Court Opinion

ID: 4660382
Source: CourtListenerOpinion
Date Created: 2021-02-16 16:00:58.738532+00
Date Added: 2024-06-11T08:02:06.257261
License: Public Domain

Case: 20-1552    Document: 66     Page: 1   Filed: 02/16/2021

        NOTE: This disposition is nonprecedential.

   United States Court of Appeals
       for the Federal Circuit
                  ______________________

   TAKEDA PHARMACEUTICAL COMPANY LTD.,
     TAKEDA PHARMACEUTICALS U.S.A., INC.,
   TAKEDA PHARMACEUTICALS AMERICA, INC.,
          TAKEDA IRELAND LIMITED,
               Plaintiffs-Appellees

                             v.

  TORRENT PHARMACEUTICALS LTD., TORRENT
               PHARMA INC.,
             Defendants-Appellants

                INDOCO REMEDIES LTD.,
                   Defendant-Appellant
                  ______________________

                   2020-1552, 2020-1598
                  ______________________

     Appeals from the United States District Court for the
 District of New Jersey in Nos. 2:17-cv-03186-SRC-CLW,
 2:17-cv-07301-SRC-CLW, Judge Stanley R. Chesler.
                 ______________________

                Decided: February 16, 2021
                 ______________________

    GREGORY A. CASTANIAS, Jones Day, Washington, DC,
 argued for plaintiffs-appellees. Also represented by JASON
 G. WINCHESTER, Chicago, IL; LISAMARIE LOGIUDICE, New
Case: 20-1552     Document: 66     Page: 2    Filed: 02/16/2021

2                TAKEDA PHARMACEUTICAL COMPANY v. TORRENT
                                     PHARMACEUTICALS LTD.

 York, NY.

     H. KEETO SABHARWAL, Pillsbury Winthrop Shaw
 Pittman LLP, Washington, DC, argued for defendants-ap-
 pellants Torrent Pharmaceuticals Ltd., Torrent Pharma
 Inc. Also represented by CEDRIC CHIA YANG TAN, YUN WEI.

    IVAN MICHAEL POULLAOS, Winston & Strawn LLP, Chi-
 cago, IL, argued for defendant-appellant Indoco Remedies
 Ltd. Also represented by ALISON MICHELLE HEYDORN,
 GEORGE C. LOMBARDI, JOHN REYNOLDS MCNAIR.
                  ______________________

         Before DYK, MAYER, and CHEN, Circuit Judges.
 CHEN, Circuit Judge.
     Torrent and Indoco (collectively, Appellants) appeal
 from the district court’s final judgment on Appellants’ in-
 validity challenges to claims 4 and 12 of U.S. Patent No.
 7,807,689, owned by Takeda. 1 See Takeda Pharm. Co. Ltd.
 v. Torrent Pharm. Ltd., No. 2:17-cv-03186-SRC-CLW, 2020
 WL 549594, at *26 (D.N.J. Feb. 4, 2020) (Takeda). The
 claims at issue are directed to alogliptin, a uracil-contain-
 ing DPP-IV inhibitor useful for treating type II diabetes,
 and pharmaceutical salts thereof. Following a two-day
 bench trial and extensive testimony from three different
 experts, the district court concluded Appellants had failed
 to prove by clear and convincing evidence that the chal-
 lenged claims are invalid for either statutory obviousness
 or non-statutory obviousness-type double patenting. In
 their appeal, Appellants challenge several different fact

     1   Torrent refers to Torrent Pharmaceuticals Ltd. and
 Torrent Pharma Inc. Indoco refers to Indoco Remedies Ltd.
 Takeda refers to Takeda Pharmaceutical Company Ltd.,
 Takeda Pharmaceuticals U.S.A., Inc., Takeda Pharmaceu-
 ticals America, Inc., and Takeda Ireland Limited.
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 TAKEDA PHARMACEUTICAL COMPANY      v. TORRENT              3
 PHARMACEUTICALS LTD.

 findings by the district court. Even assuming some of those
 challenges have merit, we discern no clear error in the dis-
 trict court’s finding that a skilled artisan would not have
 been motivated to make Appellants’ proposed scaffold and
 isosteric replacements with a reasonable expectation of
 success. On that basis, we affirm.
                         DISCUSSION
     Relevant to “the assessment of [reasonable] expecta-
 tion of success” in all three of Appellants’ invalidity theo-
 ries, Takeda, 2020 WL 549594, at *11, is the undisputed
 factual finding that “in the relevant art of pharmaceutical
 development, very small changes in molecular structure
 can have dramatic effects on the properties of the mole-
 cule,” id. at *10. Indeed, “the more distantly related two
 chemical structures are, the less probable it will be that
 they have the same biological effect.” J.A. 33375–76
 (Böhm). Against this backdrop, we turn to the details of
 Appellants’ invalidity theories.
                              A
     Torrent presents two obviousness-type double patent-
 ing theories using Feng’s 2 F162 compound as the lead com-
 pound for further modification. First, Torrent argues that
 a skilled artisan would have found it obvious to replace
 F162’s pyrimidinone scaffold with uracil, citing Böhm and
 Kim. 3 Böhm discloses that scaffold replacement tech-
 niques were known in the prior art as of the relevant pri-
 ority date. Kim reports that administering uracil lowers
 blood glucose in an animal model of diabetes but “[does] not

