Case: 22-1258 Document: 70 Page: 1 Filed: 04/01/2024
`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`JANSSEN PHARMACEUTICALS, INC., JANSSEN
`PHARMACEUTICA NV,
`Plaintiffs-Appellees
`
`v.
`
`TEVA PHARMACEUTICALS USA, INC., MYLAN
`LABORATORIES LTD.,
`Defendants-Appellants
`______________________
`
`2022-1258, 2022-1307
`______________________
`
`Appeals from the United States District Court for the
`District of New Jersey in Nos. 2:18-cv-00734-CCC-LDW,
`2:19-cv-16484-CCC-LDW, Judge Claire C. Cecchi.
`______________________
`
`Decided: April 1, 2024
`______________________
`
`BARBARA MULLIN, Patterson Belknap Webb & Tyler
`LLP, New York, NY, argued for plaintiffs-appellees. Also
`represented by ANDREW D. COHEN, ARON RUSSELL FISCHER,
`MEGHAN LARYWON.
`
` JOHN C. O'QUINN, Kirkland & Ellis LLP, Washington,
`DC, argued for all defendants-appellants. Defendant-ap-
`pellant Teva Pharmaceuticals USA, Inc. also represented
`by WILLIAM H. BURGESS; CHRISTOPHER T. JAGOE, JEANNA
`WACKER, New York, NY.
`
`

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`2
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`JANSSEN PHARMACEUTICALS, INC. v.
`TEVA PHARMACEUTICALS USA, INC.
`
`
` DEEPRO MUKERJEE, Katten Muchin Rosenman LLP, for
`defendant-appellant Mylan Laboratories Ltd. Also repre-
`sented by LANCE SODERSTROM; JITENDRA MALIK, Charlotte,
`NC; JILLIAN SCHURR, Chicago,
`IL; ERIC THOMAS
`WERLINGER, Washington, DC.
`______________________
`
`Before DYK, PROST, and HUGHES, Circuit Judges.
`PROST, Circuit Judge.
`Janssen Pharmaceuticals, Inc. and Janssen Pharma-
`ceutica NV (collectively, “Janssen”) sued Teva Pharmaceu-
`ticals USA, Inc. (“Teva”) for patent infringement in the
`United States District Court for the District of New Jersey.
`Janssen asserted U.S. Patent No. 9,439,906 (“the ’906 pa-
`tent”). Teva stipulated to infringement but challenged va-
`lidity. Relevant here, Teva argued that all representative
`claims were invalid as obvious and that claims 19–21 were
`also invalid as indefinite. After a bench trial, the district
`court found that Teva had not proven invalidity on either
`basis. Teva appeals.1 For the reasons below, we affirm the
`district court’s indefiniteness determination but vacate
`and remand its nonobviousness determination.
`BACKGROUND
`Janssen markets and sells Invega Sustenna. Invega
`Sustenna is an extended-release intramuscular injectable
`of paliperidone palmitate, which is indicated for the treat-
`ment of schizophrenia in adults. J.A. 13118. After Teva
`
`1 Janssen also sued Mylan Laboratories Ltd.
`(“Mylan”) in a separate action. In that action, the parties
`stipulated to be bound by the final judgment in the Teva
`action with respect to infringement and validity. J.A. 49
`(final judgment). Although we refer to Teva throughout,
`Mylan is also an Appellant here.
`
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`JANSSEN PHARMACEUTICALS, INC. v.
`TEVA PHARMACEUTICALS USA, INC.
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`3
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`filed an Abbreviated New Drug Application (“ANDA”) seek-
`ing FDA approval to sell a generic version of Invega Sus-
`tenna, Janssen sued and asserted various claims of the
`’906 patent. The ’906 patent, which generally relates to
`dosing regimens of paliperidone palmitate, is the last re-
`maining Orange Book patent for Invega Sustenna.
`I
`The ’906 patent is titled “dosing regimen associated
`with long acting injectable paliperidone esters.” ’906 pa-
`tent col. 1 ll. 1–3 (capitalization normalized). It was filed
`in December 2008 and claims priority to a provisional ap-
`plication filed in December 2007. Id. at col. 1 ll. 8–10. For
`purposes of this appeal, Teva does not contest that the
`’906 patent is entitled to the December 2007 priority date.
