Novartis Pharmaceuticals v. Accord Healthcare Inc.

Case: 21-1070 Document: 51 Page: 1 Filed: 06/21/2022 United States Court of Appeals for the Federal Circuit ______________________ NOVARTIS PHARMACEUTICALS CORPORATION, Plaintiff-Appellee v. ACCORD HEALTHCARE, INC., AUROBINDO PHARMA LTD., AUROBINDO PHARMA USA, INC., DR. REDDY’S LABORATORIES, INC., DR. REDDY’S LABORATORIES, LTD., EMCURE PHARMACEUTICALS LTD., HERITAGE PHARMACEUTICALS INC., GLENMARK PHARMACEUTICALS INC., USA, GLENMARK PHARMACEUTICALS LIMITED, HETERO USA, INC., HETERO LABS LIMITED UNIT-V, HETERO LABS LIMITED, MYLAN PHARMACEUTICALS, INC., PRINSTON PHARMACEUTICAL INC., STRIDES GLOBAL PHARMA PRIVATE LIMITED, STRIDES PHARMA, INC., TORRENT PHARMA INC., TORRENT PHARMACEUTICALS LTD., ZYDUS PHARMACEUTICALS (USA) INC., CADILA HEALTHCARE LTD., APOTEX INC., APOTEX CORP., SUN PHARMACEUTICAL INDUSTRIES, LTD., SUN PHARMACEUTICAL INDUSTRIES INC., SUN PHARMA GLOBAL FZE, Defendants HEC PHARM CO., LTD., HEC PHARM USA INC., Defendants-Appellants ______________________ 2021-1070 ______________________ Case: 21-1070 Document: 51 Page: 2 Filed: 06/21/2022 2 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. Appeal from the United States District Court for the District of Delaware in No. 1:18-cv-01043-KAJ, Circuit Judge Kent A. Jordan. ______________________ Decided: June 21, 2022 ______________________ JANE M. LOVE, Gibson, Dunn & Crutcher LLP, New York, NY, argued for plaintiff-appellee. Also represented by PAUL E. TORCHIA, ROBERT TRENCHARD. PAUL SKIERMONT, Skiermont Derby LLP, Dallas, TX, argued for defendants-appellants. Also represented by SARAH ELIZABETH SPIRES; MIEKE K. MALMBERG, Los Ange- les, CA. ______________________ Before MOORE, Chief Judge, LINN and HUGHES, Circuit Judges. Opinion for the court filed by Chief Judge MOORE. Dissenting opinion filed by Circuit Judge LINN. MOORE, Chief Judge. HEC Pharm Co., Ltd. and HEC Pharm USA Inc. (col- lectively, HEC) petition for rehearing of our prior decision in this case, 21 F.4th 1362 (Fed. Cir. 2022), in which we affirmed a final judgment of the United States District Court for the District of Delaware. The district court de- termined that claims 1–6 of U.S. Patent No. 9,187,405 are not invalid and that HEC infringes them. Because the ’405 patent fails to disclose the absence of a loading dose, the district court clearly erred in finding that the negative claim limitation “absent an immediately preceding loading dose” added during prosecution to overcome prior art Case: 21-1070 Document: 51 Page: 3 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 3 satisfies the written description requirement of 35 U.S.C. § 112(a). We grant HEC’s petition for panel rehearing, va- cate our prior decision, and reverse the district court’s judg- ment that Novartis’ claims are not invalid for inadequate written description. BACKGROUND The ’405 patent discloses methods of treating relaps- ing-remitting multiple sclerosis (RRMS) using the immu- nosuppressant fingolimod. E.g., ’405 patent at claim 1, 8:56–60. Each claim of the ’405 patent requires adminis- tering fingolimod “at a daily dosage of 0.5 mg, absent an immediately preceding loading dose regimen.” Id. at claim 1. A loading dose is a “higher-than-daily dose . . . usually given as the first dose.” J.A. 27 ¶ 63 (internal quotation marks omitted). The patent’s specification does not men- tion loading doses, much less the absence of a loading dose. Instead, it describes administering fingolimod at regular intervals (e.g., once daily, multiple times per day, or every other day). ’405 patent at 11:20–38. Novartis owns the ’405 patent and markets a drug un- der the brand name Gilenya that purportedly practices the patent. HEC filed an abbreviated new drug application (ANDA) with the Food and Drug Administration seeking approval to market a generic version of Gilenya. Novartis sued HEC in the District of Delaware, alleging that HEC’s ANDA infringes all claims of the ’405 patent. 1 After a four-day bench trial, the district court found that HEC’s ANDA infringes and that the claims are not in- valid, either as anticipated by Kappos 2006 or for inade- quate written description of the no-loading-dose or daily- 1 Novartis sued several other defendants who also filed ANDAs, but those cases were settled or stayed before trial. Case: 21-1070 Document: 51 Page: 4 Filed: 06/21/2022 4 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. dosage limitations. HEC appeals as to written description. We have jurisdiction under 28 U.S.C. § 1295(a)(1). DISCUSSION “Whether a claim satisfies the written description re- quirement is a question of fact that, on appeal from a bench trial, we review for clear error.” Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1308 (Fed. Cir. 2015) (quoting Alcon Rsch. Ltd. v. Barr Labs., Inc., 745 F.3d 1180, 1190 (Fed. Cir. 2014)). Under the clear error standard, we defer to the district court’s findings “in the absence of a definite and firm conviction that a mistake has been made.” Scanner Techs. Corp. v. ICOS Vision Sys. Corp. N.V., 528 F.3d 1365, 1374 (Fed. Cir. 2008) (cleaned up). Inadequate written de- scription must be shown by clear and convincing evidence. Hynix Semiconductor Inc. v. Rambus Inc., 645 F.3d 1336, 1351 (Fed. Cir. 2011) (citing ICU Med., Inc. v. Alaris Med. Sys., Inc., 558 F.3d 1368, 1376 (Fed. Cir. 2009)). A To satisfy the written description requirement, a pa- tent’s specification must “reasonably convey[ ] to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). Such possession must be “shown in the disclosure.” Id. It is not enough that a claimed inven- tion is “an obvious variant of that which is disclosed in the specification.” Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Disclosure is essential; it is “the quid pro quo of the right to exclude.” Kewanee Oil Co. v. Bicron Corp., 416 U.S. 470, 484 (1974); see also Enzo Bi- ochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 970 (Fed. Cir. 2002) (“[D]escription is the quid pro quo of the patent sys- tem.”). For negative claim limitations, like the no-loading-dose limitation at issue here, there is adequate written Case: 21-1070 Document: 51 Page: 5 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 5 description when, for example, “the specification describes a reason to exclude the relevant [element].” Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1351 (Fed. Cir. 2012); Inphi Corp. v. Netlist, Inc., 805 F.3d 1350, 1355 (Fed. Cir. 2015) (same); Nike, Inc. v. Adidas AG, 812 F.3d 1326, 1348 (Fed. Cir. 2016) (same), overruled on other grounds by Aqua Prods., Inc. v. Matal, 872 F.3d 1290, 1301 (Fed. Cir. 2017) (en banc). A reason to exclude an element could be found in “statements in the specification expressly listing the dis- advantages of using” that element. Santarus, 694 F.3d at 1351. Another reason could be that the specification “dis- tinguishes among” the element and alternatives to it. Inphi, 805 F.3d at 1357; see also In re Johnson, 558 F.2d 1008, 1017–19 (C.C.P.A. 1977) (reversing rejection for in- adequate written description where specification disclosed several species of a genus and claims recited genus but ex- cluded two species of lost interference count). The common denominator of these examples is disclo- sure of the element. That makes sense because “the hall- mark of written description is disclosure.” Ariad, 598 F.3d at 1351; see also Lockwood, 107 F.3d at 1571 (“It is the dis- closures of the applications that count.”). Silence is gener- ally not disclosure. See Seabed Geosolutions (US) Inc. v. Magseis FF LLC, 8 F.4th 1285, 1288 (Fed. Cir. 2021) (“[S]ilence does not support reading the claims to exclude gimbaled geophones.” (citations omitted)); MPEP § 2173.05(i) (9th ed. Rev. 10.2019, June 2020) (“The mere absence of a positive recitation is not a basis for an exclu- sion.”). If it were, then every later-added negative limita- tion would be supported so long as the patent makes no mention of it. While a negative limitation need not be re- cited in the specification in haec verba, there generally must be something in the specification that conveys to a skilled artisan that the inventor intended the exclusion, such as a discussion of disadvantages or alternatives. Con- sistent with our precedent in Santarus, Inphi and Nike, the Case: 21-1070 Document: 51 Page: 6 Filed: 06/21/2022 6 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. written description requirement cannot be met through simple disregard of the presence or absence of a limitation. While a written description’s silence about a negative claim limitation is a useful and important clue and may often be dispositive, it is possible that the written descrip- tion requirement may be satisfied when a skilled artisan would understand the specification as inherently disclos- ing the negative limitation. 2 For example, if the record es- tablished that in a particular field, the absence of mention of a limitation necessarily excluded that limitation, written description could be satisfied despite the specification’s si- lence. See Tronzo v. Biomet, Inc., 156 F.3d 1154, 1159 (Fed. Cir. 1998) (“[M]issing descriptive matter must necessarily be present in the . . . specification such that one skilled in the art would recognize such a disclosure.” (citing Cont’l Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268 (Fed. Cir. 1991))); see also In re Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999) (“To establish inherency [for purposes of anticipation], . . . evidence must make clear that the miss- ing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recog- nized by persons of ordinary skill.” (internal quotation 2 Novartis contends the written description require- ment may be satisfied by “implicit disclosure” as distinct from express or inherent disclosure. Novartis Br. 50–51. Yet it fails to identify any case holding that “implicit dis- closure” (whatever that means) is sufficient. Novartis cites In re Kolstad, a non-precedential decision involving express disclosure. 