, 2171, and 2179
`and certain paragraphs in Exhibits 2001, 2176, and 2149 (Paper 64 (under
`seal), Paper 68 (public version)), Patent Owner filed an Opposition (Paper
`72 (under seal), Paper 73 (public version)), and Petitioner filed a Reply
`(Paper 89 (under seal), Paper 95 (public version)).
`Patent Owner filed Observations (Paper 80) on the cross-examination
`testimony of Dr. Seth (Ex. 2258) regarding Petitioner’s Reply (Paper 42),
`and Petitioner filed a response to Patent Owner’s Observations (Paper 93).
`Patent Owner also filed Observations (Paper 81 (under seal), Paper 82
`(public version)) on the cross-examination testimony of Mr. McSorley (Ex.
`2261) regarding Petitioner’s Reply (Paper 42), and Petitioner filed a
`response to Patent Owner’s Observations (Paper 92 (under seal), Paper 94
`(public version)).
`Petitioner filed Observations (Paper 84) on the cross-examination
`testimony of Dr. Sartor (Ex. 1098) with respect to Patent Owner’s MTA, and
`Patent Owner filed a Response (Paper 90).
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`3 Patent Owner filed the MTA Reply under seal, subject to the Board’s
`ruling on Patent Owner’s Motion to Seal (Paper 54). Patent Owner filed a
`redacted public version of the MTA Reply as Paper 52.
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`An oral hearing was held on June 13, 2017, and a transcript of the oral
`hearing is of record. Paper 98 (“Tr.”).
`We have jurisdiction under 35 U.S.C. § 6. This is a Final Written
`Decision under 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73(a) regarding the
`patentability of the challenged claims. In this case, the claimed treatment
`method, administering a 20 to 25 mg/m2 dose of cabazitaxel in combination
`with prednisone to docetaxel-refractory metastatic prostate cancer patients,
`was disclosed more than one year before the earliest effective filing date to
`which the ’592 patent might be entitled.4 Therefore, for the reasons that
`follow and based on our review of the complete trial record, we determine
`Petitioner has shown by a preponderance of the evidence that claims 1–5 and
`7–30 of the ’592 patent are unpatentable. We further determine that Patent
`Owner’s Contingent Motion to Amend claims 27–30 is denied.
`A. Real Parties in Interest and Related Proceedings
`Petitioner identifies (i) Mylan Laboratories Limited, the Petitioner and
`a wholly-owned subsidiary of Mylan Inc., (ii) Mylan Pharmaceuticals Inc.,
`which is a wholly-owned subsidiary of Mylan Inc., (iii) Mylan Inc., which is
`an indirectly wholly owned subsidiary of Mylan N.V., and (iv) Mylan N.V.
`as real parties in interest. Pet. 11.
`Patent Owner identifies Patent Owner, Aventis Pharma S.A., Sanofi,
`the ultimate parent company of Aventis Pharma S.A., and Sanofi-Aventis
`U.S. LLC, an affiliate of Aventis Pharma S.A., as real parties in interest.
`Paper 6, 2.
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`4 We do not make a determination of the earliest effective filing date,
`because the references qualify as prior art regardless of that date.
`4
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`Petitioner and Patent Owner identify the following as related district
`court proceedings in the District of New Jersey regarding the ’592 patent:
`Sanofi-Aventis U.S. LLC v. Mylan Laboratories Limited, No. 15-03392;
`Sanofi-Aventis U.S. LLC v. Apotex Corp, C. A. No. 15-01835; Sanofi-
`Aventis U.S. LLC v. Breckenridge Pharmaceutical, Inc., C. A. No. 15-
`01836; Sanofi-Aventis U.S. LLC v. Accord Healthcare, Inc., C. A. No. 15-
`02520; Sanofi-Aventis U.S. LLC v. BPI Labs, LLC, C. A. No. 15-02521;
`Sanofi-Aventis U.S. LLC v. Dr. Reddy Laboratories, Inc., C. A. No. 15-
`02522; Sanofi-Aventis U.S. LLC v. Glenmark Generics Inc., C. A. No. 15-
`02523; Sanofi-Aventis U.S. LLC v. Fresenius Kabi USA, LLC, C. A. No. 15-
`02631; Sanofi-Aventis U.S. LLC v. Actavis LLC, C. A. No. 15-03107;
`Sanofi-Aventis U.S. LLC v. BPI Labs, LLC, C. A. No. 15-02521. Pet. 12;
`Paper 6, 2–3.