`Appellants’ Br. 19.
`The parties agreed that claims 2, 10, 13, and 20–21
`were representative. Janssen Pharms., Inc. v. Teva
`Pharms. USA, Inc., 571 F. Supp. 3d 281, 291 n.3 (D.N.J.
`2021) (“Opinion”). All asserted claims relate to “[a] dosing
`regimen for administering paliperidone palmitate to a psy-
`chiatric patient in need of treatment for schizophrenia.”
`’906 patent claims 1 and 8.
`Claim 2 (non-renal-impairment claim), which depends
`from claim 1, relates to a normal or non-renal-impairment
`dosing regimen. Both claims are reproduced below.
`1. A dosing regimen for administering paliperi-
`done palmitate to a psychiatric patient in need of
`treatment for schizophrenia, schizoaffective disor-
`der, or schizophreniform disorder comprising
`(1) administering intramuscularly in the
`deltoid of a patient in need of treatment a
`first loading dose of about 150 mg-eq. of
`paliperidone as paliperidone palmitate for-
`mulated in a sustained release formulation
`on the first day of treatment;
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`JANSSEN PHARMACEUTICALS, INC. v.
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`(2) administering intramuscularly in the
`deltoid muscle of the patient in need of
`treatment a second loading dose of about
`100 mg-eq. of paliperidone as paliperidone
`palmitate formulated in a sustained re-
`lease formulation on the 6th to about 10th
`day of treatment; and
`(3) administering intramuscularly in the
`deltoid or gluteal muscle of the patient in
`need of treatment a first maintenance dose
`of about 25 mg-eq. to about 150 mg-eq. of
`paliperidone as paliperidone palmitate in a
`sustained release formulation a month (±7
`days) after the second loading dose.
`2. The dosing regimen of claim 1 wherein after ad-
`ministration of the first maintenance dose, subse-
`quent maintenance doses of from about 25 mg-eq.
`to 150 mg-eq. are administered in the deltoid or
`gluteal muscle of the psychiatric patient in need of
`treatment at monthly (±7 days) intervals.
`’906 patent claims 1 and 2.
`Representative claims 10 and 13 (renal-impairment
`claims) claim dosing regimens for renally impaired pa-
`tients. Claim 10 depends from claim 8. Both claims are
`reproduced below.
`8. A dosing regimen for administering paliperi-
`done palmitate to a renally impaired psychiatric
`patient in need of treatment for schizophrenia,
`schizoaffective disorder, or schizophreniform disor-
`der comprising
`(a) administering intramuscularly in the
`deltoid of a renally impaired psychiatric
`patient in need of treatment a first loading
`dose of from about 75 mg-eq. of paliperi-
`done as paliperidone palmitate formulated
`
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`JANSSEN PHARMACEUTICALS, INC. v.
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`5
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`in a sustained release formulation on the
`first day of treatment;
`(b) administering intramuscularly in the
`deltoid muscle of the patient in need of
`treatment a second loading dose of from
`about 75 mg-eq. of paliperidone as paliper-
`idone palmitate formulated in a sustained
`release formulation on the 6th to about
`10th day of treatment; and
`(c) administering intramuscularly in the
`deltoid or gluteal muscle of the patient in
`need of treatment a first maintenance dose
`of about 25 mg-eq. to about 75 mg-eq. of
`paliperidone as paliperidone palmitate in a
`sustained release formulation a month (±7
`days) after the second loading dose.
`10. The dosing regimen of claim 8 wherein the sus-
`tained release formulation is an aqueous nanopar-
`ticle suspension.
`’906 patent claims 8 and 10.
`Claim 13 differs from claim 10 by requiring that the
`patient is in need of treatment for schizophrenia and recit-
`ing a range of 25 mg-eq. to about 50 mg-eq. for the mainte-
`nance dose.