907 F.2d 157 (Fed. Cir. 1990) (non-preceden- tial). If an implicit disclosure is one that would render the limitation obvious to a skilled artisan, such a disclosure cannot under our precedent satisfy the written description requirement. Lockwood, 107 F.3d at 1572 (“A description which renders obvious the invention for which an earlier filing date is sought is not sufficient.”). Case: 21-1070 Document: 51 Page: 7 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 7 marks and citation omitted)). When the specification is it- self silent regarding a negative limitation, testimony from a skilled artisan as to possibilities or probabilities that the recited element would be excluded would not suffice, lest such testimony could effectively eliminate the written de- scription requirement. If silence were generally sufficient, all negative limitations would be supported by a silent specification. If, however, a patent owner could establish that a particular limitation would always be understood by skilled artisans as being necessarily excluded from a par- ticular claimed method or apparatus if that limitation is not mentioned, the written description requirement would be satisfied despite the specification’s silence. B The district court found that because there is no reci- tation of a loading dose in the specification, the no-loading- dose limitation is supported. J.A. 26 ¶ 61. The district court further found that the no-loading-dose limitation is disclosed in the specification because “[t]he Prophetic Trial describes giving a ‘daily dosage of 0.5 . . . mg’ fingolimod to treat RRMS, started ‘initially.’ The Prophetic Trial tells a person of skill that on day 1, treatment begins with a daily dose of 0.5 mg, not a loading dose.” J.A. 26 ¶ 62 (citations omitted). Novartis, likewise, argues that the specification satisfies the written description requirement for the no- loading-dose limitation because it indicates that the dosing regimen starts by “initially” administering a daily dosage. Novartis Br. 44. The district court’s finding that the specification dis- closes “initially” starting with a daily dose was clearly er- roneous. The specification nowhere describes “initially” administering a daily dosage. The specification says, “Ini- tially patients receive treatment for 2 to 6 months.” ’405 patent at 11:13–14. This sentence speaks to the initial length of treatment, not the dosage with which treatment Case: 21-1070 Document: 51 Page: 8 Filed: 06/21/2022 8 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. begins. Dr. Lublin, one of Novartis’ physician experts, ad- mitted this: Q. And then . . . there’s a sentence that begins: In- itially, patients receive treatment for two to six months. Do you see that? A. I do. Q. And what does that tell you about how the dos- ing would work? A. It suggests to me they’re taking the dosing that’s outlined in that first sentence continually for two to six months. J.A. 22792 (emphasis added). The contrary testimony of Novartis’ second physician expert, Dr. Steinman, is inconsistent with the plain text of the specification and therefore carries no weight. J.A. 23343 (testifying that “initially” is “really zooming in on Day 1” and conveying that treatment starts with “a daily dose of 0.5”). “[E]xpert testimony that is inconsistent with unambiguous intrinsic evidence should be accorded no weight.” Bell & Howell Document Mgmt. Prods. Co. v. Al- tek Sys., 132 F.3d 701, 706 (Fed. Cir. 1997) (citations omit- ted). As HEC argues in its rehearing petition, the district court’s reliance on a misquotation “ferreted into trial testi- mony by Novartis’ experts” was clearly erroneous. Pet. for Reh’g 6; see J.A. 26–27 ¶¶ 62–63 (district court relying on testimony that specification describes “initially” adminis- tering daily dosage). The ’405 specification discloses neither the presence nor absence of a loading dose. Loading doses—whether to be used or not—are simply not discussed. Novartis’ experts readily admitted this. J.A. 23344 (“Q. Is there anywhere in [the specification] that you saw reference to the loading dose? A. No.”); J.A. 22791 (Dr. Lublin testifying that “in- formation of having a loading dose is not there”). Dr. Case: 21-1070 Document: 51 Page: 9 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 9 Lublin also agreed that “[n]othing in the text of the speci- fication of the ’405 patent discloses a rationale for the neg- ative limitation prohibiting an immediately preceding loading dose.” J.A. 22872–73. The fact that the specifica- tion is silent about loading doses does not support a later- added claim limitation that precludes loading doses. The district court also found, independent of the mis- quoted “initially” language, that the specification’s disclo- sure of a daily dosage combined with its silence regarding a loading dose would “tell a person of skill that loading doses are excluded from the invention.” J.A. 26 ¶ 61. That, too, was clearly erroneous. Novartis does not defend this finding. 