Trials@uspto.gov
`Tel: 571-272-7822
`
` Paper 112
`Entered: October 22, 2019
`
`
`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 ZHENYU YANG, TINA E. HULSE, and
`CHRISTOPHER M. KAISER, Administrative Patent Judges.
`KAISER, Administrative Patent Judge.
`
`FINAL WRITTEN DECISION ON REMAND
`35 U.S.C. § 318(a); 37 C.F.R. § 42.73(a)
`
`
`
`
`
`
`

`

`IPR2016-00712
`Patent 8,927,592 B2
`
`INTRODUCTION
`
`A. Background
`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, the Board
`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
`
`

`

`IPR2016-00712
`Patent 8,927,592 B2
`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 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).
`An oral hearing was held on June 13, 2017, and a transcript of the oral
`hearing is of record. Paper 98 (“Tr.”).
`On September 21, 2017, the Board issued a Final Written Decision
`(Paper 99, “Dec.”), in which it concluded that Petitioner had shown by a
`preponderance of the evidence that claims 1–5 and 7–30 of the ’592 patent
`were unpatentable and that Patent Owner had not shown by a preponderance
`of the evidence that proposed claims 31–34 were patentable. On November
`
`
`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.
`
`3
`
`

`

`IPR2016-00712
`Patent 8,927,592 B2
`17, 2017, Patent Owner appealed to the Court of Appeals for the Federal
`Circuit. Paper 103.
`On appeal, Patent Owner argued that the Board erred in denying its
`MTA. Sanofi Mature IP v. Mylan Labs. Ltd., 757 F. App’x 988, 989 (Fed.
`Cir. 2019). The Federal Circuit agreed, vacating the denial of the MTA and
`remanding. Id.
`On remand, Petitioner submitted a brief setting forth the issues for us
`to decide and its arguments on those issues. Paper 109 (“Pet. Remand Br.”).
`Patent Owner filed a responsive brief. Paper 110 (“PO Remand Br.”).
`Petitioner filed a reply. Paper 111 (“Pet. Remand Reply”).
`We have jurisdiction under 35 U.S.C. § 6, and we issue this Final
`Written Decision pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73. For
`the reasons discussed below, we conclude that Petitioner has not established
`by a preponderance of the evidence that proposed claims 31–34 are
`unpatentable. Accordingly, we grant Patent Owner’s Motion to Amend
`claims 27–30 by replacing them with proposed claims 31–34.
`
`B. The Issues on Remand
`When Patent Owner appealed the earlier Final Written Decision, it
`noted that “the issues on appeal” included
`the Board’s determination of unpatentability of claims 21 and
`30 of U.S. Patent No. 8,927,592 (“the ’592 patent”) under
`35 U.S.C. § 103, including the Board’s determination and
`application of its construction of terms in those claims; the
`Board’s denial of Patent Owner’s Contingent Motion to Amend
`claims 27-30 with proposed substitute claims 31-34, including
`the Board’s determination and application of its construction of
`terms in proposed substitute claims 31-34; the constitutionality
`of the inter partes review proceeding as raised in Oil States
`Energy Services, LLC v. Greene’s Energy Group, 639 F. App’x
`
`4
`
`

`

`IPR2016-00712
`Patent 8,927,592 B2
`639 (Fed. Cir. May 4, 2016), cert. granted, 85 U.S.L.W. 3578
`(U.S. June 12, 2017) (No. 16-712) that the Board’s findings in
`this proceeding and this proceeding itself violate due process;
`and any finding or determination supporting or related to these
`issues, as well as all other issues decided adversely to Aventis
`in any orders, decisions, rulings and opinions, all of which,
`taken together or independently, caused prejudicial harm to
`Aventis related to these issues.
`Paper 103, 1–2.
`Despite this extensive list of “issues on appeal,” the Federal Circuit’s
`decision on appeal addressed only the denial of the MTA. Sanofi, 757 F.
`App’x at 994 (“[W]e vacate the Board’s denial of Sanofi’s contingent
`motion to amend and its construction of the proposed substitute claims and
`we remand for further consideration consistent with this opinion.”).
`Because the Federal Circuit did not otherwise disturb the Board’s findings
`and conclusions, we need only decide whether to grant Patent Owner’s
`MTA. Accordingly, except to the extent that they are contradicted by any
`statement herein, we maintain the analysis, findings, and conclusions
`reached in the earlier Final Written Decision, which we incorporate by
`reference. See Paper 99.
`In opposing the MTA, Petitioner argues that the proposed claims are
`unpatentable on the following grounds:
`
`5
`
`