`Claims 20 and 21 (particle-size claims) are only repre-
`sentative as they depend from claims 1 and 8. They both
`further depend from claim 19. Because for our purposes
`the particle-size limitation of claim 19 is most pertinent,
`only claim 19 is reproduced below.
`19. The dosing regimen of claims 1, 4, 8 or 11
`wherein the sustained release depot formulation is
`an aqueous nanoparticle suspension consists es-
`sentially of
`
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`JANSSEN PHARMACEUTICALS, INC. v.
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`(a) 156 mg/ml of the paliperidone palmi-
`tate having an average particle size (d50) of
`from about 1600 nm to about 900 nm;
`(b) 12 mg/ml of polysorbate 20;
`(c) one or more buffering agents sufficient
`to render the composition neutral to very
`slightly basic (pH 8.5);
`(d) 30 mg/ml of a suspending agent wherein
`the suspending agent is polyethylene glycol
`4000; and
`(f) water q.s. ad 100%.
`’906 patent claim 19 (emphasis added).
`The ’906 patent discloses that “[p]aliperidone is the
`major active metabolite of risperidone,” an antipsychotic
`that was developed in the 1990s. ’906 patent col. 1
`ll. 36–37. It further explains that due to their chemical
`properties, “paliperidone esters such as paliperidone pal-
`mitate dissolve slowly after an [intramuscular] injection
`before being hydrolyzed to paliperidone and made availa-
`ble in the systemic circulation.” Id. at col. 1 ll. 46–49. The
`specification acknowledges that persons of skill “could eas-
`ily determine the effective amount of paliperidone to ad-
`minister,” and that for purposes of the ’906 patent’s
`invention, “[t]he amount of paliperidone palmitate is pro-
`vided in sufficient amount to provide the equivalent dose of
`paliperidone after the palmitic acid moiety is removed from
`the ester (e.g.[,] 156 mg corresponds to paliperidone
`100 mg).” Id. at col. 14 ll. 13–26.
`A tablet formulation of paliperidone was already on the
`market and indicated for the treatment of schizophrenia.
`Id. at col. 1 ll. 37–41; see also U.S. Patent No. 5,158,952
`(compound patent for paliperidone, issued in 1992). How-
`ever, the specification describes the prevalence of treat-
`ment adherence problems when patients are prescribed
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`JANSSEN PHARMACEUTICALS, INC. v.
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`oral antipsychotic medications that need to be taken daily,
`which in turn “often result in worsening of symptoms,
`suboptimal treatment response, frequent relapses and re-
`hospitalizations, and an inability to benefit from rehabili-
`tative and psychosocial therapies.” ’906 patent col. 1
`ll. 50–57.
`The specification explains that an injectable formula-
`tion of paliperidone palmitate was previously “developed to
`provide sustained plasma concentrations of paliperidone
`when administered once monthly, which may greatly en-
`hance compliance with dosing.” Id. at col. 1 ll. 58–63. And,
`it explains that U.S. Patent Nos. 6,577,545 and 6,555,544
`(“the ’544 patent”) had already described the formulation.
`Id. The ’906 specification also describes the preferred par-
`ticle size as d(50) of preferably “1600 nm to 400 nm” and
`“most preferably 1400 nm to 900 nm.” Id. at col. 7 ll. 28–31.
`In the ’906 patent, d(50) means that “at least 50% of the
`particles have a smaller diameter” than the listed meas-
`urement. Id. at col. 7 ll. 32–38.
`The ’906 patent describes several different “dosing reg-
`imen[s] for administering paliperidone esters to a psychi-
`atric patient in need of treatment” and emphasizes the
`plasma concentration of paliperidone reached when differ-
`ent variables are changed and the time frame for reaching
`it. See generally id. at col. 2 l. 11–col. 4 l. 42 (describing
`embodiments); id. at col. 5 ll. 2–5; id. at col. 6 ll. 41–59.
`It further discloses that “deltoid injections result in a
`faster rise in initial plasma concentration” and that “to fa-
`cilitate patients’ attaining a rapid therapeutic concentra-
`tion of paliperidone it is preferred to provide the initial
`loading dose of paliperidone palmitate in the deltoids.” Id.