`Petitioner further identifies IPR2016-00627 as an earlier challenge to
`U.S. Patent No. 5,847,170 directed to the compound cabazitaxel. Pet. 12.
`We denied institution in IPR2016-00627 (Paper 10) and Petitioner’s request
`for rehearing (Paper 12).
`B. Grounds of Unpatentability
`We instituted an inter partes review of claims 1–5 and 7–30 of the
`’592 patent on the following grounds of unpatentability under 35
`U.S.C. § 103:
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`Reference[s]
`
`Winquist (Ex. 1009)5 and TROPIC Listing
`(Ex. 1008)6 in view of Attard (Ex. 1021)7
`and Beardsley (Ex. 1022)8
`Winquist, TROPIC Listing, and Didier (Ex.
`1011)9
`Winquist, TROPIC Listing, and Mita (Ex.
`1012)10
`Winquist, TROPIC Listing, and Tannock
`(Ex. 1013)11
`
`Statutory
`Basis
`§ 103
`
`§ 103
`
`§ 103
`
`§ 103
`
`Challenged
`Claims
`1, 2, 5, 12, 13,
`17–20, 22–25,
`27–29
`3, 4
`
`7–9
`
`10, 11, 14, 16
`
`
`5 Eric Winquist et al., Open clinical uro-oncology trials in Canada, THE
`CANADIAN JOURNAL OF UROLOGY, 15(1), 3942–49 (February 2008)
`(“Winquist”). Ex. 1009.
`6 Sanofi-Aventis, XRP6258 Plus Prednisone Compared to Mitoxantrone
`Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer
`(TROPIC), CLINICALTRIALS.GOV (October 23, 2008) (“TROPIC Listing”).
`Ex. 1008.
`7 Gerhardt Attard et al., Update on tubulin-binding agents, PATHOLOGIE
`BIOLOGIE 54, 72–84 (Elsevier 2006) (“Attard”). Ex. 1021.
`8 Emma K. Beardsley and Kim N. Chi, Systemic therapy after first-line
`docetaxel in metastatic castration-resistant prostate cancer, Curr. Op.
`SUPPORT PALLIAT. CARE 2, 161–66 (Wolters Kluwer Health 2008)
`(“Beardsley”). Ex. 1022.
`9 U.S. Patent No. 7,241,907 B2, issued July 10, 2007 to Didier et al.
`(“Didier”). Ex. 1011.
`10 Alain C. Mita et al., Phase I and Pharmacokinetic Study of XRP6258
`(RPR116258A), a Novel Taxane, Administered as a 1-Hour Infusion Every 3
`Weeks in Patients with Advanced Solid Tumors, CLIN. CANCER RES.
`2009:15(2), 723–730 (January 15, 2009) (“Mita”). Ex. 1012.
`11 Ian F. Tannock et al., Docetaxel plus Prednisone or Mitoxantrone plus
`Prednisone for Advanced Prostate Cancer, N. ENGL. J. MED., 351:15, 1502–
`1512 (October 7, 2004) (“Tannock”). Ex. 1013.
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`Reference[s]
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`Winquist, TROPIC Listing, and Pivot (Ex.
`1010)12
`Winquist, TROPIC Listing, Pivot, and
`Tannock
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`Paper 9, 22–23.
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`Statutory
`Basis
`§ 103
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`Challenged
`Claims
`21, 26, 30
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`§ 103
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`C. The ’592 Patent
`The ’592 patent, titled “Antitumoral Use of Cabazitaxel,” issued
`January 6, 2015, from an application filed April 26, 2012. Ex. 1001. The
`’592 patent claims priority through an international application to a series of
`provisional applications, the earliest of which is dated October 29, 2009.
