Court Opinion

ID: 6330664
Source: CourtListenerOpinion
Date Created: 2022-04-13 14:04:14.33023+00
Date Added: 2024-06-11T09:23:04.152242
License: Public Domain

Case: 21-1939    Document: 44     Page: 1   Filed: 03/25/2022

        NOTE: This disposition is nonprecedential.

   United States Court of Appeals
       for the Federal Circuit
                  ______________________

                  IMMUNOGEN, INC.,
                   Plaintiff-Appellant

                             v.

   ANDREW HIRSHFELD, PERFORMING THE
    FUNCTIONS AND DUTIES OF THE UNDER
       SECRETARY OF COMMERCE FOR
 INTELLECTUAL PROPERTY AND DIRECTOR OF
 THE UNITED STATES PATENT AND TRADEMARK
                   OFFICE,
               Defendant-Appellee
             ______________________

                        2021-1939
                  ______________________

    Appeal from the United States District Court for the
 Eastern District of Virginia in No. 1:20-cv-00274-TSE-IDD,
 Judge T. S. Ellis, III.
                   ______________________

                 Decided: March 25, 2022
                 ______________________

     MICHAEL E. JOFFRE, Sterne Kessler Goldstein & Fox,
 PLLC, Washington, DC, argued for plaintiff-appellant.
 Also represented by PAULINE PELLETIER, ERIC STEFFE.

    DANIEL KAZHDAN, Office of the Solicitor, United States
Case: 21-1939    Document: 44      Page: 2    Filed: 03/25/2022

 2                             IMMUNOGEN, INC.   v. HIRSHFELD

 Patent and Trademark Office, Alexandria, VA, argued for
 defendant-appellee. Also represented by MARY L. KELLY,
 THOMAS W. KRAUSE, FARHEENA YASMEEN RASHEED;
 MATTHEW JAMES MEZGER, RAJ PAREKH, Office of the United
 States Attorney for the Eastern District of Virginia, United
 States Department of Justice, Alexandria, VA.
                  ______________________

  Before NEWMAN, CLEVENGER, and STOLL, Circuit Judges.
 CLEVENGER, Circuit Judge.
     This case involves a civil action to obtain a patent un-
 der 35 U.S.C. § 145. Appellee ImmunoGen, Inc.’s (“Immu-
 noGen”) U.S. Application No. 14/509,809 (“the ’809
 Application”) describes methods of administering the im-
 munoconjugate mirvetuximab for the treatment of cancer.
 After the Patent Trial and Appeal Board (“Board”) of the
 United States Patent and Trademark Office (“USPTO”) af-
 firmed the examiner’s rejection of the pending claims for
 obviousness and obviousness-type double patenting, Im-
 munoGen filed its § 145 suit in the Eastern District of Vir-
 ginia.
     The district court determined on summary judgment
 that the claims of the ’809 Application are “fatally indefi-
 nite and fatally obvious” as a matter of law. ImmunoGen,
 Inc. v. Iancu, 523 F. Supp. 3d 773, 799 (E.D. Va. 2021). Im-
 munoGen appeals from the summary judgment. We have
 jurisdiction under 28 U.S.C. § 1295(a)(1).
     In its analysis, the district court resolved numerous
 factual disputes against non-movant ImmunoGen, an error
 that is fatal to its ultimate ruling. We therefore vacate the
 grant of summary judgment and remand for proceedings
 consistent with this opinion.
                    THE ’809 APPLICATION
     Immunoconjugates, such as mirvetuximab, are com-
 posed of an antibody coupled to a drug via a chemical
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 IMMUNOGEN, INC.   v. HIRSHFELD                            3