`at col. 5 ll. 2–8. It states that “[a]fter the first or more pref-
`erably after the second loading dose injection patients will
`be approaching a steady state concentration of paliperi-
`done in their plasma and may be injected in either the del-
`toid or the gluteal muscle thereafter. However, it is
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`JANSSEN PHARMACEUTICALS, INC. v.
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`preferred that the patients receive further injections in the
`gluteal muscle.” Id. at col. 5 ll. 11–16.
`Relatedly, the specification explains that there was an
`observed relationship between needle length and body
`mass index (“BMI”) and time to reach ideal initial plasma
`concentrations of paliperidone. Specifically, “[p]atients
`with high BMI had lower plasma concentration of paliper-
`idone and a lessened treatment response . . . likely due to
`unintended partial or complete injection into adipose tis-
`sue, instead of deep injection into muscle.” Id. at col. 6
`ll. 44–49. As a result, the specification explains that for
`deltoid injections 1-inch needles are sufficient for patients
`weighing less than 90kg, but 1.5-inch needles should be
`used for those who weigh more. Id. at col. 6 ll. 51–57. For
`gluteal injections, the specification simply states that “1.5-
`inch needle[s] should be used” without specifying a weight-
`based preference. Id. at col. 6 ll. 57–59.
`In terms of dosing, the specification states that “[p]ref-
`erably the first two doses will be loading dose[s] of between
`from about 100 mg-eq. to about 150 mg-eq.,” id. at col. 5
`ll. 34–36; see also id. at col. 5 ll. 8–10, and “[t]he subse-
`quent doses thereafter will drop to a therapeutic mainte-
`nance dose of from about 25 mg-eq. to 150 mg-eq. per
`month (±7 days) . . . most preferably the maintenance dose
`initially will be about 50 mg[-]eq,” id. at col. 5 ll. 38–45. It
`also explains that “[t]hose of ordinary skill in the art will
`understand that the maintenance dose may be titrated up
`or down in view of the patient[’s] condition (response to the
`medication and renal function).” Id. at col. 5 ll. 49–52.
`The ’906 patent contains three figures. Each of these
`figures shows both observed and modeled plasma paliperi-
`done concentrations. For all three figures, patients were
`given a 150 mg-eq. dose in the deltoid on day 1; day 8, 36,
`and 64 doses were either 25 mg-eq (Figure 1), 100 mg-eq.
`(Figure 2), or 150 mg-eq. (Figure 3). The day 8, 36, and 64
`doses were given in either the deltoid or the gluteus. The
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`JANSSEN PHARMACEUTICALS, INC. v.
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`specification indicates that the figures make apparent that
`“the plasma profiles provided by initiating paliperidone
`with 150 mg[-]eq. followed by a subsequent dose of 100 or
`150 for days 1-36 provide a rapid rise to a therapeutic dose
`level[].” Id. at col. 31 ll. 62–65 (emphasis added).
`II
`The safety of paliperidone, its efficacy for treating
`schizophrenia, and its recommended dosing were all well
`established as of the
`’906 patent’s priority date.
`J.A. 13266–79; J.A. 16209–10; J.A. 16233. Additionally,
`long acting injectables (LAIs)—administered intramuscu-
`larly—of other antipsychotics were on the market.
`J.A. 16640, 16650–52 (label for haldol decanoate, LAI of
`haloperidol); J.A. 17911, 17941 (risperdal consta, LAI of
`risperidone, of which paliperidone is the major metabolite).
`To demonstrate obviousness of the paliperidone palmi-
`tate LAI dosing regimen claims at issue here, Teva relied
`on three primary prior-art references at trial: (1) clinical
`study protocol NCT00210548 (“the ’548 protocol”); (2) the
`’544
`patent;
`and
`(3) International
`Publication
`No. WO 2006/114384 (“WO’384”). We describe each refer-
`ence below.