`

`31–34
`
`31–34
`
`Challenged
`Claims
`31–34
`
`IPR2016-00712
`Patent 8,927,592 B2
`Statutory
`Ground
`§ 103(a) Winquist, 4 TROPIC Listing, 5 Pivot, 6 and
`NCCN7
`§ 103(a) Winquist, TROPIC Listing, Pivot, NCCN,
`and Mita8
`§ 103(a) Winquist, TROPIC Listing, Pivot, and any
`one of Takenaka,9 Hudis, 10 Trudeau, 11 or
`the Taxol Label12
`
`4 Eric Winquist et al., Open clinical uro-oncology trials in Canada, THE
`CANADIAN JOURNAL OF UROLOGY, 15(1), 3942–49 (Feb. 2008) (Ex. 1009,
`“Winquist”).
`5 Sanofi-Aventis, XRP6258 Plus Prednisone Compared to Mitoxantrone
`Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer
`(TROPIC), CLINICALTRIALS.GOV (Oct. 23, 2008) (Ex. 1008, “TROPIC
`Listing”).
`6 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, 1547–52 (Apr. 23, 2008) (Ex. 1010,
`“Pivot”).
`7 NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY: ANTIEMESIS (Feb.
`5, 2008) (Ex. 1045, “NCCN”).
`8 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), 723–30 (Jan. 15, 2009) (Ex. 1012, “Mita”).
`9 Atsushi Takenaka et al., Combination chemotherapy with weekly docetaxel
`and estramustine for hormone refractory prostate cancer in Japanese
`patients, INT’L J. UROLOGY, 15, 106–09 (2008) (Ex. 1046, “Takenaka”).
`10 Clifford A. Hudis et al., Phase II and Pharmocologic Study of Docetaxel
`as Initial Chemotherapy for Metastatic Breast Cancer, J. CLIN. ONCOLOGY,
`14, 58–65 (Jan. 1996) (Ex. 1048, “Hudis”).
`11 Maureen E. Trudeau et al., Docetaxel in Patients with Metastatic Breast
`Cancer: A Phase II Study of the National Cancer Institute of Canada-
`Clinical Trials Group, J. CLIN. ONCOLOGY, 14, 422–28 (Feb. 1996) (Ex.
`1047, “Trudeau”).
`12 MEAD JOHNSON ONCOLOGY PRODUCTS, TAXOL® (PACLITAXEL) INJECTION
`(Feb. 10, 2000) (Ex. 2093, “Taxol Label”).
`
`Basis
`
`6
`
`

`

`Basis
`
`§ 103(a)
`
`§ 103(a)
`
`IPR2016-00712
`Patent 8,927,592 B2
`Statutory
`Ground
`§ 103(a) Winquist, TROPIC Listing, Pivot, Mita, and
`any one of Takenaka, Hudis, Trudeau, or
`the Taxol Label
`Consent Form, 13 Pivot, and any one of
`NCCN, Takenaka, Hudis, Trudeau, or the
`Taxol Label
`Consent Form, Pivot, Mita, and any one of
`NCCN, Takenaka, Hudis, Trudeau, or the
`Taxol Label
`31–34
`Public Use in the TROPIC Study
`§ 102(b)
`31–34
`Lack of Eligible Subject Matter
`§ 101
`MTA Opp. 7–21, 22–25; Pet. Remand Br. 7–25; Pet. Remand Reply 1–7.
`
`Challenged
`Claims
`31–34
`
`31–34
`
`31–34
`
`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, at [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 (“sold under the brand name
`‘Taxotere®’”14), administering cabazitaxel is intended to treat prostate
`
`13 Sanofi Aventis, Minimum Information Required for Written Subject
`Information: A Randomized, Open Label Multi-Center Study of XRP6258 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®-Containing Regimen (Oct. 16, 2006) (Ex. 2182, “Consent
`Form”).
`14 Ex. 1001, 2:23.
`
`7
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`

