Single mention of dose at lower end of range is insufficient written description, DC decision affirmed

Biogen International GmbH et al. v. Mylan Pharmaceuticals Inc.

Docket No. 2020-1933 (https://cafc.uscourts.gov/opinions-orders/20-1933.OPINION.11-30-2021_1871902.pdf)

O’MALLEY (dissent), REYNA, HUGHES

November 30, 2021

Brief Summary:  DC decision finding a lack of written description based on “[t]he specification’s sole reference to” the claimed dosage amount as well as inventor and expert testimony. Summary:  Biogen appealed DC finding that the claims of US 8,399,514 directed to methods of treating multiple sclerosis with dimethyl fumarate (DMF) invalid for lack of a written description of the claimed 480 mg per day dose.  The ‘514 patent is one of eight listed on the Orange Book for Biogen’s 240 mg DMF delayed release capsule (Tecfidera®).  The ‘514 patent claims a method for treating MS by administering “therapeutically effective amount of” DMF that is “about 480 [milligrams] per day [(mg/day)].”  The DC’s decision relied in large part on its understanding of “therapeutically effective amount” from the specification as well as inventor and expert testimony.  The FC wrote that “[t]he ’514 Patent specification largely tracks that of the original ’921 Application, which Biogen entitled ‘Nrf2 Screening Assays and Related Methods and Compositions’”, “casts a wide net for a myriad of neurological disorders” including MS, “methods to explore a potential protective role for the activation of the Nrf2 pathway”, “the totality of the specification focuses primarily on drug discovery” (“[c]onsistent with the disclosure’s original title concerning Nrf2 screening”), and “the invention’s title was only amended to ‘Treatment for Multiple Sclerosis’ in 2011 after Biogen acquired Phase III clinical data for the use of DMF480 in treating MS.”  The FC panel also wrote that “method 4” of the ‘514 patent examples refers to the use of DMF for treatment of “neurological disease” and that “[s]ave for one paragraph in the specification, the disclosure does not teach potential dosage levels for DMF”, that “one paragraph” including a range of “[e]ffective doses” of from about 480 mg to about 720 mg per day” (“the one and only reference to DMF480 in the entire specification”), and that it “defines the term “effective” within a therapeutic, rather than drug-discovery, context.”  “[A]ccording to the specification,” the FC panel wrote, “the terms ‘therapeutically effective dose’ and ‘therapeutically effective amount’ refer to that amount of a compound which results in at least one of prevention or delay of onset or amelioration of symptoms of a neurological disorder in a subject or an attainment of a desired biological outcome, such as reduced neurodegeneration (e.g., demyelination, axonal loss, and neuronal death) or reduced inflammation of the cells of the CNS.”  The FC wrote that Biogen added MS-related “wholly new claims” and an additional inventor (O’Neill) in 2011 “after gathering the Phase III results that demonstrated therapeutic efficacy of DMF480” without changing the specification but amending “the invention’s title” which “enabled Biogen to claim a priority date of February 8, 2007, despite filing wholly new claims alongside the amendments.”  It also pointed out that during the DC trial, the original inventor “denied that his research could be extrapolated to a clinical dose of DMF; it ‘was never the focus of [his] work to inform the clinical dosing of [DMF].’”  And Biogen’s expert “conceded during cross examination that the sole DMF-dosage paragraph in the specification did not teach a POSA that DMF480 would be therapeutically effective for treating MS”.  The FC panel explained that “‘possession as shown in the disclosure,’ therefore, represents the hallmark of written description” (Ariad, FC 2010).  It also explained that “[t]he specification’s sole reference to DMF480 constitutes a significant fact that cuts against Biogen’s case, particularly because it appears at the end of one range among a series of ranges”, as did the inventor and expert testimony.  Citing Nuvo (FC 2019), it wrote that “[a]n inventor need not ‘prove that a claimed pharmaceutical compound actually achieves a certain result”, [“b]ut when the inventor expressly claims that result, our case law provides that [such] result must be supported by adequate disclosure in the specification.”  And, here, the FC panel found that the DC “did not clearly err in finding that a skilled artisan would not have recognized, based on the single passing reference to a DMF480 dose in the disclosure, that DMF480 would have been efficacious in the treatment of MS, particularly because the specification’s only reference to DMF480 was part of a wide DMF dosage range and not listed as an independent therapeutically efficacious dose” and Biogen’s later establishment of “the therapeutic efficacy of DMF480 is of no import to the written-description analysis.”  The FC panel therefore affirmed the DC’s decision.  Judge O’Malley dissented, writing that the DC decision should be remanded for reconsideration of the “distinction between clinical and therapeutic effects”.

This entry was posted in Generics / ANDA, Inter Parties Review (IPR), IPR, Written description. Bookmark the permalink.

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