`Ex. 1001, (60), (63). The ’592 patent is directed to the use of cabazitaxel in
`the treatment of prostate cancer, particularly metastatic castration resistant
`prostate cancer (“mCRPC”). Id. at 1:19–26. Because cancer cells may
`develop resistance to docetaxel (“Taxotere®”13), administering cabazitaxel
`is intended to treat prostate cancer in patients with advanced metastatic
`disease that has progressed despite previous treatment with a docetaxel-
`based regimen. Id. at 2:61–67. Cabazitaxel is preferably administered in
`combination with a corticoid, such as prednisone or prednisolone, at a daily
`dose of 10 mg orally. Id. at 3:2–5.
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`
`12 X. Pivot et al., A multicenter phase II study of XRP6258 administered as a
`1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer
`patients, ANNALS OF ONCOLOGY, 19, 1547–1552 (April 23, 2008) (“Pivot”).
`Ex. 1010.
`13 Taxotere® is the brand name for docetaxel. We also refer to “Taxotere”
`in this Decision.
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`The chemical name for cabazitaxel is 4α-acetoxy-2α-benzoyloxy-5β,
`20-epoxy-lβ-hydroxy-7β, 10β-dimethoxy-9-oxo-ll-taxen-13α-yl(2R,3S)-3-
`tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate. Id. at 4:28–31.
`Cabazitaxel is a taxane compound, the chemical structure of which is shown
`below:
`
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`Id. at 4:8–26. Example 1 of the ’592 patent describes a large-scale (phase
`III) comparative clinical trial of mCRPC patients whose disease had
`progressed during or after docetaxel treatment, the docetaxel-refractory
`patients being treated with either 25 mg/m2 of cabazitaxel or 12 mg/m2
`mitoxantrone, and 10 mg/day of prednisone. Id. at 10:30–48. Patients
`receiving cabazitaxel and prednisone demonstrated a median overall survival
`that was 2.4 months longer than those receiving mitoxantrone and
`prednisone. Id. at 11:28–37, 11:45–54. The claimed method is directed to
`administering cabazitaxel and a corticoid to prostate cancer patients whose
`disease has progressed in spite of previous docetaxel treatment. Id. at 5:33–
`67, 18:54–58, 20:25–30.
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`D. Challenged Claims
`Petitioner challenges claims 1–5 and 7–30 of the ’592 patent.
`Independent claims 1 and 27 are illustrative and are reproduced below:
`
`1. A method for treating a patient with prostate cancer
`that has progressed during or after treatment with
`docetaxel, comprising administering to said patient a
`dose of 20 to 25 mg/m2 of cabazitaxel, or a hydrate or
`solvate thereof, in combination with a corticoid.
`
`27. A method of increasing the survival of a patient with
`a castration resistant or hormone refractory, metastatic
`prostate cancer that has progressed during or after
`treatment with docetaxel, comprising administering a
`dose of 20 to 25 mg/m2 of cabazitaxel, or hydrate or
`solvate thereof, to the patient in combination with
`prednisone or prednisolone.
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`II. ANALYSIS OF THE ’592 PATENT CLAIMS
`A. Claim Construction
`We determine that only the following claim terms require express
`construction for purposes of this Decision. See, e.g., Wellman, Inc. v.
`Eastman Chem. Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011) (“[C]laim terms
`need only be construed ‘to the extent necessary to resolve the controversy.’”
`(citation omitted)).
`
`1. Claim 1: “A method for treating a patient”
`Petitioner argues that the preamble phrase in claim 1, “a method for
`treating,” is a non-limiting statement of the purpose of the claimed method,
`or, at most, should be construed as “a method intended to benefit a patient.”
`Pet. 17–19. In its Preliminary Response, Patent Owner opposed Petitioner’s
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`proposed construction, arguing that the preamble is limiting and should be
`construed to mean “a method that produces a therapeutic effect in a patient.”
`Prelim. Resp. 15–18. In our Institution Decision, we construed “a method
`for treating a patient” in claim 1 as a non-limiting statement of the purpose
`of the claimed method. Paper 9, 7–10. At most, the phrase would be
`construed as “a method intended to benefit a patient.” Id. (citing Bristol-
`Myers Squibb Co. v. Ben Venue Laboratories, Inc., 246 F.3d 1368, 1375–76
`(Fed. Cir. 2001) (The preamble language “a method of treating a patient,”
`“does not result in a manipulative difference in the steps of the claim,” and
`the recited method steps “are performed the same way regardless [of]
`whether or not the patient experiences a [therapeutic effect].”)).