3 And for good reason. There is significant tension in the district court’s find- ing that the specification’s disclosure excludes a loading dose, but that the Kappos 2006 abstract does not. Both are silent regarding loadings doses, and both disclose a daily dosage. The district court defended this inconsistency by claiming that “[u]nlike a patent, which is presumed com- plete, an abstract [like Kappos 2006] is not presumed to contain all of the necessary information about the study.” J.A. 30 ¶ 74. This concept that a patent is presumed “com- plete” infected the district court’s analysis and the experts’ testimony regarding the no-loading-dose limitation. For example, Dr Lublin testified: Q. What would a person of skill reading the patent have thought about [the] question [of written de- scription]? A. They would have viewed the patent as a docu- ment, as a complete document, that should give you 3 Nor could it. Novartis admittedly did not “argue below that inherency . . . applies to the ’405 Patent’s method claims.” Novartis Br. 50. Any defense of the dis- trict court’s finding is thus forfeit. Case: 21-1070 Document: 51 Page: 10 Filed: 06/21/2022 10 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. all the information you need to carry out the claims, and that information of having a loading dose is not there, and what’s instead there is exam- ples of daily dose, daily dose, daily dose. J.A. 22791. A patent is not presumed complete such that things not mentioned are necessarily excluded. We pre- sume only that a patent has adequate written description, not that it is complete. Nat’l Recovery Techs., Inc. v. Mag- netic Separation Sys., Inc., 166 F.3d 1190, 1195 (Fed. Cir. 1999) (“The presumption of validity includes a presump- tion that the patent complies with § 112.” (citing N. Tele- com, Inc. v. Datapoint Corp., 908 F.2d 931, 941 (Fed. Cir. 1990))). Importantly, the disclosure of a daily dosage cannot amount to a disclosure that there can be no loading dose, because such a finding is at odds with the prosecution his- tory. The Patent Office allowed the claims only after the applicants added the no-loading-dose limitation. J.A. 23903 (examiner’s rejection in parent application); J.A. 23892–93 (applicants’ response); see also Novartis Br. 11–12. The applicants explained that they added the no- loading-dose limitation “to specify that the [daily dosage] cannot immediately follow a loading dose regimen” and “to further distinguish their claims from the disclosure of [prior art].” J.A. 23892. If reciting “daily dosage” without mentioning a loading dose necessarily excluded a loading dose, there would have been no reason for the applicants to add the no-loading-dose limitation. Neither the applicants nor the examiner understood the words “daily dosage” without the words “no loading dose” to convey the absence of a loading dose. Accordingly, the district court’s contrary finding was clearly erroneous. There is expert testimony that the specification dis- closes the absence of a loading dose. Dr. Steinman testi- fied: Case: 21-1070 Document: 51 Page: 11 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 11 Q. And do you see the sentence there, it says, “Ini- tially patients receive treatment for 2 to 6 months.” What would that tell a person of skill? A. Well, there were two places [in the specification] that if there were going to be an immediately pre- ceding loading dose, you would give it before the in- itial treatment, so you would really necessarily want to put it right there. And the second place was earlier when you talked about a daily dosage of 0.5. But there were two gates that if you wanted to interject something about a loading dose, those were the opportunities in this. And it was zero out of two places where they, I think, necessarily would have put it in. J.A. 23334–35. This expert testimony is focused on where in the specification the patentee would have mentioned a loading dose if they intended a loading dose to be included. But the question is not whether the patentee intended there to be a loading dose; the question is whether the pa- tentee precluded the use of a loading dose. On this record, there is no evidence that a skilled artisan would under- stand silence regarding a loading dose to necessarily ex- clude a loading dose. In fact, all the experts agreed that loading doses are sometimes given to MS patients. See J.A. 22780 (Dr. Lublin explaining that loading doses have been used in trials of MS drugs and with fingolimod in par- ticular); J.A. 22794; J.A. 23347–48 (Dr. Steinman acknowl- edging that loading doses are used in MS treatments); J.A. 23475 (Dr. Jusko, Novartis’ pharmacology expert, tes- tifying that fingolimod was given to transplant patients with a loading dose, and that he “could envision the possi- bility of starting with a loading dose”). And, importantly, there is intrinsic evidence that a skilled artisan would not understand