Court Opinion

ID: 5132866
Source: CourtListenerOpinion
Date Created: 2021-12-08 17:00:44.970383+00
Date Added: 2024-06-11T08:23:32.600655
License: Public Domain

Case: 21-1360   Document: 34     Page: 1    Filed: 12/07/2021

   United States Court of Appeals
       for the Federal Circuit
                 ______________________

       TEVA PHARMACEUTICALS USA, INC.,
                  Appellant

                            v.

          CORCEPT THERAPEUTICS, INC.,
                     Appellee
              ______________________

                       2021-1360
                 ______________________

     Appeal from the United States Patent and Trademark
 Office, Patent Trial and Appeal Board in No. PGR2019-
 00048.
                  ______________________

                Decided: December 7, 2021
                 ______________________

     JOHN CHRISTOPHER ROZENDAAL, Sterne Kessler Gold-
 stein & Fox, PLLC, Washington, DC, argued for appellant.
 Also represented by UMA EVERETT, WILLIAM MILLIKEN,
 OLGA A. PARTINGTON, DEBORAH STERLING.

    ERIC C. STOPS, Quinn Emanuel Urquhart & Sullivan,
 LLP, New York, NY, argued for appellee. Also represented
 by WILLIAM ADAMS, FRANK CHARLES CALVOSA, FRANCIS
 DOMINIC CERRITO, DANIEL C. WIESNER.
                ______________________
Case: 21-1360     Document: 34      Page: 2     Filed: 12/07/2021

 2 TEVA PHARMACEUTICALS USA v. CORCEPT THERAPEUTICS, INC.

  Before MOORE, Chief Judge, NEWMAN and REYNA, Circuit
                         Judges.
 MOORE, Chief Judge.
     In a final-written decision, the Patent Trial and Appeal
 Board held that Teva Pharmaceuticals USA had failed to
 show claims 1–13 of U.S. Patent No. 10,195,214 would have
 been obvious. Teva Pharms. USA, Inc. v. Corcept Thera-
 peutics, Inc., PGR2019-00048, 2020 WL 6809812 (P.T.A.B.
 Nov. 18, 2020) (Final Decision). Teva appeals, arguing the
 Board misapplied our obviousness law. 1 For the following
 reasons, we affirm.
                                I
                                A
     In the 1980s, mifepristone was developed as an anti-
 progestin. See J.A. 1009. But researchers soon realized
 mifepristone functions as a glucocorticoid reception antag-
 onist, meaning it likely inhibits the effect of cortisol on tis-
 sues by competing with cortisol for receptor binding sites.
 See J.A. 870, 1037. As a result, they suggested using mif-
 epristone to treat Cushing’s syndrome, a disease caused by
 excessive levels of cortisol. J.A. 1034–38.
      More than 20 years later, Corcept Therapeutics, Inc.,
 initiated the first major clinical trial of mifepristone in pa-
 tients with Cushing’s syndrome. J.A. 1252. Over a 24-
 week period, 50 participants were given one daily dose of
 mifepristone, starting at a dosage of 300 mg per day and
 possibly increasing to a maximum dosage of 1200 mg per
 day. J.A. 1259. That administration “produced significant
 clinical and metabolic improvement in patients with
 [Cushing’s syndrome] with an acceptable risk-benefit

     1   Teva also argues that, under the correct standards,
 the challenged claims would have been obvious. Because
 we discern no legal error, we need not reach that argument.
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 TEVA PHARMACEUTICALS USA    v. CORCEPT THERAPEUTICS, INC. 3

 profile during 6 months of treatment.” J.A. 1259; accord
 J.A. 1259–61.
      Based on its successful study, Corcept filed a New Drug
 Application (NDA) for Korlym, a 300 mg mifepristone tab-
 let. It sought approval for the administration of Korlym to
 control “hyperglycemia secondary to hypercortisolism” in
 certain patients with Cushing’s syndrome. J.A. 982. The
 U.S. Food and Drug Administration approved Corcept’s ap-
 plication, but imposed a few postmarketing requirements
 under 21 U.S.C. § 355(o)(3). One requirement was to con-
 duct “[a] drug-drug interaction clinical trial to determine a
 quantitative estimate of the change in exposure of mife-
 pristone following co-administration of ketoconazole (a
 strong CYP3A4 inhibitor).” J.A. 984.
      To summarize the drug-drug interaction study require-
 ment, the FDA provided Corcept with an Office of Clinical
 Pharmacology memorandum. See J.A. 865–900 (hereinaf-
 ter, Lee). That memorandum explained that “[t]he degree
 of change in exposure of mifepristone when co-adminis-
 tered with strong CYP3A inhibitors is unknown . . . .”
 J.A. 865. Thus, Lee noted that co-administration “may pre-
 sent a safety risk” and that, without a drug-drug interac-
 tion study, a “lack of accurate knowledge” may “deprive the
 patients on strong inhibitors [of] the use of [m]ifepristone.”
 Id. Lee also noted that, “[b]ased on the results of this
 study, the effect of moderate CYP3A inhibitors on mifepris-
 tone pharmacokinetics may need to be addressed.”
 J.A. 866.
     In approving Corcept’s NDA, the FDA also approved
 the prescribing information for Korlym contained in its la-
 bel. J.A. 839–49. The FDA-approved Korlym label “recom-
 mended [a] starting dose [of] 300 mg once daily” and
 allowed for increasing the dosage “in 300 mg increments to
 a maximum of 1200 mg once daily” based on clinical assess-
 ments. J.A. 839. In addition to those conditions, the Kor-
 lym label warned against using mifepristone “with strong
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 4 TEVA PHARMACEUTICALS USA v. CORCEPT THERAPEUTICS, INC.