`Patent Owner’s Response applies the Board’s construction from the
`Institution Decision and does not argue for a different construction. PO
`Resp. 14; Reply 1. Therefore, we maintain our construction of the preamble
`as non-limiting for the reasons given in our Institution Decision. Paper 9, 7–
`10.
`
`2. Claim 27: “A method of increasing the survival of a
`patient”
`Petitioner argues that the preamble phrase in claim 27, “[a] method of
`increasing the survival of [a patient],” is a non-limiting statement of the
`purpose of the claimed method or, at most, should be construed as “a method
`intended to increase the survival of a patient.” Pet. 19–20. In its
`Preliminary Response, Patent Owner opposed Petitioner’s proposed
`construction, arguing that the preamble is limiting and should be construed
`to mean “a method that prolongs the life of a patient as compared to no
`treatment or palliative treatment, where that method has been demonstrated
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`to provide a statistically significant increase in overall survival.” Prelim.
`Resp. 19. In our Institution Decision, we construed the preamble in claim 27
`as a non-limiting statement of the purpose of the claimed method for the
`same reasons expressed above regarding “a method for treating a patient” in
`claim 1. Paper 9, 10. At most, the phrase would be construed as “a method
`intended to increase the survival of a patient.” Id.
`Patent Owner’s Response applies the Board’s construction from the
`Institution Decision and does not argue for a different construction. PO
`Resp. 14; Reply 1. Therefore, we maintain our construction of the preamble
`as non-limiting for the reasons given in our Institution Decision. Paper 9,
`10.
`
`3. Prosecution History of Independent Claims 1 and 27
`A review of the amendments made to independent claims 1 and 27
`during prosecution of the ’592 patent application provides further context for
`considering the parties’ dispute, discussed in Section II.B., below, over
`whether a POSA would have had a reasonable expectation of success in
`achieving the treatment method claimed in the ’592 patent.
`On April 26, 2012, patent applicant filed proposed independent
`method of treatment claims 1 and 24 (later amended and issued as claim 27).
`Ex. 1004 (Part 13), 2397–2402. Claim 1 as originally filed recited:
`
`1. A method for treating prostate cancer in a patient in
`need thereof comprising administering to said patient a
`compound of formula [cabazitaxel chemical structure]
`which may be in base form or in the form of a hydrate or
`a solvate, in combination with prednisone or prednisolone.
`Id. at 2397. Dependent claims 8 and 9, which depended directly or
`indirectly from claim 1, recited administering cabazitaxel at “a dose of
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`between 15 and 25 mg/m2” and “a dose of 25 mg/m2, respectively. Id. at
`2398. Claim 24 as originally filed recited:
`
`24. A method of increasing the survival of a patient with
`hormone refractory metastatic prostate cancer, comprising
`administering a clinically proven effective amount of a
`compound as defined in claim 1 to the patient in
`combination with prednisone or prednisolone.
`Id. at 2399 (emphasis added). The ’592 patent uses lexicography to define
`“clinically proven” to mean “clinical efficacy results that are sufficient to
`meet FDA approval standards.” Ex. 1001, 4:1–3. The ’592 patent further
`defines “effective amount” to mean “an amount of a pharmaceutical
`compound, such as cabazitaxel, that produces an effect on the cancer to be
`treated.” Id. at 3:65–67.
`On March 17, 2014, following an earlier amendment, claim 1 was
`amended as follows:
`
`1. (Currently amended) A method for treating prostate
`in a patient
`cancer
`in need
`thereof comprising
`administering to said patient an effective amount of a
`compound of formula [cabazitaxel chemical structure]
`which may be in base form or in the form of a hydrate or
`a solvate, in combination with a corticoid . . . .