`
`A
`The ’548 protocol, published in 2005, is a protocol for
`an interventional Phase III clinical trial with the brief title:
`“A Study to Evaluate the Effectiveness and Safety of 3
`Doses of Paliperidone Palmitate in Treating Subjects with
`Schizophrenia.” J.A. 13244–45. The protocol explains that
`“[t]he hypothesis is that the 3 fixed doses of paliperidone
`are each more efficacious than placebo in treating subjects
`with schizophrenia.” Id. Further, the protocol’s dosing is
`outlined as follows:
`Four injections of paliperidone palmitate 50, 100,
`or 150 milligrams equivalent administered in the
`gluteal muscle (buttocks). Injections will be given
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`on Days 1, 8, 36, and 64 of the double-blind treat-
`ment period of the study.
`Id.
`Experts on both sides provided testimony about what
`the Phase III status of the protocol would indicate to them.
`Dr. Gopal, an inventor of the ’906 patent who designed clin-
`ical trials for paliperidone palmitate, testified that Phase
`III studies were expected to meet safety and efficacy end-
`points because of the requisite preexisting Phase I and II
`data. J.A. 11124:8–20; see also J.A. 11135:9–11 (“[W]e gen-
`erally don’t like to change too many things going from
`Phase II to Phase III. We want to extrapolate as much as
`possible so we try to keep them the same.”). Teva’s expert,
`Dr. Wermeling, similarly testified that a person of ordinary
`skill in the art would understand that Phase III studies
`“us[ed] doses that are thought to be safe and effective and
`are going to be confirmed in the larger patient population.”
`J.A. 10316:17–10317:2; see also J.A. 10207:5–23.
`It is undisputed that the ’548 protocol does not contain
`any results—Opinion, 571 F. Supp. 3d at 301—and Teva
`relied on how a person of ordinary skill in the art (“POSA”)
`would understand the protocol itself considering its Phase
`III status and other background knowledge in the art. And
`while the protocol is associated with Janssen’s PSY-3003
`clinical trial, the results of the PSY-3003 trial were not
`known in the prior art. As we explain in more detail
`throughout this opinion, the import of these unknown re-
`sults influenced the district court’s view about what the
`claims require, what a POSA would need to know before
`she was motivated to modify the ’548 protocol, and what
`results would be unexpected.
`Consequently, although unavailable to a POSA, some
`information about the PSY-3003 trial results provides
`helpful context for our discussion. The 50 mg-eq. study
`arm—50 mg-eq. given on days 1, 8, 36, and 64—did not
`demonstrate a statistical difference compared to placebo.
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`J.A. 10895:6–7. In contrast, the 100 mg-eq. study arm did
`demonstrate efficacy that was significantly better than pla-
`cebo. J.A. 11061:21–24; J.A. 11147:3–9; J.A. 10893:15–17;
`J.A. 10895:11–13; J.A. 13130. However, “by [its] own
`measures,” Janssen considered the day 36 onset for efficacy
`“too late.” J.A. 11062:7–11. Finally, for the 150 mg-eq.
`study arm, because of a randomization error, most patients
`who were supposed to receive the 150 mg-eq. doses mistak-
`enly received placebo instead. J.A. 11063:24–11064:8;
`J.A. 10894:6–17. As a result, the data for that study arm
`was unusable
`for conducting statistical analyses.
`J.A. 11064:9–12; J.A. 10895:1–6; J.A. 11169:22–25. Ulti-
`mately, Janssen considered this clinical trial a failure—it
`did not believe it had sufficient data to obtain FDA ap-
`proval. J.A. 11068:3–17; J.A. 10784:15–20.
`B
`The ’544 patent, granted in 2003 and expired in 2018,
`is owned by Janssen. As the ’906 patent is now, the
`’544 patent was listed in the Orange Book for Invega Sus-
`tenna before its expiration. J.A. 17768.
`The ’544 patent claims “[a] pharmaceutical composi-
`tion suitable as a depot formulation for administration by
`intramuscular or subcutaneous injection, comprising,”
`among other things, a “therapeutically effective amount” of
`paliperidone palmitate. ’544 patent claim 1. Additionally,
`it claims a method of treating schizophrenia, or other dis-
`orders, “in a warm-blooded animal in need thereof compris-
`ing administering to the animal a therapeutically effective
`amount of” the claimed composition of paliperidone palmi-
`tate. ’544 patent claim 7.