 linker. The antibody portion allows the immunoconjugate
 to bind to a cell of interest, thereby permitting selective
 targeting of cancer cells for treatment. Mirvetuximab spe-
 cifically targets Folate Receptor 1 (“FOLR1”), which is
 overexpressed in ovarian and peritoneal cancer cells.
     Although mirvetuximab showed promise as a cancer
 treatment, Phase 1 clinical trials revealed it can have se-
 vere ocular side effects when administered at a dose of
 7 mg per kg of the patient’s total body weight (“TBW”). Im-
 munoGen determined that a dose of 6 mg per kg of the pa-
 tient’s adjusted ideal body weight (“AIBW”) successfully
 maintains exposure of the drug at the therapeutically ef-
 fective level while keeping it below the ocular toxicity
 threshold. It is undisputed that AIBW dosing had not pre-
 viously been used for mirvetuximab, let alone any other im-
 munoconjugate. 1
    ImmunoGen filed the ’809 Application to claim this
 AIBW dosing method. Claim 1 is representative:
    1. A method for treating a human patient having
    an FOLR1-expressing ovarian cancer or cancer of
    the peritoneum comprising administering to the
    patient an immunoconjugate which binds to
    FOLR1 polypeptide,
    wherein the immunoconjugate comprises an anti-
    body or antigen-binding fragment thereof that com-
    prises    the    variable   light   chain     (VL)
    complementarity determining region (CDR)-1, VL
    CDR-2, VL CDR-3, variable heavy chain (VH)
    CDR-1, VH CDR-2, and VH CDR-3 of SEQ ID NOs:

    1    See, e.g., J.A. 9916–17, 9919 (Resps. to Request for
 Admission (“RFA”) Nos. 3 & 8–9); J.A. 10445 (Shah Dep.
 Tr. at 41:1–12); J.A.10655 (Tolcher Dep. Tr. at 55:4–19);
 J.A. 9992, 10043 (Figg Dep. Tr. at 36:7–21, 87:5–9).
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 4                             IMMUNOGEN, INC.   v. HIRSHFELD

     6-9, 11, and 12,[2] respectively, and a maytansinoid,
     and
     wherein the immunoconjugate is administered at a
     dose of 6 milligrams (mg) per kilogram (kg) of ad-
     justed ideal body weight (AIBW) of the patient.
     The ’809 Application defines AIBW as “a size descriptor
 that accounts for sex, total body weight, and height.” ’809
 Application at [0071]. It defines ideal body weight (“IBW”),
 which is used to calculate AIBW, as “a size descriptor that
 is unrelated to total body weight,” as it is “an estimate of
 weight corrected for sex and height, and optionally frame
 size.” Id. at [0069]. The application further discloses that
 IBW and AIBW “are discussed in more detail in Green and
 Duffull, British Journal of Clinical Pharmacology 58: 119-
 133 (2004)” (“Green”), which it incorporates by reference.
 Id. at [0072]. Green discloses several methods for calculat-
 ing IBW and lists correction factors, each specific to a dif-
 ferent drug, that can be used to adjust IBW to AIBW.
      The AIBW and IBW definitions each includes a for-
 mula, introduced by the phrase “for example,” for calculat-
 ing the respective values. These “example” formulas are
 reproduced in Example 4, which relates to dosing
 IMGN853, i.e., mirvetuximab. As described in both the def-
 initions and Example 4, AIBW is calculated as the patient’s
 IBW plus 0.4 times their total (actual) body weight in kg
 minus their IBW. Id. at [0069], [0200]. For males, IBW is
 calculated as 0.9 times their height in centimeters minus
 88; for females, IBW is calculated as 0.9 times their height
 in centimeters minus 92. Id. at [0071], [0200]. The equa-
 tions are reproduced below:

     2   The claimed “SEQ ID Nos” and other recited fea-
 tures identify the immunoconjugate as IMGN853, which is
 also known as mirvetuximab.
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 IMMUNOGEN, INC.   v. HIRSHFELD                            5