reciting a daily dosage regimen without men- tioning a loading dose to exclude a loading dose. Case: 21-1070 Document: 51 Page: 12 Filed: 06/21/2022 12 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. We do not today create a heightened standard for neg- ative claim limitations. Just as disclosure is the “hallmark of written description” for positive limitations, Ariad, 598 F.3d at 1351, so too for negative limitations. That disclo- sure “need not rise to the level of disclaimer.” Santarus, 694 F.3d at 1351. Nor must it use the same words as the claims. Lockwood, 107 F.3d at 1572 (“[T]he exact terms need not be used in haec verba.” (citing Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995))). Rather, as with pos- itive limitations, the disclosure must only “reasonably con- vey[ ] to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Ariad, 598 F.3d at 1351. While silence will not gen- erally suffice to support a negative claim limitation, there may be circumstances in which it can be established that a skilled artisan would understand a negative limitation to necessarily be present in a disclosure. This is not such a case. CONCLUSION The district court’s finding that the no-loading-dose limitation meets the written description requirement was clearly erroneous. We grant HEC’s petition for panel re- hearing, vacate our prior decision, and reverse the district court’s judgment that the claims of the ’405 patent are not invalid. We need not reach HEC’s argument that the dis- trict court also clearly erred in finding adequate written description for the “daily dosage of 0.5 mg” limitation. REVERSED COSTS No costs. Case: 21-1070 Document: 51 Page: 13 Filed: 06/21/2022 United States Court of Appeals for the Federal Circuit ______________________ NOVARTIS PHARMACEUTICALS CORPORATION, Plaintiff-Appellee v. ACCORD HEALTHCARE, INC., AUROBINDO PHARMA LTD., AUROBINDO PHARMA USA, INC., DR. REDDY'S LABORATORIES, INC., DR. REDDY'S LABORATORIES, LTD., EMCURE PHARMACEUTICALS LTD., HERITAGE PHARMACEUTICALS INC., GLENMARK PHARMACEUTICALS INC., USA, GLENMARK PHARMACEUTICALS LIMITED, HETERO USA, INC., HETERO LABS LIMITED UNIT-V, HETERO LABS LIMITED, MYLAN PHARMACEUTICALS, INC., PRINSTON PHARMACEUTICAL INC., STRIDES GLOBAL PHARMA PRIVATE LIMITED, STRIDES PHARMA, INC., TORRENT PHARMA INC., TORRENT PHARMACEUTICALS LTD., ZYDUS PHARMACEUTICALS (USA) INC., CADILA HEALTHCARE LTD., APOTEX INC., APOTEX CORP., SUN PHARMACEUTICAL INDUSTRIES, LTD., SUN PHARMACEUTICAL INDUSTRIES INC., SUN PHARMA GLOBAL FZE, Defendants HEC PHARM CO., LTD., HEC PHARM USA INC., Defendants-Appellants ______________________ 2021-1070 ______________________ Case: 21-1070 Document: 51 Page: 14 Filed: 06/21/2022 2 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. Appeal from the United States District Court for the District of Delaware in No. 1:18-cv-01043-KAJ, Circuit Judge Kent A. Jordan. ______________________ LINN, Circuit Judge, dissenting. The majority, while recognizing that written descrip- tion support is a fact-based inquiry based on the under- standings of a person of ordinary skill in the art, and while ultimately recognizing that the standard for negative limi- tations is the same as for any other limitation, nonetheless applies a heightened written description standard to the facts of this case in requiring not only a “reason to exclude” but a showing that the negative limitation in question was “necessarily excluded.” In doing so, the majority character- izes the district court’s fact finding as clearly erroneous and concludes that written description support for the no-load limitation is lacking. In my opinion, the district court ap- plied the correct standard and found ample support in the written description for the no-load limitation. For these reasons, I respectfully dissent. I A specification that “reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date” has adequate written description of the claimed invention. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). “[T]he test requires an objective inquiry into the four corners of the specification from the perspective of a person of ordinary skill in the art.” Id. Our case law makes clear that “[c]ompliance with the written descrip- tion requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the inven- tion claimed.’” Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 963 (Fed. Cir. 2002) (quoting Vas-Cath Inc. v. Case: 21-1070 Document: 51 Page: 15 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 3 Mahurkar, 935 F.2d 1555, 1562 (Fed. Cir. 1991)). It is well established that there is no “new and heightened standard for negative claim limitations.” Inphi Corp. v. Netlist, Inc., 805 F.3d 1350, 1356 (Fed. Cir. 2015). While the court in Santarus, Inc. v. Par Pharmaceutical, Inc. observed that “[n]egative claim limitations are adequately supported when the specification describes a reason to exclude the rel- evant limitation,” we did not hold that a specification must describe a reason to exclude a negative limitation. 