`Further, the specification emphasizes the ability to
`space out administrations by three weeks to a month. Spe-
`cifically, it states that “[t]he present invention results from
`the investigations into the development of an efficient,
`well-tolerated, sustained or delayed release (depot) formu-
`lation of a [paliperidone] alkanoic acid ester which is
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`therapeutically effective for at least three weeks or more,
`in particular about 1 month.” Id. at col. 2 ll. 38–43; see also
`id. at col. 8 ll. 17–19 (“Typically, said formulation will be
`administered approximately every three weeks or even at
`longer intervals where possible.”). It further indicates that
`“effective for at least three weeks or more” means a plasma
`level of paliperidone above 10 ng/ml and below 100 ng/ml,
`id. at col. 2 ll. 43–50, and that “[t]he dosage should range
`from about 2 to 4 mg/kg body weight,” id. at col. 8
`ll. 19–20.2
`The ’544 patent discloses specific amounts of active and
`inactive ingredients for an LAI paliperidone palmitate for-
`mulation. Id. at col. 8 l. 60–col. 9 l. 7. Most pertinent for
`our purposes on appeal, the specification discusses the par-
`ticle size used in the formulations. Specifically, it states
`that “[t]he pharmacokinetic properties in humans of the
`aqueous suspensions of [paliperidone] alkanoic acid esters
`depend on the particle size to a much larger extent than
`previously held possible.” Id. at col. 3 ll. 52–55. And it gen-
`erally provides details related to applying “mechanical
`means” to reduce the effective average particle size. Id.
`at col. 6 ll. 1–47.
`The ’544 patent references “an effective average parti-
`cle size of less than 2,000 nm” several times, see, e.g., id.
`at col. 3 ll. 43–44, col. 5 ll. 15–26, which, as used in the
`’544 patent, “means that at least 90% of the particles have
`a diameter of less than 2,000 nm,” id. at col. 5 ll. 16–18. In
`other words, “effective average particle size” refers to the
`d(90) value (90% of the particles have a smaller diameter)
`in the ’544 patent—this is in contrast to the ’906 patent
`which defines effective average particle size as the d(50)
`
`2 Dr. Wermeling testified that for a population
`weighing between 50 and 90 kg, the 2 to 4 mg/kg dosage
`range would translate to 65 mg-eq. to 230 mg-eq. paliperi-
`done palmitate. J.A. 10284:16–21.
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`value (50% of the particles have a smaller diameter). Com-
`pare id., with ’906 patent col. 7 ll. 32–36.
`The ’544 patent discloses the particle sizes of four for-
`mulations:
`
`
`See Appellants’ Br. 13 (table); ’544 patent col. 8 ll. 44–57,
`col. 9 ll. 24–33 (data).
`It further discloses that “[f]ormulations C and D were
`put on a three month stability test,” id. at col. 9 ll. 33–34,
`and that “[e]ach of the four formulations A–D were admin-
`istered to four beagle dogs intramuscularly,” id. at col. 9
`ll. 48–49.
`
`C
`International Publication WO’384 was filed by Janssen
`and published in 2006. J.A. 13299–321. Although the dis-
`closure is broader, the abstract describes the invention of
`WO’384 as related to “a process for preparing aseptic crys-
`talline” paliperidone palmitate. J.A. 13299.
`As part of an example entitled “[p]reparation of fin-
`ished form,” WO’384 discloses specific amounts of active
`and inactive ingredients for an LAI paliperidone palmitate
`formulation. J.A. 13316. Janssen agrees that the compo-
`sition of this disclosed formulation matches both the com-
`position elements of claims 20 and 21 and the Invega
`Sustenna formulation. Appellees’ Br. 9. Also, as part of
`this example, WO’384 states that “[t]he suspension was
`filled aseptically into sterile syringes” in dose volumes
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`“between 0.25 ml and 1.50 ml depending on the dose
`needed,” J.A. 13317, which corresponds to 25 to 150 mg-eq.
`of paliperidone, J.A. 12163:15–20.