`IPR2016-00712
`Patent 8,927,592 B2
`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.
`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
`depicted in the figure reproduced below:
`
`
`Id. at 4:8–26. The figure above shows the chemical structure of cabazitaxel.
`Id. 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
`
`8
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`

`IPR2016-00712
`Patent 8,927,592 B2
`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.
`
`D. Proposed Claims
`Patent Owner proposes replacing claims 27–30 with claims 31–34.
`The proposed claims recite:
`31. A method of increasing survival comprising administering
`to a patient in need thereof (i) an antihistamine, (ii) a corticoid,
`(iii) an H2 antagonist, and (iv) a dose of 20 to 25 mg/m2 of
`cabazitaxel, or a hydrate or solvate thereof, wherein said
`antihistamine, said corticoid, and said H2 antagonist are
`administered prior to said dose of 20 to 25 mg/m2 of
`cabazitaxel, or hydrate or solvate thereof, in combination with
`prednisone or prednisolone, wherein said patient has castration
`resistant or hormone refractory, metastatic prostate cancer that
`has progressed during or after treatment with docetaxel.
`MTA 27.
`32. The method according to claim 31, where the cabazitaxel,
`or hydrate or solvate thereof, is administered at a dose of 25
`mg/m2.
`
`Id.
`
`33. The method according to claim 31, comprising repeating the
`administration of said antihistamine, said corticoid, said H2
`antagonist, and said cabazitaxel, or hydrate or solvate thereof,
`as a new cycle every 3 weeks.
`Id. at 28.
`34. The method according to claim 31, where the cabazitaxel,
`or hydrate or solvate thereof, is administered at a dose of 20
`mg/m2.
`
`Id.
`
`9
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`

`IPR2016-00712
`Patent 8,927,592 B2
`
`ANALYSIS
`
`A. Claim Construction
`In an inter partes review, we construe claim terms in an unexpired
`patent according to their broadest reasonable construction in light of the
`specification of the patent in which they appear. 15 37 C.F.R. § 42.100(b)
`(2017); see Cuozzo Speed Techs. LLC v. Lee, 136 S. Ct. 2131, 2144 (2016)
`(upholding the use of the broadest reasonable interpretation standard).
`Claim terms generally are given their ordinary and customary meaning, as
`would be understood by one of ordinary skill in the art in the context of the
`entire disclosure. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed.
`Cir. 2007). “[C]laim terms need only be construed ‘to the extent necessary
`to resolve the controversy.’” Wellman, Inc. v. Eastman Chem. Co., 642 F.3d
`1355, 1361 (Fed. Cir. 2011) (quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g,
`Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).
`On remand, we have been instructed to treat the preamble of claim 31
`“as an additional limitation of” the claim that “require[s] ‘increasing
`survival’” as the “intentional purpose . . . for which the [recited] method
`must be performed.” Sanofi, 757 F. App’x at 993–94 (quoting Jansen v.
`Rexall Sundown, Inc., 342 F.3d 1329, 1333 (Fed. Cir. 2003)). As instructed,
`we adopt that construction of the preamble of claim 31.
`
`
`15 A recent amendment to this rule does not apply here because the Petition
`was filed before November 13, 2018. See Changes to the Claim
`Construction Standard for Interpreting Claims in Trial Proceedings Before
`the Patent Trial and Appeal Board, 83 Fed. Reg. 51,340 (Oct. 11, 2018)
`(amending 37 C.F.R. § 100(b) effective November 13, 2018).
`
`10
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`