 CYP3A inhibitors” and limited the “mifepristone dose to
 300 mg per day when used with strong CYP3A inhibitors.”
 J.A. 839.
                              B
     Corcept conducted the drug-drug interaction study de-
 scribed in Lee, collecting data on co-administration of mif-
 epristone with a strong CYP3A inhibitor. Based on that
 data, Corcept sought and received the ’214 patent. The ’214
 patent relates to methods of treating Cushing’s syndrome
 by co-administering mifepristone and a strong CYP3A in-
 hibitor. Claim 1 is representative for purposes of this ap-
 peal:
    A method of treating Cushing’s syndrome in a pa-
    tient who is taking an original once-daily dose of
    1200 mg or 900 mg per day of mifepristone, com-
    prising the steps of:
        reducing the original once-daily dose to an
        adjusted once-daily dose of 600 mg mife-
        pristone,
        administering the adjusted once-daily dose
        of 600 mg mifepristone and a strong
        CYP3A inhibitor to the patient,
        wherein said strong CYP3A inhibitor is se-
        lected from the group consisting of ketocon-
        azole, itraconazole, nefazodone, ritonavir,
        nelfmavir, indinavir, boceprevir, clarithro-
        mycin, conivaptan, lopinavir, posaconazole,
        saquinavir, telaprevir, cobicistat, trolean-
        domycin, tipranivir, paritaprevir, and
        voriconazole.
     After Corcept asserted the ’214 patent against Teva in
 district court, Teva sought post-grant review of claims 1–
 13. Teva argued those claims would have been obvious in
 light of Korlym’s label and Lee, optionally in combination
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 TEVA PHARMACEUTICALS USA    v. CORCEPT THERAPEUTICS, INC. 5

 with FDA guidance on drug-drug interaction studies. In
 support of its petition, Teva provided a declaration from
 Dr. David J. Greenblatt. Most relevant here, Dr. Green-
 blatt opined that, based on the Korlym label and Lee, “it
 was reasonably likely that 600 mg [per day of mifepristone]
 would be well tolerated and therapeutically effective when
 co-administered with a strong CYP3A inhibitor.” J.A. 681.
 The Board instituted review on all asserted grounds.
      In its final-written decision, the Board held Teva had
 failed to prove claims 1–13 would have been obvious to a
 skilled artisan. It first construed the claims to require safe
 administration of mifepristone. Final Decision at *7–9.
 Then, the Board found Teva failed to show that a skilled
 artisan would have had a reasonable expectation of success
 for safe co-administration of more than 300 mg of mifepris-
 tone with a strong CYP3A inhibitor. Id. at *10–22. In do-
 ing so, it discredited the above-quoted statement from
 Dr. Greenblatt, finding it inconsistent with his later testi-
 mony and other evidence in the record. Teva appeals. We
 have jurisdiction under 28 U.S.C. § 1295(a)(4).
                               II
     Teva faults the Board for, in its view, committing two
 legal errors. First, it claims the Board required precise pre-
 dictability, rather than a reasonable expectation of success,
 in achieving the claimed invention. That is, Teva argues
 the Board improperly required it “to show an expectation
 that the specific dose recited in the claims would have been
 safe.” Appellant’s Br. at 41. Second, Teva claims the Board
 ought to have applied our prior-art-range precedents. In
 Teva’s view, the Board committed legal error when it found
 Teva had failed to prove the general working conditions
 disclosed in the prior art encompassed the claimed inven-
 tion. We do not agree.
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 6 TEVA PHARMACEUTICALS USA v. CORCEPT THERAPEUTICS, INC.