694 F.3d 1344, 1351 (Fed. Cir. 2012). A specification that describes a reason to exclude the relevant negative limitation is but one way in which the written description requirement may be met. The majority begins its opinion with the recognition that a written description’s silence about a negative claim limitation, while serving as a “useful and important clue,” is not necessarily dispositive of whether that limitation is adequately supported. Maj. at 6. I agree. The majority concludes with a citation to Ariad for the proposition that “as with positive limitations, the disclosure must only ‘rea- sonably convey [] to those skilled in the art that the inven- tor had possession of the claimed subject matter as of the filing date.’” Maj. at 12 (citing Ariad, 598 F.3d at 1351). With that, I also agree. But the majority in its analysis employs the heightened standard of “necessary exclusion” against which to assess the district court’s fact findings in this case and uses that standard to conclude that the dis- trict court clearly erred. With that, I cannot agree. While a showing of “necessary exclusion” would most certainly provide written description support for a negative limita- tion, it is not and should not be a requirement in every case. As noted above and as Ariad makes clear, the critical ques- tion in assessing written description support for a negative limitation is the same as for any other limitation: “Does the written description reasonably convey to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date?” See Ariad, 598 F.3d Case: 21-1070 Document: 51 Page: 16 Filed: 06/21/2022 4 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. at 1351. How that question is resolved depends on the facts of each case, assessed through the eyes of the skilled arti- san. Our precedent makes that clear. For example, in Santarus, we found that claims di- rected to a method of treatment with a pharmaceutical composition containing no sucralfate were adequately de- scribed by a specification that explained that, although su- cralfate is “possibly the ideal agent for stress ulcer prophylaxis,” it was known to have occasional adverse ef- fects. 694 F.3d 1344, 1350–51 (Fed. Cir. 2012). In Santa- rus, as in this case, there was expert testimony providing a person of ordinary skill’s understanding of the patent spec- ification. See id. at 1351. The expert testimony in Santa- rus showed that “a person of ordinary skill in this field . . . would have understood from the specification that disad- vantages of sucralfate may be avoided by the [claimed] for- mulation.” Id. In In re Bimeda Research & Development Ltd., we held that a claim that excluded a specific anti-infective, acrifla- vine, was not adequately described by a disclosure that was inconsistent with the exclusion of acriflavine but not other anti-infectives or antibiotics. 724 F.3d 1320, 1324 (Fed. Cir. 2013). The claim at issue in Bimeda was directed to a method of preventing mastitis in dairy cows by sealing the teat canal of a cow’s mammary gland with a seal formula- tion that excludes acriflavine. Other claims in the same patent excluded all anti-infective agents. We noted that the patent repeatedly distinguished the invention as able to prevent mastitis without the use of antibiotics. Based on the written description’s consistent description of the in- vention’s non-antibiotic approach to preventing mastitis, we concluded that the patent’s disclosure was “inconsistent with a claim which excludes acriflavine, but not the pres- ence of other anti-infectives or antibiotics.” Id. (citation and quotation marks omitted). We did not require that the specification describe a reason to exclude acriflavine spe- cifically; rather, we found only that a negative limitation Case: 21-1070 Document: 51 Page: 17 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 5 which is inconsistent with the disclosure is not adequately described. In Inphi, we confirmed that the written description re- quirement is satisfied where “‘the essence of the original disclosure’ conveys the necessary information—‘regardless of how it’ conveys such information, and regardless of whether the disclosure’s ‘words [a]re open to different in- terpretation[s].’” 