`*
`*
`*
`Teva argued that all asserted claims were invalid as
`obvious and that claims 19–21 were also invalid as indefi-
`nite. After a bench trial, the district court concluded that
`Teva had not proven invalidity on either basis. Teva ap-
`peals. We have jurisdiction under 28 U.S.C. § 1295(a)(1).
`DISCUSSION
`Teva first argues that the district court’s obviousness
`analysis, including its analysis of secondary considera-
`tions, was legally flawed in several key respects. Some of
`Teva’s arguments relate to all claims while others only re-
`late to a subset of claims. Ultimately, we vacate and re-
`mand with respect to all claims.
`We address: (1) whether the court required a showing
`of obviousness that was incongruent with the scope of the
`claims by requiring—(i) generalized or population-wide
`dosing (all claims) and (ii) mild renal impairment (claims
`10 and 13); (2) whether the court analyzed the prior art
`with a degree of rigidity foreclosed by KSR—(i) generally
`(all claims) and (ii) teaching away (particle-size claims);
`and (3) secondary considerations—(i) whether they pre-
`clude vacatur and (ii) whether individual secondary consid-
`erations were properly analyzed.
`Finally, we address Teva’s argument that the district
`court improperly determined that Teva had not demon-
`strated that claims 19–21 (particle-size claims) were inva-
`lid as indefinite. Although the claims may still be
`invalidated as obvious on remand, we nonetheless reach
`the question of indefiniteness and affirm the court’s deter-
`mination that claims 19–21 were not shown to be indefi-
`nite.
`
`

`

`Case: 22-1258 Document: 70 Page: 15 Filed: 04/01/2024
`
`JANSSEN PHARMACEUTICALS, INC. v.
`TEVA PHARMACEUTICALS USA, INC.
`
`15
`
`I
`Obviousness is a question of law based on underlying
`factual determinations, “including (1) the scope and con-
`tent of the prior art; (2) the differences between the claims
`and the prior art; (3) the level of ordinary skill in the perti-
`nent art; and (4) any secondary considerations of non-obvi-
`ousness.” ZUP, LLC v. Nash Mfg., Inc., 896 F.3d 1365,
`1371 (Fed. Cir. 2018); see also PAR Pharm., Inc. v. TWI
`Pharms., Inc., 773 F.3d 1186, 1193–94 (Fed. Cir. 2014). We
`review the overall determination de novo and the underly-
`ing factual findings for clear error. PAR Pharm., 773 F.3d
`at 1194. Where the court applies an incorrect legal stand-
`ard in its analysis, it can be appropriate to vacate and re-
`mand for factfindings that address the correct legal
`question. See id. at 1196 (remanding where “[t]here [we]re
`simply no findings of fact addressing th[e correct legal]
`question” about inherency); Innovention Toys, LLC v. MGA
`Ent., Inc., 637 F.3d 1314, 1324 (Fed. Cir. 2011) (remanding
`on determination of nonobviousness where the district
`court applied an improperly low level of skill in the art for
`the court to “make a finding on the level of skill in the art
`and base its obviousness analysis on that level of skill” on
`remand).
`“The combination of familiar elements according to
`known methods is likely to be obvious when it does no more
`than yield predictable results.” KSR Int’l Co. v. Teleflex
`Inc., 550 U.S. 398, 416 (2007). Assessing obviousness is
`based on an “expansive and flexible approach” that “need
`not seek out precise teachings directed to the specific sub-
`ject matter of the challenged claim, for a court can take ac-
`count of the inferences and creative steps that a person of
`ordinary skill in the art would employ.” Id. at 415, 418.
`A
`Teva makes several arguments about the district
`court’s obviousness analysis, leading with its argument
`that the district court added unclaimed limitations to the
`
`

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`Case: 22-1258 Document: 70 Page: 16 Filed: 04/01/2024
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`16
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`JANSSEN PHARMACEUTICALS, INC. v.
`TEVA PHARMACEUTICALS USA, INC.
`
`claims when analyzing obviousness—specifically: (1) gen-
`eralized or population-wide dosing (all claims); and
`(2) mild renal impairment (claims 10 and 13). We address
`both arguments in turn.