     2    Feng refers to U.S. Patent No. 7,723,344.
     3    Böhm refers to Böhm et al., “Scaffold Hopping,”
 Drug Discovery Today: Technologies 1, No. 3 (December
 2004): 217–23. Kim refers to Kim et al., “Anti-diabetic Ac-
 tivity of Constituents of Lycii Fructose,” The Journal of Ap-
 plied Pharmacology 6 (1998): 378–82.
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4               TAKEDA PHARMACEUTICAL COMPANY v. TORRENT
                                    PHARMACEUTICALS LTD.

 mention DPP-IV or DPP-IV inhibitors or scaffold hopping
 or the use of uracil as a scaffold.” See Takeda, 2020 WL
 549594, at *27. Collectively, these references, along with
 other evidence of record, do not demonstrate that uracil
 was known to possess DPP-IV inhibitory activity or other
 characteristics desirable in a scaffold for DPP-IV inhibition
 as of the relevant priority date. 4 Given that Torrent fails
 to establish that uracil was known at the time of invention
 to lower blood glucose by inhibiting DPP-IV, or was other-
 wise understood to be a desirable scaffold for DPP-IV inhi-
 bition, we conclude that the district court did not clearly
 err in finding that a skilled artisan would not have been
 motivated to replace F162’s pyrimidinone scaffold with a
 uracil scaffold with a reasonable expectation of success.
     Second, Torrent contends that a skilled artisan would
 have been motivated to replace a fluoro-olefin unit in
 F162’s pyrimidinone scaffold with an amide unit. Torrent
 argues that fluoro-olefin and amide were known isosteres
 in the prior art, and “[b]ecause the [skilled artisans] are
 medicinal chemists who are ‘always looking for a novel

     4    At oral argument, Torrent’s counsel argued that
 Kim need not disclose that uracil is a DPP-IV inhibitor be-
 cause other prior art references of record purportedly teach
 this feature. See Oral Arg. at 8:49–9:30; id. at 36:09–36:33.
 None of the record evidence counsel directed us to discloses
 that uracil was a known DPP-IV inhibitor. See, e.g., J.A.
 33246–347 (“Kanstrup,” a PCT publication pertaining to
 xanthine-based compounds, not uracil); J.A. 33496–715
 (“Mark 2004,” another patent reference pertaining to xan-
 thine-based compounds); J.A. 1473–74 (an excerpt from
 Torrent’s post-trial briefing stating that “[x]anthine-based
 compounds were known DPP-IV inhibitors” (emphasis
 added)). Notably, moreover, Torrent’s expert agreed at
 trial that the Kanstrup and Mark 2004 references “do[] not
 say one word about using a uracil scaffold.” J.A. 911–12
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 TAKEDA PHARMACEUTICAL COMPANY       v. TORRENT               5
 PHARMACEUTICALS LTD.

 compound,’ the [skilled artisan] would have been moti-
 vated to replace [F162’s] fluoro-olefin . . . with its isostere
 (an amide bond) with a reasonable expectation to develop
 a new DPP-IV inhibitor.” J.A. 1484. We discern no clear
 error in the district court’s contrary holding. Torrent has
 not identified anything in the prior art that would have mo-
 tivated a skilled artisan to dispose of F162’s fluoro-olefin
 unit, let alone replace it with an amide, given myriad more
 conservative and predictable modifications that were avail-
 able for transforming F162 into a “novel” compound. See
 Takeda, 2020 WL 549594, at *18–19. To the contrary, Tor-
 rent’s expert conceded at trial that he was unaware of any
 prior art disclosing this specific modification, despite citing
 references that taught the opposite modification—replac-
 ing an amide unit with a fluoro-olefin unit. J.A. 942–43.
 Even the reference Torrent cites to establish that fluoro-
 olefin and amide were known isosteres features fluoro-ole-
 fin compounds and is bereft of any suggestion to make the
 replacement Torrent proposes. J.A. 33349, 33352.
                               B
      As for statutory obviousness, Indoco argues that a
 skilled artisan would have been motivated to use DCAX as
 a lead compound and to replace DCAX’s xanthine scaffold
 with uracil because xanthine and uracil are “inter-
 changeab[le]” “naturally occurring nitrogenous bases.” See
 Takeda, 2020 WL 549594, at *24. Even assuming, ar-
 guendo, that the prior art would have motivated a skilled
 artisan to modify DCAX by replacing its xanthine scaffold
 with uracil, we agree with the district court that Indoco
 “failed to show that a [skilled artisan] who did so would
 have [had] a reasonable expectation of success” with “this
 particular scaffold replacement.” See id. at *24–25. The
 interchangeability references on which Indoco relies do not
 pertain to DPP-IV inhibitors or diabetes, nor do they, or
 any other prior art of record, teach substituting an existing
 xanthine scaffold for uracil, see Oral Arg. at 19:32–40 (ac-
 knowledging that Wiedeman does not show a xanthine to
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6               TAKEDA PHARMACEUTICAL COMPANY v. TORRENT
                                    PHARMACEUTICALS LTD.