805 F.3d at 1354 (quoting In re Wright, 866 F.2d 422, 424–25 (Fed. Cir. 1989) (citation and internal quotation marks omitted, emphasis in Inphi)). We ex- plained that “Santarus simply reflects the fact that the specification need only satisfy the requirements of § 112, paragraph 1 as described in this court’s existing jurispru- dence.” Id. at 1356. And we noted that the “‘reason’ re- quired by Santarus is provided, for instance, by properly describing alternative features of the patented invention.” Id. (citing In re Johnson, 558 F.2d 1008, 1019 (C.C.P.A. 1977)). In Inphi, we found that substantial evidence supported the Patent Trial and Appeal Board’s (“Board”) finding that a negative limitation which had been added during prose- cution (“DDR chip selects that are not CAS, RAS, or bank address signals”) was adequately described by an original specification which did not expressly articulate a reason to exclude RAS and CAS signals. We found the Board’s deci- sion was supported by evidence of (1) standards set by the Joint Electron Device Engineering Council, a global stand- ard-setting body for the microelectronics industry, incorpo- rated by reference in the patent, which specify that DDR signals, including CAS, RAS, CAS, and bank address sig- nals, are distinct from each other; (2) a table in the specifi- cation which excludes RAS and CAS signals; and (3) various passages from the specification, including a figure which distinguishes chip select signals, command signals (including RAS and CAS signals) and bank address signals. We concluded that the specification’s disclosure of Case: 21-1070 Document: 51 Page: 18 Filed: 06/21/2022 6 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. alternative features was sufficient to satisfy the written de- scription standard for the negative limitation. Id. at 1357. In Nike, Inc. v. Adidas AG, we reiterated that Santarus did not create a heightened standard for written descrip- tion of negative limitations. 812 F.3d 1326, 1348 (Fed. Cir. 2016), overruled on other grounds by Aqua Prods., Inc. v. Matal, 872 F.3d 1290 (Fed. Cir. 2017) (en banc). We stated that negative limitations, like all other limitations, are held to “the customary standard for the written description requirement.” Id. In Nike, we found a limitation of “flat knit edges,” which Adidas characterized as a negative lim- itation, was adequately described by three figures in the specification depicting the claimed textile element which Nike’s expert opined could be made using flat knitting in contrast to another figure’s textile element which is formed using a circular knitting machine. Id. at 1348–49. The central tenet of our written description jurispru- dence—that the disclosure must be read from the perspec- tive of a person of skill in the art—further recognizes that the disclosure need not describe a limitation in haec verba. See, e.g., All Dental Prods., LLC v. Advantage Dental Prod., Inc., 309 F.3d 774, 779 (Fed. Cir. 2002) (citing Eiselstein v. Frank, 52 F.3d 1035, 1039 (Fed. Cir. 1995) (“[T]he failure of the specification to specifically mention a limitation that later appears in the claims is not a fatal one when one skilled in the art would recognize upon reading the specifi- cation that the new language reflects what the specifica- tion shows has been invented.”); see also Ariad, 598 F.3d at 1351. The Manual of Patent Examining Procedure (“MPEP”) similarly provides for written description in various forms. In addition to stating that the “mere absence of a positive recitation” is not enough, the MPEP also correctly states that no specific form of disclosure is required and provides Case: 21-1070 Document: 51 Page: 19 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 7 for implicit written description. 1 MPEP § 2173.05(i) states that “a lack of literal basis in the specification for a nega- tive limitation may not be sufficient to establish a prima facie case for lack of descriptive support.” And MPEP § 2163 states that “newly added claims or claim limitations must be supported in the specification through express, im- plicit, or inherent disclosure.” MPEP § 2163 (emphasis added). What is critical is how a person of skill in the art would read the disclosure—not the exact words used. In other words, context and the knowledge of those skilled in the art matter. And, as the Supreme Court has made clear, when assessing what the written description reveals to a skilled artisan, common sense also matters. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007) (holding that, in an obviousness analysis, “[r]igid preven- tative rules that deny factfinders recourse to common sense, however, are neither necessary under our case law nor consistent with it”). II Here, the district court conducted “an objective inquiry into the four corners of the specification from the perspec- tive of a person of ordinary skill in the art” and found suf- ficient written description in the EAE model and the Prophetic Trial. J.A. 37 (citing Ariad, 598 F.3d at 1351). The district court found that the “Prophetic Trial describes giving a ‘daily dosage of 0.5 . . . mg’ fingolimod to treat RRMS, started ‘initially.’” J.A. 26 ¶ 62 (quoting ’405 patent col. 11 ll. 8–13). The court found, crediting expert testi- mony, that, “[i]f a loading dose were directed, the Patent would say that a loading dose should be administered ‘ini- tially.’” J.A. 26 ¶ 62 (citing J.A. 23334–35 (Tr. 1 I cite the MPEP, not because the court is bound by it but because I find its reasoning informative and persua- sive. Case: 21-1070 Document: 51 Page: 20 Filed: 06/21/2022 8 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 756:16–757:8); J.A. 23441–42 (Tr. 863:22–864:18)). The