    AIBW = IBW + 0.4(Actual weight in kg – IBW)
    IBW (male) = 0.9H – 88
    IBW (female) = 0.9H – 92
     The ’809 Application does not identify any other formu-
 las for calculating AIBW or IBW. The “0.4” value in the
 AIBW formula is a specific correction factor for mirvetuxi-
 mab, and is the only one presented in the ’809 Application.
                         DISCUSSION
      Summary judgment is appropriate when, drawing all
 justifiable inferences in favor of the non-moving party,
 there exists no genuine issue of material fact and the mov-
 ing party is entitled to judgment as a matter of law. See
 Fed. R. Civ. P. 56(c); Anderson v. Liberty Lobby, Inc., 477
 U.S. 242, 247–48 (1986). We review a district court’s sum-
 mary judgment determination under the law of the re-
 gional circuit, see Syngenta Crop Prot., LLC v. Willowood,
 LLC, 944 F.3d 1344, 1355 (Fed. Cir. 2019), which, here, is
 the Fourth Circuit. “The Fourth Circuit reviews the grant
 of a motion for summary judgment de novo, viewing all ev-
 idence in the light most favorable to the non-moving party.”
 Id. (citing cases).
     Indefiniteness and obviousness are both issues of law
 that may rely on underlying factual findings, such as the
 knowledge, level, or understanding of those skilled in the
 art. See BASF Corp. v. Johnson Matthey Inc., 875 F.3d
 1360, 1365 (Fed. Cir. 2017) (indefiniteness); Teva Pharms.
 USA, Inc. v. Sandoz, Inc., 789 F.3d 1335, 1342 (Fed. Cir.
 2015) (same); Acorda Therapeutics, Inc. v. Roxane Lab’ys,
 Inc., 903 F.3d 1310, 1328 (Fed. Cir. 2018) (obviousness).
 Obviousness may also rely on factual findings regarding
 motivation to combine, reasonable expectation of success,
 and secondary considerations of nonobviousness. Acorda,
 903 F.3d at 1328.
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 6                              IMMUNOGEN, INC.   v. HIRSHFELD

                               I
     Although neither the examiner nor the Board rejected
 the claims of the ’809 Application for indefiniteness, the
 USPTO (as permitted by statute) argued in the § 145 action
 that the term “AIBW” is indefinite. The district court
 agreed, concluding that the ’809 Application fails to define
 IBW or AIBW in such a way that a skilled artisan would be
 informed, with reasonable certainty, as to the scope of the
 invention. 3 ImmunoGen, 523 F. Supp. 3d at 787, 799.
      For support, the district court relies mainly on the def-
 initions section of the ’809 Application. In the district
 court’s view, the “for example” language preceding the
 AIBW formula “makes clear that there are multiple ways
 to calculate AIBW,” thereby “leav[ing] a skilled artisan to
 wonder or to guess whether the formula provided is the
 only one covered by the ’809 Application.” Id. at 787. This
 supposed uncertainty is compounded by the “for example”
 accompanying the IBW formula; the disclosure that IBW
 corrects “for sex and height, and optionally frame size”;
 and the incorporation of Green. Id. Although Example 4 of
 the ’809 Application discloses dosing mirvetuximab using
 the same IBW and AIBW formulas provided in the defini-
 tions section, the district court declined to read Example 4
 as “limit[ing] the scope of the claims.” Id. at 788. The dis-
 trict court likewise declined to consider expert testimony
 as to whether a skilled artisan reviewing the ’809 Applica-
 tion would understand which AIBW formula to use,

     3    As dictated by the Supreme Court, “a patent is in-
 valid for indefiniteness if its claims, read in light of the
 specification delineating the patent, and the prosecution
 history, fail to inform, with reasonable certainty, those
 skilled in the art about the scope of the invention.” Nauti-
 lus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 901
 (2014). The district court applied this standard in its anal-
 ysis. See, e.g., ImmunoGen, 523 F. Supp. 3d at 786, 787.
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 IMMUNOGEN, INC.   v. HIRSHFELD                             7