`

`IPR2016-00712
`Patent 8,927,592 B2
`B. Preliminary Issues
`In deciding a motion to amend, “if a patent owner files a motion to
`amend . . . and that motion meets the requirements of 35 U.S.C. § 316(d)
`(i.e., proposes a reasonable number of substitute claims, and the substitute
`claims do not enlarge scope of the original claims of the patent or introduce
`new matter),” then we must “determine whether the substitute claims are
`unpatentable by a preponderance of the evidence.” Memorandum,
`“Guidance on Motions to Amend in view of Aqua Products” (Nov. 21,
`2017) (available at http://go.usa.gov/xU6YV). “[I]f the entirety of the
`evidence of record before [us] is in equipoise as to the unpatentability of one
`or more substitute claims, [we] will grant the motion to amend with respect
`to such claims.” Id.
`For the reasons given in the earlier Final Written Decision, which
`were not disturbed on appeal, we find (1) that proposed substitute claims 31–
`34 are not broader than claims 27–30, which they replace, and (2) that Patent
`Owner has complied with our rules by proposing a reasonable number of
`substitute claims. Dec. 68. The record does not contain any argument that
`the proposed claims introduce new matter. MTA 1–25; MTA Opp. 1–25;
`MTA Reply 1–12; Pet. Remand Br. 1–25; PO Remand Br. 1–25; Pet.
`Remand Reply 1–7. Accordingly, we conclude that Patent Owner’s MTA
`meets the requirements of 35 U.S.C. § 316(d). We therefore proceed to
`consider whether the evidence of record shows that the proposed claims are
`unpatentable.
`
`C. Asserted Obviousness of Proposed Claims
`Petitioner argues that the subject matter of the proposed claims would
`have been obvious to a person of ordinary skill in the art given the teachings
`
`11
`
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`

`IPR2016-00712
`Patent 8,927,592 B2
`of several different combinations of the prior art of record. MTA Opp. 7–
`21, 22–25; Pet. Remand Br. 7–25; Pet. Remand Reply 1–7.
`
`1. Requirement to Prove Reasonable Expectation of Success
`“An invention is not obvious just ‘because all of the elements that
`comprise the invention were known in the prior art.’” Broadcom Corp. v.
`Emulex Corp., 732 F.3d 1325, 1335 (Fed. Cir. 2013) (quoting Power-One,
`Inc. v. Artesyn Techs., Inc., 599 F.3d 1343, 1351 (Fed. Cir. 2010)). Instead,
`“a finding of obviousness at the time of invention requires a ‘plausible
`rational[e] as to why the prior art references would have worked together.’”
`Id. (quoting Power-One, 599 F.3d at 1352). In addition to a reason to
`combine the prior-art references, proving obviousness requires showing that
`a person of ordinary skill in the art would have had “a reasonable
`expectation of achieving what is claimed in the patent-at-issue.” Intelligent
`Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367 (Fed.
`Cir. 2016).
`Although both parties agree that proving the obviousness of the
`proposed claims requires showing such a reasonable expectation of success,
`they disagree about what is required to make such a showing. Because the
`preamble of claim 31 recites only the “intentional purpose . . . for which the
`[recited] method must be performed,” Sanofi, 757 F. App’x at 993,
`Petitioner argues that a reasonable expectation of success would be shown if
`the evidence of record proves that a person of ordinary skill in the art
`reasonably would have expected to be able to carry out the recited method
`steps with the intent of increasing survival. Pet. Remand Br. 15–18. Patent
`Owner argues that a reasonable expectation of success would be shown only
`if the evidence of record proves that a person of ordinary skill in the art
`
`12
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`

