Possession of an "Effective" Dose

Update: On March 16, 2022, the U.S. Court of Appeals for the Federal Circuit denied Biogen International’s petition for panel rehearing and rehearing en banc, following a November split decision discussed below.

Judges Lourie, Moore, and Newman dissented on the denial of en banc rehearing. Judge O’Malley had dissented from the November panel decision, but retired on March 11, 2022 and only participated in the decision on panel rehearing, not the decision on rehearing en banc.

The dissent indicates that the court remains divided regarding application of the written description requirement to the facts in this case.

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When does an applicant have “enough” to file a patent application and be granted a patent?

That question continues to dog applicants in the biopharmaceutical industry, particularly in view of recent Federal Circuit decisions concerning whether a patent application provides adequate written description for claims requiring functional limitations, such as administering an “effective” amount of a therapy.

Biogen Int’l GmbH v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2021).

In this recent split decision from the Federal Circuit, the majority affirmed a District Court decision that Biogen failed to demonstrate possession of a method of treating Multiple Sclerosis (MS) with a therapeutically effective dose of dimethyl fumarate (DMF) of about 480 mg per day claimed in Biogen’s U.S. patent 8,399,514 (the ’514 patent).

Claim 1 of the ’514 patent is representative and recites:

A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof a pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 [milligrams] per day [(mg/day)].

In its decision, the majority focused on the fact that the DMF480 dose is listed only once in the specification, and that the sole reference to DMF480 appears at the end of one range among a series of ranges, including DMF concentrations of 100–1,000, 200–800, 240–720, and 480–720 mg/day. In addition, the majority observed that the specification defines the term “effective” within a therapeutic, rather than drug-discovery, context, and the sole DMF-dosage paragraph is not linked to treatment of any specific disease, much less a neurological disorder including MS. The majority contrasted this disclosure with the description of DMF720, which is referenced independently as one dose and was known to be effective in treating MS as of the February 2007 priority date. The majority agreed with the district court that it was not necessary to distinguish between clinical efficacy and therapeutic efficacy, particularly because the specification’s definition of “therapeutically effective dose” indisputably featured both clinical and therapeutic insignia.

Judge O’Malley dissented, arguing that the District Court erred by disregarding Biogen’s explanations of the distinction between clinical efficacy and therapeutic efficacy, and that “the district court’s conflation of therapeutic and clinical efficacy caused it to erroneously require clinical data, rather than therapeutic effects.” Judge O’Malley further argued that the District Court erred in applying the Court’s “blaze marks” precedent to the claimed DMF480 dose, because the specification does not provide a “laundry list” of therapeutically effective doses, and begins one of several disclosed ranges with the exact DMF480 dose that is claimed.

Biogen filed a petition for rehearing en banc, saying the majority incorrectly created a heightened written description standard to “require that Biogen prove the efficacy of its claimed method, rather than describe the claimed invention.” It also objected to the majority’s “insistence on further repetition or singling out” of the DMF480 dose, saying that there is “no requirement that a specification repeat or single out a claimed embodiment.”

Several industry groups have urged the Federal Circuit to review the decision.[1] After Mylan filed a response on February 3, it remains to be seen whether the court will provide additional clarity to applicants regarding what is “enough” for written description.

Practice Tips

Patentees must balance competing factors for timing disclosure of inventions. Filing a patent application too late risks being beaten by a competitor. Filing too soon risks not adequately describing the claimed invention, while potentially poisoning the well for future filings. In particular, care should be taken in the timing for describing specific dosing regimen. The majority noted in Biogen that an inventor need not prove that a claimed pharmaceutical compound actually achieves a certain result, but when that result is expressed claimed in the claims, “our case law provides that [such] result must be supported by adequate disclosure in the specification.” Nuvo, 923 F.3d at 1384. Thus, applicants may want to avoid early disclosure of specific dosing regimens and pursue tailored dosing claims in later filings.

When disclosing a series of ranges, applicants should consider providing “blaze marks” to the ranges or values that are more likely to be effective. As highlighted in Biogen, even a short list of ranges may not be considered adequate support for claiming a particular endpoint within the ranges that is later proven to be effective. For example, calling out DMF480 individually or specifically connecting DMF480 (or even a range covering DMF480) to therapeutic efficacy for MS would have strengthened Biogen’s case for written description.

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[1] Biotechnology Innovation Organization, a division of the American Chemical Society, and Pharmaceutical Research and Manufacturers of America all filed amicus briefs on January 19, 2022, supporting Biogen’s petition for rehearing en banc.