 uracil swap). Moreover, Indoco’s expert, as the district
 court observed, did not present any testimony or evidence
 as to the predictability of the resulting properties from re-
 placing DCAX’s scaffold with uracil. 5 See Takeda, 2020 WL
 549594, at *25. We thus decline to disturb the district
 court’s finding that Indoco failed to prove by clear and con-
 vincing evidence that a skilled artisan would have been
 motivated to replace DCAX’s xanthine scaffold with uracil
 with a reasonable expectation of success.
                               C
      Lastly, we address Appellants’ contention that the dis-
 trict court materially erred with respect to the level of or-
 dinary skill in the art. Appellants argue that the district
 court improperly ignored the parties’ dispute over whether
 a skilled artisan must have specific experience developing
 DPP-IV inhibitors and/or type II diabetes drugs—experi-
 ence Takeda’s expert did not have. 6 This specific experi-
 ence, Appellants contend, is a material difference insofar

     5    Unlike Indoco’s expert, Takeda’s expert addressed
 this critical issue, testifying that a skilled artisan would
 not have been able to predict the resulting properties from
 the “wholesale” replacement of a lead compound’s scaffold
 with uracil. See J.A. 1159–60.
     6    At oral argument, Torrent’s counsel asserted that
 the district court’s motivation analysis improperly relied
 on testimony of Takeda’s expert to the exclusion of Tor-
 rent’s expert, specifically referencing a footnote in the opin-
 ion below. See Oral Arg. at 4:43–6:50 (discussing Takeda,
 2020 WL 549594, at *12 n.3, which cites the trial transcript
 at J.A. 1178–80, 910–11). That footnote refers to testimony
 from both Takeda’s and Torrent’s experts, including testi-
 mony from Torrent’s expert agreeing that “the Kim refer-
 ence doesn’t say one word about DPP-IV inhibition,” J.A.
 910–11. Torrent’s counsel, moreover, could not identify an-
 ything factually inaccurate about the footnote.
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 TAKEDA PHARMACEUTICAL COMPANY       v. TORRENT                7
 PHARMACEUTICALS LTD.

 as it is critical to the district court’s findings regarding mo-
 tivation and reasonable expectation of success. We disa-
 gree.
      Rather than ignore the dispute, the district court con-
 sidered the prior art from both perspectives—that of a
 skilled artisan with and without specific experience with
 DPP-IV inhibitors or type II diabetes drugs—and con-
 cluded that Appellants’ had failed to prove invalidity under
 either definition of a skilled artisan. See Takeda, 2020 WL
 549594, at *11 (finding that it “need not” resolve whether
 the specific DPP-IV/type II diabetes experience urged by
 Appellants was required “because it has no effect on the
 outcome: even if [Appellants] are correct in this, they still
 fail to provide invalidity by clear and convincing evidence”).
     Given the substantive gaps in establishing motivation
 and reasonable expectation of success identified above, the
 record supports the district court’s conclusion that it would
 have reached the same outcome under either definition of
 a skilled artisan. Appellants, moreover, fail to show how
 applying a level of ordinary skill that requires experience
 with DPP-IV inhibitors or type II diabetes drugs would
 have remedied its failures of proof. While motivation and
 reasonable expectation of success need not be expressly dis-
 closed by the prior art itself and may instead come from the
 background knowledge of the skilled artisan, merely as-
 serting that a given modification would have been obvious
 to a skilled artisan does not make it so.
                          CONCLUSION
     Because we conclude that the district court did not
 clearly err in finding that a skilled artisan would not have
 been motivated to make the proposed scaffold and isosteric
 replacements with a reasonable expectation of success, we
 need not reach the parties’ remaining arguments. For the
 foregoing reasons, we affirm the district court’s judgment
 upholding the validity of claims 4 and 12 of the ’689 patent.
Case: 20-1552    Document: 66   Page: 8   Filed: 02/16/2021

8               TAKEDA PHARMACEUTICAL COMPANY v. TORRENT
                                    PHARMACEUTICALS LTD.

                       AFFIRMED