 characterizing the experts’ disagreement as nothing more
 than an “attempt[] to create a factual dispute” in a situa-
 tion where “[t]he undisputed, intrinsic evidence demon-
 strates that the term AIBW . . . is indefinite.” Id.
      Our review of the evidence, however, reveals that the
 underlying material factual findings are far from undis-
 puted. For example, the district court found that the ’809
 Application “provides no limiting or defining guidance [to a
 skilled artisan] on the calculation of AIBW.” ImmunoGen,
 523 F. Supp. 3d at 787. Similarly, the district court found
 that the ’809 Application discloses multiple formulas for
 calculating AIBW. Id. at 787–88. While the district court is
 correct that the definition section incorporates Green in its
 entirety and identifies the recited AIBW and IBW formulas
 as “example[s],” ImmunoGen identified other intrinsic evi-
 dence a skilled artisan would consider in determining the
 scope of the claims, including that: (1) the claims and spec-
 ification are drawn to a specific dosing regimen for a spe-
 cific immunoconjugate, which is significant in light of
 expert testimony that the correction factor used to calcu-
 late AIBW is drug-specific; 4 (2) Example 4 describes dosing
 mirvetuximab in accordance with the claimed method and
 uses the same AIBW and IBW formulas disclosed in the
 definitions section; 5 and (3) during the prosecution of the

     4   See, e.g., J.A. 9985–86, 10059 (Figg Dep. Tr. at
 29:17–30:4, 103:2–6); J.A. 10225–26 (Figg Opening Rpt.,
 ¶ 146); J.A. 10368–69, 10370 (Shah Reply Rpt., ¶¶ 11–12,
 15).
      5  The district court incorrectly concluded that Exam-
 ple 4 plays no role in the indefiniteness inquiry. See, e.g.,
 Interval Licensing LLC v. AOL, Inc., 766 F.3d 1364, 1373
 (Fed. Cir. 2014) (“We recognize that a patent which defines
 a claim phrase through examples may satisfy the definite-
 ness requirement.”); Enzo Biochem, Inc. v. Applera Corp.,
 599 F.3d 1325, 1336 (Fed. Cir. 2010) (holding that the
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 8                             IMMUNOGEN, INC.   v. HIRSHFELD

 ’809 Application, the USPTO never disputed the definite-
 ness, or gave any indication it failed to understand the
 meaning, of the now-allegedly indefinite term. 6 Immuno-
 Gen also presented extrinsic evidence regarding the
 knowledge of a skilled artisan. For instance, both parties’
 experts testified that AIBW dosing involves drug-specific
 formulas and correction factors. 7 This is confirmed by
 Green, which is incorporated into the ’809 Application and
 identifies drug-specific correction factors for use in calcu-
 lating AIBW. 8 When we view this evidence in the light
 most favorable to ImmunoGen—as we must in our re-
 view—we conclude that there are still disputed questions
 of material fact and summary judgment is therefore inap-
 propriate.
                              II
     The district court also held that the pending claims
 would have been obvious, concluding that the prior art
 taught every element of the pending claims, ImmunoGen,
 523 F. Supp. 3d at 792–93; that a skilled artisan would
 have been motivated to use AIBW dosing to address the
 ocular toxicity problems associated with mirvetuximab
 with a reasonable expectation of success, id. at 793–95; and

 phrase “not interfering substantially” is sufficiently defi-
 nite because a skilled artisan could use “the examples in
 the specification to determine whether interference with
 hybridization is substantial”).
     6   See, e.g., J.A. 11007 (Shah Opening Rpt., ¶¶ 197–
 200); J.A. 10369–70 (Shah Reply Rpt., ¶¶ 13–14); see also
 J.A. 10899–900.
     7   See, e.g., J.A. 9985–86, 10059 (Figg Dep. Tr. at
 29:17–30:4, 103:2–6); J.A. 10225–26 (Figg Opening Rpt.,
 ¶¶ 144, 146); J.A. 10368–69 (Shah Reply Rpt., ¶¶ 11–12).
     8   J.A. 4445; see also J.A. 10225–26 (Figg Opening
 Rpt., ¶ 146).
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 IMMUNOGEN, INC.   v. HIRSHFELD                              9