`Ex. 1004 (Part 2), 280. Patent applicant also added new claims 34, 37, 40,
`and 43 depending directly or indirectly from claim 1, which recited
`administering cabazitaxel at “a dose of 25 mg/m2.” Id. at 282–83. Claim 24
`remained in its original, un-amended form. Id. at 282. Patent applicant
`argued that the claims were patentable over Mita and Tannock, inter alia,
`because the phase III clinical trial results presented in the application (see
`Ex. 1001, Example 1, 10:28–17:33) showed “a statistically significant longer
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`overall survival compared to patients receiving . . . mitoxantrone plus
`prednisone.” Ex. 1004, 285. Patent applicant further argued that Mita’s
`disclosure of a phase I safety and dosing study for cabazitaxel, which
`showed evidence of anticancer activity at a dose of 25 mg/m2 in one
`docetaxel-refractory mCRPC patient, was insufficient to establish a
`reasonable expectation of “successfully treat[ing]” such patients. Id. at 285–
`86.
`
`The Examiner continued to reject the claims over Beardsley
`(anticipation under § 102(b)) and Mita, Tannock, and Beardsley
`(obviousness § 103). Id. at 252–268.
`On July 10, 2014, applicant’s representatives conducted a personal
`interview with the Examiner. Id. at 230. Applicant’s representatives
`presented a draft Rule 132 Declaration by Dr. Sartor, who also attended the
`interview, to demonstrate “the unpredictability and failure of other taxanes
`in Phase III clinical trials despite demonstrating efficacy in Phase I and
`Phase II clinical trials.” Id. The Examiner agreed that submission of the
`Rule 132 Declaration and amendments to independent claims 1 and 24 to
`recite “1) treatment of prostate cancer in patients who had progressed during
`or after docetaxel treatment and 2) administering a dose of 20 to 25 mg/m2
`cabazitaxel . . . in combination with a corticoid” would render the claims
`allowable. Id.
`On July 16, 2014, patent applicant filed another amendment to
`application claim 1 (issued claim 1) and claim 24 (issued claim 27) as
`follows:
`
`1. (Currently Amended) A method for treating prostate
`cancer in a patient with prostate cancer that has progressed
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`during or after treatment with docetaxel, in need thereof
`comprising administering to said patient a dose of 20 to 25
`mg/m2 of cabazitaxel, or a hydrate or solvate thereof, an
`effective amount of a compound of formula [cabazitaxel
`chemical structure] which may be in base form or in the
`form of a hydrate or a solvate, in combination with a
`corticoid.
`
`24. (Currently Amended) A method of increasing the
`survival of a patient with a castration resistant or hormone
`refractory, metastatic prostate cancer that has progressed
`during or after treatment with docetaxel, comprising
`administering a clinically proven effective amount dose of
`20 to 25 mg/m2 of cabazitaxel, or hydrate or solvate
`thereof, a compound as defined in claim 1 to the patient in
`combination with prednisone or prednisolone.
` Ex. 1004 (Part 1), 138, 140.
`In claim 1, patent applicant deleted “in need thereof” in the preamble
`(id. at 138), a phrase Patent Owner adds to the body of proposed substitute
`claim 31 in the MTA (MTA, 27). Patent applicant also deleted “an effective
`amount” from the body of claim 1 and replaced it with “a dose of 20 to 25
`mg/m2” of cabazitaxel. Ex. 1004 (Part 1), 138. Similarly, in claim 24,
`patent applicant deleted “clinically proven effective amount” and replaced it
`with a “dose of 20 to 25 mg/m2” of cabazitaxel. Id. at 140. The deletions
`removed the lexicographically-defined limitations of producing “an effect on
`the cancer to be treated” (“effective amount” in clam 1) and achieving
`“clinical efficacy results that are sufficient to meet FDA approval standards”
`(“clinically proven effective amount” in claim 24), respectively, and
`replaced them with a 20 to 25 mg/m2 dosage range. Ex. 1001, 3:65–4:3,
`10:47–48, 11:1–13:66, 17:31–18:29, Figs. 1–7.
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`In remarks, patent applicant 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. Ex. 1004 (Part 1), 145 (“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.”); id. at 148 (“the doses of cabazitaxel and prednisone are not
`disclosed [in Beardsley]”). Patent applicant further argued that the cited art
`was insufficient to justify a reasonable expectation that the claimed method
`“would successfully treat prostate cancer.” Id. at 147. A Notice of
`Allowance ensued. Id. at 91–94. The Examiner was persuaded by patent
`applicant’s arguments and evidence, particularly Dr. Sartor’s Rule 132
`Declaration statements that the prior art, while disclosing “promising early
`clinical results, . . . 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. at 93.