`
`1
`First, Teva argues that the district court’s analysis of
`obviousness required Teva to show that it would have been
`obvious to use the recited dosing regimens for the general
`population of patients—i.e., a generalized dosing regimen.
`The court found that the prior art did not demonstrate pop-
`ulation-wide safety and efficacy and thus did not teach a
`generalized dosing regimen. Teva contends that the claims
`were not directed to a generalized dosing regimen and
`therefore the district court asked for a showing of obvious-
`ness that went beyond what was claimed. We agree.
`The non-renal-impairment dosing regimen claims re-
`cite a dosing regimen for “a psychiatric patient in need of
`treatment for schizophrenia”3: (1) a 150 mg-eq. loading
`dose on day 1 administered into the deltoid; (2) a 100 mg-
`eq. loading dose on day 6 to 10 administered into the del-
`toid; and (3) a maintenance dose of 25 to 150 mg-eq. given
`a month (±7 days) after the second loading dose adminis-
`tered into the deltoid or gluteal muscle. ’906 patent claim
`2 (emphasis added). Likewise, the renal-impairment
`claims recite a dosing regimen for “a renally impaired psy-
`chiatric patient in need of treatment for schizophrenia”:
`(1) a 75 mg-eq. loading dose on day 1 administered into the
`deltoid; (2) a 75 mg-eq. loading dose on day 6 to 10 admin-
`istered into the deltoid; and (3) a maintenance dose of 25 to
`about 75 mg-eq. (or 25 to about 50 mg-eq.) given a month
`(±7 days) after the second loading dose administered into
`
`
`3 Some claims also contemplate that the patient is in
`need of treatment for a different psychiatric disorder, but
`the parties focus on schizophrenia, so we do the same.
`
`

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`Case: 22-1258 Document: 70 Page: 17 Filed: 04/01/2024
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`JANSSEN PHARMACEUTICALS, INC. v.
`TEVA PHARMACEUTICALS USA, INC.
`
`17
`
`the deltoid or gluteal muscle. ’906 patent claims 10 and 13
`(emphasis added).
`Nothing in the claims requires that the regimen be
`used for—let alone be ideal for—the patient population
`generally or a certain percentage of the patient population.
`On their face, the claims only recite a dosing regimen for a
`psychiatric patient. Because “[w]hat matters is the objec-
`tive reach of the claim,” KSR, 550 U.S. at 419, the district
`court erred to the extent it effectively defined its obvious-
`ness inquiry as one concerning the “generalized” suitability
`of the dosing regimens.
`At the district court, Janssen emphasized arguments
`and evidence related to its clinical-study design and ap-
`proval process with the FDA—both of which were keyed to
`concerns about generating population-wide data. It seems
`that the court ended up conflating Janssen’s purported dif-
`ficulties in generating data to gain approval for a “univer-
`sal” or “generalized” dosing regimen with the scope of the
`claims themselves.4 Given the scope of the claims here, it
`was important for the court to recognize the distinction and
`focus its findings on single patient administration. The
`district court did not do so.
`We are persuaded that this misunderstanding about
`the claims impacted the district court’s overall obviousness
`analysis. Certain portions of the court’s discussion provide
`
`
`4 Because we agree with Teva that it was improper
`to read this limitation into the claims, we need not assess
`what it would mean for the claimed dosing regimens to be
`“generalized” or “universal.” For example, it is unclear
`whether that requirement would indicate that physicians
`typically (or always) dose that way or that some (or all) pa-
`tients achieve a certain level of a particular unnamed re-
`sult.
`
`

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`Case: 22-1258 Document: 70 Page: 18 Filed: 04/01/2024
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`18
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`JANSSEN PHARMACEUTICALS, INC. v.
`TEVA PHARMACEUTICALS USA, INC.
`
`examples of how this legal error affected the district court’s
`analysis and factfinding here.
`For example, the district court assessed whether a
`POSA would be motivated to use the deltoid (shoulder) as
`an injection site. Teva argued that the deltoid was one of
`only three finite choices for an intramuscular injection site
`(the deltoid, g