 that ImmunoGen’s secondary considerations were unper-
 suasive, id. at 795–798.
      In reaching this conclusion, the district court improp-
 erly resolved a number of factual findings against Immu-
 noGen. For example, the district court found that “ocular
 toxicity was a known negative effect of [immunoconjugates]
 like IMGN853.” Id. at 793. But the expert testimony on
 which the district court relies does not directly support that
 statement. See id. at 793, n.40. Further, ImmunoGen pre-
 sented evidence that (1) ocular toxicity is not well-under-
 stood; 9     (2)     immunoconjugates        have      unique
 pharmacokinetic characteristics, making it difficult to gen-
 eralize pharmacological effects; 10 (3) it was not known that
 mirvetuximab would cause ocular toxicity; 11 and (4) pub-
 lished results for Phase 1 testing of mirvetuximab reported
 no study drug-related serious adverse events or dose-limit-
 ing toxicity. 12 As another example, the district court con-
 cluded, based on statements made in International
 Published Application Nos. WO 2011/106528 (“Ab ’528”)
 and WO 2012/135675 (“Carrigan ’675”), that “dosing of
 IMGN853 could ‘easily’ be determined.” ImmunoGen, 523
 F. Supp. 3d at 795 (quoting Carrigan ’675); see also id. at
 781 (quoting Ab ’528). ImmunoGen’s experts, however, tes-
 tified that the contested statements relate to dosing in the
 context of treating patients, not in the context of determin-
 ing a safe and effective dose in drug development, and that

     9   See, e.g., J.A. 10095–96 (Figg Dep. Tr. at 139:7–
 140:5); J.A. 11028 (Shah Opening Rpt., ¶ 235); J.A. 9595,
 9597 (Tolcher Opening Rpt., ¶¶ 34, 39).
     10  See, e.g., J.A. 9595 (Tolcher Opening Rpt., ¶ 34);
 J.A. 10980–81 (Shah Opening Rpt., ¶ 50).
     11  See, e.g., J.A. 9995, 10021, 10024 (Figg Dep. Tr. at
 39:6–14, 65:16–20, 68:13–22); J.A. 9941–45 (Resps. to RFA
 Nos. 64–74).
     12  See, e.g., J.A. 9541.
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 10                             IMMUNOGEN, INC.   v. HIRSHFELD

 determining a safe and effective dose for immunoconju-
 gates is difficult. 13 Similarly, the district court found that
 switching “from 6 mg/kg of [TBW] dosing to 6 mg/kg AIBW
 dosing does not significantly change the dose for patients
 who are not significantly overweight or underweight,” id.
 at 792–93, even though the ’809 Application and other evi-
 dence show that this switch to AIBW dosing reduced ad-
 verse ocular events in Phase 1 clinical trials. 14
     For each of these examples, the district court erred in
 concluding that there is no disputed question of material
 fact. This error repeats across its other factual findings, in-
 cluding those relating to motivation to combine, reasonable
 expectation of success, and secondary considerations.
                         CONCLUSION
     For the reasons stated above, we hold that the district
 court erred in granting summary judgment. We therefore
 vacate the district court’s determination that the pending
 claims of the ’809 Application are indefinite and would
 have been obvious, and remand for proceedings consistent
 with this opinion.
                VACATED AND REMANDED
                             COSTS
 No costs.

      13See, e.g., J.A. 9612 (Tolcher Opening Rpt., ¶ 106);
 J.A. 10521–25 (Shah Dep. Tr. at 117:15–121:19); J.A.
 10980–81 (Shah Opening Rpt., ¶ 50); J.A. 9595 (Tolcher
 Opening Rpt., ¶ 34).
     14 See, e.g., ’809 Application, Example 4; J.A. 11030–
 31 (Shah Opening Rpt., ¶ 239).