`As indicated by patent applicant’s final claim language, achieving a
`clinically effective treatment is not a limitation of the ’592 method claims.
`See Bristol-Myers Squibb Co., 246 F.3d at 1375 (“The express dosage
`amounts are material claim limitations; the statement of the intended result
`of administering those amounts [an antineoplastically effective amount] does
`not change those amounts or otherwise limit the claim.”); see also id. at
`1376 (“We therefore affirm the district court’s interpretation of claims 5 and
`8 as limited only to the actual steps of those claims, without regard to the
`result of performing the claimed steps” [to effect regression of a taxol-
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`sensitive tumor]). In sum, the independent method claims of the ’592 patent
`are limited to the step(s) of:
` administering a 20–25 mg/m2 dose of cabazitaxel (or its hydrate
`or solvate);
` in combination with a corticoid (claim 1), such as prednisone or
`prednisolone (claim 27);
` to a docetaxel-refractory prostate cancer patient (claim 1); or
` to a docetaxel-refractory mCRPC patient (claim 27).
`The recited method steps, although they must have utility, are
`performed without regard to whether the claimed method results in a
`clinically effective treatment.
`
`B. Ground 1: Asserted Obviousness of Claims 1, 2, 5, 12, 13, 17–20,
`22–25, and 27–29 over Winquist and the TROPIC Listing in View
`of Attard and Beardsley
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`Petitioner asserts that the subject matter of claims 1, 2, 5, 12, 13, 17–
`20, 22–25, and 27–29 of the ’592 patent would have been obvious to a
`person of ordinary skill in the art (hereafter “POSA”) based on the combined
`teachings of Winquist and the TROPIC Listing in view of the knowledge of
`a POSA.14 Pet. 25–38. Winquist and the TROPIC Listing together disclose
`
`14 The parties provide largely similar descriptions of a POSA. Compare Pet.
`9–10 with PO Resp. 14. Patent Owner acknowledges that any differences
`should not affect the outcome of this case. PO Resp. 14; Reply 1. We
`agree. For purposes of this decision, we adopt and apply Patent Owner’s
`description of a POSA as an oncologist or medical doctor specializing in
`oncology who would have had experience in the treatment of prostate
`cancer, including metastatic prostate cancer, in evaluating therapies for
`prostate cancer, and who would have had access to information regarding
`pharmacokinetics and mechanisms of drug resistance. PO Resp. 14 (citing
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`the same treatment protocol described in Example 1 of the ’592 patent (“the
`TROPIC Study”), more than one year before the earliest effective priority
`date to which the ’592 patent may be entitled (October 29, 2009). Pet. 1–2,
`6–7 (citing Ex. 1008; Ex. 1009), 25–27 (citing Ex. 1002 ¶¶ 115–121); Ex.
`1001, (60), 10:30–48. In our Institution Decision, we amended the ground
`to add “in view of Attard and Beardsley,” two prior art references cited and
`discussed by Petitioner that reflect the knowledge of a POSA. Paper 9, 16
`(citing SightSound Techs., LLC v. Apple Inc., 809 F.3d 1307, 1312–13 (Fed.
`Cir. 2015) (noting that governing statutory provisions do not limit the
`Board’s authority to proceed with AIA trial proceedings only on the specific
`statutory grounds alleged in the petition)).
`Patent Owner does not dispute that Winquist and the TROPIC Listing
`are prior art under 35 U.S.C. § 102(b) (pre-AIA). PO Resp. 37–41. Patent
`Owner’s Response to the Petition asserts that a POSA would not have had a
`reasonable expectation of successfully treating docetaxel-refractory prostate
`cancer patients with cabazitaxel. PO Resp. 16–43. Patent Owner further
`asserts that evidence of secondary considerations supports the non-
`obviousness of the challenged ’592 patent claims. Id. at 50–56. We address
`the parties’ arguments below.