                                  A
     We start by addressing Teva’s reasonable-expectation-
 of-success argument. “The presence or absence of a reason-
 able expectation of success is . . . a question of fact,” which
 we review for substantial evidence. Intelligent Bio-Sys.,
 Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1366 (Fed.
 Cir. 2016). Whether the Board applied the correct stand-
 ard in assessing reasonable expectation of success, how-
 ever, is a question of law that we review de novo. See Endo
 Pharms. Inc. v. Actavis LLC, 922 F.3d 1365, 1377–78 (Fed.
 Cir. 2019).
       The Board did not err by requiring Teva to show a rea-
 sonable expectation of success for a specific mifepristone
 dosage. The reasonable-expectation-of-success analysis
 must be tied to the scope of the claimed invention. See Al-
 lergan, Inc. v. Apotex Inc., 754 F.3d 952, 966 (Fed. Cir.
 2014) (“[F]ailure to consider the appropriate scope of the
 . . . claimed invention in evaluating the reasonable expec-
 tation of success . . . constitutes a legal error . . . .”); see also
 Intelligent Bio-Sys., Inc., 821 F.3d at 1367. Here, claim 1
 of the ’214 patent requires safe administration of a specific
 amount of mifepristone, 600 mg per day. See Final Deci-
 sion at *7–9 (construing claims to require safe administra-
 tion, rather than just administration). Thus, the Board
 was required to frame its reasonable-expectation-of-suc-
 cess analysis around that specific dosage of mifepristone.
 To be clear, this does not mean Teva was required to prove
 a skilled artisan would have precisely predicted safe co-ad-
 ministration of 600 mg of mifepristone. Absolute predicta-
 bility is not required. See, e.g., Pfizer, Inc. v. Apotex, Inc.,
 480 F.3d 1348, 1364 (Fed. Cir. 2007). But Teva was re-
 quired to prove a reasonable expectation of success in
 achieving the specific invention claimed, a 600 mg dosage.
      Applying that standard, the Board found Teva had
 failed to prove a reasonable expectation of success. It found
 that Teva had “not established . . . that [a skilled artisan]
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 TEVA PHARMACEUTICALS USA    v. CORCEPT THERAPEUTICS, INC. 7

 would reasonably have expected co-administration of more
 than 300 mg of mifepristone with a strong CYP3A inhibitor
 to be safe for the treatment of Cushing’s syndrome or re-
 lated symptoms in patients.” Final Decision at *22; see also
 id. at *10–22. It went even further, finding “the evidence
 support[ed] that [a skilled artisan] would have had no ex-
 pectation as to whether co-administering dosages of mife-
 pristone above the 300 mg/day threshold set forth in the
 Korlym label would be successful.” Id. at *20 (emphasis
 added). Because there was no expectation of success for
 any dosage over 300 mg per day, there was no expectation
 of success for the specific 600 mg per day dosage. See id. at
 *14 (finding no expectation of success for 600 mg per day
 dosage). Under our precedent, those findings were dispos-
 itive. Honeywell Int’l Inc. v. Mexichem Amanco Holding
 S.A. DE C.V., 865 F.3d 1348, 1356 (Fed. Cir. 2017) (holding
 the reasonable-expectation-of-success requirement is not
 satisfied when the skilled artisan would have had no ex-
 pectation of success). Nothing about this analysis required
 precise predictability, only a reasonable expectation of suc-
 cess tied to the claimed invention.
     The Board’s treatment of Dr. Greenblatt’s testimony is
 similar. Before institution, Dr. Greenblatt opined that “it
 was reasonably likely that 600 mg [per day of mifepristone]
 would be well tolerated and therapeutically effective when
 co-administered with a strong CYP3A inhibitor.” J.A. 681
 (emphasis added). But the Board discredited that opinion
 based on Dr. Greenblatt’s later, inconsistent testimony
 that “unequivocally” stated a skilled artisan “would have
 no expectation as to whether the co-administration of 600
 mg of mifepristone with ketoconazole would be safe.” Final
 Decision at *11 (emphasis added) (discussing testimony at
 J.A. 5493–94). The Board found the later testimony, unlike
 Dr. Greenblatt’s pre-institution testimony, was consistent
 with his other deposition testimony, id. at *12 (discussing
 J.A. 5511); his post-deposition declaration, id. (discussing
 J.A. 3096–97); and other evidence in the record, id. at *14
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 8 TEVA PHARMACEUTICALS USA v. CORCEPT THERAPEUTICS, INC.