`IPR2016-00712
`Patent 8,927,592 B2
`reasonably would have expected carrying out the recited method steps to
`result in increased survival. PO Remand Br. 2–5. Patent Owner is correct
`with respect to the applicable standard for showing a reasonable expectation
`of success.
`In Sanofi v. Glenmark Pharmaceuticals Inc., the trial court was
`presented with a claim reciting a limitation setting forth the intended purpose
`for which its method must be performed and faced with the question of how
`the party challenging the validity of the claim could prove that a person of
`ordinary skill in the art would have had a reasonable expectation of success.
`204 F. Supp. 3d 665, 671–72, 687–96 (D. Del. 2016). Specifically, the
`claim at issue required performing the recited method steps with the
`intended purpose of “decreasing a risk of cardiovascular hospitalization.”
`Id. at 671–72. The court concluded that showing a reasonable expectation of
`success required proving that a person of ordinary skill in the art “would . . .
`have had a reasonable expectation that [the recited method] would reduce
`the risk of cardiovascular hospitalization.” Id. at 691. The Federal Circuit
`affirmed that this was the correct standard to apply. 16 Sanofi v. Watson
`Labs. Inc., 875 F.3d 636, 647 (Fed. Cir. 2017).
`
`
`16 Petitioner argues that, in affirming the application of this standard, the
`Federal Circuit did not require it to be applied, merely finding that the
`appellants had accepted the standard. Pet. Remand Reply 2. This is
`incorrect. Although the Federal Circuit stated that the appellants had
`“accept[ed] the legal framework” applied in the case, the same appellants
`also argued that the trial court had “adopted an incorrect legal standard” and
`had applied “too high a standard for proving a reasonable expectation of
`success.” 875 F.3d at 646–47. Because of these arguments, it was necessary
`for the Federal Circuit to decide what the legal standard for proving a
`reasonable expectation of success should be, and it did so by affirming the
`standard applied by the district court.
`
`13
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`IPR2016-00712
`Patent 8,927,592 B2
`Petitioner argues that applying the Sanofi standard would
`“impermissibly engraft[] increased survival results onto the scope of claims
`that merely require an intended purpose, not results.” Pet. Remand Br. 15.
`Petitioner is correct that the proposed claims do not require the achievement
`of any particular results, but Petitioner is wrong to suggest that the Sanofi
`standard requires proof of such results. The Federal Circuit clearly
`distinguished the standard actually applied in Sanofi—a reasonable
`expectation that the recited method would reduce the risk of cardiovascular
`hospitalization—from a hypothetical standard in which the district court
`would have “demand[ed] known certainty as to the objective of reduced
`hospitalization.” Sanofi, 875 F.3d at 647. Accordingly, to prove a
`reasonable expectation of success with respect to a claim that recites a
`limitation setting forth achieving a particular result as the intended purpose
`for which a recited method must be performed, what is required is not proof
`that the recited method would actually bring about the recited result, but
`rather proof that a person of ordinary skill in the art would have had a
`reasonable expectation that performing the recited method would bring
`about the recited result.
`Here, the Federal Circuit has instructed us to interpret the proposed
`claims as reciting an intended purpose of increasing survival. Sanofi, 757 F.
`App’x at 993–94. Thus, proving the obviousness of the challenged claims
`does not require proving that performing the method recited in the proposed
`claims would actually increase survival, but it does require proving that a
`person of ordinary skill in the art reasonably would have expected the
`performance of the recited method to increase survival.
`
`14
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`