`1. Winquist
`Winquist is a February 2008 disclosure of open, uro-oncology clinical
`trials in Canada that qualifies as prior art under 35 U.S.C. § 102(b) (pre-
`AIA). Ex. 1009, 3942. The format of each entry is the same; a descriptive
`
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`Ex. 2176 ¶ 28). We also rely on the cited references as reflecting the level
`of ordinary skill in the art at the time of the claimed invention. Okajima v.
`Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001).
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`title of the clinical trial followed by an identification of the trial and the
`entity coordinating it, the trial design, patient population, sample size, and
`primary endpoint. Id. Winquist discloses a randomized phase III clinical
`trial coordinated by Sanofi-Aventis involving treatment of mCRPC patients
`previously treated with docetaxel (the TROPIC Study). Id. at 3948.
`Significantly, and unlike the prior art considered by the Examiner
`during prosecution, Winquist discloses the administration of a 25 mg/m2
`dose of cabazitaxel to mCRPC patients: “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 regimen.”
`Id. The primary endpoint is overall survival. Id.
`With regard to independent claims 1 and 27 of the ’592 patent,
`Winquist does not disclose expressly that the prostate cancer “has
`progressed during or after treatment with docetaxel” (id.; Pet. 25–26), but
`Petitioner contends that progression after treatment with docetaxel was
`implicit and would have been understood by a POSA. Pet. 25–26 (citing Ex.
`1002 ¶¶ 65, 94 (95), 117).
`2. The TROPIC Listing
`The TROPIC Listing was published in the ClinicalTrials.gov database
`of the National Library of Medicine, and it was archived by The Internet
`Archive on October 23, 2008. Ex. 1026, Ex. A. The TROPIC Listing also
`qualifies as prior art under 35 U.S.C. § 102(b). The TROPIC Listing
`discloses the same phase III clinical trial reported in Winquist (the Sanofi-
`Aventis TROPIC Study), a “randomized, open-label, multi-center study
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`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, 1; Ex. 1002 ¶¶ 118–120. The TROPIC
`Listing, like Winquist, discloses that cabazitaxel is to be administered every
`three weeks and that expected patient enrollment is 720 patients. Ex. 1008,
`1–2; Ex. 1009, 3948. The TROPIC Listing expressly states 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,” after previous treatment
`with docetaxel. Ex. 1008, 2. The primary outcome, as also reported in
`Winquist, is overall survival. Id. at 1; Ex. 1009. The TROPIC Listing notes
`the start date of the clinical trial was December 2006. Ex. 1008, 2.
`With regard to independent claims 1 and 27 in the ’592 patent, the
`TROPIC Listing, unlike Winquist, does not disclose an administration dose
`of cabazitaxel. Id.; Pet. 7.
`
`3. Attard and Beardsley
`
`Attard is a review article reporting, inter alia, on a phase I dosing
`study for cabazitaxel, which was originally reported in Mita (Ex. 1012). Ex.
`1021, 75 (Col. 1 ¶ 2 n.23). Mita discloses administration of a 15 mg/m2 dose
`to one prostate cancer patient and a 25 mg/m2 dose to a docetaxel-refractory
`metastatic prostate cancer patient. Ex. 1012, 727 (Col. 1 ¶ 2). Attard reports
`that Mita’s phase I cabazitaxel study showed two objective responses in
`CRPC patients, and noted that one of the patients was docetaxel refractory
`(25 mg/m2 dose). Ex. 1021, 75 (Col. 1 ¶ 2 n.23). Attard also describes
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`cabazitaxel (XRP6258) as showing improvement over paclitaxel and
`docetaxel with “higher therapeutic indices” and “activity against resistant
`tumours.” Id. at 74.
`Beardsley reports on a phase II clinical trial of cabazitaxel
`administered to docetaxel-resistant metastatic breast cancer patients, which
`was originally reported in Pivot (Ex. 1010). Ex. 1022, 163 (Col. 2 ¶¶ 4–5).
`Pivot administered an initial cabazitaxel dose of 20 mg/m2, then escalated
`the dose to 25 mg/m2 in patients who did not experience a significant
`adverse event during the first treatment cycle. Ex. 1010, 1548 (Col. 2 ¶ 3).
`Beardsley reports that the objective response rate to cabazitaxel treatment in
`docetaxel-refractory metastatic bre