Immunogen, Inc. v. Hirshfeld

Case: 21-1939 Document: 44 Page: 1 Filed: 03/25/2022 NOTE: This disposition is nonprecedential.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 Case: 21-1939 Document: 44 Page: 3 Filed: 03/25/2022 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). Case: 21-1939 Document: 44 Page: 4 Filed: 03/25/2022 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. Case: 21-1939 Document: 44 Page: 5 Filed: 03/25/2022 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. Case: 21-1939 Document: 44 Page: 6 Filed: 03/25/2022 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. Case: 21-1939 Document: 44 Page: 7 Filed: 03/25/2022 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 Case: 21-1939 Document: 44 Page: 8 Filed: 03/25/2022 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). Case: 21-1939 Document: 44 Page: 9 Filed: 03/25/2022 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. Case: 21-1939 Document: 44 Page: 10 Filed: 03/25/2022 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).