`IPR2016-00712
`Patent 8,927,592 B2
`2. Whether a Reasonable Expectation of Success Has Been
`Shown
`On the issue of whether a person of ordinary skill in the art would
`have expected the method recited in the proposed claims to increase
`survival, there is evidence of record both to support Petitioner’s position and
`to refute it, but the preponderance of the evidence does not support
`Petitioner’s position.
`
`a. Evidence That Is Neutral with Respect to a Finding
`that a Person of Ordinary Skill in the Art Would Have
`Expected Increased Survival
`As an initial matter, we note that the mere fact that the TROPIC study,
`a phase III clinical trial of cabazitaxel with the purpose of investigating
`overall survival, was underway at the time of the effective filing date of the
`’592 patent does not prove that a person of ordinary skill in the art would
`have expected treatment with cabazitaxel to increase survival. In Sanofi v.
`Glenmark, as discussed above, the claims recited a limitation requiring as a
`purpose for which the recited method must be performed the reduction of
`risk of cardiovascular hospitalization, and a phase III clinical trial was
`ongoing with the primary endpoint of “the time to first hospitalization for
`cardiovascular reasons or death from any cause.” 204 F. Supp. 3d at 679.
`The district court found that the existence of this phase III trial did not
`support finding a reasonable expectation that the treatment being tested
`would result in a reduction in the risk of cardiovascular hospitalization. Id.
`at 691–92. Instead, the district court described the phase III trial as
`providing merely “a hypothesis that requires further testing,” and the court
`proceeded to evaluate the other evidence of record to determine whether a
`person of ordinary skill in the art reasonably would have expected the
`
`15
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`