district court thus made the unremarkable, and factually supported, determination that “starting with a daily dose plainly implies that there is no loading dose.” J.A. 27. Sim- ilarly, the district court found that the “EAE example dis- closes a dosing regimen which does not involve a loading dose.” J.A. 27 ¶ 64 (citing J.A. 23345 (Tr. 767:3–5); J.A. 22793 (Tr. 215:16–21)). The district court held that the de- scription in the specification of administration of a daily dose “would tell a person of skill that loading doses are ex- cluded from the invention.” J.A. 26 ¶ 61. The court also found that “[a] loading dose is necessarily a higher-than daily dose.” J.A. 27 ¶ 63 (Tr. 766:4-766:6). Finally, the court found that, while the patent describes alternate dos- ing regimens, such as “intermittent dosing,” it does not de- scribe administering those regimens with loading doses. J.A. 27 ¶ 65. Thus, the district court concluded, “[t]he EAE model and the Prophetic Trial . . . indicate to a person of ordinary skill that the claimed invention did not include the administration of a loading dose.” J.A. 37–38. The cited passages of the specification provide clear disclosure of a dosing regimen that is not dependent upon or subject to the administration of a loading dose. The majority finds that the word “initially” “speaks to the initial length of treatment not the dosage with which treat- ment begins.” Maj. at 7–8. Here, the district court found that the “Prophetic Trial describes giving a ‘daily dosage of 0.5 . . . mg’ fingolimod to treat RRMS, started ‘initially.’” J.A. 26. While other interpretations of the word “initially” might be reasonable, the language, used in context, also supports the district court’s finding that the written description dis- closes excluding a loading dose. We are not free to substitute our own factual findings for those of the district court absent clear error because “a district court judge who has presided over, and listened to, the entire proceeding has a compara- tively greater opportunity to gain the necessary ‘familiarity with specific scientific problems and principles,’ . . . than an Case: 21-1070 Document: 51 Page: 21 Filed: 06/21/2022 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 9 appeals court judge who must read a written transcript or perhaps just those portions referenced by the parties.” Teva Pharms. USA, Inc. v. Sandoz, Inc., 574 U.S. 318, 319 (2015) (quoting Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 610 (1950)). The majority asserts that the disclosure of a daily dos- age cannot amount to a disclosure that there can be no loading dose, because such a finding is at odds with the prosecution history and the fact that the examiner allowed the claims only after the no-load limitation was added. Maj. at 10. According to the majority, if reciting a “daily dosage” necessarily excluded a loading dose, there would have been no reason to add the no-dose limitation. Id. at 10:19-22. But Novartis, in adding the no-load limitation was doing no more than what applicants regularly do to secure allowance in making explicit that which was im- plicit prior to the amendment. There is no basis to read more into the prosecution history and certainly no basis to negate the clear disclosure of a “daily dosage” and the ex- pert testimony describing the understanding of that ex- pression to skilled artisans. The majority asserts that “the question is not whether the patentee intended there to be a loading dose; the ques- tion is whether the patentee precluded the use of a loading dose.” Maj. at 11. I submit that the question posed by the majority is misstated. The question is not whether the pa- tentee precluded the use of a loading dose but whether the claim language that precludes the administration of a load- ing dose is supported by the written description passages that disclose the effective administration of nothing more than a “daily dose.” In context, that disclosure, according to the testimony of the Novartis’s experts, implies the ab- sence of a loading dose to the ordinarily skilled artisan. That is all that is required. Finally, the majority finds significant tension between the district court’s finding that the specification’s Case: 21-1070 Document: 51 Page: 22 Filed: 06/21/2022 10 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. disclosure excludes a loading dose, but the Kappos 2006 ab- stract does not. Maj. at 9. I see no tension or legal incon- sistency in the district court’s treatment of the Kappos 2006 abstract. As the court explained, Kappos was an ab- stract with no presumption of enablement or completeness, and it in any event did not include the animal trials that form an important part of Novartis’s arguments with re- spect to the ’405 patent. As importantly, the district court also found no evidence that Kappos 2006 was publicly available before the priority date because there was no ev- idence of public access. J.A. 28. For all these reasons, I respectfully dissent.