 (citing J.A. 1164–66 (Dr. Greenblatt article), 3111 (Dr.
 Dobbs declaration), 3433 (Dr. Guengerich testimony)). The
 Board then considered and rejected Teva’s attempt to
 square Dr. Greenblatt’s declaration with his deposition tes-
 timony. Id. at *13–14. Put simply, the Board found
 Dr. Greenblatt’s testimony supported a finding of no expec-
 tation of success in achieving the claimed invention, not
 that Dr. Greenblatt had failed to show the specific claimed
 dosage was absolutely predictable in advance. 2
     In sum, we see no reversible error in the Board’s rea-
 sonable-expectation-of-success analysis. The Board ap-
 plied the correct standard, requiring only a reasonable
 expectation of success and tying its analysis to the scope of
 the claimed invention.
                               B
      We next address the applicability of our prior-art-range
 cases—i.e., the cases in which a claimed range of values
 overlap the ranges disclosed in the prior art. The Board
 declined to apply those cases because it found Teva had
 failed to prove the general working conditions disclosed in
 the prior art encompass the claimed invention. The scope
 and content of the prior art is a question of fact, reviewed
 for substantial evidence. SIPCO, LLC v. Emerson Elec.
 Co., 980 F.3d 865, 870 (Fed. Cir. 2020).
     “For decades, this court and its predecessor have rec-
 ognized that where the general conditions of a claim are
 disclosed in the prior art, it is not inventive to discover the
 optimum or workable ranges by routine experimentation.”
 E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d
 996, 1006 (Fed. Cir. 2018) (quotation marks omitted). “A
 more specific application of this general principle is that a

     2   To the extent Teva challenges the Board’s credibil-
 ity findings, see Appellant’s Br. at 39–40, they are sup-
 ported by substantial evidence.
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 TEVA PHARMACEUTICALS USA    v. CORCEPT THERAPEUTICS, INC. 9

 prima facie case of obviousness typically exists when the
 ranges of a claimed composition overlap the ranges dis-
 closed in the prior art.” Id. (quotation marks and altera-
 tions omitted). But overlap is not strictly necessary for a
 conclusion of obviousness: “obviousness exists when the
 claimed range and the prior art range do not overlap but
 are close enough such that one skilled in the art would have
 expected them to have the same properties.” In re Peterson,
 315 F.3d 1325, 1329 (Fed. Cir. 2003); accord In re Brandt,
 886 F.3d 1171, 1177 (Fed. Cir. 2018); Valeant Pharms. Int’l,
 Inc. v. Mylan Pharms. Inc., 955 F.3d 25, 32 (Fed. Cir. 2020).
     Substantial evidence supports the Board’s finding that
 the general working conditions disclosed in the prior art
 did not encompass the claimed invention, i.e., there was no
 overlap in ranges. In the Board’s view, “the evidence of
 record support[ed] that the general working conditions lim-
 ited co-administration of mifepristone with a strong
 CYP3A inhibitor to just 300 mg/day.” Final Decision at
 *21. Rephrased, the prior art capped the range of co-ad-
 ministration dosages at 300 mg per day. For support, the
 Board cited the Korlym label, id., which cautioned that
 “[m]ifepristone should be used in combination with strong
 CYP3A inhibitors only when necessary, and in such cases
 the dose should be limited to 300 mg per day.” J.A. 844.
 And it also noted how industry publications echoed this
 limitation. Final Decision at *21 (citing J.A. 1279–80
 (“[T]he dose of mifepristone should not exceed 300 mg/day
 if used in combination with ketoconazole.”), 4164 (For co-
 administration with ketoconazole, “the maximum daily
 dose of mifepristone should be 300 mg.”)). The Board’s
 finding that the prior art ranges do not overlap with the
 claimed range is supported by substantial evidence.
     And the Board’s reasonable-expectation-of-success
 finding, which we have already upheld, forecloses Teva’s
 reliance on monotherapy doses above 300 mg per day. Teva
 claims those monotherapy dosages create an overlap with
 the claimed range. But monotherapy dosages alone cannot
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 10 TEVA PHARMACEUTICALS USA v. CORCEPT THERAPEUTICS, INC.

 create an overlap with the claimed range, which is limited
 to co-administering mifepristone with a strong CYP3A in-
 hibitor. Thus, the only remaining question is whether a
 skilled artisan would have expected monotherapy and co-
 administration dosages to behave similarly. As the Board
 found, a skilled artisan would have had no such expecta-
 tion. And we have already upheld that finding as sup-
 ported by substantial evidence.
                               III
      Teva claims this is an “uncommonly clear-cut obvious-
 ness case.” Appellant’s Br. at 37. It describes the prior art
 as “disclos[ing] the problem, . . . the solution, . . . and the
 way to find the solution.” Id. In doing so, it ignores the
 reasonable-expectation-of-success requirement. At best,
 the prior art directed a skilled artisan to try combining the
 Korlym Label, Lee, and the FDA guidance. But without
 showing a reasonable expectation of success, Teva did not
 prove obviousness. Since the Board applied the appropri-
 ate legal standards in finding no expectation of success and
 its fact findings are supported by substantial evidence, we
 affirm.
                         AFFIRMED