`IPR2016-00712
`Patent 8,927,592 B2
`treatment in question to reduce the risk of cardiac hospitalization. Id. at
`689–96. The phase III study at issue here was similar, seeking to test the
`hypothesis that treatment with cabazitaxel would increase overall survival,
`rather than reasonably suggesting that an increase in overall survival was to
`be expected. Ex. 1008, 1; Ex. 1009, 3948; see Ex. 2258, 41:8–42:6 (at time
`of TROPIC study, person of ordinary skill in the art would “hope” for
`increased survival, rather than “expect[ing]” it). Accordingly, we find that
`the existence of a phase III study here similar to that at issue in Sanofi v.
`Glenmark does not speak to the question of whether a person of ordinary
`skill in the art would have expected the treatment recited in the proposed
`claims to increase survival.
`
`b. Evidence Supporting a Finding that a Person of
`Ordinary Skill in the Art Would Have Expected
`Increased Survival
`There is some evidence of record that supports a finding that a person
`of ordinary skill in the art would have expected the treatment method recited
`in the proposed claims to have resulted in an increase in survival.
`
`(1) Dr. Seth’s Personal Belief at the Time
`Dr. Seth, Petitioner’s declarant, testified that, at the beginning of the
`TROPIC study, “we expected [cabazitaxel] to get FDA approval and it
`would increase overall survival.” Pet. Remand Br. 13–14 (quoting Ex. 2258,
`80:12–81:12). He also testified that “I thought we definitely would see a
`survival benefit” and that “we would see a definite benefit versus
`mitoxantrone.” Id. We note that Dr. Seth in this testimony is referring to his
`personal expectations, not to the expectations of a person of ordinary skill in
`the art. To the extent that Dr. Seth resembled a person of ordinary skill in
`the art, however, this testimony supports a finding that a person of ordinary
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`skill in the art would have expected the treatment regimen in the TROPIC
`study to increase survival.
`
`(2) Dr. Seth’s Testimony that a Person of Ordinary
`Skill in the Art Would Have Thought
`Cabazitaxel Would Work
`Dr. Seth offers some testimony that speaks directly about the beliefs
`of a person of ordinary skill in the art. First, Dr. Seth testified that “the drug
`was known and was felt to be working at 20 or 25 mg/m2.” Pet. Remand Br.
`13–14 (quoting Ex. 2258, 43:17–20). Because Dr. Seth explains that, by
`“working” he means “effective in controlling [DRmCRPC] which would
`lead to an overall survival,” this testimony also supports a finding that a
`person of ordinary skill in the art would have expected cabazitaxel treatment
`to lead to an increase in survival.
`Petitioner also argues that Dr. Seth’s testimony, “20 to 25 mg/m2, they
`would feel like it would work,” was a statement that a person of ordinary
`skill in the art would have expected cabazitaxel to increase survival at the
`specified dose. Pet. Remand Br. 13–14 (purporting to quote Ex. 2258,
`45:18–20). This argument misrepresents Dr. Seth’s testimony as more
`certain about what a person of ordinary skill in the art would feel than it
`actually is. Dr. Seth’s actual testimony was, “I can’t really say what a
`[person of ordinary skill in the art] would feel, but 20 to 25 milligrams per
`meter squared, I feel we would feel that [would work].” Ex. 2258, 45:18–
`20. This testimony is quite equivocal; at most, it weakly supports a finding
`that a person of ordinary skill in the art would have expected cabazitaxel
`treatment to lead to an increase in survival.
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`c. Evidence Opposing a Finding that a Person of
`Ordinary Skill in the Art Would Have Expected
`Increased Survival
`In opposition to the evidence discussed above, the record also
`contains significant evidence that supports a finding that a person of
`ordinary skill in the art would not have expected the treatment method
`recited in the proposed claims to have resulted in an increase in survival.
`
`(1) Dr. Seth’s and Dr. Sartor’s Testimony that a
`Person of Ordinary Skill in the Art Would Have
`Hoped For, but Not Expected, Increased
`Survival
`Both Dr. Seth and Dr. Sartor, Patent Owner’s declarant, testify that, at
`the time of the effective filing date of the ’592 patent, clinicians hoped that
`treatment with cabazitaxel would extend their patients’ lives. Ex. 1041,
`115:12–116:9 (in 2008, Dr. Sartor “hoped that the patients that [he was]
`giving cabazitaxel would have an extended life because of it”); Ex. 2258,
`51:6–20 (Dr. Seth stating that, “when you control your disease, you are in
`turn hoping that they get a progression-free survival which would lead to an
`increase in overall survival”). Petitioner argues that both Dr. Seth and Dr.
`Sartor testified that this hope for an increase in survival was the same as an
`expectation that the treatment would increase survival. Pet. Remand Br. 13
`(citing Ex. 1041, 115:12–116:9; Ex. 2258, 30:13–31:2). But neither
`declarant’s testimony actually supports this view.
`Dr. Sartor clearly agrees with the statement that he “hoped” his
`patients would have their lives extended by cabazitaxel treatment, but he just
`as clearly disagrees with the statement that he “intended” the treatment to
`have that effect, testifying that the results of the TROPIC study showing an
`increase in survival “surprised, delighted, [and] shocked” him. Ex. 1041,
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`115:12–116:9. Dr. Seth testifies that “hope” and “expectation” are different
`terms, with “expectation” having a purely legal meaning and “hope” being
`the word that oncologists prefer. Ex. 2258, 30:13–31:2. To Dr. Seth,
`“hope” and “expectation” are such different concepts that he took issue with
`the continued use of the term “expectation” in the deposition questions
`presented to him. Id.; see also id. at 41:8–15 (in response to a question
`about whether a person of ordinary skill in the art “would expect” an
`increase in survival, responding that the person of ordinary skill in the art
`“would hope” to see such a result). Thus, given the evidence of record here,
`the fact that a person of ordinary skill in the art would have hoped that the
`method recited in the proposed claims would increase survival does not
`support a conclusion that that person also would have expected such a result.
`See also OSI Pharms., LLC v. Apotex Inc., No. 2018-1925, 2019 WL
`4892078, at *8 (Fed. Cir. Oct. 4, 2019) (“[H]ope that a potentially promising
`drug will treat a particular cancer is not enough to create a reasonable
`expectation of success . . . .”); Coalition for Affordable Drugs V LLC v.
`Biogen MA Inc., IPR2015-01136, Paper 23, 10–13 (PTAB Sept. 2, 2015)
`(because “a ‘hope’ may or may not come to pass,” the existence of a hope
`that a drug “will turn out to be useful for treating [a particular condition]”
`does not support finding a reasonable expectation of success).
`
`(2) Evidence that a Person of Ordinary Skill in the
`Art Understood that Cabazitaxel Could Control
`mCRPC
`There is some evidence in the record that treatment with cabazitaxel
`could control mCRPC, but the parties disagree about whether an expectation
`that the recited treatment method would control cancer would have given
`rise to an expectation that the same method would have increased survival.
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`For example, Petitioner dir